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Selpercatinib and the Crossover Conundrum: Potential Impact of Postprogression Therapies on Overall Survival
Overall survival (OS) should be evaluated in all randomized cancer trials, even when not the primary end point, as it is clinically meaningful and measures both safety and efficacy. Crossover from the control to experimental arms in randomized trials may be incorporated to allow access to promising investigational treatments after progression on a control arm. The results of Study LIBRETTO-431, an ex-US multiregional, open-label, randomized, active-controlled trial of selpercatinib versus platinum-based and pemetrexed chemotherapy with or without pembrolizumab in patients with treatment-naïve advanced rearranged during transfection fusion–positive non–small cell lung cancer, highlight the challenges of interpreting OS in trials with high crossover rates and variable postprogression therapies. Trial results demonstrated a large improvement in progression-free survival with an acceptable safety profile, but were accompanied by an immature OS analysis with a hazard ratio of 1.26, favoring the chemoimmunotherapy arm. Regardless of the position of OS in the end point hierarchy, it is critical that OS analyses include prespecified plans for data collection and analytical methods to account for the potential impact of postprogression therapies on the interpretation of study results.
Cows visually discriminate and cross-modally recognise familiar and unfamiliar human faces in videos
Social recognition has been studied and demonstrated in many species. In domesticated species, the long evolutionary history shared with humans has led to investigations into their cognitive abilities towards humans, particularly regarding discrimination and recognition of humans. The present study investigated whether cows are capable of visual discrimination and cross-modal recognition of familiar and unfamiliar humans. Thirty-two cows were exposed to two tests: a visual preference test, during which two silent videos were shown simultaneously – each displaying either a familiar or an unfamiliar human face – and a cross-modal test, during which the videos were accompanied by either a congruent or incongruent voice. During the visual preference test, cows looked significantly longer at the video showing the unfamiliar person (p = 0.028). In the cross-modal test, they looked significantly longer at the video that was congruent with the voice being played (p = 0.014). These two results show that cows are able to discriminate between familiar and unfamiliar individuals and form cross-modal representations of these people. Based on these results, future research should explore whether cows can adjust their behaviour depending on the person they are interacting with – a capacity that may reflect their agency in human-animal relationships.
Feasibility of mobile-based noncommunicable disease risk factor data collection using WhatsApp and interactive voice response in Colombia
Relationship between physical activity and ankle osteoarthritis: Implications for metabolic diseases
Background Regular physical activity is associated with lower cardiometabolic risk, yet musculoskeletal disorders such as ankle osteoarthritis (OA) may limit activity. This study investigated the association between radiographic ankle OA severity and habitual physical activity quantified using MET-min/week. Methods In this retrospective cross-sectional study, consecutive patients evaluated for ankle OA at a tertiary referral foot and ankle clinic (Takakura stage ≥2) between June 2022 and October 2024 were included. Weightbearing ankle radiographs were used to classify OA severity (modified Takakura stage). Physical activity was assessed using the International Physical Activity Questionnaire–Short Form (IPAQ-SF; vigorous, moderate, walking, and total MET-min/week). Patient-reported outcomes were assessed using the Foot and Ankle Outcome Score (FAOS). Correlations between MET-min/week and clinical parameters were evaluated using multivariable partial-correlation analyses controlling for age, sex, BMI, and pain severity (VAS), with adjustment for multiple comparisons. Results A total of 262 patients (99 males, 163 females; mean age 66.8 years) were analyzed. Mean BMI was 26.3 kg/m². Takakura stages were: stage 2 (n = 54), stage 3a (n = 93), stage 3b (n = 52), and stage 4 (n = 63). Moderate activity MET and walking MET differed between males and females (p = 0.033 and p = 0.035, respectively). In the overall cohort, higher age correlated with lower vigorous activity MET (r=−0.155, p = 0.010) and total MET (r=−0.182, p = 0.003), and higher BMI correlated with lower vigorous MET (r=−0.129, p = 0.038), walking MET (r=−0.141, p = 0.024), and total MET (r=−0.177, p = 0.005). After adjustment for covariates, higher Takakura stage correlated with lower vigorous MET (r=−0.152, p = 0.016) and lower total MET (r=−0.127, p = 0.044). In sex-stratified analyses, Takakura stage correlated with vigorous MET in males (r=−0.226, p = 0.027) and with total MET in females (r=−0.167, p = 0.037). In Takakura stage 4, no patients reported vigorous activity, indicating a floor effect. Conclusions Demographic factors (age, BMI, sex) and radiographic severity of ankle OA were associated with lower self-reported physical activity (MET-min/week). Longitudinal studies incorporating objective activity monitoring and cardiometabolic endpoints are needed to clarify temporal relationships and potential metabolic implications. Level of evidence Level III, retrospective cross-sectional study.
Sociodemographic disparities and the distribution of open and closed food outlets in the Hartford area of connecticut
Impact of a culinary medicine intervention on diet and health metrics in patients with type 2 diabetes and elevated body mass index
Purpose Culinary Medicine (CM), an educational approach blending the art of cooking with the science of medicine, has shown promise in improving diet and health outcomes. We conducted a mixed-methods, quasi-experimental evaluation of a CM program to promote cooking and healthy dietary intake. Methods Patients with type 2 diabetes and elevated body mass index (>25) were recruited from primary care clinics in low-income neighborhoods. The program, delivered by a dietitian, includes five weekly 90-minute sessions on basic cooking skills with behaviorally-based nutrition education. An explanatory sequential mixed-methods pilot study with a pre-post survey design and post-program interviews was used to assess improvements in dietary behaviors, nutrition knowledge, and cooking skills. Results A total of 89 individuals enrolled (58 intervention, 31 control). Fifty (86%) intervention participants attended the sessions, and 45 (78%) completed post-intervention surveys, while 22 (71%) control participants completed post-intervention surveys. Compared to control, the intervention group showed statistically significant improvements in perceived health (Adjusted Odds Ratio = 16.15, 95% CI 3.47,75.23, p < 0.001) and cooking self-efficacy (Adjusted β = 0.43, 95% CI 0.03,0.84, p = 0.04), and a decrease in perceived barriers to healthy eating (Adjusted β = − 0.64, 95% CI −1.21,-0.08, p = 0.03). We found a statistically significant decrease in HbA1c in the intervention group from pre- to post-test, though between-group comparisons were not statistically significant. All other behavioral, psychosocial, and biometric variables were non-significant but trended in the expected direction. Conclusions This study is feasible and acceptable. The CM program effectively promotes cooking skills and healthy eating among low-income patients with type 2 diabetes and elevated body mass index.
Daily briefing: Bogus citations will get you banned from arXiv
Enhancing esophageal cancer detection using a deep learning framework and a novel spectrum-aided vision enhancer for virtual narrow band imaging
Abstract Esophageal cancer is a highly aggressive malignancy where early detection is critical for survival. However, early-stage lesions typically present subtle mucosal changes that are difficult to identify using standard White Light Imaging (WLI), and hardware-based Narrow Band Imaging (NBI) is not universally available. In this study, we propose a novel image processing algorithm termed the Spectrum-Aided Vision Enhancer (SAVE) to address these challenges in computer-aided diagnosis (CAD). Leveraging hyperspectral data principles, SAVE transforms standard WLI endoscopic images into enhanced, NBI-like representations, significantly improving mucosal contrast and lesion visibility without requiring additional hardware. To validate the efficacy of this approach for medical image analysis, we utilized a dataset of Squamous Cell Carcinoma (SCC) and dysplasia. We conducted a comprehensive comparative analysis using five state-of-the-art deep learning models: YOLOv8, InceptionV3, Inception-ResNet-V2, ConvNeXt-V2, and MobileNetV2. Experimental results demonstrate that models trained on SAVE-enhanced images significantly outperform those trained on traditional WLI in both classification and detection tasks. This study presents a cost-effective, software-driven solution that integrates advanced image processing with deep learning, offering a robust tool for the automated screening of esophageal malignancies.
Atomically Precise Engineering of Synergistic Binding Sites in a Zirconium Metal–Organic Framework for the Capture of Perfluorooctanoic Acid
Cornea biomechanics and biometric evaluations in immunoglobulin G4-related ophthalmic disease
Purpose To evaluate the corneal biomechanical and biometric properties in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients. Setting Ethnic Han Chinese biopsy-proven IgG4-ROD patients from a territory wide cohort and sex-, age-, smoking- and lens status-matched healthy controls. Design A case-controlled (1:1) study. Methods Corvis ST analyzer and IOL Master 700 biometry assessment. Results Sixty-seven eyes from 67 patients with IgG4-ROD (41 = males), aged 63.9 ± 13.1 years and 67 right eyes from 67 healthy ethnically Han Chinese controls were recruited. IgG4-ROD eyes were associated with a more negative applanation 2 velocity (−0.30 versus −0.27 m/s, P = 0.0143), and reduced radius of curvature (7.48 versus 7.98 mm, P = 0.0136). There was no difference in intraocular pressure, applanation 1 length, applanation 1 velocity, applanation 2 length, deformation amplitude and peak distance. Corneal astigmatism was greater in IgG4-ROD eyes (−1.2 versus −0.9 D , P = 0.0132), and the deep axis is along 90.2 degree. There is no difference in the steep and flat keratometry, deep axis, lens thickness, cornea thickness, and anterior chamber depth. Conclusions We found multiple corneal changes in biomechanics and fine structures in a cohort of biopsy-proven IgG4-ROD with potential long-term implications in ocular surface functions. A longitudinal follow-up would be useful to identify the clinical implications and observe if these changes improve with treatments.
Phyto-mediated synthesis of Ni–Fe bimetallic nanoparticles using Abrus precatorius for antioxidant, antimicrobial and photocatalytic dye degradation applications
The effect of 5-hydroxytryptophan, a serotonin precursor, on adults with high levels of Attention Deficit Hyperactivity Disorder traits: A randomised, controlled trial
Background Although several effective therapies exist for Attention Deficit Hyperactivity Disorder (ADHD), current pharmaceutical treatment carries a high risk of misuse and high levels of discontinuation, evidencing a need for alternatives. One possible avenue is serotonergic intervention, particularly within the serotonin synthesis pathway, where there are several potential loci of dysfunction in ADHD. This study aimed to assess the efficacy of acute 5-hydroxytryptophan, a serotonin precursor, in reducing distractibility in adults with high levels of ADHD traits. Trial design and methods The study consisted of a randomised, controlled trial to assess the effects of acute 5-hydroxytryptophan administration compared to placebo. Participants consisted of individuals with high (N = 56) and low (N = 56) levels of ADHD traits, determined using the Adult ADHD self-report scale screener (ASRS v1.1), with randomised allocation to intervention or placebo in a 1:1 ratio. Both participants and investigators delivering the trial were blind to the allocation. Baseline testing of distractibility using a task-relevant (Eriksen flanker) and novel task-irrelevant (N-back coupled with an auditory stimulus) paradigm was completed, participants were given the intervention or placebo, and tasks were repeated 90 min post-administration. Results and conclusions The flanker and N-back task found few differences between individuals with high and low levels of ADHD traits, and the N-back task did not produce a distractor effect as initially predicted. 5-hydroxytryptophan produced no significant positive effect in any measure of distractibility that differed between individuals with high or low ADHD traits. Only accuracy on silent trials in the N-back task was affected by 5-hydroxytryptophan administration: placebo participants showed an improvement in performance and 5-hydroxytryptophan-administered participants did not. 19.6% of participants in the 5-hydroxytryptophan group experienced adverse events of fatigue, nausea or vomiting. Although 5-hydroxytryptophan did not elicit a positive effect on ADHD traits,further work should be conducted with measures more sensitive to ADHD traits to fully understand the impact of 5-hydroxytryptophan supplementation on the condition.
Deep learning-based neonatal outcome prediction: an LSTM autoencoder framework for pattern analysis and risk assessment
Quality of pharmacy services and adherence to good pharmacy practice at points of sale in Punjab, Pakistan: A cross-sectional study
Adhering to good pharmacy practice (GPP) guidelines ensures the safe, effective, and ethical delivery of pharmaceutical services at community pharmacies, commonly referred to as Point of Sale (POS). However, developing countries such as Pakistan experience poor compliance with GPP. This study aimed to evaluate the quality of pharmacy services and adherence to GPP, focusing on technology compliance, infrastructure, legal aspects, dispensing practices, storage conditions, and other essential facilities. A descriptive cross-sectional study design was employed for the current study. The sample size was determined using the online sample size calculator Raosoft TM . The method adopted for the distribution of sample among selected cities was done by proportional sampling and the convenience sampling technique was employed for accessing individual POS. A self-designed questionnaire, consisting of five sections, i.e., i) demographic data, ii) prescription recording and data management system, iii) pharmacy infrastructure, facilities and services, iv) dispensing, preparation, administration and v) distribution of medicine and storage facilities was used to gather data from the selected POS of Punjab, Pakistan between 20 th July 2024–20 th September 2024. The data were entered and analysed using IBM SPSS 23.0. Descriptive and inferential statistics were used to describe the results. A total of 598 POS were included in the final analysis. Approximately 90.6% were independent POS, with 72.7% operating in the A category. A qualified person (QP) was observed in only 29.1% of POS. Approximately 31.9% of POS did not have any computerized technology, 52.2% lacked a system for monitoring the facility’s temperature, and a significant proportion (84.6%) were involved in prescribing for minor ailments. The mean score was higher in POS operating under category A licenses, chain setups and those with one or more QP. The highest significant ( p < 0.05) mean difference observed between chain and independent POS was 3.53 (95% CI = 2.44, 4.64), between category A licensing type and no available license was 11.99 (95% CI = 8.13, 15.84), and between the presence and absence of a QP was 2.30 (95% CI = 1.58, 3.01). The findings revealed that the lack of adherence to GPP is a common practice in the country and is significantly linked to various factors such as POS type, type of license of POS, and availability and number of QP at the POS. To enhance compliance with GPP, the collaborative efforts of various stakeholders, along with targeted interventions, are essential.
A conference taught me that scientists and journalists must work together to protect research
Uncovering hidden spermatogenesis: INPP1 and GTSF1 as non-invasive predictors of sperm retrieval in non-obstructive azoospermia
Challenges to human papillomavirus vaccination among young girls in Morocco: A national cross-sectional study
Background The human papillomavirus (HPV) vaccine helps significantly reduce the incidence of cervical cancer. However, in many countries, its adoption remains limited. In this context, our study aimed to measure the prevalence of HPV vaccination hesitancy among young girls and to identify its associated risk factors. Methods From 10 th April to 30 th June 2025, a cross-sectional survey was conducted in Morocco among girls aged 11–14 attending middle school. Face-to-face interviews gathered sociodemographic data, HPV knowledge, and vaccination attitudes. Multivariate logistic regression identified risk variables for vaccine hesitancy. Results A total of 1,836 participants were collected with a mean age of 13.0 ± 0.8 years. The percentage of vaccine hesitancy reached 88.8%. The main risk factors were unvaccinated pairs (AOR = 11.78; CI [7.67–18.0]), paternal illiteracy (AOR = 7.67; [1.99–29.55]), low recommendation of the vaccine by health personnel (AOR = 4.14; [2.44–7.02]), belief that the vaccine promotes sexual activity (AOR = 3.10; [2.01–4.79]), insufficient knowledge of the target population (AOR = 2.51; [1.63–3.85]), perception of adverse effects (AOR = 1.97; [1.31–2.98]), insufficient knowledge of the number of doses required (AOR = 1.76; [1.06–2.92]), fear of vaccination (AOR = 1.71; [1.14–2.58]), fear of regretting vaccination (AOR = 1.55; [1.02–2.36]), and age (AOR = 1.34; [1.06–1.69]). Conclusion HPV vaccination hesitancy remains high and is shaped by social, educational, and cultural factors. These findings underscore the need for targeted educational initiatives and increased awareness among healthcare professionals. Integrating vaccination into school health programs may help improve uptake.