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PubMed2026

From population to individual: advocating personalised digital tools for heat-health early warning in a changing climate.

Escalating heat extremes under climate change are imposing substantial health burdens, with 2023 and 2024 consecutively breaking global temperature records. Mounting evidence suggests that heatwaves elevate the risks of hospitalisation and mortality across multiple disease categories, including ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and acute kidney injury. Nonetheless, most existing heat-health warning systems remain primarily reliant on population-level predictions, and considering individual differences and disease-specific considerations when defining warning levels would benefit the effectiveness of early prevention for high-risk groups. In this Viewpoint, which is based on the framework of precision public health-delivering the right intervention to the right population at the right time-we propose a framework for personalised digital heat-health early warning tools comprising three dimensions: individualised, risk-stratified prediction models that generate tiered early warnings; personalised health prompts coupled with theory-informed behavioural interventions; and adaptive, equity-oriented alert delivery mechanisms tailored to diverse populations. Such tools have the potential to bridge precision disease prevention and climate adaptation, thereby helping to mitigate heat exposure risks and disease burdens, particularly among high-risk populations. Future implementation research will be essential to address substantial challenges related to feasibility, validation, and equity.

Journal Article↗

PubMed2026

Efficacy and Safety of Ultra-Low Starting Dose Febuxostat Titration in Male Patients With Primary Gout.

BACKGROUND: Since gout is a common metabolic arthritis caused by urate crystal deposition, urate-lowering therapy (ULT) is clearly indicated, but the initiation of ULT frequently causes paradoxical acute flares that in turn impair patient adherence. OBJECTIVE: This study sought to assess the effectiveness and safety of an ultra-low-dose initiation strategy for febuxostat (10 mg/day) compared to the standard starting dose (20 mg/day) in reducing initiation-related flares while maintaining long-term urate control. METHODS: 120 male patients with primary gout presenting with acute arthritis were randomly assigned to initiate febuxostat at 10 mg/day (Group A) or 20 mg/day (Group B), with protocol-mandated biweekly titration. The primary outcomes were gout flare frequency over 24 weeks (assessed using Poisson regression), serum uric acid (SUA) target attainment, and the incidence of adverse events. RESULTS: Although both groups achieved comparable target SUA levels by week 24, Group A demonstrated a significantly lower overall flare incidence (36.7% vs. 70.0%; p < 0.001), along with a greater percentage of flare-free patients (70.0% vs. 46.7%; p = 0.016). Multivariable Poisson regression revealed that Group B had an approximately twofold higher risk of flares compared to Group A (Incidence Rate Ratio = 1.95; p = 0.012), with obese patients deriving the most pronounced benefit from the ultra-low-dose approach. To avert one additional flare, the calculated number needed to treat was 4.3. Additionally, the occurrence of clinically significant liver injury (ALT/AST > 3× ULN) was low in both groups, with 3.3% in Group A and 1.7% in Group B. Multivariable regression analysis confirmed that LDL-C is an independent predictor of ALT (β = 12.90, p = 0.009), while febuxostat dosage was not linked to hepatotoxicity. CONCLUSION: Initiating febuxostat at a dose of 10 mg/day with gradual titration demonstrates a superior safety profile by effectively reducing early acute flares without compromising long-term urate control, which is particularly advantageous for high-risk cohorts, including obese patients.

Humans↗

PubMed2026

Low-salinity stress alters growth, histology, physiology, and transcriptomic profiles of the gills and antennal glands in Macrobrachium rosenbergii.

Salinity is a major abiotic constraint in freshwater aquaculture of the giant freshwater prawn Macrobrachium rosenbergii, yet the coordinated roles of the gills and antennal glands, the two primary osmoregulatory organs in decapod crustaceans, under low-salinity stress remain poorly characterized. Here, we integrated histological, physiological, and transcriptomic analyses to characterize the adaptive responses of M. rosenbergii to acute (96 h) and chronic (8 weeks) exposure to salinity 5. Chronic low-salinity stress significantly impaired growth performance and decreased the survival rate. Acute stress induced thinning of the gill filaments, partial disorganization of pillar cells, and dilation of the intermicrovillar space in the antennal glands, whereas chronic stress caused gill vacuolization, cuticle thinning, and adaptive folding of antennal gland microvilli. In parallel, acute exposure significantly decreased hemolymph sodium and potassium ion concentrations but increased magnesium ion concentration, whereas chronic exposure increased hemolymph sodium and potassium ion concentrations, upregulated gill Na+/K+-ATPase activity, and enhanced hepatopancreatic antioxidant capacity. Transcriptomic analyses revealed distinct tissue-specific responses. Under acute stress, the gills preferentially activated pathways associated with cytoskeletal remodeling, motor proteins, and tight junctions, whereas chronic acclimation shifted the transcriptional response toward the renin-angiotensin system and glutathione metabolism. In the antennal glands, acute stress rapidly activated the renin secretion pathway, whereas chronic exposure promoted membrane remodeling by enriching pathways related to lipid and glycan metabolism. These findings reveal tissue-specific functional differentiation and synergistic coordination between the gills and antennal glands that underpin M. rosenbergii's adaptive response to low-salinity stress.

Animals↗

PubMed2026

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 ≥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 ≥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 10·0 months (IQR 4·6-17·2); median follow-up for progression-free survival was 11·0 months (IQR 4·8-18·4) for STRIDE plus lenvatinib plus TACE and 8·3 months (4·1-15·5) for TACE. Median progression-free survival was 13·0 months (95% CI 12·2-16·7) for STRIDE plus lenvatinib plus TACE versus 9·8 months (8·0-11·4) for TACE (HR 0·70 [95% CI 0·57-0·86]; p=0·0007). At the second data cutoff (Feb 23, 2026) and a median follow-up for overall survival of 24·6 months (IQR 16·5-31·5) for STRIDE plus lenvatinib plus TACE and 22·9 months (14·9-30·2) for TACE, median overall survival was 39·5 months (95% CI 34·1-not reached) for STRIDE plus lenvatinib plus TACE and 34·7 months (28·8-not reached) for TACE (HR 0·84 [95% CI 0·65-1·09]; p=0·18). At this data cutoff, median progression-free survival was 12·9 months (95% CI 10·2-15·9) for STRIDE plus TACE and 8·1 months (6·5-10·2) for the first 175 participants randomised to TACE (HR 0·71 [95% CI 0·56-0·91]), with median follow-up of 10·3 months (IQR 4·6-23·7) for STRIDE plus TACE and 7·7 months (3·0-18·5) 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↗

PubMed2026

Improved comprehensive profiling of fecal bile acids through chemical derivatization combined with HPLC-MS/MS analysis.

Bile acids (BAs) facilitate the digestion and absorption of fats and influence lipid and glucose homeostasis, making them potential therapeutic targets for obesity and related metabolic disorders. The liver and intestinal microbiota modify BAs structurally, generating diverse chemical forms and isomers. Comprehensive profiling of the BA pool is critical for understanding their key biological functions and as a therapeutic approach for related diseases. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) is usually chosen as the preferred method for BA detection due to the complex chemical structures, the wide range of actual concentrations and the complexity of fecal sample matrices. However, free BAs are difficult to ionize, resulting in low detection signals and a lack of characteristic structural fragments to assist in structural identification. In this method, the labeling reagent (2-aminoethyl) trimethylammonium (AETMA) is employed to label the carboxyl group of BAs. Compared with underivatized BAs, the detection sensitivity of unconjugated BAs was enhanced by 25-180 fold, while that of conjugated BAs increased by 6-160 fold. It also generates unique fragment ions and enhances MS response, facilitating the discovery of potential BAs. Methodological parameters were validated using 38 BAs as representatives. Through methodological validation, it was verified that the precision, recovery, matrix effect and stability parameters of the method met acceptable criteria. We also identified 61 confirmed BAs and 55 additional candidate BAs in human pooled fecal samples. It has been successfully applied to fecal BA analysis in obese populations, providing valuable insights into potential therapeutic strategies for obesity.

Tandem Mass Spectrometry↗

PubMed2026

Does high fructose consumption trigger microglia activation and neuroinflammation? A systematic review.

This systematic review evaluated the effects of fructose intake on neuroinflammatory markers in rodent models. The search terms Fructose AND neuroinflammation OR Neurodegeneration OR chemokines OR interleukins OR microglia OR behaviour OR memory OR cognition were used in Google Scholar, Scopus and Web of Science. Thirteen animal studies investigating fructose-induced neuroinflammation that matched the eligibility criteria were included in the study. Across the studies, 16 inflammatory markers were identified and significantly altered following exposure to fructose. The findings consistently demonstrated elevated expression of pro-inflammatory cytokines, TNF-α, IL-6, and IL-1β, following fructose administration. Fructose consumption also dysregulated MCP-1, fractalkine, and CX3CR1 levels, thereby promoting inflammatory signalling and microglial activation. Furthermore, fructose exposure significantly increased IBA-1 and CD11b, indicating sustained neuroimmune activation. Alterations in important inflammatory pathways involving TLR4, NLRP3, NF-κB, MyD88, iNOS, and cyclooxygenases (COX-1 and COX-2) were also observed. In contrast, expression of the anti-inflammatory regulator peroxisome proliferator-activated receptor gamma (PPARγ) was reduced after fructose treatment. Overall, the findings suggest that chronic fructose consumption induces neuroinflammation through multiple inflammatory and immune-related mechanisms in the brain. These effects appear to be dose- and duration-dependent and may contribute significantly to neurodegeneration and cognitive impairment.

Microglia↗

PubMed2026

Targeted variant analysis of feline mediastinal lymphoma using MassARRAY and clinical associations.

Lymphoma is the most commonly diagnosed cancer in cats. This study used the Agena MassARRAY to genotype 40 variants across 17 genes in feline mediastinal lymphoma. These variants have previously been identified in tumors, including T- and B-cell lymphomas, acute and chronic lymphocytic leukemias, and mast cell tumors, in humans, dogs, and cats, using various methods. They were selected based on high prevalence reported in prior oncology studies, potential relevance to targeted therapy, and suitability for multiplex PCR amplification. Pleural fluid samples were collected from 76 cats with mediastinal lymphoma, including 69 domestic shorthairs, two Persians, two Siamese, two Wichienmaat, and one Scottish Fold. The most prevalent variants were found in the BCL2, KIT, STAT3, and ZEB1 genes. Specifically, BCL2 c.83275986G > A and c.83275992G > T were present in 71.1% and 57.9%, respectively. In cats with variant-positive in KIT c.163965724C > CT significantly reduced (11 days) compared to wild-type cats (94 days) (p < 0.001). In cats with variant-positive in STAT3 c.42942437C > CA, resulted in shorter median survival compared to wild-type cats (18 days vs. 77 days, p = 0.006). The findings suggest that the variant panel could be useful for the genomic landscape of feline mediastinal lymphoma and warrant further validation.

Animals↗

PubMed2026

Predictive value of anal sphincter electromyography for sacral neuromodulation test-phase outcomes.

BACKGROUND: Sacral neuromodulation (SNM) is an established therapy for refractory pelvic organ dysfunction. Anal sphincter electromyography (EMG) is commonly used preoperatively to assess sacral and peripheral nerve integrity. However, the prognostic significance of chronic neurogenic EMG changes for SNM outcomes remains unclear. OBJECTIVE: To evaluate whether chronic neurogenic changes on preoperative anal sphincter EMG predict the outcome of the SNM test phase. METHODS: We retrospectively analysed 62 consecutive patients with bladder and/or bowel dysfunction or pelvic pain who were candidates for SNM treatment and who underwent preoperative anal sphincter EMG. EMG findings were classified as normal or showing chronic neurogenic changes. SNM test-phase success was defined as a ≥50% improvement of symptoms at 24 days. Outcomes were compared between EMG groups. RESULTS: Of the 62 patients (49 women, 13 men), 30 (48%) had normal EMG findings and 32 (52%) showed chronic neurogenic changes. Overall, the SNM test phase was successful in 47 patients (76%). Success rates were similar in patients with normal EMG (72%) and neurogenic EMG changes (79%), with no statistically significant difference (p = 0.878). Sex-stratified analyses revealed no significant association between EMG findings and test-phase success in women or men. CONCLUSIONS: Chronic neurogenic changes on anal sphincter EMG do not predict SNM test-phase outcomes. These findings suggest that abnormal sphincter EMG results should not be used as a standalone criterion to exclude patients from SNM therapy. SIGNIFICANCE: Signs of neurogenic damage on anal sphincter EMG are not an indicator of reduced neuromodulatory capacity or diminished clinical response to SNM.

Humans↗

PubMed2026

RNA dysregulation as a determinant of aging and neurodegenerative vulnerability.

In the nervous system, aging causes deterioration of cellular and molecular processes that are associated with declines in cognition, sensory perception, and motor coordination. Aging is also the strongest risk factor for neurodegenerative disease, yet the mechanisms by which aging predisposes neurons to dysfunction remain incompletely understood. While genomic instability, proteostasis decline, mitochondrial dysfunction, and chronic inflammation have dominated prevailing models, recent evidence highlights RNA dysregulation as a central component of age-associated decline. In this review, we summarize recent findings suggesting that aging progressively erodes RNA regulatory fidelity through alterations in RNA-binding protein abundance, localization, biophysical behavior, and RNA interactions. We argue that age-dependent RNA dysregulation represents an important mechanism that converges with genetic risk to drive neuronal vulnerability and neurodegeneration.

RNA dysregulation↗

PubMed2026

Public health, public protest: The role of health burdens and healthcare access in protest mobilisation.

Health and politics are intertwined, yet few studies have examined the association between health and protest. This study examined whether population health burdens were associated with protest incidence and whether healthcare access modified these associations. Analysis was based on an unbalanced 2004-2023 country-year panel, combining protest counts from ACLED with rates for 22 GBD causes. Mixed-effects negative-binomial models estimated incidence-rate ratios (IRRs) with interactions for healthcare access (±1 SD). Two-way fixed-effects Poisson models were estimated as a benchmark to distinguish cross-national associations from within-country dynamics. Health burdens were systematically, but heterogeneously, associated with protest. Rates for several non-communicable burdens were associated with protest, notably musculoskeletal disorders (IRR 1.72, 95% CI 1.37-2.15), neoplasms (1.24, 1.06-1.44), substance-use disorders (1.32, 1.12-1.56) and HIV/AIDS and other STIs (1.24, 1.12-1.38). Higher healthcare access generally attenuated health-protest associations. Fixed-effects models confirmed several associations (e.g. HIV/AIDS, neoplasms) but revealed that others (e.g. maternal/neonatal disorders, enteric infections) were driven primarily by cross-national differences. Population health burdens were associated with cross-national variation in protest mobilisation. Chronic, non-communicable burdens were associated with heightened protest, whereas poverty-linked and early-life burdens were associated with lower mobilisation. Healthcare access was associated with attenuation of these relationships.

Humans↗

PubMed2026

Safety and efficacy of immune checkpoint inhibitors as a bridge to allogeneic hematopoietic stem cell transplantation in classical Hodgkin lymphoma: A systematic review and meta-analysis.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for relapsed or refractory classical Hodgkin lymphoma (cHL); however, a substantial subset of patients ultimately requires allogeneic hematopoietic stem cell transplantation (allo-HCT) to achieve long-lasting disease control. The use of ICIs as a bridge to allo-HCT has therefore gained increasing clinical interest, though concerns persist regarding post-transplant complications and incompletely-defined safety profiles. Accordingly, this systematic review and meta-analysis was conducted to evaluate outcomes of ICIs administered prior to allo-HCT in cHL. Following PRISMA guidelines, a comprehensive literature search was conducted across online databases through January 2026. Eligible studies included observational designs reporting survival and transplant-related outcomes in cHL patients treated with ICIs followed by allo-HCT. Pooled proportions for overall survival, progression-free survival, non-relapse mortality, and graft-versus-host disease (GVHD) incidence were calculated using a random-effects model. Seven studies comprising 739 patients were included. Post-transplant survival outcomes were favorable, with high pooled estimates across timepoints. Transplant-related mortality remained low, with NRM rates consistently within an acceptable range through long-term follow-up. Acute GVHD was observed at a meaningful frequency, including a smaller subset of severe cases, while chronic GVHD occurred in approximately one-quarter of patients at follow-up. Overall, these findings suggest that ICI therapy prior to allo-HCT in cHL is associated with encouraging survival and disease control and does not appear to confer excessive non-relapse mortality, supporting its use as a feasible and effective bridging strategy, while underscoring the need for future prospective studies to clarify optimal timing, risk mitigation strategies, and patient selection.

Humans↗

PubMed2026

Major cardiovascular event risk of advanced therapies in inflammatory bowel diseases: systematic review and meta-analysis.

BACKGROUND: Patients with chronic immune-mediated disorders (IMIDs), including inflammatory bowel disease (IBD), are at increased risk of cardiovascular disease. While advanced therapies show cardioprotective effects in other IMIDs, their impact on major adverse cardiovascular events (MACE) in IBD remains unclear. We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating MACE risk with advanced therapies in IBD. METHODS: Systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials identified 43 studies (36 RCTs, including 9 long-term follow-up (LTF) studies, and 7 observational studies) published between 2002 and 2024. Primary analyses estimated odds ratios (OR) for MACE comparing advanced therapy to placebo, with secondary analyses stratifying studies by drug class and length of follow-up. Sensitivity analyses were conducted using alternative methods to account for zero-event data. RESULTS: Placebo-controlled RCTs showed a nonsignificant trend toward reduced MACE risk (OR 0.60; 95% CI 0.24-1.51), with similar findings across sensitivity analyses accounting for sparse and zero-event data. Class-specific trends suggested lower MACE risk with IL-12/IL-23 inhibitors (OR 0.35; 95% CI 0.05-2.21), JAK inhibitors (OR 0.57; 95% CI 0.16-2.06), and a potential increase with Anti-TNF agents (OR: 3.04; 95% CI 0.31-29.47), though none reached statistical significance. LTF studies showed consistent findings. Observational studies suggested lower MACE risk with Anti-TNF therapies (OR 0.29; 95% CI 0.21-0.40), but not with IL-12/IL-23 (OR 4.41; 95% CI 0.49-39.28) or JAK inhibitors (OR 1.57; 95% CI 0.86-2.84). CONCLUSION: Advanced therapies did not demonstrate a clear increase or decrease in cardiovascular risk in IBD. The discrepancies between RCTs and observational studies underscore the urgent need for rigorous-designed observational research with long-term follow-up to evaluate the real-world impact of advanced therapies on MACE risk.

Humans↗

PubMed2026

Impact of climate change on pediatric health outcomes.

Climate change has become one of the most critical health issues globally in the twenty-first century with children bearing the disproportionate burden of the burden since they are more vulnerable than adults because of their physiological, behavioral, and developmental capacities. It is a systematic review that rates the evidence of the relationship between climatic exposures such as heat, air-pollution, and extreme weather events and pediatric health outcomes. The number of peer-reviewed studies involved was 23 published in 2000-2025, which represented different geographic areas and study designs and assessed acute and chronic health outcomes. The Newcastle-Ottawa Scale and the ROBINS-I tool were used to evaluate the methodological quality, and the majority of the studies had low to moderate risks of bias. The narrative synthesis shows that there are always links between air pollutants especially PM2.5, NO2 and O3 and respiratory morbidity, prevalence of asthma and hospitalization of children. Amplified temperatures as well as heat waves were associated with increased cases of heat illness, dehydration, and febrile state in infants and young children. There were elevated cases of diarrheal and vector-related infections, especially in low-resource settings, which were linked to extreme weather events especially floods. Although the overall results were similar, significant differences in the regions and methods were found, and low-income countries show little evidence. In addition, exposures as analyzed in most studies were usually considered individually, which may have underestimated the cumulative or compound climate risks.

Humans↗

PubMed2026

Mechanisms linking the gut microbiota to colorectal cancer development and progression.

Colorectal cancer remains a leading cause of global cancer mortality, with a concerning rise in early-onset cases driven by complex interactions between environmental exposures, lifestyle factors, and host genetics. Mounting evidence indicates that gut microbiota dysbiosis critically modulates this oncogenic process, acting as an active participant rather than a passive bystander. This review systematically synthesizes the dichotomous roles of the intestinal microbiome in colorectal tumorigenesis through the conceptual framework of the driver-passenger model. We discuss how early initiating driver bacteria, such as Polyketide synthase-positive Escherichia coli and enterotoxigenic Bacteroides fragilis, compromise mucosal barriers, induce chronic mucosal inflammation, and inflict direct genomic instability. As the local tumor microenvironment undergoes profound metabolic remodeling, opportunistic passenger pathogens, notably Fusobacterium nucleatum, become enriched, further promoting cellular proliferation and facilitating tumor immune evasion. Conversely, protective commensals, exemplified by Clostridium butyricum and Streptococcus thermophilus, exert robust tumor-suppressive effects through multifaceted mechanisms. These beneficial microbes actively antagonize malignant progression by redirecting tumor metabolic fluxes toward oxidative stress, orchestrating deep epigenetic reprogramming, and degrading core oncoproteins to reverse chemoresistance. Transitioning from fundamental mechanisms to clinical application, we evaluate a comprehensive spectrum of microbiota-targeted interventions, encompassing non-invasive diagnostic biomarkers, fecal microbiota transplantation, engineered bacteria, phage therapy, and postbiotics. Finally, we critically address the formidable translational challenges associated with microbial heterogeneity, long-term safety, and regulatory standardization, aiming to provide a balanced perspective on integrating microbiome-based strategies into next-generation precision oncology for colorectal cancer.

Humans↗

PubMed2026

Effect of adding umbilical cord blood derived stem cells to haploidentical stem cell transplant (haplo-cord) on post-transplant survival and graft-versus-host disease in patients with hematological malignancies: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Haploidentical stem cell transplantation (haplo-SCT) carries a substantial risk of graft-versus-host disease (GvHD), whereas umbilical cord blood (UCB) transplantation offers lower GvHD risk but slower engraftment. The haplo-cord approach combines both graft sources, aiming to mitigate GvHD while ensuring timely engraftment. This meta-analysis compares haplo-cord transplantation with haplo-SCT alone for the treatment of hematological malignancies. METHODS: Four electronic databases and two clinical trial registries were systematically searched. Effect sizes from eligible studies were pooled using odds ratios (ORs) for dichotomous outcomes and hazard ratios (HRs) for time-to-event outcomes. RESULTS: Twelve studies met the inclusion criteria. Haplo-cord was associated with a statistically significant reduction in chronic GvHD (OR = 0.62, 95%-CI: 0.42-0.93), while no significant difference was observed for grade II-IV acute GvHD (OR = 0.75, 95%-CI: 0.52-1.09). Survival outcomes favored haplo-cord, with lower HRs for overall survival (HR = 0.68, 95%-CI: 0.53-0.86) and event-free survival (HR = 0.61, 95%-CI: 0.52-0.72), while non-relapse mortality was not significant. Relapse at 3 years was significantly lower with haplo-cord (OR = 0.54, 95%-CI: 0.35-0.82). Haplo-cord also demonstrated higher day-30 engraftment, along with lower relapse-related and GvHD-related mortality, while CMV and EBV viremia showed no difference between groups. CD34 selection in the haplo graft significantly influenced effect sizes and heterogeneity in both subgroup analyses and meta-regression for acute GvHD. CONCLUSION: Haplo-cord transplantation improves GvHD outcomes, survival, and relapse risk compared with haplo-SCT alone. However, whether protocol optimization, possibly via CD34 selection, confers additional benefit remains uncertain and requires confirmation in future studies.

Humans↗

PubMed2026

Anatomy and Biomechanics of the Deltoid Ligament Complex in Healthy Ankles: Protocol for a Systematic Review and Meta-Analysis.

INTRODUCTION: Up to one in two individuals who have a history of an ankle injury will develop chronic ankle instability, which subsequently increases the risk of osteoarthritis development. Although lateral ankle ligament injuries are the most common, recent research shows that concomitant injuries to the deltoid (medial collateral) ligament complex may be more prevalent than previously recognised. However, the anatomy and biomechanics of the deltoid ligament complex are reported inconsistently in the literature. This systematic review will summarise current evidence on the anatomy and biomechanics of the deltoid ligament complex in healthy adult ankles. METHODS: Searches will be conducted in Scopus, MEDLINE, Embase, CINAHL and SPORTDiscus. Our search strategy will cover terms associated with 'deltoid ligament', 'anatomy' and 'biomechanics'. We will only include dissection and imaging studies published in English that report any of the listed clinically relevant properties of the deltoid ligament in healthy adult human ankles. Two reviewers will independently perform screening and assess study quality using the anatomical quality assessment (AQUA) tool. One reviewer will extract relevant data, which will be independently verified by co-authors. Primary outcomes include band prevalence, length, width, cross-sectional area, maximum and/or failure load and elastic modulus. If three or more studies report a primary outcome, we will conduct a meta-analysis and report findings as pooled means with 95% confidence intervals. If a meta-analysis is not feasible, outcomes will be summarised as a narrative analysis. Measures will be taken during data synthesis to address anticipated methodological heterogeneity across included studies, and pooled estimates will be interpreted with caution. DISCUSSION: This protocol details a systematic review that aims to summarise the anatomy and biomechanics of the deltoid ligament complex. Our findings will inform computational modelling, clinical management and biomechanics for ankle pathologies, as well as identifying research gaps and directions for future research. TRIAL REGISTRATION: PROSPERO: CRD420251142867.

Humans↗

PubMed2026

Therapeutic-drug-monitoring-based ATG Targeted Dosing Strategy in Unmanipulated Haploidentical Haematopoietic Stem Cell Transplantation: a randomized, multicenter, phase 3 clinical trial.

Anti-thymocyte globulin (ATG) has been a standard prophylaxis for graft-versus-host disease (GVHD). However, the pharmacokinetics of ATG in vivo vary significantly, and weight-based fixed dosing may not optimize efficacy while minimizing toxicity. We investigated the clinical results of a therapeutic-drug-monitoring (TDM)-based, dose-optimized ATG strategy versus weight-based fixed dosing in haploidentical haematopoietic stem cell transplantation (NCT05166967). Patients were randomly assigned in a 1:1 ratio to receive a targeted dose of ATG or a fixed dose of 10 mg/kg. The primary endpoint was the 365-day graft-versus-host disease-free and relapse-free survival (GRFS). From January 1, 2022, to January 16, 2024, 204 patients were enrolled, with 102 patients in each group. The 365-day GRFS was higher in the targeted dose group (66.7%) than in the fixed dose group (50.0%; hazard ratio [HR], 0.666; 95% confidence interval [CI], 0.4456 to 0.9954; P = 0.048). The cumulative incidence of moderate to severe chronic GVHD at day 365 was significantly lower in the targeted dose group (9.8%; 95% CI, 5.0 to 16.5) compared with the fixed dose group (22.5%; 95% CI, 15.0 to 31.1; P = 0.026). Fewer grade 3-5 infections were reported in the targeted dose group (44.1%) than in the fixed dose group (70.6%; P < 0.001). More patients in the targeted dose group achieved optimal ATG exposure (P = 0.007) and superior CD4+ T-cell reconstitution (P = 0.002). These findings support the clinical utility of a TDM-based individualized ATG dosing strategy that balances efficacy and toxicity for GVHD prophylaxis in allogeneic stem cell transplantation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05166967.

Humans↗

PubMed2026

Post-weaning social isolation increases reward-seeking behavior in mice.

Social isolation is a growing public health concern. Although isolation at any age is harmful, previous studies have shown that isolation during adolescence, correlating with critical periods of brain development, can impair cognitive function and increase the risk for psychiatric illness later in life. In this study, we utilized a mouse model of social isolation (SI) during adolescence (postnatal day 21-35) and compared performance of isolated and group-housed mice on a touchscreen-based continuous performance test (rCPT) and fixed ratio/progressive ratio (FR/PR) tasks in adulthood. SI improved performance in the rCPT and the improvement in performance was consistent across time bins within the 45-minute testing session. There were no effects of SI on reaction times or reward retrieval latencies. A possible confound for performance in the rCPT would be SI-induced changes in reward-seeking or motivation for the strawberry milk reward. We next compared the SI mice to their group-housed littermate controls on both PR and FR schedules of reinforcement and found that SI mice had higher breakpoints on a PR4 schedule and earned significantly more reinforcers on an FR1 schedule of reinforcement compared to their group-housed littermates, suggesting that high performance in the CPT may be due to increased motivation for food rewards. These data indicate that SI during adolescence has significant effects on reward-seeking behavior in adult mice and may provide a useful behavioral model for studying the link between SI and risk for neuropsychiatric disorders.

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