– ViaSat-3 F2, second of three ultra-high-capacity satellites Boeing is building for global network operator Viasat, launched via United Launch Alliance’s Atlas V
CAPE CANAVERAL SPACE FORCE STATION, Fla., Nov. 14, 2025 — Boeing [NYSE: BA] mission controllers confirmed the second ViaSat‑3 satellite, built on the company’s high‑power 702MP+ platform,…
Lori Carnochan,Dumfries and Galloway reporterand
Jamie Russell,BBC Scotland News
Mitchell familyA couple who decided to save their local church took just two days to raise the money to make the purchase – thanks to donations from well-wishers around the world.
Andrew and Kirsteen Mitchell crowd-funded £70,000 to buy Applegarth Church near Lockerbie following an appeal to members of Clan Jardine, whose ancient family set lies within the tiny hamlet.
Descendants from the United States, South Africa and Canada put their hands in their pockets to help secure the future of the building.
The couple, who kick-started the fundraising campaign with a £15,000 donation, have now established a charity for the church to be used as a place for weddings, funerals and events.
“In 48 hours we had raised more than the asking price of £55,000. We were astounded,” the couple said.
Mitchell familyThe church closed in 2023 and since then the Applegarth congregation has merged with others in nearby Lockerbie.
It was put on the market by the Church of Scotland earlier this year – one of several properties it is selling to cover rising costs amid shrinking congregations.
Mr and Mrs Mitchell own the neighbouring manse property, which was once home to the church minister and is also used as luxury accommodation.
The couple wanted to preserve the history of the church and the building itself, which had been earmarked for a potential recording studio or storage facility.
“I emailed families who had stayed with us over the years – not just Jardines, but those who had come to find their forebears in the churchyard. In particular a family of Beatties in Canada”, said Kirsteen.
One Jardine family donated about £30,000 towards the purchase price of the church, which dates back to 1760.
Mitchell familyMrs Mitchell said: “We believe a church has stood on this site in some capacity since around 600 AD. We’re overwhelmed by all of those who have come forward to offer support.”
The church has served as the spiritual home of the Jardine family, who were among the infamous Border Reivers and frequently carried out raids over the border between the 13th and 15th centuries.
A ceremony and a blessing to mark the keys being officially handed over to the newly established Friends of Applegarth Church, which is now a registered Scottish charity, will be held at the church on 30 November.
Clan Chief Sir William Jardine will be in attendance with his family, alongside visitors from the United States and South Africa.
“Credit to my husband Andrew who has been instrumental in establishing the charity,” Mrs Mitchell said.
“We welcome anyone with an interest in the church to come along to the ceremony.
“We are interested to hear ideas about potential future use and look forward to marking this next chapter.”
It is the second time this year a clan has saved a south Scotland church this year.
Members of Clan Turnbull stepped in to preserve Ruberslaw Parish Church at Bedrule – between Hawick and Jedburgh – during the summer.
Italian company Bending Spoons flew largely under the radar — until last month. In a span of 48 hours, the company announced the acquisition of AOL and a massive $270 million raise, quadrupling its valuation to $11 billion, up from $2.55 billion set in early 2024.
Bending Spoons has grown rapidly by acquiring stagnating tech brands like Evernote, Meetup, and Vimeo, then turning them profitable through aggressive cost-cutting and price increases. While the company’s approach is similar to private equity, there is one key difference: Bending Spoons has no plans to sell these businesses.
Andrew Dumont, the founder and CEO of Curious, a firm that also acquires and revitalizes what he calls “venture zombies,” is convinced this “hold forever” strategy will become increasingly prominent in the coming years as AI-native startups make older VC-backed software businesses less relevant.
“Our belief is that the venture power law, in which 80% of companies ‘fail,’ produces many great businesses, even if they’re not unicorns,” Dumont told TechCrunch.
Dumont defines a “great business” as one that can be purchased at a low price and quickly revived to generate substantial cash flows. This “buy, fix, and hold” strategy is the playbook for a growing number of investors, from the 30-year-old Constellation Software, which pioneered the model, to newer players, including Bending Spoons, Tiny, SaaS.group, Arising Ventures, and Calm Capital, according to Dumont.
“Our whole model is to buy these companies, make them profitable, and use those earnings to grow the business,” Dumont said.
In 2023, Curious raised $16 million in dedicated capital for buying software companies that have stalled and can no longer secure follow-on investment.
Since then, the firm has bought five businesses, including UserVoice, a 17-year-old startup that raised $9 million in VC funding from Betaworks and SV Angel.
“It’s a great business, but the cap table wasn’t aligned with keeping it. These funds get old, and these companies just sit there,” Dumont said. “We provide liquidity and also reset these companies for profitability.”
Although Dumont didn’t disclose how much he paid for UserVoice, he said that stagnant companies sell for a fraction of the valuation commanded by healthy SaaS startups, which typically sell for 4x annual revenue or more. Based on our conversation, we estimate that “venture zombies” sometimes sell for as low as 1x yearly revenue.
By implementing cost-cutting and price increases, Curious can push these businesses to achieve 20% to 30% profit margins almost immediately. “If you have a million-dollar business, you’re kicking off $300,000 in earnings,” he offered as an example.
(Bloomberg) — Asian stocks were set for a third day of gains, tracking similar advances on Wall Street as weak US consumer data lifted bets of a Federal Reserve interest rate cut next month.
Equity-index futures pointed to strong starts for Japan and Australia, with a more modest increase for Hong Kong, at Wednesday’s open. In the US, the S&P 500 rose 0.9% and the Nasdaq 100 climbed 0.6% in choppy sessions as Alphabet Inc. threatened Nvidia Corp.’s dominance in the artificial intelligence sector.
Delayed economic reports out of the US further cemented bets for a Fed cut in December, with traders now pricing in a roughly 90% chance. Retail sales rose modestly in September, suggesting consumer spending is cooling after months of strong demand. While wholesale inflation picked up, consumer confidence in November saw its steepest drop since April.
“Downbeat economic data is delivering gains to stock and bond bulls alike, as weaker-than-expected retail sales and consumer confidence numbers coincide with accelerating job losses and rising odds of a December Fed cut,” said José Torres, senior economist at Interactive Brokers.
The latest US economic reports have taken on added weight ahead of the Fed’s December meeting, given the lack of fresh data. Governor Stephen Miran underscored that outlook by reaffirming his belief that the US economy requires substantial interest‑rate reductions. While the Fed typically adjusts rates in 25‑basis‑point increments, it has on occasion moved by 50 basis points or more.
White House National Economic Council Director Kevin Hassett’s emergence as the frontrunner to replace the Fed chair helped drive Treasury yields down, with the 10‑year slipping to 4% for the first time in a month. The dollar slipped 0.3%.
Traders bolstered bets on lower rates over the next year, reflecting the view that a Hassett‑led Fed would deliver the aggressive cuts that President Donald Trump has advocated.
“The argument will be a weaker US dollar, lower front-end rates from May’s meeting onwards and steeper curves,” said Jordan Rochester, a head of macro strategy at Mizuho in London. Hassett is “a credible economist by background, previously working at the Fed as a senior economist, but some may argue his closeness to Trump makes him the patsy.”
In Asia, recent weakening of the yen is increasing the likelihood of the Bank of Japan raising its benchmark rate next month, according to a former executive director of the central bank. The currency hit a fresh 10-month low against the dollar last week and is fueling inflationary pressure via higher import costs.
AI Battle
Alphabet shares jumped 1.6%, moderating earlier gains, after a report that Meta Platforms Inc. was in talks to spend billions on Google’s artificial-intelligence chips. Nvidia shares dropped 2.6%, pulling back from gains it made in Monday’s tech-fueled rally.
“Nvidia’s dominant position is unlikely to be fundamentally threatened in the short-term, but markets are all about forward expectations, and it certainly seems like Alphabet is poised to snatch market share away from Jensen Huang’s empire,” said Chris Beauchamp, chief market analyst at IG.
The rally in Alphabet shares is poised to shake up the rankings of the world’s most valuable companies. A potential changing of the guard comes at a time when the AI industry has come under scrutiny, with stretched valuations causing some volatility.
Elsewhere in commodities, oil fell as signs of progress in peace talks between Ukraine and Russia buoyed expectations that Moscow’s supply will stay online. Gold closed little changed.
Some of the main moves in markets:
Stocks
Nikkei 225 futures rose 1% as of 7:26 a.m. Tokyo time Hang Seng futures rose 0.3% S&P/ASX 200 futures rose 1.1% Currencies
The Bloomberg Dollar Spot Index fell 0.3% The euro was little changed at $1.1571 The Japanese yen was little changed at 156.00 per dollar The offshore yuan was little changed at 7.0825 per dollar The Australian dollar was little changed at $0.6467 Cryptocurrencies
Bitcoin was little changed at $87,086.84 Ether was little changed at $2,928.49 Bonds
Australia’s 10-year yield was little changed at 4.43% This story was produced with the assistance of Bloomberg Automation.
©2025 Bloomberg L.P.
In a securities filing, JBS said the new company will be called JBS VIVA and will be owned 50% by JBS and 50% by Viva’s shareholders — Vanz Holding and Viposa.
Sign up here.
The company will process more than 20 million leathers per year, with 31 factories and over 11,000 employees, JBS said, adding that the deal still lacks conditions including the signature of definitive agreements.
JBS will name the chairman and the Chief Financial Officer of JBS VIVA, while Viva’s shareholders will appoint the Chief Executive Officer and the Chief Operating Officer, according to JBS.
Reporting by Andre Romani, Editing by Natalia Siniawski
Our Standards: The Thomson Reuters Trust Principles.
Investigators have identified the source of a leak in the Olympic pipeline two weeks after fuel was first spotted in a ditch near an Everett, Washington, blueberry farm.
Oil and gas company BP, the operator of the pipeline, shared in a statement that it had determined the leak occurred in a 20in pipeline and not a neighboring 16in pipeline, allowing that pipeline to be restarted.
“Repair plans for the 20-inch segment are being developed and a timeline for repair and restart will be shared when available,” BP said.
The news follows announcements by the Washington and Oregon governors, Bob Ferguson and Tina Kotek, respectively, declaring states of emergency due to the disruptions in fuel supplies. The Olympic pipeline carries gasoline, diesel, jet fuel and other petroleum products to both states, including 90% of Oregon’s transportation fuel and much of the Seattle-Tacoma international airport’s jet fuel.
The leak was first reported on 11 November between the Washington towns of Everett and Snohomish. The state department of ecology determined the leak consisted of a combination of gasoline, jet fuel and diesel. BP shut off two pipelines that ran side by side in the Olympic pipeline system to determine the source of the leak, either a 16in or a 20in pipeline.
On 16 November, the company restarted the 16in pipeline, but shut if off again after observing “an increase in product observed in a collection point”, it said in a statement.
Later that week, on 19 November, Ferguson issued a state of emergency in Washington, waiving state regulations to allow commercial vehicle operators to drive longer hours to transport jet fuel to Seattle-Tacoma airport.
Kotek followed suit in Oregon on Monday, declaring a similar state of emergency and waiver of commercial driving regulations.
In statements to Reuters on Monday, major airlines operating through Seattle-Tacoma and the airport itself said they had developed contingencies to prevent disruptions to holiday travel.
“We do not expect disruption to our operations at Seattle-Tacoma international airport through the Thanksgiving travel week,” Alaska Airlines said, adding that it had brought extra fuel into Seattle on inbound flights and additional trucking shipments, and added fuel stops to certain flights.
Delta Air Lines similarly said it had transported additional fuel to the airport and added refueling stops to some long-haul flights.
On Monday, BP reported that it had excavated “over 200 feet of pipeline” and expected to “continue overnight operations tonight”. By Tuesday morning, the company had found the source of the leak.
In updated statements to Reuters on Tuesday, Delta said it “is operating our full Seattle hub schedule and has discontinued fuel stops on select long-haul flights”. Alaska added that it had “discontinued all planned fuel stops but will continue to tanker and truck in additional fuel on a reduced basis as the pipeline increases to normal capacity”.
Repairs to the 20in pipeline come as Washington state’s ecology department has fined BP $3.8m for a 2023 gasoline spill from the Olympic pipeline. The Olympic pipeline has leaked at least 13 times since 1999, when a leak near Bellingham caused an explosion that killed a teenager and two younger children. According to the Pipeline Safety Trust, a Washington state-based non-profit, the pipeline has leaked three times in 2025.
“These incidents have caused over $100m in property damage,” Kenneth Clarkson, spokesperson for the Pipeline Safety Trust, said in a statement to the Associated Press. “Olympic Pipeline must explain what has changed and what they’re doing to stop it.”
On 4 November 2025 the UK High Court
handed down its judgment in the case of
Getty Images (US) Inc (and others) v Stability
AI Limited [2025] EWHC 2863 (Ch) [High
Court Judgment Template].
As one of the first and to date most high-profile intellectual
property (IP) infringement claims against an AI developer to
make it all the way to trial in the UK courts, the case was
originally envisaged as having potential to provide muchneeded
wide-ranging judicial guidance on the application
of existing UK IP law in the field of AI. However, as the
case progressed and the scope of Getty’s claims gradually
reduced to a shadow of the original, it became apparent that
this judgment, whilst still of note in respect of a number of
key issues, would not be the silver bullet which many had
originally anticipated.
At over 200 pages (alongside an accompanying glossary of
key technical terms and appendix concerning the context in
which an average consumer would encounter certain Getty
registered trade marks) the judgment is long and complex,
including detailed discussion of the witness and expert
evidence which the Court considered before reaching its
findings.
Read full insight to learn more.
The increased life expectancy is one of the greatest achievements of global health systems. However, this increase has led to a substantial rise in age-related neurological disorders, particularly Alzheimer disease and other dementias, necessitating health policies to focus [], not only on survival but also on minimizing health loss due to disability by promoting function and independence []. Estimation suggested an increase from 57 million people living with dementia in 2019 to 153 million by 2050 []. Between 1990 and 2021, the disability-adjusted life years attributed to dementia increased by 168.7% (95% CI 156.3-179.9), driven by population aging []. By 2021, dementia ranked as one of the top 10 neurological conditions globally, with a particularly high burden in people aged 80 years and older []. Mild cognitive impairment (MCI) is a bidirectional transitional stage between dementia and normal cognitive aging, often with unrecognized early symptoms, with 10%-15% of affected individuals progressing to dementia annually []—a risk 3.3 times higher than that of the general older population []. Therefore, MCI represents a critical window for dementia prevention and intervention, with early identification and intervention being essential for reducing dementia incidence. Achieving a cost-effective community intervention has become a critical priority in public health [].
Exercise intervention and cognitive training (CT) can effectively improve cognitive functions []. Mind-body exercise, such as Taichi and yoga, is a promising exercise type incorporating physical, cognitive, social, and mindfulness components in exercise [] that may have a better cognitive management effect than other types of exercise [].
Recent evidence suggests that both mind-body exercises and technology-enhanced interventions show promise for MCI prevention []. Systematic reviews demonstrate that Taichi significantly improves cognitive function in older adults with MCI, particularly executive function and memory []. Similarly, virtual reality (VR) technology has emerged as a powerful cognitive rehabilitation tool, offering ecological validity and real-time adaptability that traditional training lacks. VR-based interventions demonstrate significant improvements in memory, attention, and executive function in populations with MCI [,]. However, fewer studies synerized the potential effects of combining traditional mind-body exercise with VR technology using adaptive intervention strategies.
Systematic reviews and meta-analyses have shown that dual-task intervention combining cognitive function training and physical activity is more effective in improving cognition and physical function than physical activity intervention [,]. This synergistic effect is explained by the guided plasticity facilitation framework, whereby exercise facilitates neuroplasticity by increasing brain-derived neurotrophic factor production and cell proliferation, while cognitive interventions guide this plasticity by enhancing the survival of exercise-induced new cells. Additionally, multicomponent exercise research confirms positive effects on global cognition (effect size=0.32, 95% CI 0.03-0.61), particularly when aerobic exercise is included, supporting the mechanistic basis of the muscle-brain axis in exercise-induced neuroprotection [,].
The Healthy Ageing Through Internet Counselling in the Elderly (HATICE) trial is a multinational preventive intervention study based on coaching support and is a low-cost and scalable intervention model. HATICE provides remote personalized adaptive intervention through coaching, reduces the burden of cardiovascular disease, and improves cognitive function []. STRONGER 60+ also pays attention to the need for adaptive intervention. This model is based on the multicomponent intervention of The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) [,], but focuses more on how to achieve adaptive intervention []. However, current clinical guidelines and expert consensus on multidomain intervention for MCI and dementia prevention provide a range of content and duration that is too wide to make the specific guidance for adaptation in community and clinical practice [,,,], and the current training components and duration of multidomain intervention still depend on experience and experience-based approaches [].
The dose-response relationship study of CT found that there is an optimal point for the intervention duration, and the optimal duration of the intervention is affected by the age of the participants []. Observational studies have also found that age and comorbidities affect the prevention and progression of MCI [,]. Meanwhile, inappropriate strategy selection might reduce treatment adherence and compromise the critical intervention window []. Therefore, how to achieve adaptive intervention, explore which factors, and formulate adaptive intervention duration (or doses) based on these factors are the key to nonpharmacological prevention of MCI and remain to be developed.
We used a 2-stage sequential, multiple assignment, randomized trial (SMART) design to develop evidence-based adaptive intervention strategies [] for optimizing cognitive function among older adults with MCI. The SMART design involved CT combined with either offline Taichi (OffTC) or virtual reality Taichi (VRTC). Participants who did not respond adequately to initial treatment (early treatment nonresponders) were rerandomized to receive either treatment intensification or modified treatment components.
The primary aim was to compare the effectiveness of CT+OffTC versus CT+VRTC versus control on long-term cognitive outcomes. Among early treatment nonresponders, we evaluated whether treatment intensification or component modification produced superior cognitive improvements. We hypothesized that both active interventions would demonstrate greater cognitive benefits compared with control and that treatment intensification would be more effective than component modification among nonresponders. The secondary aims assessed baseline characteristics that predict treatment response and effect modification. We hypothesized that age, baseline cognitive function, and comorbid conditions would influence both response status and treatment effectiveness.
The study was conducted in 3 randomly selected districts in Shanghai between April and December 2023. A multistage stratified cluster random sampling method was used for participant recruitment. Based on geographical location and economic development level, 3 districts were randomly selected from the Shanghai municipality. Within each selected district, 2 subdistricts were randomly chosen, and subsequently, 3 communities were randomly selected from each subdistrict using cluster sampling. This sampling approach ensured geographical and socioeconomic diversity in the study population while maintaining feasibility for intervention delivery through existing community health service infrastructure.
This study was reported according to the Consolidated Standards of Reporting Trials (CONSORT 2025) for randomized trials, detailed in [].
OffTC intervention implemented the standardized 24-form simplified Taichi exercise regimen, developed by the National Sports Administration. Modifications were implemented for balance-intensive movements (right kick, double ear boxing, left turning kick, left standing stance, and right standing stance) to enhance safety while maintaining form integrity.
The VRTC intervention used identical 24-form simplified Taichi movements implemented through an immersive technological interface. The VR system incorporated precise arm-length calibration to accurately track upper and lower extremity movement trajectories.
CT used the Thoven Cognitive Training System (TCSA-BOT, developed by Shanghai Thoven Intelligent Technology Co, Ltd), a comprehensive platform targeting multiple cognitive domains: memory, attention, executive function, logical reasoning, and reaction time. The system was specifically adapted for this research protocol and implemented via a customized WeChat mini-program interface.
This study used a 24-week SMART design, comprising two 12-week intervention phases. In the first stage, the intervention consisted of 1 hour of weekly CT combined with 1 hour of weekly exercise per week, structured as a dual-task training program incorporating both cognitive and physical elements.
Participants were initially randomized into 3 groups: control group, CT+OffTC, and CT+VRTC. At week 12, participants were assessed based on 2 questions assessed by a 5-point Likert scale: (1) perceived effectiveness of their current intervention and (2) proficiency in both CT and Taichi exercises. Participants would be marked as nonresponders, if any question scored less than 3 points.
For the second phase, CT+OffTC responders continued their original intervention protocol. Nonresponders from CT+OffTC were randomly assigned to either CT+VRTC or doubled doses of their original intervention (2CT+2OffTC). Similarly, CT+VRTC responders maintained their initial intervention, while nonresponders were randomly assigned to either CT+OffTC or doubled doses of their original intervention (2CT+2VRTC).
All interventions were conducted at designated community health centers within the 3 participating districts in Shanghai. OffTC sessions were led by certified Yang-style Taichi instructors with a minimum of 5 years of experience teaching older adults, while VRTC sessions used Meta Quest with Guided Tai Chi software (developer: Cubicle Ninjas) providing immersive virtual environments featuring professionally recorded Yang-style Taichi instruction and real-time movement tracking without requiring external controllers or television displays. Each VRTC session included 5-minute acclimatization periods and integrated safety features. CT was delivered through the TCSA-BOT WeChat mini-program interface, with research staff supervision during weekly 60-minute community center sessions and optional home access via participants’ smartphones. Control group health education consisted of weekly 45-minute group sessions covering general wellness topics, delivered by qualified health educators in the same community facilities, detailed intervention program in and VRTC sample video in .
After baseline assessment, participants were randomly assigned to the intervention groups or the control groups. In the first 12 weeks of the 24-week SMART intervention, participants in the intervention group were randomly assigned to receive either weekly 1-hour CT plus 1-hour Taichi or CT plus VRTC. In the 12th week, participants were assessed for intervention mastery, with nonresponders those who are unable to master the content of the intervention, the Likert 5-point scale evaluates the mastery of the intervention content to be less than 3, being rerandomized to alternative or intensified interventions. The control group received only health education and routine care. Randomization was performed with the use of a computer-based code generated by members of the research team at the School of Public Health at the Shanghai Jiao Tong University School of Medicine. Due to the dosage assignment of the intervention being changed during treatment, study participants and staff were aware of treatment allocation, but researchers responsible for data analysis were masked to the allocation groups.
Participants were recruited from 3 randomly selected districts in Shanghai. We screened community-dwelling older adults using the Montreal Cognitive Assessment (MoCA) and Memory Guard score (MGs).
Study eligibility criteria included: age ≥60 years, MCI diagnosis established through positive screening on the MGs, and meeting the 2018 Chinese guidelines for MCI diagnosis []. Exclusion criteria encompassed: communication disorders, severe impairment in activities of daily living, presence of metal implants, severe psychiatric disorders, illiteracy, cognitive decline attributable to other pathologies, history of neurological diseases, exercise contraindications, color blindness, insufficient education to complete testing protocols, concurrent rehabilitation therapy, or unwillingness to complete the 24-week intervention and follow-up. Additionally, participants with regular exercise experience (eg, Taichi and Baduanjin) within the preceding 3 months were excluded to prevent contamination effects.
The primary outcome is cognitive status at 24 weeks (end of the trial), measured by MGs. MoCA was used for baseline cognitive screening and participant categorization.
The MoCA is a widely validated cognitive screening instrument that assesses multiple cognitive domains including visuospatial and executive functions, naming, memory, attention, language, abstraction, delayed recall, and orientation []. The MoCA uses a 30-point scale, with scores ≤26 indicating possible cognitive impairment []. In our study [], MoCA was administered at baseline to categorize participants into cognitive risk groups.
MGs is a computerized neuropsychological assessment device that evaluates 6 cognitive domains: orientation, memory, attention, calculation, recall, and language and executive function []. The assessment incorporates both accuracy scores (correct or incorrect responses) and response time data, using machine learning algorithms to provide a comprehensive cognitive evaluation. MGs demonstrates excellent diagnostic performance with an accuracy of 93.75% and an area under the curve of 0.923, achieving high sensitivity (91.67%) and specificity (95.45%) for MCI detection []. The interassessment agreement between MoCA and MGs reached κ=1.0, indicating perfect concordance and validating the reliability of our cognitive measurements. The computerized format allows for standardized administration, objective measurement of cognitive performance, and real-time data collection, making it particularly suitable for detecting cognitive changes in intervention studies.
The primary exposures in this study were the intervention modalities assigned through the 2-stage SMART design: control, CT+OffTC, and CT+VRTC. Detailed descriptions of each intervention component, delivery methods, and the rerandomization process for nonresponders have been provided in the “Procedures” section above.
Potential confounding variables were identified based on existing literature on cognitive function interventions and measured at baseline through standardized protocols by trained research staff. Demographic characteristics included age (continuous variable in years, assessed through participant self-report), sex (binary: male or female, obtained from participant demographics), and education level (continuous variable in years). Socioeconomic status was measured through self-reported monthly household income, categorized in Chinese yuan (¥; US $1= ¥7.11).
Clinical characteristics assessed at baseline included BMI (in kg/m², calculated from measured height and weight using calibrated equipment). Comorbid conditions were assessed as binary variables (yes or no) through self-report, including diabetes (assessed through physician diagnosis or current use of antidiabetic medications), hypertension (assessed through physician diagnosis or current use of antihypertensive medications), cancer, cardiovascular disease, chronic kidney disease, fracture history, respiratory disease, and digestive disease.
The intervention was designed to find the optimal adaptive intervention based on individual responses to initial treatment assignments. The sample size of the SMART design relied on the response rate. Response rate indicates whether the intervention is effective. According to the previous studies on physical activity intervention [,] and response rate simulation [,], we hypothesized the response rate of 0.60, the type I error rate of 0.05, a desired half-width of the CI of 0.45, and the required sample size of SMART intervention group is 54 [] based on precision-based sample size calculation.
Baseline characteristics were summarized using descriptive statistics, with continuous variables presented as means (SD) and categorical variables as frequencies (percentages). Group comparisons were performed using t test for normally distributed continuous variables and the chi-square test for categorical variables.
The primary analysis used intention-to-treat principles comparing 24-week memory scores across treatment groups (CT+OffTC, CT+VRTC, and control) using linear regression adjusted for baseline MGs, age, education, sex, hypertension, and diabetes. Pairwise comparisons between groups were conducted with Bonferroni correction for multiple testing. Effect sizes were calculated as Cohen d with 95% CIs.
Secondary analyses evaluated treatment strategies among early treatment nonresponders (defined as insufficient memory improvement at 12 weeks) using linear regression models comparing treatment intensification versus switching Tai Chi modality, adjusted for 12-week memory scores and baseline characteristics. Dynamic treatment regimen analysis compared embedded treatment sequences using the same covariate-adjusted linear regression approach. Treatment response prediction used linear regression and logistic regression models to identify baseline characteristics associated with 12-week response status. Subgroup analysis was assessed using interaction terms for age group, baseline memory function, hypertension, and diabetes status.
All statistical tests were 2-sided with a significance threshold of P<.05. Bootstrap resampling (1000 iterations) was used to construct 95% CIs and assess statistical significance.
This study was reviewed and approved by the Public Health and Nursing Research Ethics Committee of Shanghai Jiao Tong University School of Medicine (approval number: SJUPN-202008, on November 19, 2020) prior to participant recruitment and registered with the Chinese Clinical Trial Registry on January 27, 2021, ChiCTR2100042748. The study protocol, informed consent procedures, and all study materials received full ethical approval.
Written informed consent was obtained from all participants prior to enrollment. The consent process included detailed explanations of (1) study purpose, procedures, and duration; (1) potential risks and benefits of participation; (3) voluntary nature of participation and right to withdraw at any time without penalty; (4) data collection, storage, and use procedures; and (5) contact information for study personnel and ethics committee. All participants demonstrated the capacity to provide informed consent through cognitive screening assessments.
All study data were deidentified using unique participant identification codes, with the linking key stored separately from study data in a secure, password-protected database accessible only to authorized research personnel. Data analysis was conducted using only deidentified datasets.
Participants received modest compensation for their time and effort, including transportation reimbursement (¥50 [US $7] per visit; currency conversion based on exchange rate as of October 8, 2025) for assessment sessions and a completion incentive (¥200 [US $28] for those who finished the full 24-week intervention period. Compensation was provided regardless of intervention adherence or study outcomes to avoid coercion.
No images containing identifiable participant information are included in this manuscript or supplementary materials.
Harms including falls, heat exhaustion, dizziness, and VR-related symptoms were assessed nonsystematically through participant self-report and instructor observation throughout the 24-week intervention period.
Between April and December 2023, a total of 686 individuals were assessed for eligibility, of whom 563 were screened as ineligible due to normal cognitive function. Of the 123 participants who met eligibility criteria, 30 declined participation due to COVID-19 pandemic concerns regarding in-person study visits and health safety protocols, and 1 withdrew prior to randomization, resulting in 92 participants entering Stage I randomization. Participants were allocated to 3 groups: 26 to control, 33 to OffTC+CT, and 33 to VRTC+CT.
Following Stage I intervention, responders continued their allocated treatments while nonresponders proceeded to Stage II randomization with alternative interventions. In the control group, 20 participants completed the study with 6 withdrawals. Among OffTC+CT participants, 22 responders continued treatment with 21 completing it, while 11 nonresponders were randomized to alternative treatments (6 to 2OffTC+2CT and 5 to VRTC+CT). In the VRTC+CT group, 20 responders completed treatment, while 13 nonresponders underwent Stage II randomization (6 to 2VRTC+2CT and 7 to OffTC+CT) with completion rates of 4/6 and 7/7, respectively ().
The final sample consisted of 81 participants, and the response rate was 64.18% which met the assumption of sample calculation. The study population was predominantly female (65.4% overall), with similar gender distributions across groups (60.0%, 66.7%, and 67.7%, respectively; P=.84), detailed in . All interventions were delivered as intended by certified instructors showing >95% fidelity to standardized procedures.
| Variables | Overall | Control | OffTCb+CTc | VRTCd+CT | P value | |||||
| Observation | 81 | 20 | 30 | 31 | ||||||
| Female sex, n (%) | 53 (65.4) | 12 (60.0) | 20 (66.7) | 21 (67.7) | .83 | |||||
| Education (years), mean (SD) | 10.55 (2.94) | 11.10 (3.60) | 10.63 (3.02) | 10.11 (2.39) | .50 | |||||
| Income, CNY (USD), n (%) | .53 | |||||||||
| < 10,000 (< 1430) | 1 (1.2) | 0 (0.0) | 1 (3.3) | 0 (0.0) | ||||||
| 10,001-30,000 (1431-4285) | 12 (14.8) | 5 (25.0) | 5 (16.7) | 2 (6.5) | ||||||
| 30,001-60,000 (4286-8570) | 49 (60.5) | 11 (55.0) | 18 (60.0) | 20 (64.5) | ||||||
| 60,001-90,000 (8571-12,855) | 11 (13.6) | 3 (15.0) | 4 (13.3) | 4 (12.9) | ||||||
| 90,001 120,000 (12,856-17,140) | 6 (7.4) | 0 (0.0) | 2 (6.7) | 4 (12.9) | ||||||
| > 120,001 (> 17,141) | 2 (2.5) | 1 (5.0) | 0 (0.0) | 1 (3.2) | ||||||
| Age (years), mean (SD) | 71.38 (6.49) | 72.75 (7.53) | 72.37 (6.88) | 69.55 (5.00) | .13 | |||||
| Diabetes, n (%) | 11 (13.6) | 4 (20.0) | 4 (13.3) | 3 (9.7) | .57 | |||||
| Hypertension, n (%) | 24 (29.6) | 8 (40.0) | 8 (26.7) | 8 (25.8) | .50 | |||||
| BMI, mean (SD) | 24.06 (2.75) | 24.87 (2.58) | 23.75 (3.03) | 23.83 (2.56) | .31 | |||||
| MGse, mean (SD) | 27.61 (3.55) | 27.99 (3.31) | 27.25 (4.31) | 27.72 (2.92) | .75 | |||||
| MoCAf, mean (SD) | 22.19 (2.15) | 21.50 (2.28) | 22.20 (2.22) | 22.61 (1.93) | .19 | |||||
| Cancer, n (%) | 8 (9.9) | 2 (10.0) | 1 (3.3) | 5 (16.1) | .24 | |||||
| Cardiovascular disease, n (%) | 9 (11.1) | 1 (5.0) | 3 (10.0) | 5 (16.1) | .45 | |||||
| Chronic kidney disease, n (%) | 2 (2.5) | 0 (0.0) | 1 (3.3) | 1 (3.2) | .71 | |||||
| Fracture, n (%) | 8 (9.9) | 3 (15.0) | 2 (6.7) | 3 (9.7) | .62 | |||||
| Respiratory disease, n (%) | 3 (3.7) | 0 (0.0) | 3 (10.0) | 0 (0.0) | .07 | |||||
| Digestive disease, n (%) | 3 (3.7) | 0 (0.0) | 1 (3.3) | 2 (6.5) | .48 | |||||
aGroupwise comparisons for continuous variables were assessed using either ANOVA or the Kruskal-Wallis test (if not normally distributed), and categorical variables were assessed using the chi-square test.
bOffTC: offline Taichi.
cCT: cognitive training.
dVRTC: virtual reality Taichi.
eMGs: Memory Guard score.
fMoCA: Montreal Cognitive Assessment.
At 12 weeks, the adjusted mean MGs in the CT+VRTC group were 30.1 (95% CI 28.3-31.9) and 28.1 (95% CI 26.3-29.9) in the CT+OffTC group. The effect of the CT+VRTC group was significantly better than that of the CT+OffTC group, with an increase of 2.03 MGs (95% CI 0.018-3.96; Cohen d=0.558; P=.04; and ).
| Timepoint and treatment group | Adjusted mean (SE) | 95% CI | Group comparison | Estimate (SE) | t-ratio | P Value | Effect size (95% CI) | |
| Week 12 | ||||||||
| CT+OffTC | 28.1 (0.907) | 26.3- 29.9 | CT+OffTC vs CT+VRTC | –2.03 (0.961) | –2.117 | .04 | –0.558 (–1.1 to –0.018) | |
| CT+VRTC | 30.1 (0.900) | 28.3-31.9 | —b | — | — | — | — | |
| Week 24 | ||||||||
| Control | 27.8 (0.903) | 26.0 – 29.6 | CT+OffTC vs Control | 1.49 (1.050) | 1.421 | .47 | 0.416 (–0.171 to 1.00) | |
| CT+OffTC | 29.3 (0.803) | 27.7 -30.9 | CT+VRTC vs Control | 5.10 (1.070) | 4.778 | <.001 | 1.425 (0.785- 2.06) | |
| CT+VRTC | 32.9 (0.806) | 31.3 -34.5 | CT+VRTC vs CT+OffTC | 3.61 (0.936) | 3.857 | <.001 | 1.009 (0.461- 1.56) | |
aAdjusted mean Memory Guard scores, pairwise group comparisons, and effect sizes (Cohen d) are presented from linear regression models controlling for baseline Memory Guard scores, age, education, sex, hypertension, and diabetes.
| Time point and group comparison | Estimate (SE) | t-ratio | P Value | Effect size (95% CI) | |||||
| Week 12 | |||||||||
| CT+OffTC vs CT+VRTC | –2.03 (0.961) | –2.117 | .04 | –0.558 (–1.1 to –0.018) | |||||
| Week 24 | |||||||||
| CT+OffTC vs Control | 1.49 (1.050) | 1.421 | .47 | 0.416 (–0.171 to 1.00) | |||||
| CT+VRTC vs Control | 5.10 (1.070) | 4.778 | <.001 | 1.425 (0.785- 2.06) | |||||
| CT+VRTC vs CT+OffTC | 3.61 (0.936) | 3.857 | <.001 | 1.009 (0.461- 1.56) | |||||
aAdjusted mean Memory Guard scores, pairwise group comparisons, and effect sizes (Cohen d) are presented from linear regression models controlling for baseline Memory Guard scores, age, education, sex, hypertension, and diabetes.
At 24 weeks, the adjusted mean MGs in the CT+VRTC group was the highest, at 32.9 (95% CI 31.3-34.5), followed by the CT+OffTC group, at 29.3 (95% CI 27.7-30.9), and the control group at 27.8 (95% CI 26.0-29.6).
In pairwise comparisons, the CT+VRTC group showed an improvement of 5.10 (95% CI 2.93-7.27; Cohen d=1.425, 95% CI 0.785-2.060; P<.001) MGs compared with the control group, while the CT+VRTC group showed an improvement of 3.61 (95% CI 1.71-5.51; Cohen d=1.009, 95% CI 0.461-1.560; P<.001) MGs compared with the CT+OffTC group.
The embedded dynamic treatment plan analysis showed that the efficacy of different adaptive strategies was different (). The VRTC-based plan was always more effective than the control group, among which the responder plan had the highest efficacy, with an efficacy difference of 5.40 (95% CI 3.10-7.70; P<.001) MGs compared with the control group. VRTC intensification showed a significant benefit for nonresponders, with a difference of 5.66 (95% CI 1.14-10.18; P=.01) MGs, while VRTC switch showed a difference of 3.21 (95% CI 0.01-6.41; P=.05) MGs. Among the OffTC-based strategies, only OffTC intensification showed significant improvement compared with the control group, with a difference of 4.24 (95% CI 0.22-8.26; P=.04) MGs.
| Strategies | Adjusted mean (SE) | 95% CI | Comparisons | P value |
| Control | 27.6 (1.35) | 24.9-30.3 | Reference | —b |
| OffTCc Intensify | 31.8 (1.89) | 28.1-35.6 | 4.24 (2.01) | .04 |
| OffTC Switch | 29.0 (1.70) | 25.6-32.4 | 1.37 (1.83) | .45 |
| OffTC Responder | 28.4 (1.13) | 26.2-30.7 | 0.84 (1.14) | .46 |
| VRTCd Intensify | 33.3 (2.13) | 29.0-37.5 | 5.66 (2.26) | .01 |
| VRTC Switch | 30.8 (1.54) | 27.7-33.9 | 3.21 (1.60) | .05 |
| VRTC Responder | 33.0 (1.13) | 30.7-35.2 | 5.40 (1.15) | <.001 |
aAdjusted means are from models controlling for baseline Memory Guard score, age, and other control variables.
bNot applicable.
cOffTC: offline Taichi.
dVRTC: virtual reality Taichi.
The results suggest that VRTC-based adaptive interventions provide strong cognitive benefits across response patterns, while OffTC-based approaches show more limited effectiveness, with benefits primarily seen when treatment intensity is increased in nonresponders.
presents the results of response status predictors. For the response status, diabetes was a strong positive predictor (B=17.404, 95% CI 15.913-18.895; P<.001). Baseline MGs, treatment assignment in stage 1, hypertension, and age were not significant. For perceived effectiveness and content mastery, diabetes remained a significant positive predictor as the same. Additionally, lower baseline MGs was associated with higher perceived effectiveness and content mastery.
| (1) Response | (2) Perceived effectiveness | (3) Master content | |||||||||||
| Baseline MGsb | |||||||||||||
| Unstandardized regression coefficient (95% CI) | –0.146 (–0.365 to 0.073) | –0.124c (–0.245 to –0.004) | –0.115c (–0.225 to –0.004) | ||||||||||
| Robust SE | –0.604 | –0.202 | –0.151 | ||||||||||
| P value | .19 | .05 | .05 | ||||||||||
| Treatment in stage 1 | |||||||||||||
| Unstandardized regression coefficient (95% CI) | –0.061 (–1.331 to 1.208) | –0.009 (–0.818 to 0.800) | 0.122 (–0.675 to 0.918) | ||||||||||
| Robust SE | –2.043 | –0.599 | –0.362 | ||||||||||
| P value | .93 | .98 | .77 | ||||||||||
| Age | |||||||||||||
| Unstandardized regression coefficient (95% CI) | 0.001 (–0.120 to 0.122) | –0.023 (–0.105 to 0.058) | 0.005 (–0.067 to 0.077) | ||||||||||
| Robust SE | –0.373 | –0.163 | –0.123 | ||||||||||
| P value | .99 | .57 | .90 | ||||||||||
| Hypertension | |||||||||||||
| Unstandardized regression coefficient (95% CI) | –1.209d (–2.606 to 0.188) | –0.939d (–1.903 to 0.025) | –0.768 (–1.783 to 0.248) | ||||||||||
| Robust SE | –0.160 | –0.044 | –0.109 | ||||||||||
| P value | 0.09 | .06 | .15 | ||||||||||
| Diabetes | |||||||||||||
| Unstandardized regression coefficient (95% CI) | 17.404e (15.913 to 18.895) | 1.788e (0.927 to 2.649) | 1.598e (0.705 to 2.492) | ||||||||||
| Robust SE | 0.360 | 0.335 | 0.284 | ||||||||||
| P value | <.001 | <.001 | .001 | ||||||||||
| Constant | |||||||||||||
| Unstandardized regression coefficient (95% CI) | 4.926 (–8.173 to 18.026) | 8.968c (0.793 to 17.143) | 6.561d (–0.550 to 13.672) | ||||||||||
| Robust SE | 44.669 | 17.395 | 13.164 | ||||||||||
| P value | .46 | .04 | .08 | ||||||||||
| Observations, n | 61 | 61 | 61 | ||||||||||
| R2 | —f | 0.168 | 0.165 | ||||||||||
aValues represent unstandardized regression coefficients with 95% CIs and robust SEs in parentheses. Model (1): Logistic regression; Models (2-3): Ordinary Least Squares regression. Robust SEs in parentheses.
bMGs: Memory Guard score.
cP<.05.
dP<.10.
eP<.01.
fNot applicable.
Subgroup analyses revealed significant heterogeneity in treatment effects (), with younger age, lower baseline cognitive function, and the presence of comorbidities benefiting more from interventions.
Younger participants (≤71 years) benefit more cognitive improvement from CT+VRTC, achieving 33.3 (95% CI 31.4-35.2) compared with older participants at 31.9 (95% CI 29.4-34.4). Yet, younger patients with MCI were at greater risk of cognitive decline. This result suggested that younger patients with MCI may be more vulnerable to cognitive decline but also benefit more from VR interventions.
CT+VRTC demonstrated consistent effectiveness across different baseline cognitive levels. However, participants with higher baseline MGs showed greater overall benefit from interventions.
CT+VRTC maintained stable effectiveness regardless of comorbid conditions. Importantly, participants with comorbid conditions would benefit more cognitive improvement compared with those without comorbidities, suggesting potential synergy between controlling chronic diseases and cognitive function protection.
CT+VRTC demonstrated substantial cognitive improvement compared with both control and CT+OffTC groups, with large effect sizes indicating clinically meaningful benefits. Dynamic treatment regimen analysis revealed that VRTC-based adaptive strategies consistently outperformed control across different response patterns, with VRTC responders achieving the highest effectiveness. Subgroup analyses identified significant treatment heterogeneity, with younger participants, those with lower baseline cognitive function, and individuals with comorbid conditions demonstrating enhanced responsiveness to interventions. To our knowledge, this is the first SMART design to develop evidence-based adaptive intervention strategies for MCI prevention in community settings.
Compared with the FINGER trial [,], our focused population with MCI demonstrated substantially greater cognitive improvements, with CT+VRTC achieving an effect size of 1.425 (95% CI 0.785-2.060; P<.001) compared with control, suggesting that technology-enhanced dual-task training may be effective in individuals with established cognitive impairment. Consistent with emerging digital health interventions, our findings support the superiority of VR-enhanced approaches over traditional exercise modalities [-], with VRTC consistently outperforming OffTC across all treatment strategies. The effects of VRTC suggest unique advantages of VR technology in cognitive intervention.
The immersive, multisensory environment inherent in VR-based training appears to impose greater demands on sensorimotor integration and movement precision, potentially enhancing cognitive engagement through increased activation of frontoparietal networks []. Furthermore, the enhanced real-time feedback mechanisms in VR environments may facilitate neuroplastic adaptations, particularly in frontocortical regions critical for executive function and motor planning []. In addition, VRTC may strengthen cortical connectivity and increase frontal lobe activation patterns, via upregulation of brain-derived neurotrophic factor in hippocampal and prefrontal regions, enhanced recruitment of dorsal and ventral attentional networks, increased cerebellum-prefrontal functional connectivity, and modulation of default mode network activity to reduce age-related network dedifferentiation [,,]. Individuals who participated in the technology-enhanced dual-task group (CT+VRTC) showed more stable intervention effects regardless of whether they had chronic diseases or not and their baseline cognitive status.
The enhanced treatment responsiveness observed in participants with comorbidities reflects potential synergistic effects between intervention modalities and chronic disease management. Patients with comorbidities benefited more, which is consistent with the findings of current intervention studies [,]. Hypertension can lead to white matter injury through small vessel disease in the brain, while diabetes is associated with insulin resistance, inflammatory responses, and oxidative stress, all of which contribute to neurodegenerative processes []. Therefore, cognitive impairment in these patients may result from multiple interrelated factors. Intervention strategies may exert beneficial effects by improving vascular function, reducing inflammation, or enhancing neuroprotective pathways [,].
Our predictive modeling showed that diabetes consistently predicted enhanced response, while hypertension showed opposite effects. These findings suggest that patients with comorbidity may benefit more from intervention. The immersive cognitive-motor training may help counteract diabetes-induced neuroinflammation and vascular dysfunction through enhanced neuroplasticity, while the engaging nature of VR technology may improve treatment adherence and motivation—factors that are often compromised in patients with chronic metabolic disorders []. These predictive results were aligned with subgroup analysis that patients with comorbidity may benefit more from intervention modality with high confidence.
Beyond the benefits observed of individual intervention components, our study showed the importance of adaptive treatment strategies. Traditional cognitive interventions have predominantly used fixed protocols with predetermined duration and intensity, failing to account for individual variability in treatment response. The coaching-based intervention represented an early attempt at adaptive intervention [-], using remote support to prevent cognitive function decline. However, these adaptations remained largely experience-driven rather than systematically evidence-based. Our study addressed limitations of subjective feelings as response indicators by examining the agreement between subjective response assessment and objective assessment criteria at 12 weeks. Subjective assessment used patient-reported measures of intervention mastery and perceived effectiveness to guide treatment decisions, and objective assessment used improvement of MGs at 12 weeks. The moderate agreement (κ=0.42) between subjective response assessment and objective cognitive improvement validated our classification approach, demonstrating that participants showing both subjective benefit and objective gains could continue original protocols while nonresponders required treatment modification.
Dynamic treatment regimen analysis revealed that adaptive strategies consistently outperformed static approaches, with treatment intensification proving more effective than modality switching for nonresponders in both intervention groups. This approach represents a potential shift from an experience-based approach toward precise management, providing clinicians with evidence-based decision rules that may improve treatment efficiency and optimize resource allocation in community-based MCI prevention programs.
Further research is needed to advance this field. First, investigation of motivation and adherence factors is essential to identify predictors of intervention engagement and develop evidence-based strategies for enhancing long-term adherence to VR-based cognitive training, particularly examining how individual characteristics and intervention design features influence sustained participation and treatment response. Second, optimization of SMART design parameters is warranted, including validation of alternative response assessment time points and development of objective response criteria that integrate cognitive, physiological, and behavioral indicators to reduce reliance on subjective measures. Third, multicenter trials in diverse populations and health care settings are needed to establish the generalizability and implementation feasibility of VR-enhanced adaptive interventions, particularly examining effectiveness across different MCI subtypes and socioeconomic contexts.
This study advances MCI prevention research through several methodological and practical innovations. First, we developed the first SMART-based adaptive intervention framework for cognitive health, moving beyond fixed-protocol designs that dominate current practice. The 12-week objective response assessment criteria—integrating subjective mastery evaluation with cognitive performance metrics—provide clinicians with standardized decision rules for treatment modification, replacing experience-dependent judgments that vary across providers and settings. Second, our finding that treatment intensification outperforms modality switching for nonresponders establishes a specific clinical pathway: rather than abandoning ineffective interventions, clinicians should increase intervention dose before switching modalities. Third, the identification of diabetes as a positive predictor and hypertension as a negative predictor of treatment response enables risk stratification and personalized intervention selection prior to treatment initiation.
The clinical utility of these findings extends beyond research settings. Community health workers can implement the standardized decision rules without specialized neuropsychological training, as the response assessment requires only basic cognitive screening tools already deployed in Chinese primary care. The VR-Taichi protocol leverages culturally familiar mind-body exercises, addressing adherence barriers that limit Western-developed interventions in Asian populations. Our subgroup analyses identify priority populations for targeted screening: adults aged 60-71 years, individuals with MoCA scores indicating lower baseline function, and patients with metabolic comorbidities. These groups demonstrated 15%-25% greater cognitive improvement compared with their counterparts, suggesting that resource-limited settings should prioritize these populations for intensive intervention.
This precision medicine approach addresses a critical gap in current dementia prevention guidelines, which provide broad recommendations without specifying how to tailor interventions to individual characteristics or when to modify treatment based on early response. Our findings support policy development for technology-integrated cognitive health programs within urban community health systems, with potential adaptation to other metropolitan areas possessing similar digital infrastructure and hierarchical medical delivery systems.
Our findings support the feasibility of implementing standardized VR-based protocols within existing community health service centers, leveraging Shanghai’s robust digital infrastructure and established hierarchical medical system. The demonstrated effectiveness of adaptive treatment strategies, particularly the superior performance of VRTC-based interventions across diverse participant characteristics, suggests that technology-enhanced approaches can be successfully integrated into routine community-based MCI prevention programs. The identification of diabetes as a positive predictor and hypertension as a negative predictor of treatment response provides practical guidance for community health workers in optimizing intervention selection and resource allocation.
The scalability of our intervention model is supported by several practical considerations specific to urban community settings. First, the Taichi protocol used in VRTC is culturally familiar to Chinese older populations, facilitating acceptance and adherence. Second, the objective response assessment criteria developed through our SMART design provide clear decision rules that can be implemented by trained community health personnel without requiring specialized clinical expertise. Third, the significant effect sizes observed suggest that even with some implementation variability expected in real-world settings, meaningful cognitive benefits are likely to be maintained. These findings support the development of evidence-based public service recommendations for integrating VR technology into Shanghai’s community health infrastructure, with potential for adaptation to other metropolitan areas with similar health care delivery systems and technological capabilities.
Our study has several limitations that should be considered. The sample was predominantly recruited from urban communities in Shanghai, which may limit generalizability to rural populations or different health care settings. Additionally, while our follow-up period was adequate for demonstrating intervention effects, longer-term outcomes remain to be evaluated. Subjective evaluation of intervention content mastery as a criterion for assessing participants’ responsiveness is not comprehensive, especially for aerobic exercises such as Taichi. Although robustness analysis showed no significant difference between the 2 response definitions, we still recommended that future evaluations incorporate physiological, cognitive, psychological, and behavioral indicators to fully capture participants’ responses to the intervention. Assessment based on VO₂ max, Geriatric Depression Scale (GDS), and quality-of-life measures is suggested as a robust approach for evaluating the effectiveness of nonsubjective interventions.
This study represents the SMART design to develop evidence-based adaptive intervention strategies for MCI prevention in community settings, demonstrating that technology-enhanced dual-task training with VR significantly outperforms traditional exercise modalities and control conditions. The CT+VRTC intervention achieved substantial cognitive improvements (Cohen d=1.425, 95% CI 0.785-2.060; P<.001) that exceeded those reported in previous multidomain trials, with adaptive treatment strategies consistently outperforming static approaches across diverse participant characteristics. Our predictive modeling revealed that individuals with diabetes showed enhanced treatment responsiveness across all outcome measures, while those with hypertension demonstrated reduced response, highlighting the critical importance of comorbidity-informed treatment selection. The systematic approach to treatment adaptation provides clinicians with evidence-based decision rules for optimizing intervention delivery in real-world settings. These findings establish a foundation for precision-based cognitive health management, potentially bridging the gap between traditional multidomain approaches and personalized medicine strategies while offering a scalable, cost-effective solution for community-based MCI prevention programs.
These findings establish a foundation for precision-based cognitive health management, potentially bridging the gap between traditional multidomain approaches and personalized medicine strategies while offering a scalable, cost-effective solution for community-based MCI prevention programs. The demonstrated large effect sizes and adaptive treatment protocols provide evidence-based recommendations for implementing VR-enhanced cognitive interventions within Shanghai’s existing community health service infrastructure, supporting the development of technology-integrated public health strategies for urban older populations.
This study is supported by the Yunnan Key Research Program (grant 202402AD080004). This study is funded by The Shanghai Public Health System Construction 3‐Year Action Plan (grant no. GWVI-11.1-48). The funder had no involvement in the study design, data collection, analysis, interpretation, or the writing of the manuscript.
The datasets generated or analyzed during this study are available from the corresponding author on reasonable request.
All authors contributed to the article and approved the submitted version. After unmasking of the outcome data, all authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. DB and CY verified the raw data in the study. GL, CS, and DB conceptualized the study. CS proposed the experimental design and algorithm framework. CS and CY implemented the model design and evaluation. CY was responsible for using the data analysis software in the study. All authors validated the findings of the study. All authors contributed to the formal analysis of the data. DB and CY conducted the investigation. DB, CS, and GL provided the resources necessary for the study. DB and XH curated the data. CY and DB wrote the original draft of the manuscript. All authors reviewed and edited the manuscript. CY created the visualizations of the study findings. CS and GL supervised the research activities. GL managed the project administration. GL contributed to funding acquisition. CS (shihchenshu@hotmail.com) and GL contributed equally as co-corresponding authors.
None declared.
Edited by A Mavragani, S Brini; submitted 18.Jun.2025; peer-reviewed by Z Zhang, LF Belo, A Hu; comments to author 14.Sep.2025; accepted 17.Oct.2025; published 25.Nov.2025.
©Chenhao Yu, Dongsheng Bian, Jiatao Zhang, Xiao Han, Chenshu Shi, Guohong Li. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 25.Nov.2025.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research (ISSN 1438-8871), is properly cited. The complete bibliographic information, a link to the original publication on https://www.jmir.org/, as well as this copyright and license information must be included.
AstraZeneca’s IMFINZI® (durvalumab) in combination with standard-of-care FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) has been approved in the US for the treatment of adult patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers. The approved regimen includes neoadjuvant IMFINZI in combination with chemotherapy before surgery, followed by adjuvant IMFINZI in combination with chemotherapy, then IMFINZI monotherapy.
The approval follows Priority Review by the Food and Drug Administration (FDA) and is based on event-free survival (EFS) and overall survival (OS) data from the MATTERHORN Phase III trial. The EFS results were presented during the Plenary Session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The New England Journal of Medicine. OS results from MATTERHORN were presented in a Proffered Paper session at the European Society for Medical Oncology (ESMO) Congress 2025.
Gastric cancer is the fifth leading cause of cancer death globally, with nearly one million people diagnosed each year.1 In 2024, there were roughly 6,500 drug-treated patients in the US in early-stage and locally advanced gastric or GEJ cancer.2
Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “This approval ushers in a new clinical paradigm for patients with early gastric and gastroesophageal junction cancers, with IMFINZI plus FLOT delivering a durable survival benefit that increases over time. As the third US approval for a perioperative IMFINZI-based regimen, this milestone further validates the perioperative approach and underscores our focus on bringing novel treatments to early-stage cancers where cure is the goal.”
Yelena Y. Janjigian, MD, Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center (MSK), New York and principal investigator in the MATTERHORN trial, said: “Today’s approval marks the first immunotherapy regimen approved in the neoadjuvant setting for gastric and gastroesophageal junction cancers—with durvalumab demonstrating a clear overall survival benefit and opening an entirely new chapter in the treatment of early-stage disease. Nearly seven in 10 patients were alive at three years following treatment with the durvalumab-based perioperative regimen. This survival benefit, observed regardless of PD-L1 status, establishes a new standard of care in this curative-intent setting.”
Aki Smith, Founder and Executive Director, Hope for Stomach Cancer, said: “From personal experience as a caregiver to my father, I know that for too long patients diagnosed with early gastric or gastroesophageal junction cancer have faced a high risk of their cancer returning, even after undergoing surgery and therapy intended to cure it. Today’s approval represents a major step forward in improving outcomes and offering renewed hope to those affected by this devastating disease.”
In a planned interim analysis, patients treated with the IMFINZI-based perioperative regimen showed a 29% reduction in the risk of disease progression, recurrence or death versus chemotherapy alone (based on an EFS hazard ratio [HR] of 0.71; 95% confidence interval [CI] 0.58-0.86; P<0.001). Estimated median EFS was not yet reached for the IMFINZI arm versus 32.8 months for the comparator arm. An estimated 78.2% of patients treated with the IMFINZI-based perioperative regimen were event-free at one year, compared to 74.0% in the comparator arm; the estimated 24-month EFS rate was 67.4% versus 58.5%, respectively.
In the final OS analysis, results showed the IMFINZI and FLOT perioperative regimen reduced the risk of death by 22% compared with chemotherapy alone (based on a HR of 0.78; 95% CI 0.63-0.96; P=0.021). An estimated 69% of patients treated with the IMFINZI-based regimen were alive at three years compared with 62% in the FLOT-only arm. With longer follow-up, the OS curves showed continued separation, signaling a greater magnitude of benefit over time for the IMFINZI-based regimen. An OS benefit was observed regardless of PD-L1 status.
The safety profile for IMFINZI and FLOT chemotherapy was consistent with the known profiles of each medicine, and the percentage of patients that completed surgery was similar compared to chemotherapy alone. Grade 3 or higher adverse events due to any cause were similar between the two arms (71.6% for IMFINZI and FLOT arm; 71.2% for FLOT-only arm).
The US regulatory submission was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, the IMFINZI and FLOT perioperative regimen is also under review by regulatory authorities in Australia, Canada, and Switzerland for the same indication. Regulatory applications are also under review in the European Union (EU), Japan and several other countries.
IMPORTANT SAFETY INFORMATION
There are no contraindications for IMFINZI® (durvalumab).
Immune-Mediated Adverse Reactions
Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
IMFINZI can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC or BTC when given in combination with chemotherapy.
Immune-Mediated Colitis
IMFINZI can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions.
Immune-Mediated Hepatitis
IMFINZI can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions.
Immune-Mediated Endocrinopathies
Immune-Mediated Nephritis with Renal Dysfunction
IMFINZI can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
Immune-Mediated Dermatology Reactions
IMFINZI can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 and CTLA-4 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions.
Other Immune-Mediated Adverse Reactions
The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI or were reported with the use of other immune-checkpoint inhibitors.
Infusion-Related Reactions
IMFINZI can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.
Complications of Allogeneic HSCT after IMFINZI
Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.
Embryo-Fetal Toxicity
Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and advise them to use effective contraception during treatment with IMFINZI and for 3 months after the last dose of IMFINZI.
Lactation
There is no information regarding the presence of IMFINZI in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI, advise women not to breastfeed during treatment and for 3 months after the last dose.
Adverse Reactions
The safety and effectiveness of IMFINZI has not been established in pediatric patients.
Indication:
IMFINZI in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) as neoadjuvant and adjuvant treatment, followed by single agent IMFINZI, is indicated for the treatment of adult patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).
Please see additional Important Safety Information throughout and Full Prescribing Information including Medication Guide for IMFINZI.
You may report side effects related to AstraZeneca products.
Notes
Gastric and gastroesophageal junction cancers
Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth-highest leading cause of cancer mortality.1 Nearly one million new patients were diagnosed with gastric cancer in 2022, with approximately 660,000 deaths reported globally.1 In many regions, its incidence has been increasing in patients younger than 50 years old, along with other gastrointestinal (GI) malignancies.3 In 2024, there were roughly 43,000 drug-treated patients in the US, EU and Japan in early-stage and locally advanced gastric or GEJ cancer.2 Approximately 62,000 patients in these regions are expected to be newly diagnosed in this setting by 2030.4
GEJ cancer is a type of gastric cancer that arises from and spans the area where the esophagus connects to the stomach.5
Disease recurrence is common in patients with resectable gastric cancer despite undergoing surgery with curative intent and treatment with neoadjuvant/adjuvant chemotherapy.6 Approximately one in four patients with gastric cancer who undergo surgery develop recurrent disease within one year, and the five-year survival rate remains poor, with less than half of patients alive at five years.6-7
MATTERHORN
MATTERHORN is a randomized, double-blind, placebo-controlled, multi-center, global Phase III trial evaluating IMFINZI as perioperative treatment for patients with resectable Stage II-IVA gastric and GEJ cancers. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, 948 patients were randomized to receive a 1500mg fixed dose of IMFINZI plus FLOT chemotherapy or placebo plus FLOT chemotherapy every four weeks for two cycles prior to surgery. This was followed by IMFINZI or placebo every four weeks for up to 12 cycles after surgery (including two cycles of IMFINZI or placebo plus FLOT chemotherapy and 10 additional cycles of IMFINZI or placebo monotherapy).
In the MATTERHORN trial, the primary endpoint is EFS, defined as time from randomization until the date of one of the following events (whichever occurred first): RECIST (version 1.1, per blinded independent central review assessment) progression that precludes surgery or requires non-protocol therapy during the neoadjuvant period; RECIST progression/recurrence during the adjuvant period; non-RECIST progression that precludes surgery or requires non-protocol therapy during the neoadjuvant period or discovered during surgery; progression/recurrence confirmed by biopsy post-surgery; or death due to any cause. Key secondary endpoints include pathologic complete response rate, defined as the proportion of patients who have no detectable cancer cells in resected tumor tissue following neoadjuvant therapy, and OS. The trial enrolled participants in 176 centers in 20 countries, including in the US, Canada, Europe, South America and Asia.
IMFINZI
IMFINZI® (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.
In GI cancer, IMFINZI is approved in combination with chemotherapy in locally advanced or metastatic biliary tract cancer (BTC) and in combination with tremelimumab-actl in unresectable hepatocellular carcinoma (HCC). IMFINZI is also approved as a monotherapy in unresectable HCC in Japan and the EU.
In addition to its indications in GI cancers, IMFINZI is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, IMFINZI is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of tremelimumab-actl and chemotherapy for the treatment of metastatic NSCLC. IMFINZI is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy for the treatment of extensive-stage SCLC.
Perioperative IMFINZI in combination with neoadjuvant chemotherapy is approved in the US, EU, Japan and other countries for patients with muscle-invasive bladder cancer based on results from the NIAGARA Phase III trial. Additionally, in May 2025, IMFINZI added to Bacillus Calmette-Guérin induction and maintenance therapy met the primary endpoint of disease-free survival for patients with high-risk non-muscle-invasive bladder cancer in the POTOMAC Phase III trial.
IMFINZI in combination with chemotherapy followed by IMFINZI monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in the US and EU). IMFINZI in combination with chemotherapy followed by olaparib and IMFINZI is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in the EU and Japan.
Since the first approval in May 2017, more than 414,000 patients have been treated with IMFINZI. As part of a broad development program, IMFINZI is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, bladder cancer, breast cancer, ovarian cancer and several GI cancers.
AstraZeneca in GI cancers
AstraZeneca has a broad development program for the treatment of GI cancers across several medicines and a variety of tumor types and stages of disease. In 2022, GI cancers collectively represented approximately 5 million new cancer cases leading to approximately 3.3 million deaths.8
Within this program, the Company is committed to improving outcomes in gastric, liver, biliary tract, esophageal, pancreatic, and colorectal cancers.
In addition to its indications in BTC and HCC, IMFINZI is being assessed in combinations, including with tremelimumab-actl, in liver, esophageal and gastric cancers in an extensive development program spanning early to late-stage disease across settings.
Fam-trastuzumab deruxtecan-nxki, a HER2-directed antibody drug conjugate (ADC), is approved in the US and several other countries for HER2-positive advanced gastric cancer. Fam-trastuzumab deruxtecan-nxki is jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.
Olaparib, a first-in-class PARP inhibitor, is approved in the US and several other countries for the treatment of BRCA-mutated metastatic pancreatic cancer. Olaparib is developed and commercialized in collaboration with Merck & Co., Inc (MSD outside the US and Canada).
The Company is also assessing rilvegostomig (AZD2936), a PD-1/TIGIT bispecific antibody, in combination with chemotherapy as an adjuvant therapy in BTC, in combination with bevacizumab with or without tremelimumab-actl as a 1st-line treatment in patients with advanced HCC, and as a 1st-line treatment in patients with HER2-negative, locally advanced unresectable or metastatic gastric and GEJ cancers. Rilvegostomig is also being evaluated in combination with Fam-trastuzumab deruxtecan-nxki in previously untreated, HER2-expressing, locally advanced or metastatic BTC.
AstraZeneca is advancing multiple modalities that provide complementary mechanisms for targeting Claudin 18.2, a promising therapeutic target in gastric cancer. These include sonesitatug vedotin, a potential first-in-class ADC licensed from KYM Biosciences Inc., currently in Phase III development; AZD5863, a novel Claudin 18.2/CD3 T-cell engager bispecific antibody licensed from Harbour Biomed in Phase I development; and AZD4360, an antibody drug conjugate, currently being evaluated in a Phase I/II trial in patients with advanced solid tumors.
In early development, AstraZeneca is developing C-CAR031 / AZD7003, a Glypican 3 (GPC3) armored CAR T, in HCC. C-CAR031 / AZD7003is being co-developed with AbelZeta in China where it is under evaluation in an IIT.
AstraZeneca in immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumor immune response and stimulate the body’s immune system to attack tumors.
AstraZeneca strives to redefine cancer care and help transform outcomes for patients with IMFINZI as a monotherapy and in combination with tremelimumab-actl as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers.
AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical program, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on social media @AstraZeneca.
Media Inquiries
|
Fiona Cookson Lauren-Jei McCarthy |
|
+1 212 814 3923 +1 347 918 7001 |
|
|
US Media Mailbox: usmediateam@astrazeneca.com
References
1. World Health Organization. International Agency for Research on Cancer. Stomach fact sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/7-stomach-fact-sheet.pdf. Accessed November 2025.
2. AstraZeneca PLC. Investor relations epidemiology spreadsheet. Available at: https://www.astrazeneca.com/investor-relations.html. Accessed November 2025.
3. Li Y, et al. Global burden of young-onset gastric cancer: a systematic trend analysis of the global burden of disease study 2019. Gastric Cancer. 2024;27(4):684-700.
4. Kantar Health, validated with SEER stage at diagnosis and Cabasag et al. And Kuzuu et al. 2021.
5. National Cancer Institute. Gastroesophageal junction. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/gastroesophageal-junction. Accessed November 2025.
6. Li Y, et al. Postoperative recurrence of gastric cancer depends on whether the chemotherapy cycle was more than 9 cycles. Medicine. 2022;101(5):e28620.
7. Ilic M, Ilic I. Epidemiology of stomach cancer. World J Gastroenterol. 2022;28(12):1187-1203.
8. World Health Organization. World cancer fact sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf. Accessed November 2025.
MSK Disclosure: Dr. Janjigian provides consulting and advisory services to AstraZeneca.
