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PubMed2026

Automated CEAP Classification of Venous Duplex Reports Using Multimodal Artificial Intelligence.

OBJECTIVE: To develop and internally validate a prototype multimodal artificial intelligence system for automated CEAP (Clinical, Etiological, Anatomical and Pathophysiological) classification of venous duplex ultrasound (VDUS) reports, integrating natural language processing of free-text components with computer vision analysis of hand-drawn anatomical diagrams. METHODS: Single centre retrospective observational study using routinely collected clinical data. One thousand consecutive venous duplex ultrasound reports from Cambridge University Hospitals NHS Foundation Trust, UK (July 2024 - May 2025) were labelled according to the CEAP classification, excluding the Etiological component, which could not be reliably determined from duplex reports alone. Transfer learning was applied using ClinicalBERT for text and MobileNetV3 for diagrammatic data. Clinical classes were predicted from request line text. Text- and image-based pathophysiological models were developed for four anatomical territories (Great Saphenous Vein, Small Saphenous Vein, Deep system, Perforators), combined using late fusion with probability averaging. RESULTS: The clinical CEAP model achieved accuracy of 0.91, macro-F1 of 0.82, and macro-AUC of 0.98. Pathophysiological prediction varied, with text models broadly outperforming image models. Fusion yielded heterogeneous benefits, improving SSV performance but reducing Deep system accuracy. The performance of the final pathophysiological CEAP fusion models varied across anatomical territories: accuracy ranged from 0.70-0.92 and macro-AUC from 0.80-0.92. CONCLUSION: This study demonstrates the feasibility of automated CEAP classification from VDUS reports. Despite class imbalance affecting minority class predictions, the strong discriminatory performance validates this multimodal ML model for extracting clinically meaningful information from real-world data. This approach offers potential, pending external validation, to streamline vascular services through automated triage and guideline-compliant decision making.

Artificial intelligence↗

PubMed2026

Late hiatal hernia after Roux-en-Y gastric bypass: a systematic review.

Obesity is a global public health issue. This condition is linked to gastroesophageal reflux disease (GERD) and hiatal hernia (HH), both of which are exacerbated by increased intra-abdominal pressure. Roux-en-Y gastric bypass (RYGB) is one of the most widely performed techniques for treating obesity and is considered a versatile option suitable for most patients. The development of a symptomatic HH and pouch migration can lead to various symptoms and complications. PubMed, EMBASE, and Cochrane Central were searched for studies with late HH after RYGB. We pooled outcomes for symptom resolution. Secondary outcomes were recurrence rate and operation characteristics (mesh use, cruroplasty, gastropexy, reoperation, length of stay, and operative time). A meta-analysis could not be conducted due to significant heterogeneity in HH. HH following RYGB presents with GERD (39-93.6%), obstructive symptoms (29%-88%), and abdominal pain (28.6%-71%). Diagnostic methods include endoscopy, computed tomography scans, and upper gastrointestinal series. Surgical management varies, with primary cruroplasty being the most common approach, sometimes incorporating mesh or fundoplication. Postoperative symptom resolution rates range from 42.9% to 100%, with HH recurrence occurring in 5%-6.54% of cases. Follow-up durations varied, showing improvement in most patients, though some continued to experience reflux and dysphagia HH contributes to obstructive and reflux symptoms, with contrast-enhanced imaging offering the highest diagnostic accuracy. Bioabsorbable mesh may reduce recurrence, highlighting the need for long-term monitoring.

Humans↗

PubMed2026

Operationalizing Local Ecological Knowledge for Aquatic Biodiversity Conservation: A Systematic Review and Management Framework.

Effective conservation and management of aquatic biodiversity is severely constrained by the absence of long-term ecological data in small-scale, tropical, and data-poor fisheries, where roughly one-quarter to one-third of freshwater fish species and 37.5% of elasmobranchs are threatened with extinction once Data Deficient species are accounted for. Conventional monitoring and stock-assessment tools are often financially and technically inaccessible in these systems, leaving managers without the evidence needed to prioritize conservation action or implement precautionary governance. Local Ecological Knowledge (LEK) is a largely underutilized resource for natural resource management that can provide temporal depth, spatial resolution, and species-specific ecological insights unavailable from scientific records. We conducted a systematic review and bibliometric synthesis of 60 peer-reviewed studies (1997-2025) applying LEK to assess fish conservation status, examining how, where, and through what methods this knowledge has been used. Our analysis identifies four complementary pathways through which LEK informs conservation management: reconstructing multi-decadal population changes, documenting spatial contraction and habitat loss, detecting extreme rarity and local extirpation, and characterizing intrinsic sensitivity to exploitation based on life-history traits. Despite growing methodological rigor, freshwater systems and African fisheries remain critically underrepresented, and formal integration of LEK into fisheries governance and biodiversity assessment remains the exception rather than the rule. We propose a practical three-stage framework to operationalize LEK within existing management and conservation systems. Recognizing fishing communities as legitimate co-producers of ecological knowledge is both scientifically necessary and an equity imperative for achieving global biodiversity commitments under the Kunming-Montreal Global Biodiversity Framework.

Biodiversity↗

PubMed2026

A chromosomal gtrB homolog and dam differentially contribute to dry-heat and high hydrostatic pressure resistance in Salmonella enterica.

Salmonella enterica can persist in low-moisture foods and shows enhanced dry-heat resistance under low water activity, posing significant food safety challenges. However, the genetic basis of extreme dry-heat resistance and its relationship with other processing stresses remain unclear. In this study, twelve S. enterica strains were screened for dry-heat treatment at 60 °C and 80 °C, with S. Infantis CICC21649 identified as the most resistant strain. Comparative genomics and transcriptional analysis identified candidate genes related to envelope integrity and regulation, including gtrB and dam. Deletion of the chromosomal gtrB homolog reduced dry-heat resistance, producing an additional 0.91-log10 reduction relative to the parent strain at 80 °C. Deletion of dam caused broader stress sensitivity, reducing resistance to both dry heat and high hydrostatic pressure, with the stronger phenotype observed under high hydrostatic pressure. Proteomic analysis of the chromosomal gtrB homolog mutant revealed broad alterations in envelope-associated proteins, transport functions, oxidative stress pathways, and central metabolism under dry-heat stress. These findings indicate that the chromosomal gtrB homolog is an important contributor to extreme dry-heat resistance, whereas dam contributes to resistance against both dry-heat and high hydrostatic pressure, likely through a broader regulatory role in stress adaptation. These results reveal distinct structural and regulatory layers underlying stress adaptation in S. enterica and provide practical guidance for low-moisture food processing by highlighting the need to account for strain-dependent and stress-specific resistance during process validation.

Hydrostatic Pressure↗

PubMed2026

Sodium Glucose Co-Transporter 2 Inhibitors and Ventricular Arrhythmias in Patients with Type 2 Diabetes: A Systematic Review of Observational Studies.

BACKGROUND: Sodium glucose co-transporter 2 inhibitors (SGLT2i) may exert antiarrhythmic effects, but their association with ventricular arrhythmias remains unclear. OBJECTIVE: We conducted a systematic review to evaluate the association between SGLT2i use and the risk of ventricular arrhythmias, cardiac arrest, and sudden cardiac death compared with other antidiabetic medications or no SGLT2i use among patients with type 2 diabetes mellitus. METHODS: MEDLINE, EMBASE, and CENTRAL were searched for observational studies published between March 2013 and March 2026. Quality was assessed using the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool, alongside evaluation of pharmacoepidemiology-specific biases. RESULTS: A total of 17 studies (16 cohort and one nested case-control) were included. Based on ROBINS-I, seven studies had moderate, eight serious, and two critical risks of bias. Eleven studies had at least one pharmacoepidemiology-specific bias. For ventricular arrhythmias, estimates ranged from a protective effect (hazard ratio [HR] 0.20, 95% confidence interval [CI] 0.04-0.97) to a potential increased risk (odds ratio 1.87, 95% CI 0.89-3.95) with SGLT2i use. For cardiac arrest, estimates consistently reported a lower risk with estimates that ranged from HR 0.63 (95% CI 0.59-0.68) to HR 0.85 (95% CI 0.82-0.88). The only study on sudden cardiac death reported a potential risk reduction (HR 0.62, 95% CI 0.38-1.01). CONCLUSIONS: While the association between SGLT2i and ventricular arrhythmias remains inconsistent, the use of SGLT2i likely reduces cardiac arrest and may reduce sudden cardiac death, suggesting a possible protective effect on ventricular arrhythmias among patients with type 2 diabetes.

Journal Article↗

PubMed2026

Effectiveness of different anaesthetic techniques, agents and adjunctive interventions in handling pain during dental treatment of MIH-affected teeth: a systematic review.

BACKGROUND: Molar incisor hypomineralisation (MIH) is frequently associated with hypersensitivity, dental anxiety and reduced efficacy of local anaesthesia, complicating pain control during dental treatment in children. AIM: To evaluate, based exclusively on randomised controlled trials (RCTs), the effectiveness of different local anaesthetic techniques, agents and adjunctive interventions in reducing pain during dental treatment of MIH-affected teeth in children. METHODS: A systematic review was conducted following PRISMA 2020 guidelines and registered in PROSPERO (CRD420251150485). MEDLINE, Cochrane Central, ScienceDirect, SCOPUS, EBSCO, and LILACS were searched up to September 2025. Eligible studies were RCTs involving children and adolescents (6 - 18 years-of-age) with MIH, assessing pain outcomes during dental procedures. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE approach. RESULTS: Eight RCTs were included. Low-certainty evidence suggested that intraosseous anaesthesia and 4% articaine may reduce intra-operative pain compared with conventional techniques or 2% lidocaine. Adjunctive cryotherapy and pre-emptive ibuprofen showed potential benefits, but evidence was of very low certainty and limited to single trials. Findings for photobiomodulation were inconsistent across studies. Most trials were judged to be at high risk of bias, primarily due to lack of blinding and reliance on subjective pain outcomes. CONCLUSION: Current evidence supporting specific pain management strategies for MIH-affected teeth is limited and of low certainty. Whilst 4% articaine and intraosseous anaesthesia appear promising, well-designed, adequately powered RCTs with standardised pain outcomes are required to inform robust clinical recommendations.

Local anaesthesia↗

PubMed2026

Positive Margin Rate Following Transoral Surgery in T2-T3 Laryngeal Carcinoma - a Systematic Review and Meta-Analysis.

BACKGROUND: Transoral endoscopic surgery, using either conventional laser techniques or supported by robotic assistance, represents an established treatment modality for selected patients with T2-T3 laryngeal carcinoma. The goal is complete tumor removal, as positive resection margins have been associated with worse oncological outcomes. This systematic review and meta-analysis aimed to determine the positive margin rate following transoral endoscopic surgery for T2-T3 laryngeal carcinoma and to evaluate its impact on oncologic outcomes. METHODS: A systematic search of Medline, Embase, Web of Science, Cochrane CENTRAL, and Google Scholar was performed from inception through March 2025, identifying studies reporting on surgical margin status after transoral resection of T2 and/or T3 laryngeal carcinoma. A random-effects meta-analysis of proportions was used to estimate a pooled positive margin rate. The oncologic impact of margin status is presented descriptively owing to data heterogeneity. RESULTS: Thirty-nine studies comprising 3,281 patients with T2-T3 laryngeal carcinoma met the inclusion criteria. The positive margin rate was 22.0% (95% CI 17.6 - 27.3, I2 = 83.8%) for the total T2-T3 cohort, with stratified rates of 22.4% for T2 and 30.8% for T3 tumors. Among the eight studies assessing the impact of positive margins in T2-T3 stages, three found a significant association with worse oncological outcomes. Conclusion A 22% positive margin rate was identified in T2-T3 laryngeal cancer treated with transoral endoscopic resection. However, the impact of margin status on oncological outcomes remains uncertain, largely due to challenges in sampling and histopathological assessment.

Humans↗

PubMed2026

The genomic origins and evolutionary path to a key innovation in the world's most venomous snakes.

Evolutionary innovation is a catalyst for the colonization of new environments and the adaptive radiations of major groups. Novel traits typically evolve through the modification of preexisting characters, but the genetic paths underlying their origin have been challenging to trace, and the general requirements for and relative order of different kinds of gene mutations have been difficult to assess. Here, we trace the genomic origins of four procoagulant venom toxins (factor X, factor V, group I phospholipase A2, and Kunitz-type toxins) that collectively underlie a novel, especially potent blood-clotting venom type in the recently evolved Australian brown snake and taipan clade. We find evidence for a previously unknown fifth toxin, coagulation factor VII, and show that the toxins evolved through two distinct genetic paths. The factor X and factor V toxins evolved through the sequential de novo co-option of ancestral clotting factor proteins that entailed their heterotopic expression in the venom gland, the fixation of segmental duplications containing each locus, and subsequent gain-of-function mutations that rendered factor X and factor V constitutively active. In contrast, the phospholipase A2 and Kunitz-type toxins evolved by modifying the functions of neurotoxins that were part of the venom arsenal. Our findings support models in which innovative mutations in single-copy genes precede gene duplication in the evolution of novel proteins and offer a rare view into the genesis of a complex trait that has played a central role in a major adaptive radiation.

Animals↗

PubMed2026

Gastric carcinoma classification in the WHO 6th edition (2026): Updated framework and emerging entities.

The sixth edition of the WHO Classification of Digestive System Tumours (2026) represents an important step in the continuing evolution of gastric carcinoma classification. While preserving morphology as the foundation of diagnosis, it incorporates advances in molecular pathology, genotype-phenotype correlations, tumour evolution, and predictive biomarker assessment. This review summarizes the development of the WHO classification from the third edition (2000) to the sixth edition (2026) and highlights its relationship with other major classification systems, including those of Laurén, Nakamura, and the Japanese Gastric Carcinoma Association (JGCA). Major histological categories remain largely unchanged; however, several important conceptual and diagnostic refinements have been introduced. These include recognition of crawling-type adenocarcinoma as a distinctive variant of tubular adenocarcinoma, subclassification of poorly cohesive carcinoma into signet-ring cell and non-signet-ring cell subtypes, introduction of the concept of pure signet-ring cell carcinoma, and increased emphasis on tumour evolution. The sixth edition also expands and refines the spectrum of uncommon gastric carcinoma subtypes, including gastric carcinoma with lymphoid stroma, AFP-producing carcinoma, micropapillary adenocarcinoma, gastric adenocarcinoma of fundic-gland type, and gastric sarcomatoid carcinoma. Crucially, molecular subgroups originally proposed by The Cancer Genome Atlas (TCGA) and actionable biomarkers-including HER2 (ERBB2), Claudin 18.2, mismatch repair deficiency/microsatellite instability (dMMR/MSI), and programmed death-ligand 1 (PD-L1)-have transitioned from research-based categories into essential tools for precision oncology. Rather than providing exhaustive diagnostic criteria, this review offers a conceptual framework and encourages consultation of the original WHO text for full details. These advances illustrate the transition of gastric carcinoma classification from a predominantly morphology-based system toward an integrated histomolecular framework that more closely links pathological diagnosis with tumour biology, prognostication, and therapeutic stratification.

Crawling-type adenocarcinoma↗

PubMed2026

Post-Breakup Instagram Surveillance: Attachment Style, Personality Traits, and Breakup Distress as Predictors.

The end of a romantic relationship is one of the most emotionally challenging life events. Social media platforms such as Instagram enable users to monitor an ex-partner, a behavior known as Interpersonal Electronic Surveillance (IES), which may complicate coping. This study examined associations with retrospectively reported IES on Instagram during the first 3 weeks post-breakup, focusing on attachment, personality, and breakup-related emotional distress. Previous studies suggest that higher anxious attachment and emotional distress are related to increased monitoring behaviors on Facebook. The present research extends this approach to Instagram, a popular platform among Generation Z, and additionally examines personality factors. Data from N = 232 participants (aged 18-27 years; 84 percent women), who had experienced a breakup within the past year and followed their ex-partner on Instagram, were collected using a cross-sectional online questionnaire. The survey included standardized measures and self-constructed items. Hierarchical regression analyses including breakup-related variables, mediation analyses, and independent-samples t-tests were conducted. Due to extremely low internal consistency, Agreeableness was excluded from inferential analyses. The analyses indicated that Extraversion was the only personality trait directly associated with increased IES. Attachment styles showed no direct associations after emotional distress was included in the model. Emotional distress emerged as the most consistent factor associated with IES, showing patterns consistent with indirect associations involving Neuroticism and anxious attachment, suggesting a central role of emotional distress in post-breakup surveillance behavior. These findings highlight digital monitoring as a potentially maladaptive coping strategy and underscore the importance of addressing social media use in post-breakup adjustment.

Humans↗

PubMed2026

Determinants of private health insurance uptake and its association with healthcare utilization in Gulf Cooperation Council countries: a systematic review.

All Gulf Cooperation Council (GCC) countries have a multi-payer healthcare system that comprises governmental health coverage (GHC), funded by the government, and private health insurance (PHI), mainly sponsored by employers and purchased by individuals. Both are expected to influence healthcare utilization and contribute to system efficiency and patient well-being. This systematic review explored the determinants of PHI uptake and its association with healthcare service utilization in the presence of GHC in GCC countries. We systematically searched CINAHL, PubMed, Scopus, Web of Science, and Cochrane Library for peer-reviewed studies published between January 2012 and October 2022. Study quality was assessed using the Critical Appraisal Skills Programme (CASP) checklists for both quantitative and qualitative studies, following PRISMA guidelines. Twenty-six studies met the inclusion criteria. Determinants of PHI uptake were mapped to Andersen's Behavioral Model of Health Services Use (BMHSU) and categorized into (1) predisposing factors (sex, age, marital status, and education), (2) enabling factors (employment/income and health system-related factors such as access and perceived service quality), and (3) need factors (health status, including chronic noncommunicable diseases). PHI uptake was positively associated with being male, married, highly educated, employed with a high income, and having chronic diseases. PHI was positively associated with healthcare utilization, particularly routine check-ups, preventive services, and the use of prescribed medicines. In GCC countries, PHI uptake is influenced by sociodemographic and socioeconomic characteristics, health status, and perceived service quality. PHI is also associated with higher healthcare utilization, underlining the need for evidence-informed policies that enhance equity and expand coverage.

Humans↗

PubMed2026

Gelified ethanol for percutaneous sclerotherapy of bone lesions: a systematic review of clinical applications and outcomes.

PURPOSE: To systematically review the available evidence on the feasibility, safety, and clinical effectiveness of percutaneous sclerotherapy using radiopaque gelified ethanol (RGE, Discogel®) for bone lesions. METHODS: A systematic search of MEDLINE, Embase, Web of Science, and Cochrane CENTRAL was performed. Primary studies reporting clinical, technical, and safety outcomes following RGE sclerotherapy for bone lesions were included. Data on patient characteristics, lesion type, procedural details, and outcomes were extracted and synthesized descriptively. RESULTS: Six retrospective studies involving 55 patients (mean age 22.2 ± 20.4 years; range 3-65; 26 females) with 56 lesions and 119 procedures were included (mean 2.16 procedures per patient). Aneurysmal bone cysts (80%) and aggressive vertebral hemangiomas (18%) were the main indications. Technical success was reported in 100% of procedures. Pain outcomes were available for 28 patients, with complete resolution in 64.3% (18/28), partial reduction in 32.1% (9/28), and persistence in 3.6% (1/28). Radiological follow-up (50 lesions) demonstrated complete response in 96% and partial response in 4%. No major adverse events were reported according to CIRSE (≥ 4) or CTCAE (≥ 4) criteria. One SIR grade 3 vertebral fracture occurred without confirmed causal association to RGE. Subsequent surgery was required in 3.6% of lesions. CONCLUSION: Although limited to small retrospective series, current evidence suggests that RGE sclerotherapy is a safe and effective minimally invasive option for selected benign bone lesions. Prospective comparative studies with longer follow-up are warranted.

Humans↗

PubMed2026

Leading with Innovation: Maternal Health Transformation in New York City Health + Hospitals.

New York City's (NYC) maternal health crisis drew close attention in the late 2010s, driven by alarming data: Approximately 30 women died annually during childbirth in NYC, Black non-Hispanic women were 12 times more likely to die than white women, and more than 3,000 women experienced life-threatening birth complications each year. In response, NYC committed $12.8 million in July 2018 to reduce maternal mortality and eliminate racial disparities.NYC Health + Hospitals (H+H)-the nation's largest public health system, serving 1.1 million patients annually with roughly 15,000 births per year-became the primary vehicle for this initiative. With 80 percent of the system's deliveries covered by Medicaid and a patient population that is 51.2 percent Hispanic and 27.1 percent Black, H+H is uniquely positioned to lead the fight against maternal health inequity.Three flagship programs anchor H+H's response to the city's maternal mortality rate. The OB Simulation Program, launched in 2012 and expanded in 2018, was the first in the nation to use mannequins of color to train thousands of providers in obstetric emergencies. The Maternal Home Program, piloted at H+H's Kings County Hospital in 2019 and scaled system-wide by 2021, has served more than 10,341 patients, generating more than 33,000 referrals for social, behavioral health, and community resources. The Cardio-Obstetrics Program located at Kings County Hospital targets cardiovascular disease-the leading cause of maternal death among Black women-through screening, education, and community outreach. These programs are a health equity imperative, made more urgent by impending federal Medicaid cuts resulting from the H.R.1 One Big Beautiful Bill Act (passed on July 4, 2025).

Humans↗

PubMed2026

Beyond Glycaemia: Fear of Hypoglycaemia, Cognition and Functional Mobility After Advanced Hybrid Closed-Loop Therapy in Older Adults With Type 1 Diabetes: A Prespecified Secondary Analysis of a Randomised, Single-Centre Study.

BACKGROUND: Evidence on psychological, cognitive and functional outcomes of advanced diabetes technologies in older adults with long-standing type 1 diabetes (T1D) remains limited. We evaluated whether initiation of advanced hybrid closed-loop (AHCL) therapy was associated with changes in fear of hypoglycaemia, diabetes distress, psychological well-being, cognition, frailty-related measures and mobility-related function in adults aged ≥ 65 years with T1D. METHODS: This prespecified, exploratory secondary analysis was conducted within a single-centre, open-label, randomised, controlled, parallel-group trial including adults aged ≥ 65 years with long-standing T1D. Participants were randomly assigned (1:1) to initiate AHCL therapy using the MiniMed 780G system or to continue standard diabetes treatment. The secondary outcomes included WHO-5, the 17-item Diabetes Distress Scale (DDS), Hypoglycemia Fear Survey-II (HFS-II), Montreal Cognitive Assessment, Digit Symbol Substitution Test, Fried frailty phenotype and performance-based functional measures. No formal sample-size calculation was performed for these secondary outcomes. RESULTS: Thirty-one participants were randomised and 29 completed 12 months of follow-up and were included in the treatment-effect analyses. In the baseline-adjusted primary analysis, AHCL therapy was associated with a lower HFS-II score than standard treatment (adjusted mean difference -18.9; 95% CI: -32.4 to -5.4; nominal p = 0.008), although this finding did not remain statistically significant after Holm correction (adjusted p = 0.104) or in an exploratory model additionally adjusted for sex (difference -13.6; 95% CI: -32.2 to 5.0; p = 0.145). Diabetes distress, psychological well-being, global cognition and processing speed did not differ between groups. In sex-adjusted sensitivity analyses, the between-group differences remained statistically significant for 6-min walk distance (92.6 m; 95% CI: 36.8 to 148.3; p = 0.002) and Timed Up and Go performance (-2.27 s; 95% CI: -4.28 to -0.27; p = 0.028), but not for gait speed (0.27 m/s; 95% CI: -0.05 to 0.59; p = 0.099). At 12 months, 12 of 14 AHCL participants were robust and 2 were pre-frail; in the control group, 11 of 15 were robust and 4 were pre-frail. No participant was classified as frail at follow-up. CONCLUSIONS: In this small, selected cohort, AHCL therapy was associated with a nominally lower fear-of-hypoglycaemia score and better performance on selected mobility-related tests over 12 months. The fear-of-hypoglycaemia finding did not remain statistically significant after correction for multiple comparisons or additional adjustment for sex. Six-minute walk distance and Timed Up and Go remained statistically significant in the exploratory sex-adjusted sensitivity analyses, whereas the gait-speed difference did not. No measurable between-group deterioration in global cognition or processing speed was observed. These exploratory findings require confirmation in larger studies with balanced representation by sex and direct measurement of physical activity. These findings also support a person-centred clinical message: older age alone should not be regarded as a barrier to AHCL when treatment is introduced with individualised education and appropriate ongoing support.

Humans↗

PubMed2026

Symptom Networks and Core Symptoms in Patients with Solid Tumors Undergoing Chemotherapy: A Systematic Review.

OBJECTIVES: To summarize symptom network characteristics in patients with solid tumors undergoing chemotherapy and synthesize evidence on core symptoms, bridge symptoms, and temporal associations. METHODS: We systematically searched eight databases through October 2025 to identify studies that applied symptom network analysis to adults with solid tumors receiving chemotherapy. Eligible studies assessed symptoms using cross-sectional, longitudinal, or interventional designs. Two reviewers independently screened articles and extracted data on study characteristics, symptom assessment, and network outcomes. Methodological quality was assessed using the National Institutes of Health Study Quality Assessment Tool. RESULTS: Twenty-seven studies involving 13,452 participants were included, yielding 79 symptom networks. Fatigue was the most frequently identified core symptom (10/20, 50%), whereas sadness, lack of appetite, and nausea each occurred in 10% of studies, with variation across cancer types, treatment phases, and latent classes. Bridge symptoms included disturbed sleep, lack of appetite, and dry mouth (2/7, 28.6%). Studies evaluating temporal associations found that symptoms such as sadness, dyspnea, somnolence, and dry mouth predicted subsequent changes in appetite, distress, nausea, and other outcomes. Strength metrics showed acceptable stability (correlation stability coefficients: 0.28-0.83). CONCLUSIONS: Fatigue was frequently identified as a central symptom across studies, largely reflecting evidence from breast cancer studies. Core symptoms varied across cancer types, treatment phases, and latent classes, suggesting heterogeneity. IMPLICATIONS FOR NURSING PRACTICE: These findings highlight the importance of considering relationships among symptoms in clinical care. Focusing on key symptoms such as fatigue, while tailoring management strategies to cancer-specific symptom patterns, may support more effective symptom management.

Humans↗

PubMed2026

Active Site Assembly by SMG5 as a Mechanism for SMG6 Endonuclease Licencing in Nonsense-mediated mRNA Decay.

Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic surveillance pathway that eliminates transcripts containing premature termination codons (PTCs). Substantial progress has been made in defining the transcript features that mark aberrant translation termination for NMD activation, yet key mechanistic steps remain incompletely understood - including how recruitment of the central NMD factor UPF1 is coupled to the downstream effector phase in which targeted mRNAs are nucleolytically degraded. In metazoans, NMD employs an endonucleolytic route mediated by SMG6, a PIN-domain nuclease, alongside SMG5 and SMG7, which act downstream of PTC recognition. SMG5 has recently been proposed to licence SMG6 activity, yet the molecular basis of this licencing has remained elusive. Here, we combine AlphaFold structural predictions with biochemical assays to investigate interactions among human SMG5, SMG6, and SMG7. Structural models predict a high-confidence interface between SMG5 and SMG6 PIN domains that forms a composite active site: a conserved SMG5 aspartate (D893) complements the SMG6 acidic triad to reinstate the canonical tetrad required for PIN-domain catalysis. In vitro, SMG6 alone exhibits weak endonucleolytic activity, which is enhanced ∼10-fold by the SMG5 PIN domain. Mutational analyses confirm that conserved residues from both proteins are essential for this composite configuration. Our findings reveal that the SMG5 PIN domain, previously considered catalytically inert, plays a critical role in activating SMG6 by completing its active site. This work provides mechanistic insight into the SMG5-dependent licencing step and uncovers a composite PIN nuclease architecture at the heart of the metazoan NMD effector phase.

Nonsense Mediated mRNA Decay↗

PubMed2026

Optimizing focal vibration therapy for balance and gait: A systematic review.

OBJECTIVE: This systematic review evaluated the efficacy of focal (localized) vibration therapy (FVT) applied to muscles/tendons on balance, gait, and mobility, with a specific focus on defining optimal vibration protocols (frequency, amplitude, dosing) and muscle-targeting strategies to maximize sensorimotor recovery. METHODS: A systematic review was conducted across six databases (CINHAL, Embase, Medline, Web of Science, Scopus, CENTRAL) from January 2000 to May 2025. Studies were included if they involved human participants, applied FVT therapeutically, and reported balance, gait, or mobility outcomes. Data extraction included study characteristics, intervention protocols, and outcomes. Methodological quality was assessed using the PEDro scale. RESULTS: Sixty-two studies (n = 2090 participants) were included. Methodological quality assessment (PEDro scale) indicated 44% of studies met high-quality standards. Biomechanical analysis identified the quadriceps, gastrocnemius/soleus, and plantar muscles as the most effective vibration sites, given their critical roles in gait propulsion and postural stability. The synthesis of protocol data indicated a promising therapeutic window characterized by a vibration frequency of 80-120 Hz (primarily fixed sinusoidal waveforms at a single frequency) and an amplitude of 0.2-0.5 mm (reported only in 12 studies; amplitude was not reported in 23 studies), applied bilaterally for a minimum of 3 sessions per week over 4-12 weeks, which could lead to improved balance and gait performance with benefits sustained for up to 5 months. CONCLUSION: FVT shows potential to improve gait and balance, particularly when targeting lower-extremity muscles with optimized vibration parameters. To advance the field, future research must prioritize the development of standardized protocols and investigate neurophysiological mechanisms to refine FVT as a precision bioengineering solution for mobility deficits.

Humans↗

PubMed2026

Macroprolactinemia as a diagnostic pitfall in hyperprolactinemia: a systematic review and quantitative synthesis.

CONTEXT: Macroprolactinemia is a well-recognized cause of hyperprolactinemia and an important diagnostic pitfall in endocrine practice. However, interpretation of published quantitative prolactin data remains sparse as studies vary in confirmation method, assay platform, polyethylene glycol (PEG) recovery cutoff, and reporting of prolactin measurement. EVIDENCE ACQUISITION: PubMed, Embase, Scopus, Web of Science, the Cochrane Library, and Google Scholar were systematically searched. Eligible studies reported macroprolactinemia-specific quantitative prolactin data in patients with confirmed macroprolactinemia defined by PEG precipitation, gel filtration chromatography (GFC), or both. Two reviewers independently performed study selection, data extraction, and quality assessment. Findings were summarized using study-level descriptive synthesis. The review was prospectively registered in PROSPERO and conducted in accordance with PRISMA 2020 guidelines. EVIDENCE SYNTHESIS: Forty-five studies encompassing 2853 macroprolactinemia cases from 21 413 screened patients with hyperprolactinemia across 22 countries were included. Among 33 studies eligible for primary quantitative analysis, the median study-level central total prolactin attributed to macroprolactinemia was 61.4 ng/mL ([IQR] 42.0-80.0; range 28.1-137.6), and the median study-level post-PEG monomeric prolactin was 11.7 ng/mL (IQR 8.3-13.2; range 4.0-17.0)). The median study-level maximum total prolactin was 264.5 ng/mL (IQR 97.0-425.5; range 81.8-663.0); extreme elevations were attributable to coexisting prolactinomas. CONCLUSION: In confirmed macroprolactinemia, total prolactin elevation is typically moderate, and post-PEG monomeric prolactin is usually within or near the normal range. The post-PEG monomeric prolactin value, rather than percent recovery alone, is the most informative parameter for distinguishing isolated macroprolactinemia from coexisting true hyperprolactinemia. These quantitative benchmarks may help clinicians to avoid unnecessary investigation or treatment.

Humans↗