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Building capacity through training and education is recommended to support meaningful engagement of patient partners in health research. The Patient and Community Engagement Research (PaCER) programme is a 12-month initiative that enables patients and community members to co-design and conduct qualitative health research projects. Learners are sponsored by clinician researchers, community organisations, and/or jurisdictional health organisations. This study aimed to assess the experiences and impact of the PaCER programme on: (1) past learners' personal development and engagement in health research; and (2) sponsors' research programmes. We conducted a qualitative impact evaluation involving past learners (alumni) and sponsors of the PaCER programme from 2019 to 2024. A purposive sampling strategy was used, whereby selected alumni and sponsors from the 2019-2024 cohorts were invited to participate in an online semi-structured interview. Sponsors and alumni with diverse characteristics, including variation in age, ethnicity, educational attainment, and geographic location were invited. The interview guide included questions on the experiences in the PaCER programme, post-programme research activities, and perceptions of the programme's impact. Data were analysed using a reflexive thematic analysis approach. Eighteen participants (12 PaCER alumni and 6 sponsors) were interviewed, and four main themes were identified: (1) seeing the value of the training programme; (2) Diverse people and groups working together; (3) Learner readiness and capacity; (4) Academic opportunities for learners and career growth. Alumni described significant personal impact, empowerment, academic contributions, and increased access to meaningful patient partner opportunities. Alumni reported co-authoring publications and presenting their work at academic conferences and to various stakeholders, including health system leadership. Many alumni had no prior experience with qualitative participatory research, and participation in the programme supported the development of these research skills. Sponsors also noted impacts on their research programmes, such as securing additional funding informed by PaCER project findings. The findings demonstrate that structured, experiential training for patients and community members supports meaningful engagement in health research, contributes to sustained capacity development, and positively influences the patient-oriented research landscape. Patient partners were involved in the design and conduct of the study (data collection), analysis and interpretation of the data, and in the preparation of this manuscript.

Background: Allergy/immunology (A/I) fellowship recruitment occurs within a competitive match environment, with most interviews conducted virtually. Program web sites play a critical role in informing applicants and shaping program perception. Despite established literature that demonstrates the importance of program web sites across specialties, the comprehensiveness of A/I fellowship web sites has not been systematically evaluated. Objective: The purpose of this study was to evaluate existing A/I fellowship program web sites with the intent to identify opportunities for improvement. Methods: A list of 91 A/I fellowship programs was obtained from the American Academy of Allergy, Asthma & Immunology web site. Eighty-nine programs with accessible web sites were included. Each web site was evaluated for the presence of 24 predefined metrics derived from previous residency and fellowship web site studies. Sixteen programs affiliated with World Allergy Organization (WAO) Centers of Excellence in the United States were analyzed as a subgroup. Mean metric counts were compared by using a two-sample t-test. Results: Web sites contained a mean ± standard deviation (SD) of 13.7 ± 4.9 of 24 metrics. WAO-affiliated programs contained a mean ± SD of 13.2 ± 4.6 metrics, with no statistically significant difference when compared with all the programs (p = 0.70). Although most web sites listed program leadership, curriculum, and training sites, fewer included alumni information (40%), job placement (38%), or wellness initiatives (18%). Conclusion: A/I fellowship program web sites vary widely in content and may lack information, particularly with regard to wellness, alumni outcomes, and trainee demographics. Enhancing web site comprehensiveness represents an opportunity to improve recruitment, branding, and applicant engagement in a competitive application environment.

The INSPIRE project, funded by the European Marie Skłodowska-Curie Action (MSCA) program, was a doctoral network designed to train early-stage researchers (ESRs) and stimulate exploratory research in cardiovascular safety pharmacology (SP). From 2020 until 2024, INSPIRE trained 15 doctoral candidates hosted by a consortium of academic and industrial partners. The current publication summarizes the outcomes of INSPIRE and reflects on the impact to the field. As part of INSPIRE, ESRs were engaged in individual research projects covering a range of topics, yet grounded in 4 thematic clusters to facilitate collaboration. The first cluster focused on human induced pluripotent stem cells-derived cardiomyocyte (hiPSC-CM) assays and explored additional readouts such as morphological profiling, miRNAs panels and artificial intelligence assisted analyses. The second cluster aimed to develop a new telemetry platform with integrated positioning system, but technical drawbacks required initiation of alternative plans still aligned with the mission to refine in vivo SP studies. A third cluster explored new concepts for hemodynamic assessment, such as arterial stiffness and in silico modelling. Finally, the fourth cluster involved mechanistic research in cardio-oncology. Some ESR projects, especially those hosted by industry partners, delivered tangible prototype products or services with potential for commercialization. Alternative outcomes included optimized experimental workflows, datasets with reference compounds and mechanistic insights. Overall, INSPIRE delivered on its mission to initiate explorative research in SP, although many results will require further development, standardization and establishment of their context of use. This highlights the difficulty of achieving regulatory relevance within PhD timelines. For the latter, sustained engagement from industry beyond the duration of the doctoral program seems essential. Educationally, 8 ESRs have successfully defended their PhD thesis and a few ESRs have transitioned into permanent roles in drug R&D. Mobility of ESRs was a crucial, mandatory element of the training resulting in 23 secondments. The close interaction with industrial partners significantly enhanced trainee awareness of regulatory thinking, experimental robustness, and translational constraints. A yearly summer school was organized to facilitate mutual learning and build group cohesion. Meanwhile, the INSPIRE summer school has become a legacy with close to 100 alumni and offers a mix of theoretical lectures and broader sessions on career development. Looking ahead, ongoing revisions of international SP guidance (ICH S7A) and increasing interest in new approach methodologies (NAMs) create opportunities for a next-generation training network. In this context, we propose a roadmap for initiating INSPIRE v2.0 and have launched a call for input and participation to help shaping the future of SP.

Primary care continues to face pressure to improve clinical outcomes with limited resources. Point-of-care ultrasound (POCUS) offers potential value by improving diagnostic efficiency and procedural safety; yet early adoption in family medicine has been limited by faculty expertise, time constraints, and infrastructure barriers. In 2014, we developed a structured POCUS curriculum to address resident demand and programmatic gaps in family medicine training. We implemented a 4-week required postgraduate year (PGY) one ultrasound rotation designed to function with limited faculty availability. The curriculum integrates asynchronous learning, simulation, supervised scanning with standardized patients and sonographers, structured image review, and competency assessment. Residents complete a defined number of scans in high-yield applications including cardiac, lung, abdominal aorta, venous thrombosis, musculoskeletal/soft tissue, and obstetric ultrasound. Longitudinal reinforcement was later added through quarterly hands-on sessions and a PGY-3 advanced ultrasound rotation emphasizing competency reassessment and near-peer teaching. Over 10 years, faculty capacity expanded primarily through training program graduates. An alumni survey (2015-2022 graduates; 58% response rate) demonstrated continued POCUS use in 44% of respondents, with higher utilization among rural physicians and billing rates exceeding national primary care averages. Common barriers included time constraints and equipment access, while skin/soft tissue, musculoskeletal, and procedural applications were most frequently used. A scalable, longitudinal POCUS curriculum in family medicine is feasible despite limited protected faculty time. Tailoring training to anticipated practice settings, emphasizing ambulatory-relevant applications, and addressing workflow and billing education may improve long-term adoption and sustainability.

"Athlete's heart" refers to the physiological cardiac hypertrophy observed in competitive athletes, which reverts to normal after retirement from competition. However, few studies have examined long-term follow-up. This study investigated whether former college athletes with a history of an athlete's heart have a higher risk of developing heart disease later in life and examined its association with angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphisms. A total of 980 participants (mean age, 52.0 ± 15.7 years) from the Juntendo University Alumni Study were analyzed. Information on Athlete's heart during college and subsequent heart disease, including left ventricular hypertrophy, was obtained through self-administered questionnaires in 2018. The ACE I/D genotype was determined based on the rs4341 C/G polymorphism. Of all participants, 177 (18.1%) reported Athlete's heart during college, and 15 (1.5%) were diagnosed with left ventricular hypertrophy later in life. Former athletes with Athlete's heart had a 7.3-fold higher prevalence of left ventricular hypertrophy than those without such a history. Moreover, carriers of the D allele showed a further increased risk (odds ratio, 13.63; 95% confidence interval, 1.31-142.41). These findings suggest that regular cardiac monitoring may be warranted to identify potential late-onset cardiac remodeling in former athletes with Athlete's heart carrying the ACE D allele.

Identifying tumors with homologous recombination deficiency (HRD) is critical to determining appropriate treatment options for advanced ovarian cancer. We investigated concordance of HRD status and other associated biomarkers between Food and Drug Administration-approved MyChoice® CDx and 4 assays commercially available in various regions. DNA was isolated from pretreatment tissue samples from trial participants with platinum-sensitive relapsed ovarian cancer without a germline BRCA mutation (BRCAm). HRD status was assessed using MyChoice CDx and FoundationOne®CDx, SOPHiA DDM™ Dx HRD Solution, Thermo Fisher Oncomine™ Comprehensive Assay Plus (OCA Plus), and whole-genome copy number variation-based Thermo Fisher OncoScan™. Therapeutic efficacy was simulated in silico using data from the phase 3 PAOLA-1 study. Biomarker assessment success rate was ≥87% for all next-generation sequencing-based assays and 71.6% for Thermo Fisher OncoScan. With MyChoice CDx as reference, for HRD status, overall percentage agreement (OPA) ranged 76.0%-88.7%; positive percentage agreement (PPA) ranged 81.6%-93.8%, and negative percentage agreement (NPA) ranged 70.3%-90.4%. For genomic instability, OPA ranged 74.7%-87.5%, PPA ranged 67.6%-91.5%, and NPA ranged 71.1%-88.4%. For BRCAm status, OPA ranged 90.0%-96.9%, PPA ranged 50.0%-86.4%, and NPA ranged 94.4%-100%. Among simulated HRD-positive participants, mean progression-free survival hazard ratio was 0.40 at PPA of 80% and NPA of 85%, and 0.38 at PPA of 75% and NPA of 90%. Using MyChoice CDx as reference, commercially available assays showed concordance in detecting HRD, genomic instability, and BRCA mutations, indicating their potential clinical utility in identifying appropriate treatment options for ovarian cancer.

Prohibitin 1 (PHB1) and prohibitin 2 (PHB2) are highly conserved, ubiquitously expressed scaffold proteins that play central roles in cellular physiology by forming heterodimeric ring-shaped complexes. Their subcellular localization to mitochondria, the nucleus, cytoplasm, and plasma membrane underpins a remarkable functional pleiotropy that is profoundly exploited in cancer. This review provides a comprehensive synthesis of the current understanding of PHBs in tumor biology, spanning structural features, post-translational modifications, and their integration into multiple oncogenic signaling networks. We systematically describe how PHB1 directly activates the RAS-RAF-MEK-ERK cascade through regulated phosphorylation, how both PHB1 and PHB2 fine-tune the PI3K/Akt/mTOR axis through ubiquitination-dependent scaffolding and degradation of negative regulators, and how they exert bidirectional control over Wnt/β-catenin and NF-κB pathways. A major focus is the dual role of the mitochondrial PHB complex: protecting cristae architecture and regulating the OMA1-OPA1 axis, orchestrating respiratory chain supercomplex assembly, metabolic substrate switching, and mitophagy, while simultaneously suppressing or, in specific contexts, promoting reactive oxygen species signaling and ferroptosis. The review further dissects how dynamic nucleocytoplasmic shuttling of PHBs couples metabolic status to cell cycle progression, stemness, and epigenetic remodeling through interactions with transcription factors (E2F1, p53, Sp1) and chromatin modifiers (MLL2, HDAC1). Within the tumor microenvironment, PHBs emerge as critical immunometabolic hubs that influence macrophage polarization, cGAS-STING activation, and sexual dimorphism in immune responses. We summarize the cancer-type-specific expression patterns of PHB1/2 and their prognostic value, and provide an in-depth analysis of the mechanisms by which PHBs confer resistance to platinum drugs, paclitaxel, PARP inhibitors, and radiotherapy through stabilization of anti-apoptotic proteins, mitochondrial protection, and maintenance of cancer stem cell properties. Finally, we catalogue the expanding armamentarium of PHB-targeted interventions, including small-molecule ligands, stapled peptides, DNA aptamers, and siRNA delivery platforms, and discuss the challenges and opportunities for clinical translation. By integrating molecular mechanisms with translational perspectives, this review highlights PHBs as unique regulatory nodes at the intersection of metabolism, signaling, and immunity, and advocates for precision strategies that exploit context-specific PHB functions to overcome therapy resistance and improve cancer treatment.

Twisted graphene multilayers exhibit strong electronic correlations leading to a range of experimental signatures. Yet how these signatures relate to each other and to the microscopic ground states-and how twist angle and band structure reshape them-remains poorly understood. Here we study this interplay by correlating local thermodynamic and transport measurements in twisted trilayer graphene with unequal angles and flat electronic bands. We use a scanning single-electron transistor to map the impact of electron-electron interactions in the sample by selecting a region with smooth local twist angle evolution. We observe gapped correlated insulator states and asymmetric oscillations in the inverse electronic compressibility, both exhibiting pronounced electron-hole asymmetry with distinct 'magic' angles for conduction and valence bands. Subsequent transport measurements in the same region reveal robust superconductivity with a similar electron-hole asymmetry. Our measurements indicate that superconductivity is not directly tied to the correlated insulator states. Instead, its critical temperature correlates closely with the strength of the compressibility oscillations, suggesting a common origin or link between the two. By combining a local probe with transport measurements, we uncover connections between superconductivity and thermodynamic correlation signatures that are not apparent from either technique in isolation. These findings highlight the power of our dual approach.

This research takes entrepreneurship education beyond venture checklists and investigates how higher education links with innovative and entrepreneurial competence. We test a psychological model according to which growth mindset is positively related to innovative and entrepreneurial competence indirectly through entrepreneurial self-efficacy, where the perceived university support of entrepreneurship enhances the entrepreneurial self-efficacy-competence relationship. The survey was cross-sectional and conducted in four non-megacity Chinese ecosystems: Hangzhou, Nanjing, Wuhan and Xi'an to sample the difference in industrial foundation and university facilities. A preliminary power analysis suggested a target of about 450; given the anticipated loss of response, 630 questionnaires were mailed, 513 of them returned, and 472 of them passed quality preregistered data-quality checks. Innovative and entrepreneurial competence was represented as a hierarchical construct and the model was estimated in SmartPLS (v4) in a two-stage form with 5000 bootstraps. The values of reliability, convergent and discriminant validity, multicollinearity, and common-method diagnostics were at accepted levels. Growth mindset was positively correlated with innovative and entrepreneurial competence (&#x3b2;&#xa0;=&#xa0;0.18, p&#xa0;<&#xa0;.001) and entrepreneurial self-efficacy (&#x3b2;&#xa0;=&#xa0;0.50, p&#xa0;<&#xa0;.001); and entrepreneurial self-efficacy was positively correlated with innovative and entrepreneurial competence (&#x3b2;&#xa0;=&#xa0;0.52, p&#xa0;<&#xa0;.001). Growth mindset partially mediated this relationship with competence, with the indirect effect of growth mindset on competence through entrepreneurial self-efficacy being significant (&#x3b2;&#xa0;=&#xa0;0.26, p&#xa0;<&#xa0;.001). Additionally, the relationship between entrepreneurial self-efficacy and perceived University support was also significant (&#x3b2;&#xa0;=&#xa0;0.11, p&#xa0;=&#xa0;.003), suggesting that the influence of entrepreneurial self-efficacy on the relationship with competence was strengthened by University support. The model explained 25% of the variance in entrepreneurial self-efficacy and 49% of the variance in innovative and entrepreneurial competence.

Microplastics and nanoplastics are ubiquitous environmental contaminants, with growing evidence of their ecological and human health risks. However, a clear understanding of their impacts remains limited due to challenges in isolating MPs/NPs from complex environmental and biological matrices, insufficient sensitivity at the submicron scale, lack of standardized testing protocols, and inconsistent biological outcomes arising from variability in particle properties and cell models. Lab-on-a-chip (LoC) systems offer an integrated solution by combining automated sample handling, on-chip particle enrichment, multimodal characterization, and physiologically relevant culture models under controlled microenvironments. This review first examines current analytical techniques for MPs/NPs, followed by a detailed analysis of state-of-the-art LoC strategies for particle sampling, detection, characterization, and biological impact assessments. From filtration and density-based separation for sample preparation to advanced on-chip enrichment and detection techniques such as surface-enhanced Raman spectroscopy (SERS)-coupled microfluidic platforms, we evaluate the strengths and weaknesses of each approach, identify analytical bottlenecks, and provide directions for system integration to improve sensitivity, specificity, and throughput. For biological impact evaluation, we compare 2D monolayers, co-cultures, organoids, and organ-on-a-chip models, highlighting sources of experimental variation and providing guidelines for improved reproducibility and relevance. Ultimately, we aim to outline future directions for leveraging the advantages of LoC systems to enable high-throughput, standardized and meaningful ecological analysis of MPs/NPs, advancing their potential for long-term environmental monitoring of plastic pollution as well as human toxicity screening and health impact assessment.

Super-resolution ultrasound imaging (SRUI) surpasses the diffraction limit of conventional ultrasound, enabling visualization of microvascular architecture and hemodynamics with potential applications in neurology, oncology, and cardiology. However, clinical adoption remains limited by complex parameter optimization, subjective interpretation, and time-consuming workflows. We present a multimodal artificial intelligence framework that integrates a custom SRUI platform with large language models of DeepSeek-R1 for natural language processing and of MiniCPM-V for image recognition. Clinicians issue voice commands to initiate imaging tasks, which are translated into acquisition parameters, including temporal windows and adaptive microbubble filtration. The system performs super-resolution reconstruction, extracts quantitative vascular metrics, and generates structured diagnostic reports incorporating relevant clinical context. Filtration thresholds were dynamically determined using the Microbubble Similarity Score. Structured reports were generated within approximately four minutes. Evaluation by fourteen clinicians demonstrated good structural integrity and standardized terminology. This framework streamlines SRUI workflows and supports AI-assisted, clinically contextualized super-resolution ultrasound imaging. Trial registration: Chinese Clinical Trial Registry ChiCTR2100048361 registered July 6, 2021.

Obstructive sleep apnea (OSA) severity varies by sleep position and sex; however, it is unknown whether these factors affect hypoglossal nerve stimulation (HGNS) treatment effectiveness. Thus, this study evaluates HGNS control of OSA by sleep position and sex. To enhance real-world clinical applicability of results and address concerns regarding appropriate postoperative sleep study criteria to evaluate HGNS outcomes, our study also proposes and utilizes a standardized HGNS titration study scoring protocol to assess apnea-hypopnea index (AHI). A retrospective cohort of adult patients underwent device implantation at a tertiary care center between January 2018 and June 2021. Outcome measures included response rate by sleep position and sex using Sher criteria (reduction of AHI &#x2265;50% to&#x202f;<&#x202f;20/hr) and AHI normalization (<5/hr). Of 181 patients implanted, 113 patients met inclusion criteria. Patients were primarily older (median 65.0 years), overweight (BMI 30.0), white (91.2%) males (67.3%) with severe OSA (AHI 32.0/hr). HGNS success by Sher criteria and AHI normalization were 77.0% and 54.1%, respectively, in lateral sleep compared to 52.9% and 23.5% in supine sleep. Females attained a greater supine AHI reduction (p&#x202f;<&#x202f;0.04, Wilcoxon rank-sum test) and success by both response criteria (both p&#x202f;<&#x202f;0.03, chi-square tests of independence). Subgroup analyses using fixed-voltage home sleep apnea tests were underpowered and limited by low counts. Thus, HGNS more effectively controlled OSA in lateral sleep and for females, suggesting clinically meaningful differences by sleep position and sex that may help inform clinical decision making for patients with similar demographics.

Nicotine and tobacco products (NTP) and cannabis co-use entail unique risks. However, research on the correlates of co-use is limited, focusing on small samples, subpopulations, or specific correlates, without holistically examining multiple risk behaviors. Using an exploratory, hypothesis-generating approach, this study aimed to identify classifiers of past 30-day co-use of cannabis and NTP using random forest regression in a nationally representative adolescent sample. Data were drawn from the 2023 Youth Risk Behavior Survey (YRBS). Participants were 20,103 US adolescents in grades 9-12. Complete-case analyses included 8263 participants. The sample was 51.9% male and racially and ethnically diverse. The primary outcome was a binary indicator of past 30-day co-use of cannabis and NTPs. Classifiers included demographic, behavioral, and psychosocial factors. Random forest regression, including hyperparameter tuning, importance ranking of classifiers, and model robustness measures, were conducted in complete-case and multiply imputed data. Ten variables emerged as consistent and strongest classifiers of co-use, including past 30-day alcohol use (Mrank=1.00; SD=0.00), ever having had sexual intercourse (Mrank=2.36; SD=0.50), past 30-day binge drinking (Mrank=2.64; SD=0.50), and alcohol or drug use during last sexual intercourse (Mrank=4.00; SD=0.00). Models using imputed data achieved lower OOB error rates compared to the complete-case model. Among US adolescents, alcohol use and sexual behavior were the most salient classifiers of cannabis and NTP co-use. These findings highlight the importance of holistic examinations of multiple health risk behaviors.

Slow-wave activity (SWA), a key indicator of sleep homeostasis, is often diminished in individuals with treatment-resistant depression (TRD). Ketamine, a rapid-acting antidepressant, increases SWA during the first period of non-rapid eye movement (NREM1) sleep. However, research into how ketamine affects sleep and its connection to treatment outcomes in TRD has been limited by small sample sizes and a lack of comparison with healthy volunteers (HVs). This placebo-controlled study compared the effects of ketamine on NREM1 SWA in a large sample of unmedicated TRD patients (n&#x2009;=&#x2009;91; 51&#x2009;F/40&#x2009;M) and HVs (n&#x2009;=&#x2009;42; 23&#x2009;F/19&#x2009;M). Linear mixed-effects models and regression analyses, with post-hoc testing (paired ttests and Wilcoxon matched-pairs signed rank tests), were used to assess condition-related effects across baseline, ketamine, and placebo in TRD and HV participants. Age-related moderation of ketamine-associated NREM1 SWA changes and condition-related changes in sleep variables were also examined. At baseline, TRD patients had lower NREM1 SWA than HVs. Ketamine, but not placebo, increased NREM1 SWA in TRD patients, particularly in responders. In contrast, ketamine had no effect on NREM1 SWA in HVs. Following ketamine, TRD patients also showed significant increases in total sleep time and sleep efficiency and a reduction in sleep latency. In TRD patients, the ketamine-related increase in NREM1 SWA diminished with increasing age. Together, the results indicate that ketamine's antidepressant effects appear closely associated with its ability to modulate early SWA. These effects may also be linked to ketamine's ability to improve sleep architecture in TRD. Clinical Trials Identifier: www.clinicaltrials.gov , NCT00088699, NCT01204918.

Colorectal cancer (CRC) stands as the third most prevalent malignancy and represents the second primary cause of cancer-associated deaths. Lipid metabolic reprogramming constitutes a cancer hallmark, distinguished by markedly elevated lipid synthesis and extensive lipid-droplet accumulation. Puerarin, an isoflavone from pueraria lobata, shows lipid metabolism regulation and anticancer activity. In this investigation, we examined whether puerarin could modulate lipid metabolism for the treatment of CRC and delved into the underlying mechanisms. A network pharmacology-bioinformatics framework was developed to determine the potential targets of puerarin in CRC. For in vitro experiments, HCT-116, HCT-116/Oxa, SW480 and SW620 CRC cell models were chosen. We utilized western blotting (WB), quantitative real-time PCR (qRT-PCR), cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) cell proliferation assay, Transwell, lipid-droplet immunofluorescence (IF) assay, RNA-sequencing analysis and flow cytometry analysis to examine the molecular mechanisms by which puerarin modulates lipid metabolism in CRC treatment. For in vivo experiments, we established two murine paradigms-a dextran sulfate sodium (DSS)-driven orthotopic CRC model and a subcutaneous xenograft model-and comprehensively evaluated the in vivo efficacy of puerarin against murine CRC, together with its underlying mechanisms, by colonoscopy, enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin (H&E), immunohistochemical (IHC), IF and WB analyses. Our findings established that peroxisome proliferator-activated receptor gamma (PPAR&#x3b3;) as a bona fide target through which puerarin rewireed lipid metabolism in CRC. Loss of PPAR&#x3b3; was tightly linked to aggressive disease progression, whereas puerarin-by activating PPAR&#x3b3;-boosted downstream fibroblast growth factor 21 (FGF21) expression, suppressed the phosphoinositide 3-Kinase (PI3K)/ protein kinase B (AKT)/ mechanistic target of rapamycin (mTOR) axis, and thereby disrupted tumor lipogenesis. This signaling rewiring attenuated malignant growth and chemoresistance both in vitro and in vivo. Puerarin halted the malignant progression of CRC by reprogramming tumor lipid metabolism. Puerarin thus hold promise as a clinically deployable lipid-centric agent that could synergistically potentiate conventional anticancer drugs.

Childhood and adolescent poisoning is a significant health problem globally, especially in low- and middle- income countries. Globally, around a million childhood cases of poisoning were reported in 2019. In Pakistan, unintentional childhood and adolescent poisoning is higher, including organophosphates, snake bites, and animal bites. Therefore, this study aims to identify the most common agents causing poisoning, risk factors, management, and outcomes of childhood and adolescent poisoning incidents. This study included childhood and adolescent poisoning cases from March to May 2025 presented at Jinnah Postgraduate Medical Center Karachi, Pakistan. A total of 110 children were included in the study between the ages of 0-18 years. Exposure was poisoning, and there were two outcomes: length of hospital stay (days) and status on follow-up (alive/dead). Acute poisoning was suspected in children who presented a clear history of recent exposure, fast onset of symptoms, and clinical characteristics such as vomiting, altered level of consciousness, convulsions, respiratory distress, aberrant pupil size, or distinctive odor. Organophosphate poisoning was diagnosed based on clear exposure history, identification of substance containers, presence of classical cholinergic toxidrome (vomiting, salivation, lacrimation, pinpoint pupils, fasciculations) and clinical response to atropine. Chi-square and Fisher's exact test were performed, considering a p-value&#x2009;<&#x2009;0.05 being significant. The median age was 17 years with an equal distribution of males and females. Organophosphate poisoning (60.91%) was the most reported poisoning, followed by snake bites (21.82%). Only one (0.91%) case had prior poisoning history. Around 82.00% of poisoning cases occurred at home, and 58.18% of cases occurred due to deliberate intent. Organophosphate poisoning (p&#x2009;<&#x2009;0.001), median respiratory rate of 20 (p&#x2009;=&#x2009;0.034), and heart rate of 100 (p&#x2009;=&#x2009;0.007), were significantly associated with longer hospital stay. This study highlights organophosphate poisoning as the most common cause, often intentional and occurring at home due to easier access and unsafe storage. This study helps in the identification of patients who are prone to a longer hospital stay than others, providing clinicians with a means to personalize patient care.

To evaluate the short- and mid-term volume reduction rate(VRR) after percutaneous ethanol injection(PEI), at 1,3 and 6 months, in patients with cystic or predominantly cystic thyroid nodules(CNs/pCNs, respectively), conducting a systematic review and meta-analysis of published data on VRR outcomes across these intervals. A systematic search of articles published up to October 30,2025 identified studies reporting PEI treatment for CNs/pCNs.Characteristics of the study design, CNs/pCNs cohorts, and outcomes of interest(VRR at 1,3 and 6 months of follow up)were extracted.Statistical analysis included a random-effects meta-analysis, assessment of heterogeneity with use of the I2 statistic, and meta-regression and subgroup analyses to explore potential sources of heterogeneity. Six studies comprising 431 CNs/pCNs were included.The pooled VRRs at 1,3 and 6 months post-PEI were 85.18%(95% CI: 80.72-89.64),91.50%(95% CI: 88.88-94.12) and 93.11%(95% CI: 90.91-95.31),respectively. Stratifying by nodule cystic composition, the VRR at consecutive follow-up time points was significantly different between the 1- and 3-month intervals in both subgroups [CN: VRRs at 1, 3 and 6 months were 91.16% (88.38-93.93), 95.69% (94.16-97.22) and 96.02% (94.16-97.87), respectively; pCN: VRRs at 1,3 and 6 months were respectively 80.19% (77.04-83.33), 87.08% (84.95-89.2) and 90.01%(88.83-91.19)].A secondary meta-regression analysis with baseline mean volume as covariate demonstrated a significant inverse association with VRR at 1 and 3 months in pCN(p&#x2009;=&#x2009;0.02). By providing pooled VRRs for the short- and mid-term follow-up, this meta-analysis should be regarded as an initial step, paving the way for larger, high-quality studies aimed at standardizing the PEI procedure and supporting its incorporation into future dedicated guidelines.

Proctological diseases are common worldwide, yet their true burden is often underestimated due to delayed presentation and limited standardized reporting with a diverse population, rising case numbers, and evolving minimally invasive techniques. Understanding local trends is essential for improving the quality of care. This study aims to evaluate five-year trends in proctologic surgical procedures, patient characteristics, and referral patterns in a tertiary referral centre in Dubai. This retrospective trend analysis study reviewed all patients who underwent proctological surgeries at a tertiary hospital in Dubai from July 2020 to June 2025. Demographic data, case characteristics, procedure types, and operative details were extracted from electronic records. Trends were summarized as frequency and percentages, and Poisson regression was used to assess associations between patients' characteristics and procedure patterns, considering a p-value&#x2009;&#x2264;&#x2009;0.05 significant. A total of 967 patients underwent proctological surgeries during the five years. The mean age was 41.5 years, and most patients were male. Hemorrhoid procedure was the most common (42%), followed by anal fistula and abscess-related surgeries. More than half of the cases were identified as minor, while 159 (16.44%) were major. Most cases were classified as elective (856, 88.52%). Yearly trends showed a rise in the rate of hemorrhoid and fistula surgeries. Men have a significantly higher relative likelihood of surgery compared to women, by 23% [aRR: 1.23, 95% CI: 1.08-1.41]. The relative risk of no incision was more than twice that of a clean wound class [aRR: 2.14, 95% CI: 1.72-2.66]. This study reports that age and gender remain significant contributors to the high risk of proctology surgeries. Males are predominantly at higher relative likelihood of surgery. The trends show that hemorrhoids were the common problem for which almost half of the patients underwent surgery. Despite advancements in minimally invasive surgical techniques. Challenges such as high recurrence rates. This study highlights the need for a standardized approach in proctology to enhance patient outcomes and streamline treatment processes.