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  • Avinash Sable undergoes knee surgery in Mumbai

    Avinash Sable undergoes knee surgery in Mumbai

    “I’ve completed my surgery under the expert care of Dr. Dinshaw Pardiwala and his team at Kokilaben Hospital, to whom I’m grateful beyond words… I’ll be back faster and stronger.”

    The ACL and meniscus are crucial structures in the knee. Injuries to both typically require surgery and a lengthy rehabilitation process, often sidelining athletes for six months or more.

    The 30-year-old Indian steeplechase star crashed out of the Monaco Diamond League on July 11, stumbling during a water jump after another competitor in front lost his footing. Sable limped off the track in visible pain and was helped away for immediate medical assessment.

    The Monaco meet was Sable’s first outing since winning the Asian 3000m steeplechase title in May and his third Diamond League appearance of the 2025 athletics season.

    He had finished 13th in Xiamen (8:22.59) and eighth in Shanghai (8:23.85), later revealing he had been competing with calf and hamstring issues.

    Avinash Sable holds the Indian national record in the men’s 3000m steeplechase with a time of 8:09.91, set at the 2024 Paris Diamond League. He is also the Asian Games champion and a Commonwealth Games silver medallist in the same events.

    Sable also holds the half marathon national record, courtesy of his 1:00:30 run at the Delhi Half Marathon in 2020.

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  • Samsung Launches Galaxy Z Fold7, Galaxy Z Flip7 and Galaxy Watch8 Series Globally – Samsung Newsroom U.K.

    Samsung Launches Galaxy Z Fold7, Galaxy Z Flip7 and Galaxy Watch8 Series Globally – Samsung Newsroom U.K.

    Multimodal AI-powered foldables debut alongside ultra-comfortable smartwatches that deliver instant health insights — experience the latest devices at your nearby store

    Pre-orders for the latest Galaxy Z foldable smartphones have exceeded targets, making it the largest ever pre-order for Galaxy Z foldables in the UK

    Samsung Electronics Co., Ltd. announced the global availability of its latest foldable smartphones, Galaxy Z Fold7 and Galaxy Z Flip7, and its new Galaxy Watch8 series. The Galaxy Z series has reached the highest number of pre-orders for Galaxy Z foldables ever in the U.K., with targets exceeded before the end of the pre-order period.

     

    Galaxy Z Fold7 and Z Flip7: Ultra-Thin and -Light with Intuitive Intelligence

     

    Refined by years of breakthrough engineering and elevated with advanced intelligence, Galaxy Z Fold7 and Z Flip7 represent the next leap in smartphone. Galaxy Z Fold7 and Z Flip7 are Samsung’s thinnest, lightest and most advanced Z series devices yet. Powered by cutting-edge performance and seamlessly integrated Galaxy AI[1], they are intelligent, adaptive companions that anticipate and respond to user needs in real time. With expansive, flexible displays, pro-grade cameras and context-aware intelligence, Galaxy Z Fold7 and Z Flip7 open up new realms of productivity, creativity and connection.

     

     

     

    Galaxy Z Fold7 brings Galaxy advancements together and broadens their scope, delivering the Ultra -level experience in the thinnest, lightest and most advanced Z Series yet. It offers immersive, high-octane performance on an expansive screen, empowering you to game, stream, connect and create all at once. Galaxy’s true AI companion experience has also been optimised for the foldable format, enabling fluid interactions across more apps and the larger screen. And with Camera and screen sharing with Gemini Live[2], users can talk naturally to Gemini about what they’re viewing. They can simply share a picture of a local delicacy while they’re exploring a new city and ask Gemini whether there is a nearby restaurant where they can try it.

     

    Plus, Galaxy Z Fold7’s ultra-grade 200MP high-resolution camera gives the freedom to shoot at flexible angles, putting professional-quality content creation at user’s fingertips. For example, convenient editing features like Generative Edit[3] now automatically detects passers-by in the background of photos and proactively recommends what to remove, eliminating the need to make manual selections and edits. Apart from these features, Galaxy Z Fold7 brings familiarity and durability in a head-turning new design that unfolds into something extraordinary.

     

    Galaxy Z Flip7 distills flagship power, intelligence and personality into a compact and iconic form. With its edge-to-edge FlexWindow, you can express yourself, access key features at a glance and stay connected, all without opening the device.

     

    Built for dynamic lifestyles, Galaxy Z Flip7 transforms the way users capture and share content, from flawless selfies to cinematic video, all with the agility and creativity only Flip devices can offer. Now Bar[4] delivers helpful information right on Galaxy Z Flip7’s FlexWindow to help users stay in control of their day, such as what song is playing, workout progress and even rideshare ETAs at a glance. Gemini Live also allows users to share what they see through their camera and chat with Gemini in real time directly on FlexWindow. So, they can ask for travel tips while road tripping with their dog or outfit suggestions based on the day’s weather. Users can also simply share the camera in Flex Mode and converse with Gemini hands-free.

     

    Galaxy Z Flip7’s FlexCam makes it easier than ever to capture the perfect selfie. Real-time filters on the FlexWindow instantly enhance users FlexCam selfies, so that they can be ready to post or share without the need for any extra editing. And with fun new features like Portrait Studio3 for pets, users can instantly transform any snapped or downloaded pet photo into a work of art. They can choose from styles that resemble artistic paintings, 3D cartoons, fisheye lens photos or professional-quality portraits, and create frame-worthy masterpieces with one quick tap.

     

    Years of breakthrough engineering have led foldables to become flexible canvases for the new AI experience. As a new class of smartphones designed to fit in with and elevate user lives, Galaxy Z Fold7 and Galaxy Z Flip7 represent this achievement. Familiar yet transformative, they blend power, portability, style and substance, whether users seek a revolutionary, ultra-level experience or an AI powerhouse that fits in their pocket. As form factors evolve to look and think differently, this generation of foldables represents the next leap in smartphone innovation.

     

     

    Galaxy Watch8 Series: Ultra-Comfort Meets Real-Time Health Motivation

     

    Completing the Galaxy ecosystem, the Galaxy Watch8 series — including Galaxy Watch8 and Galaxy Watch8 Classic — brings the same spirit of re-engineering found in the new phones to the wrist. Galaxy Watch8 features advanced sensor technology and creates an intuitive AI-powered experience to help users fulfill a healthier, more connected life, while its ultra-thin cushion design and Dynamic Lug system flex naturally for all-day comfort and more precise sensor contact. Leveraging Samsung’s BioActive Sensor for continuous health tracking, the watches deliver real-time insights and instant rewards or alerts across sleep, stress, nutrition and activity, turning healthy intentions into immediate, motivating feedback. Plus, for the first time in a smartwatch, Galaxy Watch8 has introduced the Antioxidant Index[5], enabling users to measure carotenoid levels in just five seconds and make informed lifestyle choices for healthy aging.

     

    Hands-On With the Galaxy Z Series and the Watch8 Series at Galaxy Experience Spaces

     

    After Unpacked, Samsung opened its Galaxy Experience Spaces in major cities including Dubai, London, New York, Paris and Seoul. Designed to offer consumers an early, hands-on experience of the newest Galaxy devices, these spaces featured interactive zones that highlighted the devices’ design, performance and Galaxy AI features. Samsung also partnered with local communities including running, photography, and skateboarding groups to host various sessions, teaching visitors how they can get the most out of their new devices.

     

    In the UK, Samsung announced a takeover of Outernet London, transforming the space into an immersive cultural destination for a limited time. Visitors can expect to find interactive zones, exclusive talks, a deep dive into Korean culture, and a chance to win unmissable prizes or more information, please visit: https://www.samsung.com/uk/store/samsung-kx/discover/Galaxy-experience-space-london.

     

     

     

     Availability

    Galaxy Z Fold7, Galaxy Z Flip7, Galaxy Watch8, and Galaxy Watch8 Classic are available for purchase at samsung.com and in stores worldwide starting July 25.

     

    Galaxy Z Fold7 is offered in Blue Shadow, Silver Shadow, Jetblack [6] and the online-exclusive Mint[7] – available at samsung.com. Galaxy Z Flip7 comes in Jetblack, Blue Shadow, Coralred[8] and the online-exclusive Mint[9] – available at samsung.com. Galaxy Z Flip7 FE, which brings the foldable experience to a wider audience, is available in Black or White.

     

    So far, Blue Shadow has emerged as the most popular colour for both Galaxy Z Fold7 and Z Flip7, accounting for nearly 41% of UK pre-orders for both devices.

     

    The Galaxy Z Fold 7 and Flip7 are now available from Samsung.com/uk/ and selected retailers. Buy and try the new Galaxy Z Series devices for 100 days, and if you decide it’s not for you, you can send it to us and receive back what you paid. Terms and Conditions apply[10].

     

    Galaxy Watch8 is available in two sizes — 44 mm and 40 mm — and comes in Graphite or Silver. Galaxy Watch8 Classic comes in 46 mm with Black or White options, while the new Galaxy Watch Ultra is offered in four titanium finishes, including the new Titanium Blue.

     

    Claim a Duo Wireless Charger & a Camel Hybrid Band worth £130 when you purchase a Samsung Galaxy Watch8 or Watch8 Classic from samsung.com or Participating Retailers between 9th July – 2nd September 2025.[11]

     

    For your peace of mind, Samsung Care+ offers cover for accidental damage, repairs, and replacements. Starting 9 July 2025, new customers can enjoy three months of Samsung Care+ for free, with monthly payments beginning only from the fourth month. This limited-time offer is available until 23 September 2025.[12]

     

    Get expanded access to Google AI Pro and 2TB of cloud storage for 6 months at no cost with Galaxy Z Flip7 and Galaxy Z Flip7 FE.

     

    For more information about the Galaxy Z series and Galaxy Watch8 series, please visit: Samsung Newsroom, SamsungMobilePress.com and Samsung.com.

     

    Pricing

     

    Galaxy Z Fold7 RRP

    • Samsung Galaxy Z Fold7 – 12GB RAM + 256GB- £1799
    • Samsung Galaxy Z Fold7 – 12GB RAM + 512GB – £1899
    • Samsung Galaxy Z Fold7 – 16GB RAM + 1TB – £2149

     

     

    Galaxy Z Flip7 RRP

    • Samsung Galaxy Z Flip7 – 12GB RAM + 256GB – £1,049
    • Samsung Galaxy Z Flip7 – 12GB RAM + 512GB – £1,149
    • Samsung Galaxy Z Flip7 FE – 8GB RAM +128GB – £849
    • Samsung Galaxy Z Flip7 FE – 8GB + 256GB – £909

     

     

    Galaxy Watch8

    • 40mm BT – £319.00
    • 40mm LTE – £369.00
    • 44mm BT – £349.00
    • 44mm LTE – £399.00

     

    Galaxy Watch8 Classic RRP:

    • 46mm BT – £449.00
    • 46mm LTE – £499.00

     

    Galaxy Watch Ultra RRP:

     

     

    [1]Samsung Account login may be required to use certain AI features. Samsung does not make any promises, assurances or guarantees as to the accuracy, completeness or reliability of the output provided by AI features. Availability of Galaxy AI features may vary depending on the region/country, OS/One UI version, device model and phone carrier.

    [2]Compatible with selected languages only. Google account login and network connection required. Google and Gemini are trademarks of Google LLC. Samsung account login is required for certain AI features

    [3]Samsung Account login and network connection required. A visible watermark is overlaid on the saved image to indicate it was generated by Galaxy AI. Accuracy of output is not guaranteed.

    [4]Availability of functions supported within the apps may vary by country. Some functional widgets may require a network connection and/or Samsung Account login.

    [5]Service only available with Galaxy Watch Ultra or later released Galaxy Watch Series. To measure, place the centre of your finger on the sensor at the back of the Watch and hold it for 5 seconds. While Anti-oxidant index can be measured using any finger, the thumb is recommended for the most accurate result. Repeat measurement due to uneven skin texture may lead to inaccurate results

    [6]Colour availability may vary depending on country or carrier.

    [7]Online exclusive colours only available on Samsung.com.

    [8]Colour availability may vary depending on country or carrier.

    [9]Online exclusive colours only available on Samsung.com.

    [10] Purchase between 09/07/2025 – 19/08/2025 from a participating retailer. Payment capped at the product RRP and subject to product condition.  Registration required within 30 days of purchase at https://samsungoffers.claims/ukbuyandtry and claim between 45-100 days of purchase. Sim-free purchases only. For full T&C’s https://samsungoffers.claims/ukbuyandtry

    [11]Purchase a Galaxy Watch8, Watch8 Classic, or Watch Ultra by 02.09.2025 from a Participating Retailer. Claim by visiting: : www.samsungoffers.claims/GalaxyWatch2025 by 02.10.2025. UK/ROI. 18+ only. For full T&C’s, see here

    [12]Samsung Care+ provides cover for accidental damage, including cracks, spills, and drops – with the option to add theft cover for even greater peace of mind. Whether shopping online or in-store, customers can enroll in Samsung Care+ at the time of purchase or within 60 days of buying their new device. Samsung Care+ is underwritten by Assurant General Insurance Limited. Terms, conditions, and excesses apply. Offer available to UK customers only, aged 18 and over

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  • Columbia scientists turn yogurt into a healing gel that mimics human tissue

    Columbia scientists turn yogurt into a healing gel that mimics human tissue

    Researchers from Columbia Engineering have established a framework for the design of bioactive injectable hydrogels formulated with extracellular vesicles (EVs) for tissue engineering and regenerative medicine applications.

    Published on July 25 in Matter, Santiago Correa, assistant professor of biomedical engineering at Columbia Engineering, and his collaborators describe an injectable hydrogel platform that uses EVs from milk to address longstanding barriers in the development of biomaterials for regenerative medicine. EVs are particles naturally secreted by cells and carry hundreds of biological signals, like proteins and genetic material, enabling sophisticated cellular communication that synthetic materials cannot easily replicate.

    In this study, Correa and colleagues designed a hydrogel system where EVs play a dual role: they act as bioactive cargo but also serve as essential structural building blocks, by crosslinking biocompatible polymers to form an injectable material. Using an unconventional approach that leveraged milk EVs from yogurt, the team was able to overcome yield constraints that hinder the development of EV-based biomaterials. The yogurt EVs enabled the hydrogel to both mimic the mechanics of living tissue and actively engage surrounding cells, promoting healing and tissue regeneration without the need for additional chemical additives.

    “This project started as a basic question about how to build EV-based hydrogels. Yogurt EVs gave us a practical tool for that, but they turned out to be more than a model,” said Correa who led the study with Artemis Margaronis, an NSF graduate research fellow in the Correa lab. “We found that they have inherent regenerative potential, which opens the door to new, accessible therapeutic materials.”

    Correa directs the Nanoscale Immunoengineering Lab at Columbia University, where his research focuses on drug delivery and immunoengineering. He is also a member of the Herbert Irving Comprehensive Cancer Center and collaborated on this project with Kam Leong, a fellow Columbia Engineering faculty member. The study was further strengthened through international collaboration with researchers from the University of Padova, including Elisa Cimetta (Department of Industrial Engineering) and graduate student Caterina Piunti. By combining Padova team’s expertise in agricultural EV sourcing with the Correa lab’s experience in nanomaterials and polymer-based hydrogels, the team demonstrated the power of cross-disciplinary, global partnerships in advancing biomaterials innovation.

    By using yogurt-derived EVs, the team defined a design space for generating hydrogels that incorporate EVs as both structural and biological elements. They further validated the approach using EVs derived from mammalian cells and bacteria, demonstrating that the platform is modular and compatible with diverse vesicle sources. This could open the door to advanced applications in wound healing and regenerative medicine, where current treatments often fall short in promoting long-term tissue repair. By integrating EVs directly into the hydrogel structure, the material enables sustained delivery of their bioactive signals. Because the hydrogel is injectable, it can also be delivered locally to damaged tissue.

    Early experiments show that yogurt EV hydrogels are biocompatible and drive potent angiogenic activity within one week in immunocompetent mice, demonstrating that agricultural EVs not only enable fundamental biomaterials research but also hold therapeutic potential as a next-generation biotechnology. In mice, the material showed no signs of adverse reaction and instead promoted the formation of new blood vessels, a key step in effective tissue regeneration. Correa’s team also observed that the hydrogel creates a unique immune environment enriched in anti-inflammatory cell types, which may contribute to the observed tissue repair processes. The team is now exploring how this immune response could help guide tissue regeneration.

    “Being able to design a material that closely mimics the body’s natural environment while also speed up the healing process opens a new world of possibilities for regenerative medicine,” said Margaronis. “Moments like these remind me why the research field in biomedical engineering is always on the cusp of something exciting.”

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  • Worst-case scenario of famine unfolding in Gaza, UN-backed food security body says – live updates

    Worst-case scenario of famine unfolding in Gaza, UN-backed food security body says – live updates

    No 10 sees Trump’s language on Gaza as a toughening of his outlookpublished at 08:12 British Summer Time

    Chris Mason
    Political editor, reporting from Aberdeenshire

    Donald Trump is on his first trip to the UK since his re-election, visiting his new golf course north of Aberdeen.

    Yesterday Trump and Prime Minister Keir Starmer spent more than half an hour talking one on one, before a classic of the Trumpian genre – a rolling, free-wheeling question-and-answer session with reporters, lasting more than an hour.

    Both leaders agreed on the need for more aid to enter into Gaza, with Trump saying there is “real starvation” in the territory.

    Downing Street is pleased that the president’s language on Gaza amounts to what they see as a toughening of his outlook and what they hope might be an alignment with the discussions the UK, France and Germany have been having in recent days.

    Let’s see.

    Later today, the cabinet will gather at 14:00 for a rare summer meeting, some ministers attending in person in Downing Street, others joining remotely.

    The focus will be on Gaza – and the latest move from many to see if, collectively, the beginnings of a solution can be found to the horrific pictures we’re currently seeing from the Middle East.

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  • Letter for the article Dynamic Immune Indicator Changes as Predictors

    Letter for the article Dynamic Immune Indicator Changes as Predictors

    Dear editor

    The study investigating dynamic immune indicator changes as predictors of ARDS in septic ICU patients, published in the International Journal of General Medicine,1 merits commendation for its ambition to advance predictive biomarkers. However, its conclusions warrant critical re-evaluation due to methodological shortcomings, biological oversimplifications, and unresolved barriers to clinical implementation.

    Methodological Limitations: Overfitting and Narrow Generalizability

    External validation of sepsis-related ARDS predictive models using the MIMIC-IV database consistently demonstrates AUC reduction to 0.7–0.8,2 underscoring the biological implausibility of Lu et al’s reported nomogram (AUC 0.998) in heterogeneous sepsis populations. Such extreme performance likely reflects overfitting to the single-center Chinese cohort (n=1836), given regional variations in sepsis etiology, treatment protocols, and demographic profiles. Critical omissions include external validation, calibration testing (eg, Hosmer–Lemeshow statistics), and early timepoint analysis (eg, 24-hour cytokine surges). Excluding days 1–2 immune dynamics ignores IL-6/TNF-α-driven endothelial injury, which precedes 60–70% of sepsis-related ARDS cases within 48–72 hours.3 Temporal myopia compromises predictive relevance for time-sensitive interventions like lung-protective ventilation.

    Biological Paradoxes: Immunosuppression Misinterpretation

    The assertion that immune suppression (eg, reduced CD4+, CD8+, Treg counts) protects against ARDS contradicts established pathophysiology. ARDS patients exhibit immunosuppressive states marked by lymphopenia and hypogammaglobulinemia, reflecting compensatory anti-inflammatory response syndrome (CARS) rather than adaptive protection. Immunomodulatory therapies (eg, corticosteroids, tocilizumab) further confound associations, as these agents suppress lymphocyte counts by 30–50% independent of ARDS risk.4 Framing immune paralysis as “protective” ignores its role in secondary infection susceptibility and unresolved alveolar inflammation.

    Clinical Barriers: Timing, Feasibility, and Confounding

    Practical implementation faces three obstacles: 1) delayed biomarker sampling (days 3–7) postdates critical intervention windows; 2) resource-intensive flow cytometry/immunoglobulin panels limit usability in low-resource settings; and 3) unaddressed confounders (eg, survivorship bias, hospital-acquired pneumonia) risk misclassification. The model’s exclusion of ventilator-induced biases (eg, stroke volume variation inaccuracy under ≤6 mL/kg tidal volumes) further reduces applicability to modern ICUs. Without prospective validation incorporating early timepoints, cost-effectiveness analyses, and confounder adjustment, clinical utility remains unproven.

    Discussion

    To transition from academic novelty to clinical impact, ARDS prediction frameworks must undergo fundamental redesign prioritizing three pillars: temporal urgency, biological dynamism, and contextual generalizability.

    Firstly, predictive algorithms must incorporate point-of-care biomarkers (eg, CRP/PCT ratios, lactate clearance) that provide actionable data within the critical 6-hour therapeutic window for ARDS prevention. Delays inherent in batch immune profiling render current models retrospective rather than prospective tools.

    Secondly, statistical approaches must evolve from static snapshots to kinetic analyses – tracking cytokine trajectories (eg, IL-6 doubling time) and lymphocyte subset slopes that better reflect the dynamic interplay between pro-inflammatory and compensatory anti-inflammatory responses.5 This shift acknowledges that immune exhaustion in sepsis follows predictable temporal phases rather than discrete day-specific measurements.

    Finally, validation strategies must encompass multicenter cohorts reflecting global sepsis heterogeneity, including viral/bacterial etiologies, varying antimicrobial stewardship practices, and resource availability gradients. Until models demonstrate portability across high-income and low-resource settings while integrating real-time data streams, they will remain laboratory curiosities rather than bedside necessities.

    Until these gaps are addressed, this work remains a proof-of-concept – not a paradigm shift.

    Disclosure

    The author declares no conflicts of interest in this communication.

    References

    1. Lu X, Chen Y, Zhang G, Zeng X, Lai L, Qu C. Dynamic immune indicator changes as predictors of ARDS in ICU patients with sepsis: a retrospective study. Int J Gen Med. 2025;18:1163–1172. PMID: 40051893; PMCID: PMC11882469. doi:10.2147/IJGM.S501252

    2. Chen Y, Zong C, Zou L, et al. A novel clinical prediction model for in-hospital mortality in sepsis patients complicated by ARDS: a MIMIC IV database and external validation study. Heliyon. 2024;10(13):e33337. PMID: 39027620; PMCID: PMC467048. doi:10.1016/j.heliyon.2024.e33337

    3. Villar J, Herrán-Monge R, González-Higueras E, et al. Genetics of Sepsis (GEN-SEP) network. Clinical and biological markers for predicting ARDS and outcome in septic patients. Sci Rep. 2021;11(1):22702. PMID: 34811434; PMCID: PMC8608812. doi:10.1038/s41598-021-02100-w

    4. Cui Z, Wang L, Li H, Feng M. Study on immune status alterations in patients with sepsis. Int Immunopharmacol. 2023;118:110048. PMID: 36989895. doi:10.1016/j.intimp.2023.110048

    5. Yang AC, Ma WM, Chiang DH, et al. Early prediction of sepsis using an XGBoost model with single time-point non-invasive vital signs and its correlation with C-reactive protein and procalcitonin: a multi-center study. Intellig Med. 2025;11:100242. doi:10.1016/j.ibmed.2025.100242

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  • Pakistan begin training in Lauderhill for T20I series against West Indies

    Pakistan begin training in Lauderhill for T20I series against West Indies

    The Pakistan cricket team has kicked off its preparations for the upcoming T20I series against the West Indies with an intense training session at Central Broward Park & Broward County Stadium in Lauderhill.

    Currently touring the United States for a three-match T20I series, the squad underwent a comprehensive three-hour practice session under the supervision of their coaching staff.

    The session included fielding drills, net practice, and skill-specific routines designed to sharpen the players’ match readiness.

    The day began with physical warm-ups before progressing to focused net sessions aimed at improving both execution and technique.

    The opening T20I against the West Indies is scheduled for July 31 at the same venue in Lauderhill, with Salman Ali Agha leading the side for the series.

    Following the T20I matches, the tour will shift to the Caribbean, where Mohammad Rizwan will assume captaincy duties for the three-match ODI series, starting August 8 at the Brian Lara Cricket Academy in Trinidad & Tobago.

    Pakistan’s recent white-ball tour of Bangladesh ended in a 2-1 defeat in a T20I series. The series was head coach Mike Hesson’s second assignment, following a 3-0 whitewash over Bangladesh at home in May.

    Pakistan T20I Squad:

    Salman Ali Agha (c), Abrar Ahmed, Faheem Ashraf, Fakhar Zaman, Haris Rauf, Hasan Ali, Hasan Nawaz, Hussain Talat, Khushdil Shah, Mohammad Haris (wk), Mohammad Nawaz, Sahibzada Farhan (wk), Saim Ayub, Shaheen Shah Afridi, Sufyan Moqim

    Pakistan ODI Squad:

    Mohammad Rizwan (c), Salman Ali Agha, Abdullah Shafique, Abrar Ahmed, Babar Azam, Faheem Ashraf, Fakhar Zaman, Hasan Ali, Hasan Nawaz, Hussain Talat, Mohammad Haris (wk), Mohammad Nawaz, Naseem Shah, Saim Ayub, Shaheen Shah Afridi, Sufyan Moqim

    Series Schedule:

    • July 31 – First T20I v West Indies – USA

    • Aug 2 – Second T20I v West Indies – USA

    • Aug 3 – Third T20I v West Indies – USA

    • Aug 8 – First ODI v West Indies – Trinidad & Tobago

    • Aug 10 – Second ODI v West Indies – Trinidad & Tobago

    • Aug 12 – Third ODI v West Indies – Trinidad & Tobago

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  • CMS advises Iberdrola on the creation of a joint venture with Echelon

    CMS advises Iberdrola on the creation of a joint venture with Echelon

    CMS Albiñana & Suárez de Lezo advises Iberdrola on the creation of a joint venture with Echelon (owned by the Starwood Capital fund) to build and operate data centres in Spain. This is the largest binding agreement of its kind in Europe between an energy company and a developer of this type of technological infrastructure.

    Through this collaboration, Iberdrola will hold a 20% stake through its subsidiary CPD4Green and will be responsible for identifying and securing land with connectivity to the electricity grid where the centres will be developed. In addition, electricity will be supplied to the centres 24/7.

    For its part, Echelon, a Dublin-based technology company owned by Starwood Capital Group, will own 80% of the company and will be responsible for the development, design and marketing of the data centre and the day-to-day management of the joint venture.

    Iberdrola already sells more than 11 TWh to technology companies and operators of these infrastructures worldwide, making it a leader in the supply of electricity to data centres. In addition, its subsidiary CPD4Green, dedicated to facilitating the development of data processing infrastructures, already has a portfolio of sites for 700 MW in Spain and potential for another 5,000 MW.

    The transaction was coordinated by our managing partner, César Albiñana, Corporate/M&A partner Ignacio Zarzalejos, and Public Law and Regulated Sectors partner Juan Moreno, as well as lawyer Ana Vázquez from the Corporate/M&A area.

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  • Differential Effects of SGLT-2 Inhibitors on Liver Function and Noctur

    Differential Effects of SGLT-2 Inhibitors on Liver Function and Noctur

    Introduction

    Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) were initially introduced as treatments for type 2 diabetes but have since shown utility in various areas, such as preventing and improving renal and heart failure.1–4 Consequently, the use of SGLT-2is has expanded across multiple fields. Recently, studies have highlighted their efficacy in addressing fatty liver disease.5–7 Approximately 65% of patients with type 2 diabetes are estimated to have metabolic dysfunction-associated steatotic liver disease (MASLD).8,9 Moreover, the prevalence of metabolic dysfunction-associated steatohepatitis (MASH) in these patients can be as high as 66.44%,8 indicating that a considerable portion of MASLD in these patients corresponds to MASH. If left untreated, MASH can lead to progressive fibrosis, increasing the risk of severe liver failure and cardiovascular events.10–12 Therefore, improving liver function is as critical a therapeutic goal as glycemic control in patients with diabetes.

    However, SGLT-2is are associated with several side effects, and frequent urination is one of the most common, affecting approximately 5% of patients who are prescribed these drugs.13

    In particular, nocturia in older adults can lead to sleep disturbances because of nighttime awakenings, reduced quality of life,14,15 and even increased risks of depression and dementia,16 as well as falls and fractures.17,18 Therefore, addressing this issue is a critical challenge.

    In this study, we investigated whether the fatty liver improvement effects of SGLT-2i differ by individual drugs or represent a class effect (a common effect across all drugs in this group), using three different SGLT-2is for evaluation. In addition, we focused on the fact that tofogliflozin has the shortest half-life in the blood and the shortest duration of action among SGLT-2is,19 and investigated whether its effect on nocturia differs from that of other SGLT-2is.

    Materials and Methods

    Study Design and Participants

    The participants in this study were adults aged 30 years or older who were diagnosed with type 2 diabetes and fatty liver and were classified as having MASLD. Type 2 diabetes is diagnosed when at least two of the following criteria are fulfilled: a fasting plasma glucose level of 126 mg/dL (7.0 mmol/L) or higher, a 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) or higher during a 75-g oral glucose tolerance test, a random plasma glucose of 200 mg/dL (11.1 mmol/L) or higher, and a hemoglobin A1c level of 6.5% (48 mmol/mol) or higher.20 Alternatively, patients who have already been diagnosed with type 2 diabetes based on the above tests. In addition, lipid droplets in more than 5% of hepatocytes, using ultrasonography, are defined as steatosis, referred to as fatty liver.21 Currently, hepatic steatosis involving more than 5% of the liver parenchyma can be diagnosed using B-mode ultrasonography.22,23

    SGLT-2is were initiated or added to the treatment regimen for patients with HbA1c levels ≥7.5% (58 mmol/mol). MASLD was diagnosed according to the presence of fatty liver and at least one of the following five criteria:24 1. a BMI of ≥23.0 kg/m² or a waist circumference ≥94 cm for men and ≥80 cm for women; 2. prediabetes or diabetes treated with anti-diabetic medication; 3. blood pressure ≥130/85 mmHg or treatment with antihypertensive medication; 4. triglyceride (TG) levels ≥150 mg/dL or treatment with lipid-lowering medication; and 5. high-density lipoprotein cholesterol (HDL-C) levels ≤40 mg/dL for men or ≤50 mg/dL for women, or treatment for low HDL-C levels.

    The exclusion criteria included patients already receiving SGLT-2is, those using insulin, and individuals with severe liver cirrhosis, severe renal dysfunction, pregnancy, or severe mental illness. In addition, patients with conditions known to cause nocturia, such as prostatic disorders or uterine prolapse, were excluded from the study.

    Randomization

    Eligible participants were randomized using a permuted block method stratified by age (≥65 years or <65 years), sex (male or female), HbA1c levels (≥9.0% or <9.0% [≥75 mmol/mol or <75 mmol/mol]), body weight (BMI ≥25.0 or <25.0 kg/m²), and duration of diabetes (≥10 years or <10 years). The participants were assigned to one of the following three groups in a 1:1:1 ratio: tofogliflozin group (Tofo group), empagliflozin group (Empa group), or dapagliflozin group (Dapa group). This trial is a prospective, randomized, open-label, blinded endpoint (PROBE) study conducted at a single center. The evaluation of liver fibrosis markers and nocturia frequency was independently performed by physicians and research staff from the adjudication committee, both of whom were blinded to treatment allocation.

    Study Treatment

    In the Tofo group, the participants received tofogliflozin at a dose of 20 mg. In the Empa group, the participants received empagliflozin at a dose of 10 mg. In the Dapa group, the participants received dapagliflozin at a dose of 5 mg. All these SGLT-2is were administered orally after breakfast.

    During the study period, discontinuation of these SGLT-2is or the addition of other medications was not permitted unless adverse events occurred. The participants were followed up at outpatient visits initially after 1 month and subsequently every 2 months for a total of 6 months, resulting in a 7-month observation period. At each visit, measurements of height, weight, BMI, waist circumference, blood pressure, blood tests, body composition, and ultrasound elastography were conducted.

    Outcomes

    The primary endpoints were changes in the frequency of nocturia and liver function markers, namely aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GPT), fibrosis-4 (FIB-4) index, and mac-2 binding protein glycan isomer (M2BPGi). In addition, liver fibrosis was evaluated using ultrasound elastography (Aplio i700, Canon Medical Systems, Tokyo). Shear wave speed measurements were interpreted as follows: values between 1.00 and 1.66 m/sec were classified as fibrosis grade (F) 0–1 (normal to mild fibrosis), with higher values indicating progression of fibrosis, ie, increased F score.25–27

    Nocturia was defined as waking to urinate at least once during the night,28 with “nighttime” defined as the time between 11:00 pm and 5:00 am in this study.

    Secondary endpoints included changes in HbA1c levels, fasting blood glucose, body weight, waist circumference, the lipid profile, and blood pressure. This study was conducted with the approval of the Institutional Review Board (IRB) of Shinkomonji Hospital. Written informed consent was obtained from all of the participants before enrollment. In addition, we confirmed that all research was performed following relevant guidelines/regulations.

    This study has been performed in compliance with the Declaration of Helsinki. The trial protocol was registered with the UMIN Clinical Trial Registry (https://www.umin.ac.jp/ctr/) under the number UMIN000054278, with an initial registration date of 28/04/2024. The trial protocol is available in the Supplementary Material accompanying this manuscript.

    Statistical Analyses

    The sample size was calculated on the basis of the assumption that nighttime was defined as from 11:00 pm to 5:00 am, with the frequency of nighttime urination (nocturia) estimated to be 0.8 times in the Tofo group and 2.1 times in the Empa and Dapa groups. Nocturia frequency was calculated using a method based on the results of a pilot study (data not shown). Assuming a standard deviation of 2, an α error of 0.05, a statistical power of 0.8, and a 10% dropout rate over the 7-month follow-up, a 1:1:1 allocation required 43 participants in each group, resulting in a total sample size of 129 participants. Regarding the baseline characteristics, continuous variables are expressed as the mean ± standard deviation for descriptive analysis, and categorical variables are expressed as frequencies (%). To examine whether there were any variations in the samples between the groups at baseline, a test of homogeneity of variance (F-test) was conducted. Comparisons of continuous variables between the three groups at baseline and at each time point (1, 3, 5, and 7 months) were performed using an analysis of variance (ANOVA) with Dunnett’s test, and the Tofo group was set as the control. Temporal changes in continuous variables within each group were assessed using an ANOVA with Dunnett’s test, setting the baseline values as the control. In all cases, comparisons of categorical variables were performed using an m×n chi-square test. In this study, a p-value <0.05 was not considered significant. Instead, p-values adjusted using the Bonferroni correction (ie, 0.05 divided by the total number of pairwise comparisons) were considered significant under the concept of multiple comparisons. Statistical analyses were performed using SPSS ver. 17.0 (SPSS Inc., Chicago, IL, USA) and R software (version 4.1.1).

    Results

    Baseline Characteristics

    The participants were recruited between April and the end of September 2024. A total of 135 participants were randomly assigned to the three groups (Figure 1). The participants had a mean age of 61 years and 43% were female. The mean BMI was 24.5 kg/m², the mean HbA1c level was 8.7%, the mean FIB-4 index was 1.84, the mean shear wave speed was 1.51 m/sec, and the mean number of nocturia episodes was 0.6 times. No significant differences in these variables were observed between the groups (Table 1).

    Table 1 Baseline Characteristics

    Figure 1 Screening, randomization, and follow-up. A total of 135 participants were randomly assigned to three groups of 45, each receiving a prescribed drug: the Tofo group received 20 mg of tofogliflozin, the Dapa group received 5–10 mg of dapagliflozin, and the Empa group received 10–25 mg of empagliflozin. All participants were followed for seven months. During the study, there were dropouts: 4 in the Tofo group, 5 in the Dapa group, and 4 in the Empa group. However, all participants were included in the analysis according to the intention-to-treat and per-protocol set criteria.

    Primary Outcome of MASLD

    All groups showed significant reductions in AST, ALT, and γ-GTP levels and the FIB-4 index compared with baseline (all p-values <0.05). In addition, a gradual reduction in shear wave speed-based fibrosis grade was observed compared with baseline across all groups (all p-values <0.05). However, no significant differences in these variables were found between the three groups. Furthermore, no significant changes in M2BPGi levels were observed in any group compared with baseline (Figure 2).

    Figure 2 Changes in liver function and nocturia frequency with SGLT-2i treatment. Blue square, tofogliflozin group; purple diamond, dapagliflozin group; sky-blue circle, empagliflozin group. T-bars showed the standard deviations. * To assess time effects using analysis of variance followed by Dunnett’s test, baseline measurements (0 months) were compared with those at 1, 3, 5, and 7 months, in each of the three groups. † Comparisons between the Tofo group and the Dapa and Empa groups were conducted at each time point (0, 1, 3, 5, 7 months). The Bonferroni correction defined statistical significance as p<0.05/([4×3] + [2×5]) = 0.00227. Therefore, * and † denote p <0.00227.

    Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; γ-GPT, gamma-glutamyl transpeptidase; FIB-4, fibrosis-4; M2BPGi, mac-2 binding protein glycan isomer.

    Primary Outcome of the Frequency of Nocturia

    In the Empa and Dapa groups, the frequency of nocturia significantly increased to 1.7 and 1.9 times, respectively, 1 month after starting medication compared with baseline. In contrast, the Tofo group showed an increase in the frequency of nocturia by only 0.8 times, which was not statistically significant. Consequently, the Tofo group showed a significantly lower frequency of nocturia than the other two groups (p<0.001). This difference persisted until 3 months after the initiation of treatment; however, the frequencies were 1.3, 1.2, and 0.7 times, respectively, with a p-value of 0.010, which did not meet the significance threshold after Bonferroni correction (p < 0.00227). In addition, the difference diminished after the fifth month. Over time, the frequency of nocturia decreased in all three groups, with no significant changes from baseline or differences between the groups (Figure 2).

    Secondary Outcomes

    All three groups showed a significant reduction in weight and waist circumference compared with baseline, with no significant differences between the groups. No significant changes in systolic or diastolic blood pressure were observed in any group compared with baseline. Fasting plasma glucose and HbA1c levels were significantly decreased in all three groups compared with baseline. While the Dapa and Empa groups showed a slight trend of a greater reduction in these variables than the Tofo group, no significant differences were observed between the groups. A significant reduction in TG levels was observed in all three groups, with no significant intergroup differences. In females, no significant changes in HDL-C levels were observed in any group. In contrast, in males, all three groups showed a significant increase in HDL-C levels at 1 month compared with baseline, with no differences between the groups (Figure 3). Low-density lipoprotein-cholesterol levels remained unchanged in all groups compared with baseline, with no difference between the sexes (data not shown).

    Figure 3 Changes in body weight, blood pressure, blood glucose, and lipid levels with SGLT-2i treatment. Blue square, tofogliflozin group; purple diamond, dapagliflozin group; sky-blue circle, empagliflozin group. T-bars showed standard deviations. *To assess time effects using analysis of variance followed by Dunnett’s test, baseline measurements (0 month) were compared with those at 1, 3, 5, and 7 months in each of the three groups. Comparisons between the Tofo group and the Dapa and Empa groups were conducted at each time point (0, 1, 3, 5, 7 months). The Bonferroni correction defined statistical significance as p<0.05/([4×3] + [2×5]) = 0.00227. Therefore, *denotes p <0.00227.

    Abbreviations: BMI, body mass index; BP, blood pressure; HbA1c, glycated hemoglobin; FPG, fasting blood glucose; TG, triglycerides; HDL-C, high-density lipoprotein-cholesterol; LDL, low-density lipoprotein-cholesterol.

    Sub-Analysis

    A sub-analysis was conducted by stratifying the participants according to diabetes duration, age, baseline HbA1c levels, and sex. Based on the baseline distributions, participants were categorized into tertiles: 33–59, 60–71, and 72–89 years for age, and 7.5–8.9%, 9.0–10.3%, and 10.4–12.4% for HbA1c levels.

    This analysis revealed that older age and higher baseline HbA1c levels were associated with greater effectiveness of tofogliflozin in reducing the frequency of nocturia (Table 2). No significant differences in these variables according to sex were observed. In addition, the frequency of daytime (5:00 a.m. to 11:00 p.m.) urinations increased to 7.9 times in the Tofo group, 7.1 times in the Dapa group, and 6.9 times in the Empa group after one month, with a significant difference among the three groups (p = 0.0014). Subsequently, urinary frequency gradually declined, and no significant differences were observed among the groups after three months (Figure 4).

    Table 2 Frequency of Nocturia

    Figure 4 Frequency of daytime urination. The daytime urinary frequency increased after one month to an average of 7.9 times in the Tofo group, 6.9 times in the Dapa group, and 7.1 times in the Empa group, with a statistically significant difference among the three groups (p = 0.0014). Subsequently, urinary frequency gradually declined, and no significant differences were observed among the groups after three months. * To assess time effects using analysis of variance followed by Dunnett’s test, baseline measurements (0 month) were compared with those at 1, 3, 5, and 7 months in each of the three groups. † Comparisons between the Tofo group and the Dapa and Empa groups were conducted at each time point (0, 1, 3, 5, 7 months). The Bonferroni correction defined statistical significance as p <0.05/([4×3] + [2×5]) = 0.00227. Therefore, * and † denote p < 0.00227.

    Adverse Events

    Genital mycotic infections and urinary tract infections were observed in all three groups (Table 3). No significant differences in the incidence rates of these events were observed between the three groups.

    Table 3 Frequency of Adverse Events

    Discussion

    In this study, tofogliflozin, dapagliflozin, and empagliflozin showed reduced and improved liver function and fibrosis markers associated with MASLD. However, no significant differences in these markers were detected between the three groups. Notably, tofogliflozin significantly reduced the frequency of nocturia 1 month after initiating treatment compared with the other two drugs. However, the difference disappeared after three months. There was no significant difference in weight loss, an improvement in blood glucose levels, or a change in lipid profile between the groups.

    Effect of SGLT-2is on MASLD

    Recently, there has been an increase in reports showing the efficacy of SGLT-2is in improving MASLD.5–7 However, whether this effect represents a class effect of SGLT-2is remains unclear. Our findings suggest that SGLT-2is have a class effect in improving fatty liver or, at least, that the three drugs used in this study have beneficial effects on MASLD.

    A total of 68.8% of patients with type 2 diabetes have been reported to have coexisting MASLD,8 which is associated with an increased risk of liver fibrosis.29 However, randomized controlled trials on SGLT-2is have shown a reduction in hepatic fat content as measured by magnetic resonance imaging.30,31

    SGLT-2is lower blood glucose levels by inhibiting SGLT-2, a protein predominantly expressed in the renal tubules, thereby reducing glucose reabsorption in the kidneys. This mechanism is associated with an improvement in insulin resistance, a reduction in free fatty acids, decreased hepatic fat deposition, and amelioration of intrahepatic inflammation and fibrosis.32 In our study as well, significant improvement in liver fibrosis was observed at five months after the initiation of treatment. Furthermore, SGLT-2is have been shown to enhance insulin sensitivity by increasing adiponectin levels33 and to promote glucagon-like peptide 1 secretion,34,35 both of which may contribute to the improvement of MASLD. Notably, SGLT-2 expression is not limited to the kidneys; it has also been detected in hepatocytes and bile duct epithelial cells.36 This finding suggests that SGLT-2is exert direct effects on the liver or affect hepatic function indirectly through bile acids and the gut microbiota, resulting in reduced hepatic fat deposition and inflammation. The use of SGLT-2is in the treatment of type 2 diabetes has shown potential therapeutic benefits in MASLD, possibly through mechanisms that may indirectly influence the progression of liver disease.37,38 In addition, as discussed later, although tofogliflozin has a shorter half-life compared to the other two agents, no significant differences in liver function improvement, including antifibrotic effects, were observed among the three groups. These findings suggest that, similar to its glucose-lowering effects, the improvement in liver function may be independent of the drug’s half-life duration.

    Effect of SGLT-2is on Nocturia Frequency

    Nocturia is defined as the need to urinate during the night, interrupting sleep at least once.28 Nocturia is associated with sleep disturbances,15 an increased risk of falls and fractures,17,18,39 and an elevated risk of depression and dementia.16 These effects can greatly reduce quality of life, especially in older adults,40–42 highlighting the importance of preventing and treating nocturia.

    Frequent urination is a common side effect of SGLT-2is, leading to increased urination during the day and at night, which may contribute to nocturia. A randomized controlled trial reported that approximately 5% of individuals experience this side effect.13 However, other studies have shown that empagliflozin increases daily urine volume by 500 mL,43 and nearly all individuals taking SGLT-2is exhibit some increase in urinary frequency.44 The change in frequency of urination can vary according to the type of SGLT-2i used and the patients’ underlying conditions. However, SGLT-2is contribute to the development of frequent urination. This effect is particularly prominent in patients with poor glycemic control at the time of prescription, because osmotic diuresis and nephropathy are thought to further increase the frequency of urination.13 On the contrary, several studies have noted that while polyuria is a frequent early complaint, it often subsides within weeks of treatment initiation.1,45,46 This timeline coincides with the period in which blood glucose begins to normalize, suggesting a strong correlation between the resolution of polyuria and improved glycemic control. The EMPA-REG and CANVAS studies involving SGLT-2is demonstrated the greatest improvement in glycemic control at 12 to 13 weeks (approximately 3 months) following drug initiation,1,46 aligning with the 3-month time point observed in the present study. Frequent urination caused by SGLT-2is is largely due to osmotic diuresis driven by glucosuria. As blood glucose control improves, the filtered load of glucose decreases, leading to reduced glucosuria and, consequently, decreased urinary frequency.47

    The blood half-life of tofogliflozin is 5–6 hours,19 which is shorter than that of empagliflozin (9.88–13.1 hours)48 and dapagliflozin (12.9 hours).49 Therefore, when tofogliflozin is taken in the morning, its effects are likely to diminish by nighttime. In this study, the frequency of nocturia in the Tofo group did not significantly increase (0.8 times), and this small increase was notably less than that in the other two groups (1.7 and 1.9 times, respectively).

    This trend was particularly evident in patients with higher baseline HbA1c levels or older age. Therefore, when initiating SGLT-2i therapy, tofogliflozin may be a more appropriate option for patients with baseline HbA1c levels ≥ 9.0% or those aged ≥ 72 years, given its potential benefit in reducing nocturia frequency. Conversely, the nocturia-reducing effect of tofogliflozin may be limited in patients with baseline HbA1c levels ≤ 8.9% or age ≤ 59 years.

    In addition, we did not find any significant differences in the daytime urination frequency or a reduction in HbA1c levels among the three groups.

    Adverse Events of SGLT-2is

    Regarding adverse events, urinary tract infections and genital infections were observed in all SGLT-2i groups. However, the incidence of these events is comparable to previously reported rates,13 with no significant differences between the groups.

    Study Limitation

    This study has several limitations, such as its single-center design, the fact that only Japanese participants were included, and the 7-month study duration. Liver function may continue to change beyond 7 months. While a significant difference in the frequency of nocturia was observed at 1 and 3 months, this difference diminished over time, suggesting that additional long-term studies may not be required.

    Conclusion

    All three SGLT-2is led to a reduction in MASLD-related parameters, but no significant differences in these parameters were observed between the groups. These findings suggest that the improvement in fatty liver associated with SGLT-2is may be a class effect. SGLT-2 is are now widely recognized not only for their glucose-lowering effects in patients with diabetes but also for their cardioprotective and renoprotective effects. The findings of this study may contribute to the growing body of evidence supporting the potential hepatoprotective effects of SGLT-2 is. Tofogliflozin significantly reduced the frequency of nocturia compared with the other two SGLT-2is. This finding suggests that the shorter half-life in the blood of tofogliflozin may be particularly beneficial for patients with baseline HbA1c levels ≥ 9.0% or age ≥ 72 years.

    Data Sharing Statement

    Some or all datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

    Ethics Approval and Consent to Participate

    This study was conducted with the approval of the Institutional Review Board (IRB) of Shinkomonji Hospital. Written informed consent was obtained from all of the participants before enrollment. In addition, we confirmed that all research was performed following relevant guidelines/regulations.

    Author Contributions

    All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

    Funding

    This study was supported by a grant from the Fukuoka Medical Association (T.K.). The sponsor did not contribute to the design, collection, management, analysis, interpretation of data, writing of the manuscript, or the decision to submit the manuscript for publication.

    Disclosure

    All the authors declare no competing interests in this work.

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    43. Mordi NA, Mordi IR, Singh JS, et al. Renal and cardiovascular effects of sglt2 inhibition in combination with loop diuretics in patients with type 2 diabetes and chronic heart failure: the RECEDE-CHF trial. Circulation. 2020;142(18):1713–1724. doi:10.1161/CIRCULATIONAHA.120.048739

    44. Saijo Y, Okada H, Hata S, et al. Reasons for discontinuing treatment with sodium-glucose cotransporter 2 inhibitors in patients with diabetes in real-world settings: the KAMOGAWA-A study. J Clin Med. 2023;12(22):6993. doi:10.3390/jcm12226993

    45. Vallon V:. State-of-the-art-review: mechanisms of action of SGLT2 inhibitors and clinical implications. Am J Hypertens. 2024;37(11):841–852. doi:10.1093/ajh/hpae092

    46. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–657. doi:10.1056/NEJMoa1611925

    47. Heerspink HJ, Perkins BA, Fitchett DH, Husain M, Cherney DZ. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation. 2016;134(10):752–772. doi:10.1161/CIRCULATIONAHA.116.021887

    48. Scheen AJ. Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor. Clin Pharmacokinet. 2014;53(3):213–225. doi:10.1007/s40262-013-0126-x

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  • Share your ideas at The Fashion Pulpit on how to cope with rising temperatures

    Share your ideas at The Fashion Pulpit on how to cope with rising temperatures

    SINGAPORE – Temperatures are rising due to climate change, and the need to help people – especially those from vulnerable communities – cope with the heat is becoming more urgent.

    But with warm temperatures being something that many people living in tropical Singapore are already accustomed to, at what point does the heat become a public health risk?

    And how is Singapore taking steps to protect people with high exposure to heat, such as outdoor workers?

    Join us for a timely dialogue with experts on the issue at the fourth ST Podcasts Live event on Aug 12, which will be held at local swopping boutique The Fashion Pulpit in Jalan Besar.

    Titled “Heat Stress & Us”, the dialogue is part of The Straits Times’ Green Pulse podcast, which provides a South-east Asian perspective on climate change and environmental issues.

    New episodes are aired every first and third Tuesday of the month.

    ST deputy foreign editor David Fogarty and assistant news editor Audrey Tan, who co-host Green Pulse, will be speaking with Associate Professor Jason Lee, director of the Heat Resilience and Performance Centre at the NUS Yong Loo Lin School of Medicine.

    Prof Lee is also the lead principal investigator of Project HeatSafe, a research initiative that studies the threat that heat poses to human health, wellbeing, and productivity in South-east Asia.

    ST Podcasts Live on Aug 12 will address the pressing environmental issues of heat stress and human-wildlife conflict.

    ST Podcasts Live on Aug 12 will address the pressing environmental issues of heat stress and human-wildlife conflict.

    The dialogue will also involve Ms Jaime Lim, director of the major hazards and the occupational safety and health specialist departments at the Ministry of Manpower.

    The Manpower Ministry had in 2023 rolled out new measures that required employers to take steps to protect outdoor workers from heat. Employers, for example, had to provide hourly rest breaks for workers when it gets too hot.

    Following the discussion on heat, a second podcast recording will take place.

    The second dialogue will touch on the reasons behind the increasing encounters between humans and wildlife in urban Singapore, and how such interactions should be managed to reduce conflict.

    One of the recent cases of human-wildlife encounters involve long-tailed macaques spotted within a once-forested area in Punggol that is now a residential area.

    The Straits Times earlier reported that the authorities had received over 200 reports of these monkeys over a seven-month period. The animals were spotted rummaging through bins and breaking into homes in search of food.

    As Singapore embarks on greening initiatives to infuse the urban landscape with more vegetation, experts have warned that encounters between humans and wildlife will only increase.

    A key point of the discussions will be how Singapore can achieve better co-existence between humans and the native wildlife that call the country home.

    ST correspondents Shabana Begum and Ang Qing, who were the co-hosts of ST’s award-winning experiential podcast series Green Trails, will helm the second discussion.

    They will host Mr Kalaivanan Balakrishnan, the co-chief executive of wildlife rescue group Animal Concerns Research & Education Society (Acres), and Ms Jasvic Lye, the campaign manager of Our Wild Neighbours, an initiative to educate the public on wildlife etiquette.

    Passionate about animal welfare, Mr Balakrishnan carried out Acres’ first reptile repatriation in 2017 and was instrumental in ensuring that the wildlife rescue group continued to help animals during the Covid-19 pandemic.  Ms Lye, a fine arts graduate, started her ongoing “Death By Man” photo series in 2017 to shed light on the devastating effects of urbanisation on wildlife.

    Guests who sign up will be able to experience a live podcast recording session, and engage in a Q&A segment with panellists. Those interested can sign up at https://str.sg/podcastlive

    ST Podcasts Live is a series launched this year to commemorate The Straits Times’ 180th anniversary.

    The first ST Podcasts Live, on the topic of historic buildings, took place on Feb 12 at The Foundry. This was followed by the second event on April 15 at The Projector, which discussed diverse definitions of success.

    In the third event on June 3 at Raffles Place Rasa, panellists spoke on how to build a fulfilling career. The live podcast on 12 Aug on environmental issues is the fourth in the series.

    ST Podcast Live at The Fashion Pulpit

    Where:  #04-00 Allenby House, 298 Jln Besar When: August 12, 2025, 7pm to 9pm Topics: [Green Pulse Podcast] Heat Stress & Us [Green Pulse Podcast] Human-wildlife conflict How to sign up: str.sg/podcastlive

    Source: The Straits Times © SPH Media Limited. Permission required for reproduction

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  • Burn: Korea trip is a ‘full circle moment’

    Burn: Korea trip is a ‘full circle moment’

    The Magpies defender was ten years old when the country co-hosted the 2002 World Cup, and could get the opportunity this week to play in two venues built for the tournament.

    United take on Team K League at the Suwon World Cup Stadium on Wednesday before facing Tottenham Hotspur at the 66,704-capacity Seoul World Cup Stadium on Sunday.

    Burn and his team-mates were welcomed by masses of supporters as they landed at Incheon Airport on Monday evening, following a successful visit to Singapore.

    And the England international centre-back admitted: “Being a Newcastle fan myself, sometimes you think that it’s only the city of Newcastle that supports the team, but coming away and seeing thousands of people in the airport and how excited they were to see us shows why we do come over here.

    “Obviously it’s good commercially good for the club, but for the players and staff to feel the love that we had was very exciting.

    “We’re very, very happy to be here. We feel in a very lucky position – I think it’s somewhere that probably we wouldn’t get to experience, South Korea, if it wasn’t for football.

    “My first experience of football was the 2002 World Cup, which was in South Korea and Japan, where we visited last year, so it feels like a bit of a full circle moment for me.

    “I’m excited to play the game. It’s going to be tough – a lot of the players will be in the middle of their season, so I’m expecting them to be very sharp compared to where we are in our pre-season. The heat will be a big factor as well, but I think it’s good that we can play the heat and get ourselves ready for the Premier League season.”

    Joining Burn and the rest of the squad in South Korea was new signing Seung-Soo Park, who joined the Magpies from K League 2 side Suwon Bluewings last week.

    The 18-year-old winger, who was born in Seoul, trained with his new colleagues in Singapore and was an unused substitute against Arsenal at the weekend, but could feature on Wednesday evening.

    “From a player’s point of view, it’s probably been an exciting but difficult first few weeks,” said Burn. “He’s been in England for a little bit and now travelled again, so it’s been nice to spend time with him.

    “He spoke at his first training session – he seemed thankful to be here and get to know people, and I think for us as a team it’s about trying to make it as comfortable as possible for him.”

    Team K League is selected from the best players in South Korea’s top flight, including Pohang Steelers pair Lee Tae-seok and Brazilian midfielder Oberdan, who finished top of a recent public vote.

    Albania international Jasir Asani – who came up against Burn and England in the summer – is also set to play, and Burn added: “We are expecting a tough team, along with the conditions, and we will be have to be at top of our game.

    “We were a lot better in the Arsenal game than the Celtic game and I think going into that week probably a little less fatigued helped as well. So we’re building. We’re expecting a big support for the K League team but we’ve got a lot of Newcastle support as well.

    “Hopefully it’s a game where we can get our forward players on the ball as much as possible. We signed Anthony Elanga, who is very, very quick; Jacob Murphy scored a great goal against Arsenal; Anthony Gordon, Harvey Barnes and I think Will Osula has done really well.

    “With Alex (Isak) not being here, it’s given him game time he may not not have got as much of, but he played really well the other night so hopefully he will continue that.”

    But while Wednesday night’s game – and the subsequent fixture against Spurs – are United’s current focus, the main priority is the campaign ahead.

    “We had a very good season last season,” said Burn. “Champions League qualification and winning the cup was amazing, but we don’t want to just sit on that. We want to build again.

    “We’ve got that experience of the Champions League this year from two years ago to learn from, so I think we’ll be better prepared for that, and we want to keep moving forward.

    “For me, I just want to keep playing well with Newcastle. I had a really good season last year. I want to improve on that and hopefully international games will come from that – and maybe the World Cup.”

    All of the Magpies’ pre-season fixtures, including the game against Team K League, are available for supporters around the world (subject to broadcast rights) to watch live on the Official Newcastle United website and app. Click here for more information.

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