Search PubMedSearch

SEARCH · Search PubMed

Results for “Developing Countries”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

702 records · Page 19Linked to original sources

Systematic Review of Pharmacologic Treatment for Migraine Prevention in Adults: Report of the AAN Guidelines Subcommittee and the American Headache Society.

BACKGROUND AND OBJECTIVES: This systematic review (SR) provides updated evidence-based conclusions regarding the use of pharmacologic migraine prevention in adults to inform a new joint American Academy of Neurology (AAN) and American Headache Society practice guideline. METHODS: A multidisciplinary panel conducted an SR following the 2017 AAN Clinical Practice Guideline Process Manual. Randomized controlled trials evaluating pharmacologic preventive treatments for adults with episodic or chronic migraine were included. Searches encompassed MEDLINE, Embase, and ClinicalTrials.gov from database inception through June 6, 2024. Studies were screened in duplicate, with dual independent risk-of-bias assessment. Outcomes included change in monthly headache days, ≥50% responder rate, and validated patient-reported quality of life (QOL) measures. Raw mean differences, standardized mean differences, and risk ratios were calculated. A modified Grading of Recommendations Assessment, Development, and Evaluation process was used to classify certainty of evidence. RESULTS: A total of 217 studies met inclusion criteria. For episodic migraine, high-confidence evidence showed that galcanezumab and erenumab are more effective than placebo in reducing headache frequency. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, fremanezumab, propranolol, topiramate, and valproate. Several additional oral agents including amitriptyline, bisoprolol, flunarizine, fluoxetine, levetiracetam, metoprolol, nifedipine, pizotifen, and telmisartan had low-confidence evidence suggesting possible benefit. For chronic migraine, high-confidence evidence supported reductions in headache frequency with fremanezumab, galcanezumab, and onabotulinumtoxinA. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, erenumab, topiramate and valproate. Across both episodic and chronic migraine populations, erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, atogepant, topiramate and onabotulinumtoxinA demonstrated improvements in patient-reported QOL outcomes on validated instruments. Evidence comparing active treatments was limited and generally of low or very low confidence, restricting conclusions about comparative effectiveness. DISCUSSION: This SR provides a comprehensive synthesis of evidence on pharmacologic migraine prevention in adults. High- and moderate-confidence findings confirm the efficacy of several established and newer preventive therapies and demonstrate improvements in patient-reported outcomes across multiple validated measures. These conclusions informed the development of evidence-based recommendations, presented in a companion publication, to guide clinicians in selecting preventive medications for adults with episodic and chronic migraine.

Humans

Risk Factors and Predictive Model for Postoperative High Myopia in Children Undergoing Congenital Cataract Surgery With Intraocular Lens Implantation.

PURPOSE: To identify risk factors associated with the development of high myopia following congenital cataract surgery and to establish a robust predictive model. DESIGN: Retrospective clinical cohort study. SUBJECTS: This retrospective study included 106 pediatric patients who underwent congenital cataract surgery with primary IOL implantation (mean follow-up 8.19 years). The model was externally validated in an independent cohort of 72 patients with a mean follow-up of 7.83 years. METHODS: Preoperative and postoperative ocular biometric parameters were collected. Risk factors for postoperative high myopia were analyzed using Cox proportional hazards regression, which served as the basis for model construction. The predictive performance of the model was rigorously evaluated for discrimination and calibration. Discriminative ability was quantified using Harrell's C-index and the area under the receiver operating characteristic curve (AUC). Model calibration was assessed via calibration plots by comparing predicted probabilities with actual observed outcomes. Internal validation was performed using a bootstrapping method (500 iterations) to ensure model stability and adjust for potential overfitting. RESULTS: An initial postoperative refraction of <+0.75D, and a higher IOL Power to Axial length Ratio (IOL/AL ratio) were identified as significant risk factors for the development of postoperative high myopia. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. The predictive model demonstrated robust performance, achieving a C-index of 0.711 (internal validation C-index: 0.713). The area under the receiver operating characteristic curve (AUC) values for predicting high myopia at 5 and 10 years were 0.858 and 0.745, respectively. Furthermore, calibration curves demonstrated excellent agreement between the predicted and observed outcomes throughout the follow-up period. In external validation, the model achieved a C-index of 0.825, 5-year AUC of 0.833, and 10-year AUC of 0.713. CONCLUSIONS: Our analysis established that initial postoperative refraction <+0.75D, and an elevated IOL/AL ratio are key determinants of high myopia risk following surgery. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. This predictive framework provides clinicians with a practical tool to optimize preoperative IOL selection and identify high-risk infants who require vigilant myopia prevention and balanced amblyopia management.

Humans

Multi-omics panorama of glaucoma: Pathogenesis, biomarkers, and novel therapeutic strategies.

Glaucoma is a group of irreversible, blinding eye diseases characterized by progressive loss of retinal ganglion cells, leading to gradual visual field defects that severely impact patients' quality of life. Its complex pathophysiological mechanisms remain incompletely understood, limiting the development of early diagnostic and effective therapeutic strategies. Advances in omics technologies have provided new insights into elucidating the pathophysiology of glaucoma. We summarize specific alterations in genomics, transcriptomics, proteomics, metabolomics, epigenomics, and microbiomics associated with glaucoma. We emphasize the systematic analysis of disease mechanisms, identification of clinically applicable biomarkers, and discovery of novel therapeutic targets through the integration of these data. This approach paves new pathways for glaucoma subtype diagnosis and personalized treatment, while also outlining future research directions and challenges.

Humans

Assessing the threat of Bacillus cereus: From toxin characterization to modern detection strategies.

Bacillus cereus is a spore-forming pathogen responsible for both diarrheal and emetic foodborne illnesses worldwide. Its significance in food safety has received growing attention. Recent advances, including the discovery of novel virulence factors and the development of emerging detection technologies, have provided new insights into its pathogenic mechanisms and surveillance strategies. This review critically examines the global burden of B. cereus infections, and molecular mechanisms of its major virulence factors, and the performance characteristics of current detection knowledge gaps such as the viable-but-non-culturable state and regulatory blind spots for emetic toxins, and discuss unresolved challenges in clinical management. By integrating epidemiological, microbiological, and technological perspectives with critical lens, this review aims to provide a valuable reference for future research and food safety practices.

Bacillus cereus

Diagnostic Performance of Machine Learning for Systemic Lupus Erythematosus: Systematic Review and Meta-Analysis.

BACKGROUND: Early and accurate diagnosis of systemic lupus erythematosus (SLE) and its organ involvement is essential. Previous reviews of machine learning (ML) in SLE combined heterogeneous tasks and validation strategies and may have overinterpreted model performance. OBJECTIVE: This study evaluated the diagnostic performance of ML and deep learning (DL) models for 3 clinically distinct SLE-related tasks: SLE classification or diagnosis, lupus nephritis (LN) diagnosis, and neuropsychiatric systemic lupus erythematosus (NPSLE) discrimination. We also assessed methodological quality and certainty of evidence. METHODS: PubMed, Embase, Cochrane Library, Web of Science, and IEEE Xplore were searched from January 2014 to April 2026. Eligible peer-reviewed diagnostic accuracy studies developed or validated ML or DL models for 1 of the 3 prespecified tasks, used an accepted reference standard, and provided data for a 2&#xd7;2 contingency table. Bivariate random-effects meta-analyses with the Hartung-Knapp-Sidik-Jonkman adjustment were used to pool sensitivity and specificity. We reported 95% prediction intervals (PIs), assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies for Artificial Intelligence tool (QUADAS-AI; Viknesh Sounderajah [Imperial College London]), and evaluated certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation framework for diagnostic test accuracy. RESULTS: Twenty-nine studies were included: 17 for SLE classification, 5 for LN diagnosis, and 7 for NPSLE discrimination. In the primary task-stratified analysis, pooled sensitivity was 0.91 (95% CI 0.86-0.94; 95% PI 0.56-0.99), and pooled specificity was 0.94 (95% CI 0.91-0.96; 95% PI 0.69-0.99), with low heterogeneity (I&#xb2;=23.9% and 22.9%, respectively). DL models showed a sensitivity of 0.93 and specificity of 0.95, compared with 0.88 and 0.94 for traditional ML models. Certainty of evidence was high for most analyses but low for LN diagnosis because of inconsistency and imprecision. All studies were retrospective, and only 9 of 29 (31%) performed independent external validation. Overall risk of bias was high or unclear in 22 of 29 (75.9%) studies. No study reported model calibration, decision-curve analysis, or net clinical benefit. CONCLUSIONS: ML models showed promising diagnostic accuracy across 3 distinct SLE-related tasks, but wide PIs, limited external validation, and pervasive risk of bias restrict conclusions about real-world generalizability. Prospective multicenter studies with standardized tasks and reference standards, independent external validation, and formal assessment of calibration and clinical utility are required before clinical implementation.

Humans

Fracture-related infection following open forefoot fractures caused by dropped objects.

INTRODUCTION: This study evaluated the rate of fracture-related infection (FRI) of open forefoot fractures caused by dropped objects, and examined associations of treatment characteristics, including intravenous and oral antibiotics and operative debridement, with FRI. METHODS: Patients aged 18-80 years who sustained an open metatarsal or phalanx fracture caused by a dropped object between January 2021 and June 2024 were retrospectively identified from two Level 1 trauma centers. The primary outcome was FRI, determined based on the FRI consensus criteria. FRI rates were compared between those who underwent irrigation and debridement (I&D) at bedside versus in the operating room, and between those who received oral versus intravenous (IV) antibiotics. Patient characteristics were also analyzed to determine host factors associated with FRI. RESULTS: A total of 86 patients (median age 41 years [IQR: 29-56], 58% male) were included. Eighty-five patients (99%) received antibiotics, 31 (36%) of whom received intravenous antibiotics. Sixty-six patients (77%) received an I&D at presentation, 57 (66%) at bedside and 9 (10%) in the operating room. Thirteen patients (15%, 95% CI: 8.3%-24%) developed FRI. No significant difference in FRI rate was found between patients who underwent I&D at bedside versus in the operating room (12% versus 11%, p&#x202f;>&#x202f;0.99). Among patients who did not undergo I&D in the operating room, no significant difference in FRI rate was found between patients who received oral versus IV antibiotics (17% versus 13%, p&#x202f;=&#x202f;0.74). Insulin-dependent diabetes was associated with an increased risk of FRI (60% versus 12%, p&#x202f;=&#x202f;0.02). CONCLUSIONS: In this cohort, one in seven patients developed FRI. No statistically significant differences in FRI rates were observed by I&D setting (bedside versus operative) or antibiotic route (oral versus IV), including in a subgroup analysis excluding patients treated with operating room I&D. These findings are limited by sample size and potential treatment selection bias and should not be interpreted as evidence of equivalence. Management should be individualized based on clinical judgement, resource availability, and patient factors. These findings can help guide the management protocols for "dropped objects" open forefoot fractures presenting to urgent care and the emergency department. LEVEL OF EVIDENCE: Therapeutic Level III.

Humans

A standardised risk-stratified approach to the urological management of children with spina bifida.

BACKGROUND: The establishment of a multidisciplinary spina bifida (SB) clinic in 2006 resulted in a review of the literature and an audit of renal outcomes based on then management practices. The audit showed 17% new onset renal scarring over a mean 5.8-year follow-up period. This prompted the development of a local protocol based on risk stratification combining serial ultrasound and non-invasive bladder function assessments, with invasive urodynamic studies reserved for high-risk patients. OBJECTIVE: This study sought to assess the impact of a risk stratified protocol on renal scarring and continence outcomes in children with SB. METHODS: A single centre, retrospective case review of SB patients treated after the introduction of the protocol was conducted. Electronic medical records were used to access patient demographics, continence status and the results of investigations and adherence to the local management protocol. Management that deviated from the protocol was deemed non-adherence. Renal scarring was determined by the presence of scarring on DMSA renogram. Continence was defined as having no urinary incontinence or no more than a single episode of incontinence in a month in patients above the age of 5. For statistical analysis, descriptive statistics in percentages were used, for comparisons of dichotomous variables the Students t-test was performed and to calculate statistical significance a Fisher exact test was done. RESULTS: 167 SB patients were identified with a mean follow up of 56 months. 141 patients were considered adherent to the protocol, 26 were non-adherent. In the protocol adherent group 5 patients (3.5%) developed renal scarring compared with 6 patients (23%) managed out of protocol (p = 0.002). Overall, 49/108 patients were continent either self-voiding 8/108 (7%), with urethral CIC 19/108 (20%) and 22/108 (45%) of them required bladder augmentation. Urinary continence improved with age with 26% continence at age 10, 64% continence by age 15 and 90% continent above 15 years of age. CONCLUSION: A management approach based on risk stratification resulted in incidence of renal scarring that is better than historical controls and comparable to published outcomes. Social continence was achieved in 90% of SB patients by 15 years of age. Hostile bladder changes can be readily identified using non-invasive assessment methods. An expectant treatment approach based on risk stratification is associated with good long term renal outcome and utilises invasive urodynamic resources for SB patients at high risk of renal injury or to address urinary continence in the older child.

Humans

GATA2 deficiency: enhancer deregulation, immune surveillance failure, and clonal evolution.

Germline mutations in GATA2 cause a syndromic inborn error of immunity characterized by cytopenia, infections, immune dysregulation, and a marked predisposition to myelodysplastic syndrome and acute myeloid leukemia. Initially defined by the DCML phenotype-dendritic cell, monocyte, B- and NK-cell deficiency-GATA2 deficiency is now recognized as a disorder of global immune-hematopoietic homeostasis. Recent multi-omics and experimental models reveal enhancer-driven inflammatory rewiring, IRF8-dependent lineage imbalance, and premature hematopoietic aging. In parallel, adaptive immune defects, including impaired B- and T-cell development and function, contribute to defective immune surveillance. These alterations not only explain susceptibility to infection but also shape clonal evolution and malignant transformation. Clinically, improved risk stratification and transplant outcomes underscore the importance of early recognition and monitoring of immune dysfunction. GATA2 deficiency thus represents a paradigm linking immune dysregulation, inflammatory stress, and cancer predisposition.

Humans

Oropouche virus: viral evolution, epidemiological trends, and challenges for control.

PURPOSE OF REVIEW: In recent years, OROV has emerged as a significant public health threat beyond the Amazon region. Here we review current epidemiological, virological, clinical and ecological knowledge of OROV to inform health practitioners, public health authorities and the scientific community and to facilitate the development of effective control strategies for OROV. RECENT FINDINGS: We describe the epidemiological, virological, ecological and clinical characteristics of OROV, focusing on lessons from the recent expansion, and highlighting needs for control and management of this emerging arbovirus. SUMMARY: This review aims to inform health practitioners, public health authorities and the scientific community of the recent reemergence and expansion of OROV beyond the Amazon Basin. The ecology, epidemiology, virology of OROV and clinical presentations of OROV infection are discussed, and knowledge gaps are identified.

Humans

Quality of life and gender identity in females with congenital adrenal hyperplasia after genital restoration surgery: A single-center experience.

BACKGROUND: Legislation restricting surgical interventions in children with differences of sex development (DSD) has intensified debate about female genital restoration surgery (FGRS) in patients with congenital adrenal hyperplasia (CAH). Long-term patient-reported outcomes are needed regarding the optimal timing of surgery. OBJECTIVE: We aimed to assess health-related quality of life (HRQoL), gender identity, and family satisfaction regarding surgical timing and outcome in females with CAH following genital restoration surgery. STUDY DESIGN: Cross-sectional survey of CAH patients who underwent surgery between January 2007 to December 2016 at our institution. Validated instruments (KINDL questionnaire for HRQoL, Utrecht Gender Dysphoria Scale, UGDS) and structured telephone interviews were employed. RESULTS: Data on HRQoL was available for 25 patients (self- and/or parent-reported) out of 56 eligible patients (45% response rate). Median age at first surgery was 6 months (range: 3-137 months). Patients' age at time of participation ranged from 2 to 28 years. All had 21-hydroxylase deficiency (92% salt-wasting form) with Prader grades ranging from II-V. Wound dehiscence requiring secondary suturing occurred in 15% of patients with primary surgery at our center, while only one (4%) patient developed vaginal stenosis after early primary vaginoplasty. Two additional patients (8%) with prior outside surgery required vaginal revision after FGRS at age 12. HRQoL scores were comparable to healthy reference populations across most age groups. Children aged 3-6 and adolescents and young adults showed no significant difference from reference values, while children aged 7-13 showed a slight elevation. None of five patients &#x2265;14 years demonstrated gender dysphoria (all UGDS scores <40, threshold &#x2265;40). 14 patients and families were also interviewed by telephone. All preferred early surgical timing. No family expressed regret about the decision or preferred delayed surgery. DISCUSSION: This study provides validated intermediate-term patient- and parent-reported outcomes after FGRS in CAH. Key limitations include the small sample size, single-center design, and young age of most patients. Selection bias may exist, though participating families included those who underwent revision surgery. The absence of a non-operated comparison group reflects current clinical reality, as nearly all CAH patients with urogenital sinus underwent surgical correction. CONCLUSIONS: Females with CAH reported normal HRQoL and a comfortable female gender identity after early FGRS. The patients and their families expressed a preference for early surgery. However, there is need for longer-term follow-up to assess sexual function and reproductive outcomes as well comparison of outcomes with a non-operated group.

Humans

Insights into the fate and dynamics of antibiotic resistance in multidrug-resistant Bacillus cereus during in vitro simulated gastrointestinal digestion.

Bacillus cereus, an important pathogen responsible for causing foodborne diseases worldwide, releases pore-forming enterotoxins, which target host epithelial cells, leading to osmotic lysis and ultimately manifesting as diarrheal syndrome. Moreover, some B. cereus strains carry antimicrobial resistance genes that confer multidrug resistance against a spectrum of antibiotics. Characterizing the survival traits of multidrug-resistant (MDR) B. cereus strains in the intestinal microenvironment is essential for developing targeted strategies to effectively manage diarrheal foodborne diseases caused by this pathogen. This study used whole-genome sequencing (WGS) to evaluate the pre- and post-digestion toxigenic potential, antimicrobial resistance profiles, and genetic diversity of MDR B. cereus strains isolated from food samples in Guangdong Province, China. The four B. cereus isolates investigated in this study exhibited a genetic diversity, as determined by multilocus sequence typing analysis of WGS data. All four isolates produced the diarrheal toxins Hbl, Nhe, and CytK to varying levels, indicative of their potential to cause outbreaks of foodborne diseases. Each of the four isolates exhibited resistance to more than three classes of antibiotics, fulfilling the criterion for multidrug resistance. At an initial concentration of 9 log colony-forming units (CFU)/mL, the intestinal concentration of these four isolates crossed the threshold required to induce widespread diarrhea in the general population. Under rice slurry protection, all tested isolates maintained intestinal concentration beyond the threshold when the initial concentration was increased to &#x2265;8 log CFU/mL. Moreover, the upregulations of genes associated with acid tolerance, bile tolerance and stress response were observed in the surviving MDR B. cereus isolates. Digestion markedly altered the antibiotic resistance profiles of the MDR B. cereus isolates. In the absence of a food matrix, the MDR isolates lost their resistance to imipenem, meropenem, amoxicillin-clavulanic acid, and trimethoprim-sulfamethoxazole post-digestion and was influenced by the initial concentration of the strains. In the presence of food matrix rice slurry, the effects of digestion on the antibiotic resistance of MDR B. cereus isolates can be mitigated, enabling them to maintain their antibiotic resistance to the greatest extent. Most remarkably, after digestion, the isolates Bce055 and Bce166 exhibited newly emergent resistance to cefotetan and trimethoprim-sulfamethoxazole, respectively. Our findings clarify the fate of MDR B. cereus isolates in the gastrointestinal tract and inform the development of prevention and control strategies for foodborne diseases caused by this pathogen.

Drug Resistance, Multiple, Bacterial

The identification of growth-promoting lncRNAs in oral cavity squamous cell carcinoma.

Oral Cavity Squamous Cell Carcinoma (OCSCC) is an aggressive tumor that develops within the mouth of patients. Tumor-suppressor gene loss and genomic arrangements fuel tumorigenesis and transcriptional reprogramming. Understanding how these alterations contribute to OCSCC growth and cell survival may identify new therapeutic vulnerabilities or biomarkers. We profiled the role of long non-coding RNAs (lncRNAs) in the growth of three OCSCC cell lines using a CRISPRi-screen and identified 19 lncRNAs that contribute to OCSCC proliferation. By comparing these lncRNAs to other screens, we find that these lncRNAs are uniquely required in OCSCC and not other malignancies. We show that these lncRNAs are abundantly expressed in OCSCC cells and tumors. Independent testing of candidate lncRNAs confirms their role in supporting OCSCC growth. Our results show that a novel subset of lncRNAs are required for the growth of OCSCC cancer cells and that these lncRNAs are cell lineage specific.

CRISPRi

Durvalumab and tremelimumab, with or without lenvatinib, combined with transarterial chemoembolisation in participants with embolisation-eligible hepatocellular carcinoma (EMERALD-3): a global, randomised, open-label, sponsor-blinded, phase 3 study.

BACKGROUND: Transarterial chemoembolisation (TACE), a standard treatment for embolisation-eligible hepatocellular carcinoma (HCC), induces tumour immune responses. Single tremelimumab regular interval durvalumab (STRIDE) is a standard treatment in advanced HCC. In this phase 3 trial, we assessed the efficacy and safety of STRIDE, with or without lenvatinib, plus TACE, in participants with embolisation-eligible HCC. METHODS: EMERALD-3 is a phase 3, randomised, open-label, sponsor-blinded study, conducted at 177 medical sites in 21 countries. Eligible participants were 18 years or older (aged &#x2265;21 years in Egypt or Singapore) at screening and had confirmed HCC (by imaging or histopathologically from biopsy specimen, surgery, or both) not amenable to curative surgery, curative ablation, or transplantation but amenable to TACE. Participants had Child-Pugh class A liver function, an Eastern Cooperative Oncology Group performance status of 0-1, and at least one measurable target intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours. Participants were randomly allocated in a 1:1:1 ratio to receive STRIDE plus lenvatinib plus TACE, STRIDE plus TACE, or TACE until each group reached its preplanned enrolment target of 175 participants. After the STRIDE plus TACE group reached its enrolment target, randomisation was adjusted to continue in a 1:1 ratio between the STRIDE plus lenvatinib plus TACE group and TACE group until approximately 275 participants were enrolled in each of these two groups. Randomisation used a centrally assigned interactive response technology system, stratified by region, baseline tumour burden, and previous palliative embolisation. In the STRIDE plus lenvatinib plus TACE group, on the first day, participants were given 300 mg tremelimumab intravenously, followed by 1500 mg durvalumab plus oral lenvatinib (8 mg for <60 kg bodyweight or 12 mg for &#x2265;60 kg bodyweight); participants then received 1500 mg durvalumab every 4 weeks plus once-daily lenvatinib for up to 36 cycles. In the STRIDE plus TACE group, participants were given 300 mg tremelimumab and 1500 mg durvalumab intravenously on the first day, followed by 1500 mg durvalumab every 4 weeks. The technique and number of TACE procedures were at the investigators' discretion, with the first procedure administered at least 7 days after the first dose of durvalumab in the two investigation treatment groups and within 7 days of random allocation in the TACE group. The primary endpoint was progression-free survival for STRIDE plus lenvatinib plus TACE versus TACE. Key secondary endpoints were overall survival for STRIDE plus lenvatinib plus TACE versus TACE and progression-free survival and overall survival for STRIDE plus TACE versus TACE. This study was registered with ClinicalTrials.gov (NCT05301842), with enrolment completed. FINDINGS: From March 28, 2022, to Nov 20, 2024, 1124 participants were screened. The full analysis set comprised 760 participants, who were randomly allocated to STRIDE plus lenvatinib plus TACE (n=293), STRIDE plus TACE (n=175), or TACE (n=292). 633 (83%) participants were male and 127 (17%) were female; 548 (72%) were Asian. At the first data cutoff (Sept 2, 2025); the overall median follow-up for progression-free survival was 10&#xb7;0 months (IQR 4&#xb7;6-17&#xb7;2); median follow-up for progression-free survival was 11&#xb7;0 months (IQR 4&#xb7;8-18&#xb7;4) for STRIDE plus lenvatinib plus TACE and 8&#xb7;3 months (4&#xb7;1-15&#xb7;5) for TACE. Median progression-free survival was 13&#xb7;0 months (95% CI 12&#xb7;2-16&#xb7;7) for STRIDE plus lenvatinib plus TACE versus 9&#xb7;8 months (8&#xb7;0-11&#xb7;4) for TACE (HR 0&#xb7;70 [95% CI 0&#xb7;57-0&#xb7;86]; p=0&#xb7;0007). At the second data cutoff (Feb 23, 2026) and a median follow-up for overall survival of 24&#xb7;6 months (IQR 16&#xb7;5-31&#xb7;5) for STRIDE plus lenvatinib plus TACE and 22&#xb7;9 months (14&#xb7;9-30&#xb7;2) for TACE, median overall survival was 39&#xb7;5 months (95% CI 34&#xb7;1-not reached) for STRIDE plus lenvatinib plus TACE and 34&#xb7;7 months (28&#xb7;8-not reached) for TACE (HR 0&#xb7;84 [95% CI 0&#xb7;65-1&#xb7;09]; p=0&#xb7;18). At this data cutoff, median progression-free survival was 12&#xb7;9 months (95% CI 10&#xb7;2-15&#xb7;9) for STRIDE plus TACE and 8&#xb7;1 months (6&#xb7;5-10&#xb7;2) for the first 175 participants randomised to TACE (HR 0&#xb7;71 [95% CI 0&#xb7;56-0&#xb7;91]), with median follow-up of 10&#xb7;3 months (IQR 4&#xb7;6-23&#xb7;7) for STRIDE plus TACE and 7&#xb7;7 months (3&#xb7;0-18&#xb7;5) for the first 175 participants randomly allocated to TACE. The most common adverse events of maximum grade 3 or 4 were hypertension (34 [12%] of 287) for STRIDE plus lenvatinib plus TACE, post-embolisation syndrome and anaemia (ten [6%] of 175 each) for STRIDE plus TACE, and post-embolisation (17 [6%] of 290) for TACE. 184 (64%) participants receiving STRIDE plus lenvatinib plus TACE, 89 (51%) receiving STRIDE plus TACE, and 68 (23%) receiving TACE had serious adverse events. Treatment-related adverse events with an outcome of death during the treatment-emergent period occurred in seven (2%) of 287 participants who received STRIDE plus lenvatinib plus TACE (two for myocarditis; and one each for hepatic failure, haemophagocytic lymphohistiocytosis, septic shock, cardiac failure, and unknown cause), none of 175 participants who received STRIDE plus TACE, and two (1%) of 290 participants who received TACE (one each for acute myocardial infarction and unknown cause). INTERPRETATION: STRIDE plus lenvatinib plus TACE showed a statistically significant progression-free survival improvement versus TACE. These findings support a STRIDE-based regimen as a potential new treatment option for people with embolisation-eligible HCC; additional follow-up is being conducted for final analysis of overall survival across treatment groups. FUNDING: AstraZeneca.

Adult

Compliance With Ecological Momentary Assessment Among Patients With Cancer: Systematic Review and Meta-Analysis.

BACKGROUND: Patients with cancer often experience substantial fluctuations in psychological states during disease management. Traditional research tools are limited in capturing these dynamic changes in real time, constraining clinicians' understanding of patients' true conditions. Ecological momentary assessment (EMA) enables high-frequency, real-time data collection, providing patient-reported data with greater ecological validity. However, the effectiveness of EMA studies critically depends on patient compliance, and reported compliance rates vary widely, with a lack of systematic quantitative synthesis. OBJECTIVE: This study aims to systematically review and quantitatively analyze compliance with EMA among patients with cancer, and to examine whether EMA design characteristics were associated with compliance. METHODS: Web of Science, PubMed, Embase, Cochrane Library, CINAHL, PsycINFO, CNKI, and Wanfang databases were searched for literature published up to April 30, 2026. Compliance was defined as completed prompts divided by delivered prompts. Single-group proportions were pooled using logit transformation and random-effects models with the Hartung-Knapp-Sidik-Jonkman adjustment. Prediction intervals were calculated to describe the expected distribution of compliance in future comparable settings. Subgroup analyses, univariable meta-regressions, leave-one-out sensitivity analyses, and tests for small-study effects were performed. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data, methodological reporting quality was assessed using a modified Checklist for Reporting EMA Studies, and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Twenty-three studies involving 13,565 participants were included. The pooled compliance rate was 78.55% (95% CI 73.48%-82.87%), with a prediction interval of 48.59%-93.41%. Subgroup analyses identified no robust differences across study characteristics. Although study length showed a statistically significant subgroup test, the result was not stable after excluding singleton categories. Meta-regression analyses similarly found no significant linear associations for study length, prompts per day, items per prompt, or assessment window. Leave-one-out analyses showed that no single study drove the pooled estimate. Regarding the risk of bias, 2 studies were judged as low, while 21 were judged as moderate risk. Quality scores ranged from 6.5 to 9.0, and the certainty of evidence for the pooled compliance rate was rated as very low according to the Grading of Recommendations Assessment, Development, and Evaluation approach. CONCLUSIONS: Overall compliance with EMA among patients with cancer was moderate to high, suggesting that repeated real-world assessment may be feasible in oncology research settings. Nevertheless, the very high heterogeneity, wide prediction interval, and very low certainty of evidence indicate that compliance is context-dependent. The pooled estimate should therefore be interpreted as an approximate benchmark rather than a universal expected rate. Future oncology EMA studies should use standardized compliance denominators, report missing prompts transparently, and prospectively evaluate patient-centered design strategies that reduce burden while preserving data quality.

Humans

Multimodal alignment improves generalizability of genomic biomarker prediction in computational pathology.

Computational pathology models that use digitized histopathology whole-slide images have the potential to become a cost-effective and scalable alternative to molecular assays for the prediction of genomic biomarkers, a key task in precision oncology. However, as new genomic biomarkers are discovered or quantified, large, labeled datasets must be prospectively collected to train new models. To address this challenge, we developed multimodal alignment for biomarker learning and generalization (MARBLE), a multimodal contrastive pretraining strategy that integrates structured biomarker knowledge into representation learning of histopathology images. MARBLE aligns histopathology-derived representations with representations of genomic biomarkers generated by a large language model (LLM) and a protein language model (PLM). This biologically informed alignment enables data-efficient generalization to novel, out-of-distribution biomarkers. Using the MSK-IMPACT cohort of over 40,000 patients across multiple biomarker panel versions, we design experiments grounded in real-world data to demonstrate the value of our proposed approach.

CP: computational biology

First Report of Fibromyxoma in a Greater Amberjack (Seriola dumerili) From Aquarium of Genoa.

In teleosts, mesenchymal tumours like fibromas are frequently observed, whereas their malignant counterparts, fibrosarcomas, occur only sporadically. In our study, an adult female greater amberjack (Seriola dumerili) reared at the Aquarium of Genoa developed a slow-growing mass protruding from the ventral right side of the head. The tissue was firm and white greyish with localized cranial haemorrhaging on the external surface. Cut-section examination showed a homogeneous, dry, whitish and richly vascularized tissue layout. Tissue samples from the mass were stained with Masson's Trichrome, Alcian Blue-PAS (pH&#x2009;2.5), and Toluidine blue for differential diagnosis. Microscopically, it was characterized by alternating collagenous spindle-cell septa and hypocellular metachromatic myxoid areas positive for acidic mucopolysaccharides and glycosaminoglycans. The absence of cellular atypia, mitotic activity and necrosis confirms the diagnosis of fibromyxoma. Documenting rare tumours in aquarium fish expands comparative pathology literature and highlights public aquaria as valuable research platforms for long-term health monitoring under controlled husbandry conditions.

fibromyxoma

Community-tailored One Health educational intervention to enhance knowledge and practices for zoonotic disease prevention in rural Thailand: A protocol for a prospective cluster randomised controlled Trial in Chanthaburi, Thailand (Saan Suk trial).

BACKGROUND: Zoonotic infectious disease risk arises at human-animal-environment interfaces where pathogen spillover can occur. Rural communities living in biodiverse settings may experience frequent contact with wildlife and shared environments through livelihoods, food practices, and economic activities. Reducing spillover risk and strengthening pandemic prevention requires both structural and individual-level change. Community-based interventions that promote awareness, risk perception, self-efficacy, pro-environmental behaviour, and safe coexistence with wildlife may support prevention by shifting behavioural determinants of zoonotic disease risk. The Saan Suk intervention was co-developed with rural communities in Thailand using a Human-Centred Design approach and is grounded in the Health Belief Model and One Health principles. The intervention is intended to be feasible, acceptable, and deliverable through Thailand's established Village Health Volunteer (VHV) system. METHODS: This protocol describes a parallel-arm, cluster-randomised controlled superiority trial that will be conducted during July - October 2026, in Chanthaburi Province, Thailand. 24 villages will be equally randomised to the Saan Suk intervention or the current practice (control). In intervention villages, trained VHVs will deliver, once a week over four weeks, a multimodal One Health educational intervention designed to improve knowledge of zoonotic spillover, promote protective behaviours, reduce risky wildlife-related contacts, and support respectful coexistence with wildlife. Trained outcome assessment teams will conduct structured interviews with 42 adult participants per village, yielding a total sample size of 1,008 participants. The sample size was calculated for the primary outcome, accounting for clustering, with 90% power to detect a medium effect size (6 points on the 0-100 knowledge scale) at a significance level of 0.05, accounting for a design effect with an ICC of 0.028. The primary outcome is knowledge of zoonotic spillover, transmission pathways, risk factors, protective and risky behaviours, and safe coexistence with wildlife. Secondary outcomes include attitudes, self-efficacy, preventive and risky behaviours, and reported contacts with major local reservoir hosts. A structured questionnaire was developed, expert-reviewed, and piloted for the outcome assessment. Outcomes will be analysed using mixed-effects regression models with random effects for village and adjustment for relevant pre-specified confounders. Primary analyses will follow the intention-to-treat principle. DISCUSSION: This trial will evaluate whether a co-designed, VHV-delivered One Health educational programme can improve knowledge of zoonotic disease prevention and behavioural determinants in rural communities living in close contact with wildlife and shared ecosystems. If effective and feasible, Saan Suk could inform integration into routine VHV training and community-based zoonotic disease and pandemic prevention strategies. TRIAL REGISTRATION: The Saan Suk trial is registered with the German Clinical Trials Register (DRKS). Registration ID: DRKS00038582; date of registration: 11 May 2026.

Zoonoses

Computational metabolomics at scale: from open data to insight.

Metabolomics data are currently generated at scale thanks to the evolution of technologies that have led to marked improvements in the number of metabolites detected, spanning all chemical classes. These data are increasingly submitted to public repositories for data reuse, integration, and interpretation. Despite the availability of public resources and associated computational tools, the field still lacks a widely adopted, consistent data and analytics infrastructure capable of transforming this wealth of information into scientific insight. Indeed, the metabolomics field is just now scratching the surface of being able to harness the power of new computational technologies. In this review, we summarize discussions from the "Dagstuhl-Seminar 24181 Computational Metabolomics: Towards Molecules, Models, and their Meaning" with a focus on public data availability, open data standards, data and knowledge integration, and education. Our goal is to raise awareness and adoption of the latest open science resources while highlighting key areas needing further development.

Metabolomics