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  • Metformin Fails to Improve Survival in Metastatic Hormone-Sensitive Prostate Cancer

    Metformin Fails to Improve Survival in Metastatic Hormone-Sensitive Prostate Cancer

    Prostate cancer under the microscope: © heitipaves – stock.adobe.com

    A large-scale, randomized, phase 3 trial, part of the STAMPEDE (NCT00268476) platform, has found that adding metformin to standard-of-care treatment in nondiabetic patients with metastatic hormone-sensitive prostate cancer (mHSPC) did not significantly improve overall survival (OS).1

    While the widely used antidiabetic agent did reduce adverse metabolic effects associated with androgen-deprivation therapy (ADT), its primary end point of improved OS was not met in the overall study population.

    These findings provide crucial evidence regarding the utility of metformin in this patient cohort, particularly given previous preclinical data and smaller studies suggesting potential anticancer activity.

    Study Design and Patient Cohort

    The STAMPEDE trial, conducted across 112 hospitals in the United Kingdom and Switzerland, recruited patients with high-risk locally advanced or metastatic adenocarcinoma of the prostate.1,2 This specific analysis focused on nondiabetic patients with metastatic disease, adequate renal function, and a WHO performance status of 0 to 2. Patients were randomized 1:1 to receive either standard of care or standard of care plus metformin 850 mg twice daily. Standard of care typically included ADT, with or without radiotherapy, and with or without docetaxel or an androgen receptor pathway inhibitor (ARPI) such as abiraterone (Zytiga), enzalutamide (Xtandi), or apalutamide (Erleada).

    Between September 5, 2016, and March 31, 2023, a total of 1874 patients with metastatic disease were randomized.1 The median age was 69 years, and the median prostate-specific antigen (PSA) level at baseline was 84 ng/mL. A substantial majority of patients (94%) had newly diagnosed metastatic disease, and 82% received ADT plus docetaxel.

    No Overall Survival Benefit Observed

    The primary end point was OS. After a median follow-up of 60 months, 473 deaths were reported in the standard-of-care group, with a median survival of 61.8 months. In the metformin group, 453 deaths were reported, with a median survival of 67.4 months. The hazard ratio (HR) for OS for the metformin group compared with standard of care was 0.91 (95% CI, 0.80–1.03; P =.15), indicating no statistically significant improvement in overall survival with the addition of metformin.

    Similarly, there was no evidence of an effect on prostate cancer-specific survival in the overall population (HR, 0.97; 95% CI, 0.85–1.12; P =.70). Progression-free survival (PFS) and failure-free survival also showed no significant overall benefit.

    Potential Benefit in High-Volume Disease

    While the overall population did not demonstrate a survival benefit, a prespecified subgroup analysis explored the impact of metformin based on metastatic disease volume, categorized by CHAARTED criteria. In patients with high-volume disease, the HR for OS was 0.79 (95% CI, 0.67–0.94; P =.0072) favoring metformin. Conversely, for patients with low-volume disease, the HR was 0.98 (range, 0.78–1.23; P =.87). Although the P-value for interaction was 0.12, which did not meet strict statistical significance for heterogeneity, this finding warrants further investigation into whether a subset of patients with more aggressive disease might derive some oncological benefit. A similar trend was observed for PFS and metastatic PFS in the high-volume disease subgroup.

    Mitigating Metabolic Adverse Effects of ADT

    A significant secondary finding of the study was metformin’s ability to mitigate the adverse metabolic effects commonly associated with ADT. Patients in the metformin group experienced significantly less weight gain compared with the standard-of-care group. At 104 weeks, patients on standard of care gained a mean of 4.40 kg, while those on metformin gained a mean of 2.00 kg (mean difference, –2.48 kg; 95% CI, –3.55 to –1.41; P <.0001).

    Metformin also led to statistically significant improvements in changes from baseline for fasting glucose, total cholesterol, LDL cholesterol, and HbA1c. These metabolic benefits were consistent across various time points (24, 48, and 104 weeks).

    Safety Profile

    PC-3 human prostate cancer cells: © heitipaves – stock.adobe.com

    The safety profile of metformin was consistent with its known effects. Grade 3 or worse adverse events were reported in 57% of patients in the metformin group compared with 52% in the standard of care group. The most notable difference was in gastrointestinal adverse events, which were more common with metformin. Diarrhea was reported by 65% of patients in the metformin group vs 37% in the standard-of-care group, with grade 3 diarrhea occurring in 5% and 3% of patients, respectively. Nausea was also more frequent in the metformin arm. Other body systems showed no significant differences in grade 3 or worse adverse events. There was 1 drug-related death in the metformin group compared with 6 in the standard-of-care group.

    Implications for Clinical Practice

    The results of the STAMPEDE trial, the first large-scale randomized study of its kind in this population, do not support the routine addition of metformin to the standard of care for all nondiabetic patients with mHSPC for the purpose of improving OS. However, the observed metabolic benefits are noteworthy, as ADT-induced metabolic changes, including weight gain and increased cardiovascular risk, are significant concerns for patients.

    “[The] addition of metformin to standard of care produced clear metabolic benefits irrespective of disease volume, inducing significant and sustained reductions in circulating glucose and HbA1c and total cholesterol and LDL cholesterol concentrations,” study authors wrote. “Additionally, metformin significantly reduced clinically relevant weight gain induced by systemic treatment with ADT. These findings are novel and represent a substantial and potentially valuable treatment benefit for men with this lethal form of prostate cancer. Use of metformin as a supplement to ADT-based standard of care will have to be weighted against side effects, namely [diarrhea].”

    The intriguing signal of potential anticancer effect in patients with high-volume disease warrants further exploration. This may suggest that a more tailored approach, perhaps based on disease characteristics or specific biomarkers, could identify a subset of patients who might benefit from metformin beyond its metabolic effects. Ongoing research stemming from the STAMPEDE platform, including a metabolic substudy, aims to delve deeper into these mechanisms and identify optimal patient selection.

    REFERENCES:
    1. Gillessen S, Murphy L, James ND, et al. Metformin for patients with metastatic prostate cancer starting androgen deprivation therapy: a randomised phase 3 trial of the STAMPEDE platform protocol. Lancet Oncol. 2025 Jul 7:S1470-2045(25)00231-1. doi: 10.1016/S1470-2045(25)00231-1. Online ahead of print.
    2. Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE). ClinicalTrials.gov. Updated April 18, 2023. Accessed July 25, 2025. https://clinicaltrials.gov/study/NCT00268476

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  • Kenilworth friends plan Paris charity cycle after health scares

    Kenilworth friends plan Paris charity cycle after health scares

    Elliot Ball

    BBC News, West Midlands

    Ziyad Azad Ziyad Azad and Aaron Moloney cycling along the waterfront with boats and a large hill behind them. Mr Azad is taking the selfie photo while cycling and wearing a white hat and black fleece. Mr Moloney is seen in the background wearing a beige cap and an off-white polo top. Ziyad Azad

    Ziyad Azad and Aaron Moloney hope to raise £1,000 for their selected charities

    Two friends have set themselves the challenge of cycling from London to Paris within 24 hours for charity.

    Ziyad Azad and Aaron Moloney, both from Kenilworth, Warwickshire, want to raise money for two charities, the British Thyroid Foundation and Kidney Research UK. They have set themselves a goal of £1,000.

    The pair both had health reasons for taking up cycling. Mr Moloney, 26, had a thyroid cancer scare while Mr Azad, 27, said he had many issues incoming with his health if he did not do something about his weight. He said he had weighed 155kg (24st) at age 18.

    The duo are set to depart London on 15 September.

    Mr Moloney discovered a lump on his neck leading to seven months of biopsies before having surgery to remove it.

    “I was fine and then I wasn’t. It was scary, I was scared,” he said.

    He also lost his previously “fit and healthy” grandad to a rare kidney disease in 2024.

    Mr Azad said his weight had impacted his quality of life, such as running out of breath while walking.

    “And at 18, I was borderline diabetic. I had so many health issues that were incoming if I didn’t do something about it.”

    ‘We made a pact’

    He added: “After Aaron had his thyroid cancer scare when December rolled around we made a pact to have a new years’ resolution and to stick to it.”

    The men started with cycling and quickly found it was an easy way to chat to one another while exercising.

    Mr Azad said: “As the weeks went on we got better and faster on our bike rides so we said we’d go to Wales or the Peak District.

    “And I then I think it was Aaron who randomly mentioned, ‘shall we just ride to Paris?’

    “It was a joke but we turned that joke into reality.”

    “We’re using this challenge not only to push ourselves physically but to raise awareness and funds for the amazing work these charities do,” Mr Moloney said.

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  • ‘We were half-drunk’: Patrick Watson on Covid hit and Spotify record-breaker Je Te Laisserai Des Mots | Culture

    ‘We were half-drunk’: Patrick Watson on Covid hit and Spotify record-breaker Je Te Laisserai Des Mots | Culture

    Patrick Watson, singer, songwriter, piano

    I’d been commissioned to do the score for a French film, Mères et Filles [released with the English title The Hidden Diary, 2009], starring Catherine Deneuve. I’ve done quite a few scores and usually you talk to the director, then it’s your job to help the storyline do what it needs to. There’s a scene at the end of the film where the main character leaves a letter under the door, which to me suggested the title Je Te Laisserai des Mots, meaning: “I will leave you some words.”

    In my studio in Montreal, I came up with what I thought was a nice little melody. I’m from Quebec, so although I’m an English-speaking person, I’ve always been surrounded by French. Whenever I have the opportunity to sing or write in French, I do. Although I like singing in French, it’s a very difficult language to sing in because of the vowel structure. There aren’t many words in Je Te Laisserai Des Mots and the first verse is entirely wordless. I didn’t think it needed any more words so I just made vocal sounds. Also I probably imagined the song starting to play at the end of the film while there is still dialogue, so didn’t want words to clash. We were kind of half-drunk when we did the strings arrangement. It was a really fun night – but outside the film, I didn’t think anyone would ever listen to the song.

    It initially appeared as a bonus track on my debut album. Then it suddenly took off in the pandemic. Because I couldn’t tour, I was doing lots of live Instagrams, which prompted someone to send me a video they’d made of Je Te Lasserai Des Mots. It had a million views and once those algorithms get going, you can’t stop them. Sometimes certain emotions hit at a certain time and a song can become the soundtrack of that moment. Before I knew it, people all over the world were making their own lockdown videos featuring Je Te Lasserai Des Mots.

    When I first came into the music business, execs didn’t take me seriously because I didn’t have “radio songs”, but the advent of synchs and then streaming have made a new kind of hit possible. The song’s now had something like 200,000 TikTok videos featuring it, more than 60 billion TikTok plays and it’s the first French language song to hit more than a billion streams on Spotify. I find such huge numbers hard to digest but the song is much more famous than I am. I might be renting skis or something and they’ll see the name and go: “Oh, you have the same name as the singer.” I’m like: “It’s me!” And they don’t believe me.

    Mélanie Vaugeois, violin

    Our string quartet played with Patrick for 15 years and we’re still close. When we started touring with him, our kids were quite young so Patrick named us Mommies on the Run. We were his first experiment with a string quartet but after a while on tour we were wilder than him. We’d shout: “No kids!”

    It was such a great adventure and we all spent a lot of time together. We’d go to Patrick’s place, there would be things everywhere and you’d put your violin case on the ping-pong table. Patrick would play on the piano and we’d improvise around that. One night Patrick said: “I have a French song. What do you think of my accent?” He speaks French very well but had never sung in it and there were a lot of mistakes in the pronunciation, but they were part of the charm so he kept them in.

    It was a fun session and at one point we had some Jameson whiskey. We tried for a long time to find the right notes and got a little drunk. Everything was starting to slide when suddenly it all just fell into place. There’s almost no rhythm to Je Te Laisserai Des Mots, which again is part of the charm. It’s a beautiful song that makes your heart melt, and during the pandemic, when we were all very lonely, it touched a lot of people’s hearts. I first became aware that it was taking off when my kids were on TikTok and I heard the song. I went: “That’s my quartet!” They couldn’t believe it. They told me: “That song’s everywhere.”

    Although Patrick isn’t obliged to give us songwriting royalties, every year he gives us a symbolic amount to show his gratitude, which is really nice and shows that he respects the fact that people pulling together in that moment created something special.

    Patrick Watson’s new album, Uh Oh, is released in the UK on 26 September. He plays the Troxy, London, on 7 November

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  • Diaphragm assessment by multimodal ultrasound imaging in patients with

    Diaphragm assessment by multimodal ultrasound imaging in patients with

    Introduction

    Chronic obstructive pulmonary disease (COPD) represents a significant global public health challenge and poses a grave risk to human health.1–3 This condition is marked by a progressive obstruction of the airways, because the diaphragm serves as the mainly principle muscle of inspiration, its function plays a critical role in the pathophysiology of COPD.

    Evaluating diaphragm function is crucial for COPD patients, ultrasound offers a noninvasive, real-time visualization method for assessing diaphragm function and is increasingly used in clinical practice.4–7 The reliability of this technique has been extensively examined8,9 and several studies10–12 suggest that ultrasound can aid in evaluating and monitoring diaphragmatic dysfunction in COPD patients. Nonetheless, data specific to COPD patients remain limited. In this study, we assessed various parameters related to diaphragm contraction and motion, as well as tissue Doppler imaging (TDI) parameters. The aim of this study is to compare all of this diaphragm ultrasound parameters in COPD patients and healthy subjects to investigate the effectiveness of the diaphragm ultrasound method for COPD patients and provide valuable ultrasound parameters for clinical evaluation. In addition, examine the relationship between these parameters and pulmonary function test parameters.

    Methods

    Study Procedure

    We prospectively enrolled patients coming to the Department of Respiratory Diseases of Zhoupu Hospital in Pudong New Area, Shanghai, during the period from January 2024 to December 2024. At the same time, healthy volunteers with similar age and BMI and without any diagnosed disease were selected as the control group. Informed consent was obtained from all subjects who agreed to participate in the observational study. All procedures were performed in accordance with the Declaration of Helsinki, and the study has been approved by the Ethics Committee of Zhoupu Hospital (2024-C-013-E01). Baseline characteristics data such as age, gender, body mass index (BMI) of all participants were recorded, spirometry test results and diaphragm ultrasound were collected. The flowchart of the subject process is shown in Figure 1.

    Figure 1 The flowchart of the subject process.

    Subjects

    COPD patients were eligible if they had a confirmed COPD diagnosis by a specialist in accordance with the GOLD guideline for COPD.1 Eligibility also required a post-bronchodilator spirometry result showing a forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio of less than 70%. Eligibility had to be in a stable condition with no exacerbation at least for the previous month. The exclusion criteria were as follows: (1) age < 18 years old; (2) congestive heart failure, neuromuscular disease, history of cerebrovascular events; (3) recent use of systemic steroids for a COPD exacerbation within the last month, and those receiving home oxygen therapy or noninvasive mechanical ventilation. (4) patients with conditions such as apnea, active malignancy, or use of medications affecting bone metabolism or muscle strength. (5) bioimpedance analysis (BIA) was contraindicated (eg, presence of a cardiovascular stent, pacemaker, joint prosthesis, or visible oedema).

    Healthy subjects without any diagnosed disease and nonsmokers were included in the study. Exclusion criteria: (1) age < 18 years old; (2) pregnant women; (3) diaphragmatic palsy, phrenic nerve injury, diaphragmatic bulging; (4) a history of chest and abdomen trauma in the past 3 months.

    All volunteers unable to cooperate with deep inspiration and forced expiration manoeuvres were excluded in the study.

    Ultrasonic Diaphragmatic Examination

    Ultrasonic diaphragmatic examination was performed after spirometry was well done and before therapy. In addition, ultrasonic diaphragmatic examination on the right side of diaphragm in the liver as the acoustic window, volunteers take supine position.

    Resona 8 ultrasound system (Mindray Medical International, China), with convex array probe SC6-1, linear array probe L11-3U, phased array probe M9CV was used for data collection; All the ultrasound data were collected by two senior sonographers with 10 years of experience in lung ultrasound.

    Diaphragm Contraction Related Parameters

    The 3–11 MHz linear array transducer was used for the assessment of diaphragm thickness (DT)and diaphragm thickening fraction (DTF) in the right anterior axillary line at the 8–9 intercostal space. The diaphragm is a hypoechoic tissue structure located between these two linear echoes and normally moves in the direction of the probe during inspiration. DT was measured by placing electronic calipers just inside the two hyperechoic lines where the lines were most parallel and the DT at the end of inspiration and expiration was measured by B-mode, respectively (Figure 2). DTF was calculated as a percentage using the following formula:

    Figure 2 Measurement of diaphragm thickness in B mode.

    DTF = [Diaphragm thickness at the end of tidal inspiration (DT-insp) – diaphragmatic thickness at the end of tidal expiration (DT-exp)]/ DT-exp.

    Diaphragmatic Motion-Related Parameters

    The 1–6MHz convex array probe was held and placed at the intersection of the right midclavicular line or right anterior axillary line and the lower edge of the costal arch, and pointed to the medial, cephalic and dorsal sides. After the patient was asked to breathe smoothly, satisfactory two-dimensional images were obtained. The ultrasound beam was perpendicular to the posterior 1/3 of the diaphragm, and M-ultrasound was used to monitor the movement of the right diaphragm. Diaphragm excursion (DE) and time(T) in a single breath was obtained by using the menu of measurement speed (Figure 3), which marked the trough and peak of the waves. Diaphragmatic contraction velocity (DCV) was calculated.

    Figure 3 Measurement of diaphragm mobility in M mode.

    DCV=DE /T.

    The data were measured separately during quiet and deep breathing, and the measurements were averaged three times.

    TDI Parameters

    The 9 MHz phased array probe was placed in the subcostal position between the mid-clavicular and anterior axillary lines as the ultrasound beam to reach perpendicularly the middle or posterior third of the hemidiaphragm. The sample volume was initially selected at 20.0 mm to incorporate the whole range of diaphragmatic motion. The velocity scale used was 10 cm/sec to match the lower velocity of the moving diaphragm. The TDI was commenced, and the data regarding diaphragm motion such as peak contraction velocity (PCV), peak relaxation velocity (PRV), velocity-time integral (VTI) were collected (Figure 4).

    Figure 4 Diaphragmatic Tissue Doppler Imaging (TDI) during quiet breathing. Diaphragmatic TDI exhibits two waves, one during diaphragmatic contraction (above the baseline) and one during diaphragmatic relaxation (below the baseline).

    Statistical Analysis

    Statistical analyses were performed using SPSS (version 23.0) and MedCalc (version 20.104). Measurement data were expressed as (x ± s), and comparison between the two groups was analyzed using the group t test. The count data were expressed as relative numbers, and the comparison between the two groups was analyzed by chi-square test. Pearson correlation analysis was conducted to examine the relationships between continuous variables. The predictive power of each parameter for COPD was evaluated based on the AUC. The cut-off value was used as the diagnostic reference. P<0.05 was considered statistically significant.

    Results

    General Conditions

    There were 75 COPD patients (60 males and 15 females) and 75 healthy subjects (60 males and 15 females) completed all data collection. Upon comparing the age, BMI, sex of individuals, there was no significant difference between COPD patients and healthy subjects (p > 0.05). There was a significant difference between COPD patients and healthy subjects in terms of FEV1/FVC and FEV1 predicted (p < 0.05) (Table 1).

    Table 1 Basic Information Compared Between Healthy Subjects and Patients with Stable COPD

    There were significant differences between the two groups in all diaphragm ultrasound parameters except DT_exp and diaphragmatic contraction velocity during deep breathing (DCV_DB) (p < 0.05) (Table 2). The DT_insp, DTF, diaphragm excursion during deep breathing (DE_DB) were significantly lower in COPD patients than in healthy subjects, but the diaphragm excursion during quiet breathing (DE_QB), diaphragmatic contraction velocity during quiet breathing (DCV_QB), PCV, PRV and VTI were higher in COPD patients than in healthy subjects, indicating a more pronounced respiratory movement compared to healthy subjects during quiet breathing.

    Table 2 Comparison of Healthy Subjects and Patients with Stable COPD According to Ultrasound Measurements

    The diaphragm ultrasound parameters in COPD Patients of different severity is shown in Table 3. The values of DT_insp, DTF, DE_DB decreased as the severity of COPD increased, conversely, DE_QB, DCV_QB, PCV, PRV and VTI increased with the severity of COPD(p < 0.05).

    Table 3 Diaphragm Ultrasound Parameters in COPD Patients of Different Severity

    Variables Associated with COPD

    The correlation between diaphragm ultrasound parameters and pulmonary function is shown in Table 4. The results showed that DTF was positively correlated with FEV1 predicted (r=0.713, P=0.000), DE_QB (r=−0.740 and −0.889), PCV (r=−0.609 and -0.778), PRV (r=−0.686 and −0.857) were negatively correlated with FEV1/FVC and FEV1 predicted (P=0.000).

    Table 4 Correlation Between Diaphragm Ultrasound Parameters and Pulmonary Function

    Parameters Predictor of COPD

    ROC curves with sensitivity, specificity, positive predictive value, negative predictive value to predict COPD were calculated (Table 5). DTF was positively correlated with FEV1 predicted (r=0.713, P=0.000), DE_QB (r=−0.740 and −0.889), PCV (r=−0.609 and −0.778), PRV (r=−0.686 and −0.857) were negatively correlated with FEV1/FVC and FEV1 predicted (P=0.000). Meanwhile, DE_QB, DCV_QB, PCV and PRV exhibited superior performance in predicting COPD, with AUC values of 0.906, 0.833, 0.859 and 0.833, respectively. DE_QB exhibited 81.33% sensitivity, while DTF, DE_QB, DE_DB, PCV and PRV showed high specificity (98.67%, 90.67%, 96.00%, 97.33% and 100%, respectively). Notably, PRV showed 100% positive predictive value.

    Table 5 The Value of Diaphragm Ultrasound Parameters for Predicting COPD

    Discussion

    In COPD patients, prior research has documented alterations in diaphragmatic function compared to healthy individuals.13 This study observed that DT-insp was reduced in COPD patients relative to healthy controls and further diminished as the severity of COPD increased, a finding consistent with earlier studies.10,14 The underlying cause may involve sarcomere adaptation in muscle fibers that maintains static diaphragm thickness, along with compensatory hypertrophy due to overuse and hyperinflation associated with increasing COPD severity.15 DTF is more sensitive than diaphragm thickness measurement in reflecting diaphragm contraction, it was observed that DTF was lower in COPD patients compared with healthy subjects and varied according to disease severity. This could be attributed to the force-length relationship that restricts contractility.16

    During quiet breathing, DE was higher in COPD patients than in healthy subjects, likely due to increased inspiratory effort resulting from pulmonary hyperinflation, which aligns with previous findings.17,18 Conversely, during deep breathing, DE was lower in COPD patients, primarily because of air trapping, Shiraishi et al confirmed this factor.19

    TDI is a widely utilized ultrasound technique, using a low-pass filter to capture low-velocity, high-amplitude signals, provides comprehensive insights into regional and global myocardial systolic and diastolic function. Soilemezi et al were pioneers in applying TDI to evaluate diaphragm function.20 This study utilized TDI indices to assess diaphragmatic contractile performance in COPD patients. Notably, PCV and PRV exhibited the highest area under the curve (AUC) values, indicating excellent sensitivity and specificity. PRV, in particular, showed high positive predictive value. Therefore, utilizing TDI enables the direct measurement of the diaphragmatic relaxation rate, indicating a promising application for this non-invasive parameter in quantifying diaphragmatic function in routine clinical practice and its utility in prognosis.

    In this study, diaphragm ultrasound parameters were found to correlate with pulmonary function, DTF showed a positive correlation with FEV1 predicted, while DE_QB, PCV exhibited negative correlations with both FEV1/FVC and FEV1 predicted, consistent with previous literature.21,22 It was concluded that a significant relationship between impaired respiratory mechanics and the severity of abnormal pulmonary function in COPD patients.

    The limitation of this study include a limited sample size and the inability to conduct a fine stratified study. Additionally, influencing diaphragm activity, such as smoking, lifestyle, age, ethnic differences, were not statistically analyzed. In order to gain deeper insights into the diaphragm ultrasound parameters associated with COPD and their significance, we plan to conduct a comprehensive investigation through multi-center studies with larger sample volume.

    In conclusion, diaphragm ultrasound parameters are effective means of evaluating diaphragmatic function in COPD patients, with changes correlating with the severity of COPD. These parameters also correlate with pulmonary function test results, making diaphragm ultrasound suitable as a routine monitoring tool for COPD patients. However, it is important to acknowledge certain limitations of this study. Firstly, the small patient cohort limits the establishment of robust diagnostic reference values and stratified analysis; Secondly, the study fails to explore the potential impact of other variables such smoking, lifestyle, age, BMI, ethnic differences and comorbidity on COPD assessment.

    Conclusion

    Multimodal ultrasound imaging offers a sensitive approach for detecting diaphragmatic dysfunction in COPD patients. Diaphragm ultrasound parameters correlate with pulmonary function and COPD severity, indicating that these parameters can provide valuable insights into disease progression and management.

    Data Sharing Statement

    The validation dataset used and/or analyzed during the current study is available from the corresponding author upon reasonable request.

    Funding

    This study was supported by The Medical Discipline Construction Program of Shanghai Pudong New Area Health Commission (the Key Weak Disciplines Program) [grant number: PWZbr2022-05].

    Disclosure

    The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

    References

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    2. F Y Wang ZYL, He WW, Chen RC, Chen RC. Annual research progress in chronic obstructive pulmonary disease 2024. Zhonghua Jie He He Hu Xi Za Zhi. 2025;48(1):60–65. doi:10.3760/cma.j.cn112147-20241011-00598

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    4. Abdallah F, Anthony B, Adam O, et al. Diaphragm: pathophysiology and ultrasound imaging in neuromuscular disorders. J Neuromusc Dis. 2018;5(1):1–10. doi:10.3233/jnd-170276

    5. Massimo Z, Massimiliano G, Speranza B, Luca C, Paolo B, Alberto Z. Assessment of diaphragmatic dysfunction in the critically ill patient with ultrasound: a systematic review. Intensive Care Med. 2016;43(1):29–38. doi:10.1007/s00134-016-4524-z

    6. Aymeric Le N, François P, Marta L, et al. Diagnostic accuracy of diaphragm ultrasound to predict weaning outcome: a systematic review and meta-analysis. Int J Nurs Stud. 2021;117:103890. doi:10.1016/j.ijnurstu.2021.103890

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    11. Nuttapol R, Vilasinee M, Benjamas C, Jamsak T, Laurent B. Ultrasound evaluation of parasternal intercostal, diaphragm activity and their ratio in male patients with COPD. Am J Respir Crit Care Med. 2024. doi:10.1164/rccm.202310-1769le

    12. Michael RB, Leili S, Eric JS, et al. B-mode ultrasound assessment of diaphragm structure and function in patients with COPD. Chest. 2014;146:680–685. doi:10.1378/chest.13-2306

    13. Jaber SA, Tope O, Jithin KS, et al. Diagnostic and clinical values of non-cardiac ultrasound in COPD: a systematic review. BMJ Open Resp Res. 2020;7(1):e000717. doi:10.1136/bmjresp-2020-000717

    14. Sanket J, Girija N, Abhishek N, Abhay U. Study of the diaphragm in chronic obstructive pulmonary disease using ultrasonography. Lung India. 2019;36(4):299–303. doi:10.4103/lungindia.lungindia_466_18

    15. Sawsan BE. Impact of chronic obstructive pulmonary disease severity on diaphragm muscle thickness. Egypt J Chest Dis Tuberculosis. 2017;66(4):587–592. doi:10.1016/j.ejcdt.2017.08.002

    16. Ceyhun T, Eylem TÜTÜN Y, Mustafa H, Suat K. Examination of diaphragm thickness, mobility and thickening fraction in individuals with COPD of different severity. Turkish J Med Sci. 2022;52:1288–1298. doi:10.55730/1300-0144.5435

    17. Camilo C, Alain B, Jorge Hugo V, Luciano Z. Diaphragmatic mobility loss in subjects with moderate to very severe COPD may improve after in-patient pulmonary rehabilitation. Respiratory Care. 2018;63:1271–1280. doi:10.4187/respcare.06101

    18. Magdalena R, Małgorzata P, Paweł L. Diaphragmatic mobility loss in subjects with moderate to very severe COPD may improve after in-patient pulmonary rehabilitation. Respiratory Care. 2021;66(2):354.1–354. doi:10.4187/respcare.08687

    19. Masashi S, Yuji H, Ryuji S, et al. Diaphragmatic excursion correlates with exercise capacity and dynamic hyperinflation in COPD patients. ERJ Open Res. 2020;6(4):00589–2020. doi:10.1183/23120541.00589-2020

    20. Eleni S, Savvoula S, Panagiota S, Dimitrios S, Matthew T, Dimitrios M. Tissue Doppler imaging of the diaphragm in healthy subjects and critically ill patients. Am J Respir Crit Care Med. 2020;202(7):1005–1012. doi:10.1164/rccm.201912-2341oc

    21. Andrea S, Riccardo I, Linda T, Alessandro Di Marco B, Salvatore V, Giuseppe Maria C. Ultrasonographic assessment of the diaphragm in chronic obstructive pulmonary disease patients: relationships with pulmonary function and the influence of body composition – A pilot study. Respiration. 2014;87(5):364–371. doi:10.1159/000358564

    22. Bianca S, Diego Condesso de A, Yves Raphael S, et al. Ultrasonography as a way of evaluating the diaphragm muscle in patients with chronic obstructive pulmonary disease. Medicine. 2024;103(38):e39795. doi:10.1097/md.0000000000039795

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  • Australia rugby legend Shannon Parry surprises local girls in Melbourne with coaching masterclass ahead of Women’s Rugby World Cup England 2025

    Australia rugby legend Shannon Parry surprises local girls in Melbourne with coaching masterclass ahead of Women’s Rugby World Cup England 2025

    • ChildFund Rugby’s Grassroots to Global Series and the Gallagher High Performance Academy join forces, delivering two-day forum and masterclass for female rugby leaders
    • Global programme visits Melbourne, Australia, ahead of Women’s World Cup 2025, as part of World Rugby’s mission to strengthen women’s coaching pathways and increase opportunities for female leaders in rugby
    • Shannon Parry – former captain of the Wallaroos squad and now head coach of the Australia A women’s sevens team – joined by more than 20 girls, women and youth leaders, who are actively involved in strengthening and developing the women’s game
    • Two-day event held at Melbourne University Rugby Club, as build-up to Women’s Rugby World Cup 2025 continues

    Held in more than 25 countries, each forum supports the women’s game at local, national and international levels, with a view to driving change and increasing the number of women involved in the sport, both on and off the field.

    The Australia Forum was held at Melbourne University Rugby Club and attended by more than 20 young, inspirational female leaders. From players, coaches, match officials, first aiders, team managers, event organisers and club administrators, each of the delegates are deeply entrenched in the local rugby community, and came together to share experiences, strengthen networks, and inspire change.

    Grassroots to Global Forums underscore the direct impact that female coaches have on driving female participation at community levels, highlighting the critical importance of increasing female coaching opportunities. Following a similar event held in England in June, this was the latest forum to partner with Gallagher and its High Performance Academy (GHPA) – a fully immersive global development and leadership programme that’s enhancing the prominence of female coaches and increasing the competitiveness of the women’s game – in the build-up to Women’s Rugby World Cup.

    Founded by World Rugby and Gallagher – with a focus on talent identification, professional support and championing the next generation of international coaches – the Academy develops existing coaching talent, and identifies opportunities for new coaches and women in other high-performance roles. Since 2023, 43 female coaches have been supported by the GHPA, which aims to realise a target of 40 per cent female coaches at this year’s record-breaking tournament.

    ChildFund Rugby’s Grassroots to Global Series and the GHPA work together towards the common goal of getting more girls and women into rugby coaching, and are integral to World Rugby’s strategic plan to develop opportunities for women at all levels of the game.

    As part of the two-day forum, participants exchanged ideas and created action plans for enhancing gender inclusion within their rugby communities. This included identifying the key drivers and barriers facing women in rugby leadership.

    A highlight of the event was the surprise attendance and support of former Wallaroos captain, Shannon Parry. The Rio 2016 gold medallist  represented Australia in four Women’s Rugby World Cups (2010, 2014, 2017 and 2021) and captained the squad from 2014 until her retirement in 2023. Parry was part of the GHPA during the HSBC SVNS series in 2024, and ideally placed to lean on her experiences and share her wealth of knowledge gained from transitioning from a player to head coach of the Australia A women’s sevens team.

    Joining her was one of Australia’s top women’s rugby sevens players Maddison Levi, who  was named World Rugby Women’s Sevens Player of the Year in December 2024 after a fantastic 12 months, which included a record-breaking 14 tries at the Paris 2024 Olympic Games.

    Shannon joined the Grassroots to Global leaders in delivering a fun and engaging masterclass, which welcomed local girls and young women in a practical, on-pitch session. This enabled delegates to put into practice the leadership skills developed in the forum, while also inspiring and engaging the next generation of rugby stars in a fun, inclusive and supportive environment.

    “It has been a real privilege to come down to Melbourne University Rugby Club to coach and inspire a fantastic group of young women, who I hope are now motivated to be the rugby leaders of the future. I’ve really enjoyed seeing the impact of their participation in the forum and masterclass, and having the opportunity to discuss my own experiences as both a player and a coach”, said Shannon Parry, Gallagher Ambassador and GHPA HSBC SVNS 2024 alumni.

    “I have benefited myself from the Gallagher High Performance Academy, and cannot stress enough how important pathways like them are in growing women’s rugby. They are vital in driving awareness and inspiring young women to not only fall in love rugby and want to succeed in it, but also in creating vital opportunities to elevate female coaching. Gallagher knows that to do so, we need to invest from grassroots all the way through to the pinnacle of the sport, and it has been fantastic to stand alongside them here in Melbourne.”

    ChildFund Rugby Co-Director Meg Knight said: “This Grassroots to Global Forum wraps up a global series of 32 forums in 29 countries. Data from each of these events will now be looked at to build a global picture of leadership in community rugby around the world. In August, delegates from these countries will come together and advocate to rugby’s decision makers for support to bring, and keep, more women into the game as coaches and role models. Gallagher has played a critical role in making this possible by supporting forums in Canada, England, and now Australia, and uniquely connecting them with the Gallagher High Performance Academy.”

    Gallagher’s Chief Marketing Officer Christopher Mead added: “Gallagher works with ChildFund to deliver masterclasses that help to elevate women through the game of rugby. Our partnership has given many talented women the opportunity and tools to expand their experience and elevate the game. This masterclass was an important milestone for Gallagher in the run up to the Women’s Rugby World Cup 2025 tournament, continuing our commitment to advancing women in rugby at the grassroots and international levels.”

    “With Women’s Rugby World Cup 2025 fast approaching, it’s inspiring to see the impact that ChildFund Rugby’s Grassroots to Global Forums are already having, by bringing together such passionate female leaders from the rugby community.”

    World Rugby’s Chief of Women’s Rugby, Sally Horrox said: “Driving change on and off the field starts with building strong networks and creating clear pathways for women in coaching and leadership roles. The partnership with Gallagher’s High Performance Academy is helping us to accelerate this progress, and together we are laying the foundations for a more inclusive and competitive women’s game.”

    ChildFund Rugby is World Rugby’s Global Social Impact Partner for Women’s Rugby World Cup 2025. ChildFund Rugby is championing the power of sport to create lasting, positive change across the globe, impacting lives at every level of the game. Find out more at www.childfundrugby.org.

    Gallagher is the Official Insurance Partner of Women’s RWC 2025 and WXV. More information on the Gallagher High Performance Academy, can be found here.

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  • Thailand, Cambodia agree on immediate ceasefire to end border clashes – RADIO PAKISTAN

    1. Thailand, Cambodia agree on immediate ceasefire to end border clashes  RADIO PAKISTAN
    2. Cambodia and Thailand agree to ‘immediate and unconditional ceasefire’  BBC
    3. Thailand and Cambodia to hold ceasefire talks in Malaysia  Al Jazeera
    4. Thailand and Cambodia agree truce after 5 days of fighting  Dawn
    5. ‘Like my other half’: man mourns wife and children killed buying snacks amid Thailand-Cambodia clashes  The Guardian

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  • ‘Making Women’s Euro trophy cases was a privilege’

    ‘Making Women’s Euro trophy cases was a privilege’

    A Merseyside-based carpenter who created this year’s UEFA Women’s Euro trophy presentation boxes said the project had been “one of the most rewarding things I’ve ever worked on”.

    Yana Daniels, a former Liverpool striker and Belgian international, handcrafted all the wooden boxes for the competition’s Player of the Match trophies in her workshop in Wirral.

    Ms Daniels was approached by Visa, which had helped her to set up her business through its careers development programme for female players after they retire.

    “Being entrusted with this responsibility was a privilege,” she said.

    The England team won the competition with a 3-2 victory over Spain after a 1-1 draw at St Jakob-Park in Basel, Switzerland.

    Ms Daniels, who has also made a range of products for LFC retail, said creating the boxes by hand had been “a labour of love”.

    “Every detail, from the grain of the wood to the final engraving, was created with pride and care, knowing these boxes will be part of a moment that matters,” she said.

    She added the boxes were “a keepsake for those who gave their all, and left their mark on European football”.

    Ms Daniels, who represented her home nation at the tournament in 2017, said the women’s sport had “grown immensely” in recent years.

    “It’s not a taboo any more. Women’s football is normal, which should have always been the case,” she said.

    “I had to play with boys teams. I was the only girl for about five years. You can’t compare it to 20 years ago.

    “Now every girl can dream of being a professional footballer, which is amazing.”

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  • Get over 60% off the “secret weapon for top mix engineers” right now at Plugin Boutique

    Get over 60% off the “secret weapon for top mix engineers” right now at Plugin Boutique

    Plugin Boutique is offering a huge saving on the tool hailed as a “secret weapon” for the best mix engineers in the game: the Soundtoys Decapitator.

    This analogue saturation modeller plugin offers subtle sounds all the way to “extreme hardware-modelled” saturation, delivering the classic tones of tubes, transistors, and circuitry being pushed to the max.

    Now available for just £62, down from a list price of £159.95, Soundtoys created this plugin by collecting and analysing both vintage and modern hardware, including consoles, preamps, input channels, EQs, compressors, and studio distortion units. Selecting those with “the most distinctive sound and unique character when used both subtly and at extremes”, the brand then created their own versions.

    Decapitator offers five different analogue saturation models to experiment with, and includes a modelled tone control for shaping the saturated sound, and a mix control made to blend in dry signal for parallel processing, without the need for routing and sub-mixes.

    An added feature of Decapitator is its brutal Punish button – this boosts the gain, pushing it “over the edge” for analogue tone that squeals in pain, according to Soundtoys. So far, the plugin has been praised by the likes of Fabrice ‘Fab’ Dupont (Marc Ronson, Santigold, Jennifer Lopez), Tchad Blake (Sheryl Crow), and Ryan Hewitt (Red Hot Chili Peppers).

    Check out the plugin in the video below:

    Plugin Boutique is also offering a generous number of other deals on Soundtoys products, including a saving of £266 on the Soundtoys 5.5 plugin collection. You can also get 70 percent off on its Crystallizer, FilterFreak, and SuperPlate plugins.

    To find out more about the Soundtoys Decapitator, or purchase now, head over to Plugin Boutique.

    Rachel is a DIY musician who began learning guitar and keyboard from her bedroom at 14. She has written news and features for MusicTech since 2022, and also has bylines across Kerrang!, Guitar.com, and The Forty-Five. Though a lover of heavy music, her guilty pleasure is 2000s pop.

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  • Membrane protein’s unique structure helps bacterial predator devour its rivals | Research

    Membrane protein’s unique structure helps bacterial predator devour its rivals | Research

    Advanced imaging has revealed how a membrane protein’s unique structure enables a bacterial predator to attack and consume other microbes. The researchers behind the work say that the findings could inspire new ways to target harmful bacteria, bringing potential applications in medicine and biotechnology.

    The new research focuses on PopA, a porin-like protein found in the outer membrane of Bdellovibrio bacteriovorus (B. bacteriovorus) – a predatory microbe that targets a wide range of other Gram-negative bacteria. Unusually, PopA can move between the outer membrane of one cell and into the inner membrane of another, explains Andrew Lovering, a structural biologist at the University of Birmingham in the UK, who led the project.

    ‘This goes against all conventional rules of how membrane proteins are put into membranes and what shape they take,’ he explains.

    Lovering’s PhD student Rebecca Parr started the work on PopA just before the Covid-19 pandemic.

    ‘This was in the era before AlphaFold prediction was as confident – so we had lots of questions: what do you look like? Why do you look like that? Does that help you exist both in inner membranes and outer membranes,’ says Lovering.

    Using x-ray crystallography and cryo-electron microscopy, Parr discovered that the protein formed a unique fivefold structure, unlike the usual single or three-part structures seen in other outer membrane proteins.

    At first, Lovering was sceptical when Parr told him what she’d found. ‘I said you’re probably a bit mistaken, because these things come in threes, but she said: “No, no, it’s definitely five.”’ he recalls. ‘As the imaging improved and the map improved, we were like: “Whoa – this is totally different!”’

    It’s a trap!

    To find out more about the function of PopA, they introduced it to Escherichia coli (E. coli) bacteria where it appeared to cause significant defects in cells’ outer and inner membranes. This suggested that PopA may play in a role in how B. bacteriovorus attacks and consumes other bacteria.

    The team also discovered that the PopA protein has a bowl-like shape in which it can capture lipid molecules. ‘Because this traps the lipid inside … you’re messing with the ratios of lipid in the membrane,’ explains Lovering. ‘Most membrane proteins sit in this cloud of lipopolysaccarides … whereas [PopA] just clears them out the way.’

    Further analysis uncovered homologues of PopA across a variety of bacterial species that form tetramers, hexamers and sometimes even nonamers, and all had the same lipid-trapping feature.

    Alphafold models showing PopA family members that form tetramers, pentamers and hexamers, all featuring a central chamber

    Lovering says that research on outer membrane proteins has been dominated by E. coli and Pseudomonas, leading to a ‘restrictive view’. Finding ‘rulebreakers’ like PopA in other species gives scientists a deeper understanding on what these biomolecules are capable of, he notes.

    ‘So if you’re interested in the wider biology, you’re not shackled by the textbook view,’ he says. ‘This is [one example] – as soon as we start getting a few, we can change our expectation of what membrane proteins can do.’

    Mohammed Kaplan, a microbiology expert at the University of Chicago, US, who was not involved in the project, is intrigued by the findings.

    ‘The interesting thing is this protein is found in a small predator, which captures other Gram-negative bacteria and consumes them. This protein goes from the outer membrane of this predatory bacteria to the inner membrane of the prey cell, and so it plays a big role in predation,’ he says. ‘Understanding this predation process is a very important thing … [because] it has repercussions in understanding fundamental biological questions related to evolution and cell–cell interaction.’

    However, Kaplan notes that the findings raise new questions for microbiologists. ‘One important question, which [Lovering’s team] also highlights, is how does PopA go from the predator to the prey? Is it secreted through an outer membrane vesicle or by another way? That’s still unknown.’

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  • NIH researchers develop AI agent that improves accuracy of gene set analysis by leveraging expert-curated databases

    NIH researchers develop AI agent that improves accuracy of gene set analysis by leveraging expert-curated databases

    Monday, July 28, 2025

    Researchers at the National Institutes of Health (NIH) have developed an artificial intelligence (AI) agent powered by a large language model (LLM) that creates more accurate and informative descriptions of biological processes and their functions in gene set analysis than current systems.

    The system, called GeneAgent, cross-checks its own initial predictions—also known as claims—for accuracy against information from established, expert-curated databases and returns a verification report detailing its successes and failures. The AI agent can help researchers interpret high-throughput molecular data and identify relevant biological pathways or functional modules, which can lead to a better understanding of how different diseases and conditions affect groups of genes individually and together.

    AI-generated content is produced by LLMs trained on enormous amounts of text data from across the internet. LLMs use those data to recognize patterns and predict what words might follow each other in a sentence. However, LLMs are not designed to verify truth, meaning AI-generated content can be false, misleading, or fabricated, a phenomenon called AI hallucinations. Additionally, LLMs are prone to circular reasoning—fact-checking their generated results against their own data—which makes them sound more confident in the output even when the information is false.

    Staving off AI hallucinations is important when using LLM tools for gene set analysis—the process of generating collective functional descriptions of grouped genes and their potential interactions. Previous studies that taught LLMs to answer genomic questions or summarize biological processes in a given gene set did not explicitly address hallucinations in the generated content.

    GeneAgent mitigates this issue by taking its own claims and independently comparing them to established knowledge compiled in external, expert-curated databases. The research team first tested GeneAgent on 1,106 gene sets sourced from existing databases with known functions and process names. For each gene set, GeneAgent first generated an initial list of functional claims. It then independently used its self-verification agent module to cross-check these claims against the curated databases and create a verification report that noted whether each of its claims was supported, partially supported, or refuted.

    To best determine its accuracy in the self-verification step, the researchers next brought in two human experts to manually review 10 randomly selected gene sets with a cumulative 132 claims and judge whether GeneAgent’s self-verification reports were correct, partially correct, or incorrect. Of the self-verification reports generated by GeneAgent, the experts determined that 92% of its decisions were correct, indicating high performance in its ability to conduct self-verification, especially when compared to GPT-4. Their detailed review confirmed the model’s effectiveness in minimizing hallucinations and generating more reliable analytical narratives.

    The research team also looked at real-world application of GeneAgent on animal-model gene sets. When applied to seven novel gene sets derived from mouse melanoma cell lines, GeneAgent was able to offer valuable insight into novel functionalities for specific genes. This could mean knowledge discovery for things such as potential new drug targets for diseases like cancer.

    While LLMs such as GeneAgent are still limited by the information they can use and their inability to reason as humans, GeneAgent’s ability for self-driven fact-checking shows remarkable promise in mitigating AI hallucinations.

    About the National Library of Medicine (NLM): NLM is a leader in research in biomedical informatics and data science and the world’s largest biomedical library. NLM conducts and supports research in methods for recording, storing, retrieving, preserving, and communicating health information. It creates resources and tools that are used billions of times each year by millions of people to access and analyze molecular biology, biotechnology, toxicology, environmental health, and health services information. Additional information is available at https://www.nlm.nih.gov.

    About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

    NIH…Turning Discovery Into Health®

    ​​​​​​​Reference

    Wang, Z., Jin, Q., Wei, CH. et al. GeneAgent: self-verification language agent for gene-set analysis using domain databases. Nat Methods (2025). https://doi.org/10.1038/s41592-025-02748-6

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