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PubMed2026

Chinese herbal medicine Xiangsu Hewei Granules in treating non-erosive gastroesophageal reflux disease with liver stomach stagnation heat syndrome: A multicentre, randomized, double-blind, placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiangsu Hewei Granules are an herbal preparation that has shown potential for controlling symptoms of nonerosive gastroesophageal reflux disease (NERD) in preliminary studies. However, high-quality randomized controlled evidence for its use in NERD remains lacking. AIM: To verify the efficacy and safety of Xiangsu Hewei Granules in treating NERD with liver stomach stagnation heat syndrome. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, multicentre phase III trial included 480 patients (aged 18-65 years) with confirmed NERD (GerdQ≥8; negative H. pylori) and traditional Chinese medicine (TCM) liver stomach stagnation heat syndrome. Patients were randomized 3:1 to receive either Xiangsu Hewei Granules or placebo, thrice daily for 8 weeks. The primary outcomes were the effective rate of the response based on visual analog scale (VAS) scores for heartburn and acid regurgitation at week 8. The secondary outcomes included reductions in the TCM syndrome score, etc. RESULTS: 479 participants (mean age 48.5 years, SD10.2; 54.3% female) entered the full analysis set and safety set (360 tests group; 119 control group, 1 participant in the control group withdrawing before medication). At week 8, compared with the control group, the test group demonstrated significantly better effective rate of VAS score response for heartburn(76.39% vs 21.01%, 95% CI 55.38 (45.98, 62.94) %, p < 0.01),acid regurgitation (79.72% vs 23.53%, 95% CI56.39 (46.90, 64.12) %, p < 0.01), and TCM syndrome score (69.23% vs 30.13%, p < 0.01) at week 8. CONCLUSION: In this selected population of NERD patients with liver-stomach stagnation heat syndrome (e.g., negative H. pylori, no pH-impedance phenotype, and low anxiety/depression scores), Xiangsu Hewei Granules demonstrated efficacy and safety in improving heartburn, acid regurgitation, and TCM syndrome scores. However, generalizability to the broader NERD population and its comparative effectiveness against standard proton pump inhibitor therapy require further investigation.

Humans↗

PubMed2026

Clinical outcomes of Epstein-Barr virus infection/reactivation following CAR-T cell therapy: A systematic review.

BACKGROUND: Epstein-Barr virus (EBV) infection or reactivation is an emerging but underrecognized complication following chimeric antigen receptor T-cell (CAR-T) therapy and is likely associated with treatment-induced immune dysregulation. Data regarding its clinical impact remain limited. OBJECTIVE: To evaluate the reported occurrence, clinical manifestations, and outcomes of EBV infection or reactivation in adults undergoing CAR-T therapy. METHODS: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Embase, and Cochrane CENTRAL were searched from inception to March 2025 for studies reporting EBV infection or reactivation after CAR-T therapy in adults. Due to limited and heterogeneous data, results were synthesized descriptively. RESULTS: Five studies comprising 80 patients were included (median age, 55 years; 52.6% male among patients with reported sex data [10/19]). Across the included studies, 11 EBV infection/reactivation events were identified among 80 described CAR-T recipients, representing 13.8% of the reported sample rather than a true incidence estimate. Among events with usable individualized timing data, the median interval from CAR-T infusion to EBV detection/reactivation was 9.8 months (approximate range, 1-44 months). Because EBV surveillance strategies and definitions were inconsistently reported across studies, this proportion should not be interpreted as a true incidence estimate. Four patients (36.4%) developed EBV-associated disease, including three cases of EBV-related lymphoproliferative disorder and one case of EBV-associated diffuse large B-cell lymphoma. Among seven patients with reported post-CAR-T treatment response, four achieved Complete Remission/ Continuous Complete Remission; treatment response should be interpreted separately from final survival status. Confirmed EBV-related mortality occurred in 2/11 patients with reported EBV infection/reactivation and in 2/4 patients with EBV-associated disease; all-cause mortality could not be reliably estimated because patient-level vital status could not be fully attributed to the EBV-reactivated subgroup. Reported toxicities predominantly consisted of low-grade cytokine-release syndrome; however, toxicity data were limited. CONCLUSION: Although infrequently reported, EBV infection or reactivation after CAR-T therapy may be associated with substantial morbidity and mortality among affected patients. However, the available evidence is limited by the small sample size, heterogeneous study designs, and inconsistent EBV surveillance practices.

Humans↗

PubMed2025

Impact of Chewing Behavior Change on Cognition and Cerebral Hemodynamics.

BACKGROUND: Impaired chewing ability is a recognized risk factor for cognitive decline in older adults, potentially due to reduced neural stimulation in cognition-related brain regions. While short-term studies have demonstrated transient increases in neural activity from chewing, the sustained cognitive and neurophysiological effects of encouraging thorough chewing habits in daily life remain unclear. OBJECTIVE: This randomized controlled trial investigated whether promoting thorough chewing during meals could improve cognitive function and cerebral hemodynamics in older adults. METHODS: Fifty participants aged 65 y or older were randomly assigned to either a 1-mo intervention group, which used a wearable device to monitor and increase chewing strokes during meals, or a control group that maintained usual chewing habits. Chewing behavior, cognitive performance (including memory and executive function via the color Stroop test), and cerebral hemodynamics in the dorsolateral prefrontal cortex (DLPFC) were measured at baseline and after 1 mo. Statistical analyses included t tests, chi-square tests, 2-way analysis of variance with post hoc tests, Pearson correlations, and generalized linear models to evaluate group differences and associations between chewing and cognitive outcomes. RESULTS: Significant time-by-group interactions were observed for memory, F(1, 48) = 6.24, P = 0.043, and hemodynamic responses in the left DLPFC, F(1, 48) = 6.19, P = 0.013. The intervention group showed increased chewing frequency (P = 0.017), improved memory performance, and reduced left DLPFC responses compared with controls. Chewing frequency was positively correlated with Stroop test scores (r = 0.53, P = 0.010) and negatively with hemodynamic changes in the left DLPFC (r = -0.30, P = 0.040). Although improvements in other cognitive outcomes and hemodynamic measures favored the intervention group, these differences did not reach statistical significance. CONCLUSIONS: Promoting intentional chewing habits for 1 mo may enhance memory-related cognitive performance and neural efficiency in the DLPFC during working memory tasks in older adults. This nonpharmacologic, low-burden strategy warrants further research with longer interventions to support cognitive health and dementia prevention. TRIAL REGISTRATION ID: UMIN000044280Knowledge Transfer Statement:This study demonstrates that promoting thorough chewing habits in older adults can improve memory and enhance neural efficiency in the brain. Encouraging intentional mastication is a simple, nonpharmacologic approach that may help maintain cognitive health and prevent dementia, providing a practical strategy for clinicians and policymakers to support healthy aging.

Humans↗

PubMed2026

A Randomized Phase II Study of Combination Atezolizumab and Varlilumab (CDX-1127) with or without Cobimetinib in Previously Treated Unresectable Biliary Tract Cancer.

PURPOSE: The addition of MEK inhibition (MEKi) to programmed cell death ligand 1 (PD-L1) blockade improves progression-free survival (PFS) in patients with advanced biliary tract cancer. Although MEK inhibitors may increase tumor cell immunogenicity, they can impair T-cell priming/effector function, limiting combination efficacy. We hypothesized that the addition of a CD27 agonist could restore T-cell function and enhance antitumor immunity in this combination. PATIENTS AND METHODS: We conducted a randomized, phase II trial evaluating atezolizumab (840 mg, intravenously, days 1 and 15) in combination with the CD27 costimulatory monoclonal antibody [CDX-1127/varlilumab (3 mg/kg, intravenously, days 1 and 15)], with/without the addition of an MEK inhibitor [cobimetinib (60 mg, orally, daily, days 1-21, off days 22-28)] in unresectable biliary tract cancer following at least one metastatic therapy. Overall response rate (ORR) and PFS were coprimary endpoints. Treatment-related changes in CD8+ tumor-infiltrating lymphocytes (TIL) were the primary correlative outcomes. RESULTS: The trial was closed early following interim preplanned ORR analysis. At closure, 57 patients had been enrolled [n = 29 in the cobimetinib + atezolizumab + varlilumab (CAV) arm; n = 28 in the atezolizumab + varlilumab (AV) arm]. A majority (67%) had intrahepatic cholangiocarcinoma, and 32% were immunotherapy experienced. Both regimens were well tolerated without new safety signals. Objective responses were rare [0% (CAV); 3.8% (AV)]. The median PFS (mPFS) was 2.40 (CAV) and 1.84 (AV) months [hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.38-1.18]. Among immunotherapy-experienced patients, the mPFS was 3.62 (CAV) and 1.84 (AV) months (HR, 0.54; 95% CI, 0.18-1.62). Treatment with CAV increased intratumoral CD8+ T-cell density compared with treatment with AV. CONCLUSIONS: The combinations of atezolizumab and varlilumab with/without cobimetinib were safe, but neither meaningfully improved outcomes in biliary tract cancer treated in the later lines. Correlative tissue studies validated preclinical work that MEKi increases CD8+ TILs.

Humans↗

PubMed2026

Efficacy and Safety Profile of a Triple Single-Pill Combination of Valsartan/Amlodipine/Chlorthalidone in Patients with Uncontrolled Hypertension.

PURPOSE: This randomized, double-blind, multicenter Phase III study evaluated the efficacy and safety profile of a single-pill triple combination of valsartan/amlodipine/chlorthalidone (KDF1901, Valdipine Plus) compared with a dual combination of valsartan/amlodipine (KDF1901-R) in patients with essential hypertension. METHODS: Patients (n = 294) with inadequately controlled hypertension after a 4-week run-in phase with valsartan/amlodipine (80/5 mg) were randomized to receive KDF1901 (valsartan/amlodipine/chlorthalidone 160/10/25 mg, n = 147) or KDF1901-R (valsartan/amlodipine 160/10 mg, n = 147) for 8 weeks. The primary efficacy endpoint was the change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8. Secondary endpoints included changes in mean sitting diastolic blood pressure (MSDBP), BP normalization rates, and response rates. Safety profile outcomes assessed treatment-emergent adverse events (TEAEs), laboratory parameters, and serious adverse events. FINDINGS: At week 8, the KDF1901 group exhibited a significantly greater reduction in MSSBP (-22.8 ± 1.0 mmHg) compared with the dual therapy group (-16.7 ± 1.0 mmHg, P < 0.0001). Similarly, the mean MSDBP reduction was significantly greater with KDF1901 (P = 0.0006). BP normalization rates (75.9% vs 54.5%, P < .0001) and response rates (73.8% vs 51.7%, P < 0.0001) were significantly higher in the triple combination group. Overall, the incidence of TEAEs was similar between groups (24.7% vs 21.5%, P = 0.5783), with mild cases of dizziness were most commonly reported. Exploratory ad hoc analyses showed statistically greater changes in sodium, potassium, and uric acid levels with triple therapy, but clinically meaningful extreme electrolyte abnormalities were rare in both groups, and the overall laboratory profile remained acceptable. IMPLICATIONS: This trial reported that the single-pill triple combination KDF1901 significantly improved BP control compared with dual therapy without compromising tolerability. GOV IDENTIFIER: NCT07116863.

Humans↗

PubMed2026

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↗

PubMed2026

Effectiveness of an educational video for caregivers of children with neurogenic bladder: A randomized controlled trial.

BACKGROUND: The complexity of neurogenic bladder (NGB) management underscores the importance of caregiver education, yet high-quality education materials remain scarce. This study aims to assess the effectiveness and acceptability of an educational video designed to improve knowledge about NGB among caregivers of children with this condition. METHODS: We identified English-speaking caregivers of patients aged zero to 18 years, diagnosed with NGB, without prior major bladder reconstructive surgery, who received care at our institution from 2018 to 2022. Caregivers were randomly assigned into control or video groups using a block randomization model based on age. The control arm completed a six-item knowledge assessment before viewing the video, while the video group watched the video first. All participants rated the video's acceptability. Qualitative analysis of the open-ended responses to the acceptability questionnaire followed principles of thematic analysis. RESULTS: Of 409 eligible participants, 106 (25.9%) completed the study. Video (n = 48) and control (n = 58) groups were demographically similar. In the video group, 64.6% answered correctly all questions in the knowledge questionnaire, compared to 31% in the control group. After adjusting for patient age, caregivers in the video group were more likely to answer any question in the knowledge assessment correctly (relative probability: 1.13, 95% CI [1.06, 1.21], p < 0.01). Evidence for a difference in correct response rate among individual questions was strongest for question #1, which asked about common urological conditions for which NGB patients are at higher risk (95.8% vs. 79.3%, p = 0.01), and question #6, which asked about indications for bladder surgery (87.5% vs. 67.2%, p = 0.01), with the video group more likely to answer correctly for both questions. Qualitative analysis identified three major themes regarding parents' acceptance of the educational video: 1) attitudes towards video content and presentation, 2) usefulness of video as an educational tool, and 3) future directions. CONCLUSIONS: Our study found that an educational video about NGB effectively enhanced parental understanding of the condition and was deemed acceptable by parents as an introductory educational tool. The literature shows the benefit of using technology and visual aids to enhance health literacy for patients and caregivers, a key first step towards optimizing health outcomes for pediatric urologic patients.

Humans↗

PubMed2026

Feasibility of implementation, diagnostic accuracy, and end-user impact of an electronic health record (EHR)-based ureteral stent tracking tool in a pediatric population.

INTRODUCTION & OBJECTIVES: Ureteral stent tracking systems have reduced stent retention in adults, but their accuracy and impact in pediatrics have been minimally explored. With low event rates in children, such tools may yield high false positives, raising questions on balancing event prevention with provider burden. We aimed to evaluate the feasibility, diagnostic accuracy, and end-user impact of an Electronic Surveillance Tool for Evaluating Nephroureteral stent Tracking (eSTENT) at our institution. STUDY DESIGN: eSTENT, implemented in 1/2024, flags ureteral stents at risk for retention based on implant documentation, expected explant date, and explant documentation. Monthly reports are generated for stents missing explant documentation. We retrospectively evaluated the diagnostic performance of eSTENT from 1/2024-8/2025 at our pediatric hospital. A usability survey including a validated 1-7 implementation score (higher = easier implementation) was distributed to pediatric urologists and operating room nurses. RESULTS: Of 172 cases with ureteral stent placement, eSTENT flagged 28 events (16%) in 24 patients. Of these, 26 represented documentation gaps where explant had been appropriate. Two flags had no documentation of explant, representing near miss events that were identified. No retained stents occurred, consistent with high sensitivity and modest specificity. There were no flags in the last 6 months of the study period. Survey response rate was 100% for surgeons and 55% for nurses. Before eSTENT, stents were not routinely tracked. All surgeons and 93% of nurses reported no added burden, despite occasional misidentification of retained stents. Three surgeons found eSTENT beneficial, four were neutral, and free-text responses generally cited eSTENT's "fail safe" nature as positive. Nurses suggested improvements, including user support and integrated documentation reminders. The average implementation score among both groups was 6/7, indicating easy adoption. DISCUSSION: While the impact of stent tracking tools in adult literature has been positive, our study emphasizes the feasibility of broader adoption at a pediatric hospital. Integration of eSTENT may avoid the potentially devastating consequences of a retained stent. Prioritizing sensitivity over specificity appears acceptable for a "never event" in patient safety. Our study is limited by the retrospective nature of data collection and survey bias. CONCLUSIONS: Though no stents were retained in the study period, eSTENT appropriately flagged two cases without added burden to most end-users. Further optimization is warranted, but adoption in pediatric centers may enhance care reliability.

Humans↗

PubMed2026

Orchard netting impacts on biodiversity leading to cascading effects at the ecosystem level.

Agriculture must ensure food production without further compromising the ecosystem functions upon which it depends. Agricultural practices should therefore avoid harming farmland biodiversity, especially of taxa that supply the key ecosystem services (e.g. pollination, pest control and nutrient uptake) that ultimately support crop production. Orchards are among the largest permanent plantations worldwide and are increasingly characterised by the spread of plastic nets used to protect fruits/nuts from either abiotic (anti-hail, anti-rain, shade nets) or biotic (exclusion nets) hazards. Despite having received little attention to date, these nets may impact natural communities, acting both as physical barriers and as drivers of habitat changes to which biota must respond. Species-level responses to netting depend on the organism's ability to enter the netted environment and successfully exploit available resources. Net-mediated ecological filtering and plastic behavioural responses may alter species interactions, leading to cascading ecological impacts that may create species-poorer 'netted communities' with simplified ecological networks. Such changes may erode biological control potential, other ecosystem functions, and overall system stability. We conducted a systematic review on the effects of protection nets on biota, and reported novel empirical evidence on anti-hail nets' impacts on communities of orchard-dwelling birds, flower-visiting insects, and rodents. In total, we identified 48 studies from the literature, however this literature was strongly biased towards apple orchards, western countries, and pest taxa. Net deployment was highly effective in deterring target pest species, in some cases regardless of their original function, as even weather-protection nets limited pest populations. Side effects on non-target taxa were also often reported, such as decreases in pollinators and natural enemies, and/or increases in secondary pests or microbial diseases. However, most assessments largely disregarded non-pest taxa and the broader ecological consequences of netting. The few studies that addressed the effects of nets at the guild/community level, including our empirical study, confirmed that orchard netting resulted in species-poor assemblages, with possible ecosystem-level consequences. We propose that future assessments should pay more attention to the indirect effects of netting on non-target taxa, and on the supply of crop-supporting ecosystem services mediated by wild species occurring in agroecosystems. Due to the trade-offs between these services and net-mediated crop protection, integrated alternatives should be tested to improve the environmental sustainability of food production and biodiversity conservation in farmed landscapes.

Biodiversity↗

PubMed2026

Evaluation of the clinical and mechanistic role of MCM2 expression in the prediction of meningioma recurrence after radiotherapy.

OBJECTIVE: Postoperative radiotherapy is an effective treatment for meningiomas; however, treatment response varies among patients. In addition, practical methods for predicting tumor recurrence after radiotherapy have not been well established. Minichromosome maintenance protein 2 (MCM2), a key regulator of DNA replication licensing, was recently implicated in highly proliferative molecular subtypes of meningioma. In this study, the authors evaluated whether MCM2 immunohistochemical expression predicts response to radiotherapy in patients with meningiomas. METHODS: The authors retrospectively analyzed the records of patients with WHO grade 1-3 meningiomas treated with resection followed by radiotherapy at a single institution between July 2003 and November 2023. The MCM2 labeling index was assessed immunohistochemically, and patients were stratified into MCM2-high and -low groups using a cutoff of 35%. Progression-free survival (PFS) was defined as the interval from the completion of radiation therapy to postoperative radiological tumor recurrence or regrowth. Patients who showed no progression were censored at their last follow-up. PFS was estimated using Kaplan-Meier analysis and subsequently evaluated with Cox proportional hazards models. To further investigate the biological mechanisms associated with MCM2 expression, comprehensive transcriptomic analyses, including gene set enrichment analysis, was performed to elucidate the molecular processes that occur within MCM2-high tumors. RESULTS: The study population included 15 men (42%) and 21 women (58%), with a mean age of 63 years. Ten tumors (28%) were classified as MCM2-high meningiomas and 26 (72%) as MCM2-low meningiomas. High MCM2 expression was significantly associated with WHO grades 2-3 histology and higher Ki-67 labeling indices. During a median follow-up of 2.52 years, tumor progression after radiotherapy occurred in 47% of the patients. High MCM2 expression (HR 8.34, p = 0.03) was significantly associated with shorter PFS and remained an independent predictor of recurrence after adjustment for WHO grade, tumor size, and Ki-67 labeling index. Transcriptomic analyses of MCM2-high tumors revealed upregulation of cell proliferation-related pathways, accompanied by increased signaling through the E2F8-CHEK1 axis associated with radiation resistance and suppression of the TNF-α signaling pathway implicated in radiosensitivity. CONCLUSIONS: In meningiomas, high MCM2 expression is associated with early recurrence following radiotherapy. The study findings suggest that this association is driven by diverse biological mechanisms related to cell cycle regulation and radioresistance. Immunohistochemical assessment of MCM2 expression may serve as a practical and accessible biomarker for risk stratification and may support the future development of individualized postoperative radiotherapy strategies.

Humans↗

PubMed2026

Pre-clinical immunogenicity and safety evaluation of H2 strain Hepatitis A Inactivated Vaccine in rhesus macaques.

BACKGROUND: Hepatitis A is a viral infection of the liver that can cause mild to severe illness. Currently, two types of HAV vaccines are used worldwide, inactivated hepatitis A vaccines, which are used in most countries, and live attenuated vaccines (H2 and L-A-1 strain), which are mainly used in China. The major disadvantage of live attenuated virus to cause secondary infections among contacts and mutation shifts of the live vaccine strain. The H2 strain was selected for the development of an inactivated hepatitis A vaccine to further reduce biosafety risks. Rhesus macaques high genomic homology with humans and the incubation period after hepatitis A vaccination and human natural infections are similar. We use rhesus macaques to assess immunogenicity and safety of the H2 strain Hepatitis A Inactivated Vaccine. METHODS: The vaccine was assessed in rhesus macaques, divided into four groups (n = 10 per group): the control group (adjuvant buffer; aluminum content 0.35 mg/mL; 2 mL per dose), the low-dose group (320EU, 0.5 mL of 640EU/mL with aluminum content 0.35 mg/mL), the medium-dose group (640EU, 1 mL of 640EU/mL with aluminum content 0.35 mg/mL), and the high-dose group (1280EU, 2 mL of 640EU/mL with aluminum content 0.35 mg/mL). Animals were injected intramuscularly at multiple sites in the hind limbs and received four inoculations at 4-week intervals. Test items including Clinical indicators, immunogenicity indicators and Histopathological examination. RESULTS: No abnormalities were observed in any group in terms of general clinical condition throughout the study period except for slight decreases in body temperature after immunization. Hematological parameters, serum biochemistry indices, and histopathological findings showed fluctuated to different degrees of fluctuation after immunization across all groups. Immunogenicity assessments showed that the inactivated hepatitis A vaccine (H2) induced both humoral and cellular immune responses effectively, and the levels of antibodies increased with certain dose- and time-response trends. CONCLUSION: The inactivated hepatitis A vaccine (H2 strain, human diploid cell) was safe and immunogenic in non-human primates. The results provide strong preclinical support for the further clinical development of this vaccine candidate.

Animals↗

PubMed2026

Comparative efficacy and safety of pharmacokinetically guided and body surface area-based 5-fluorouracil dosing in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Body surface area (BSA)-based 5-fluorouracil (5-FU) dosing remains the standard in colorectal cancer despite substantial interpatient pharmacokinetic variability, which may lead to underexposure, treatment failure, or severe toxicity. This systematic review and meta-analysis evaluated whether pharmacokinetically guided 5-FU dosing improves efficacy and safety compared with conventional BSA-based dosing. METHODS: PubMed/MEDLINE, Embase, and Scopus databases were searched from inception to the final search date. The search identified 1,802 records: PubMed/MEDLINE, 47; Embase, 118; and Scopus, 1,637 records. Comparative randomized and non-randomized studies evaluating pharmacokinetically guided, area under the curve-guided, or therapeutic drug monitoring-based 5-FU dosing versus BSA-based dosing in colorectal cancer were included. Random-effects models were employed. The risk of bias was assessed using RoB 2 and ROBINS-I, and the certainty of evidence was evaluated using GRADE. RESULTS: Five studies comprising 809 unique patients were included. Across the primary severe-toxicity analysis, the pooled denominator was 1,338 reported observations, including 625 in the PK-guided 5-FU dosing arm and 713 in the BSA-based 5-FU dosing arm, because one study reported severe toxicity by treatment cycle rather than by patient. PK-guided dosing was associated with lower severe or grade ≥ 3 toxicity (RR 0.50, 95% CI 0.33-0.76; P = 0.001; I²=79%). PK-guided dosing was also associated with a higher objective response rate (RR 1.50, 95% CI 1.24-1.80; P < 0.0001) and disease control rate (RR 1.18, 95% CI 1.07-1.30; P = 0.001). Severe diarrhea was reduced (RR 0.33, 95% CI 0.18-0.62; P = 0.0006), whereas mucositis, neutropenia/leukopenia, and hand-foot syndrome were not significantly different between dosing strategies. CONCLUSION: PK-guided 5-FU dosing was associated with lower severe toxicity and diarrhea and higher objective response and disease-control rates than conventional BSA-based dosing. However, the evidence was derived from a small and clinically heterogeneous group of studies, and progression-free or overall-survival benefits could not be established. The findings apply predominantly to metastatic colorectal cancer treated with infusional 5-FU within FOLFOX- or FOLFIRI-based regimens. CLINICAL TRIAL REGISTRATION: Not applicable. This study was a systematic review and metaanalysis, and not a clinical trial.

Humans↗

PubMed2026

Effects of continuous isomaltulose-containing gummy intake on interstitial glucose and salivary hormones during an 18-hole golf round: a randomized, double-blind controlled pilot study.

BACKGROUND: Golf is a prolonged, moderate-intensity sport requiring sustained physiological stability to manage cumulative stress and maintain performance. Although carbohydrate intake is commonly used to reduce fatigue, rapidly absorbed sugar-induced rapid blood glucose fluctuations may induce volatile arousal and latent metabolic stress. Isomaltulose, a slow-digesting disaccharide, provides a steadier glucose supply compared with sucrose. This exploratory pilot study examined the effects of isomaltulose intake on physiological stress markers, glycemic dynamics, and subjective responses during a competitive 18-hole golf round. METHODS: Twenty-three male collegiate golfers were randomized to either the isomaltulose group (ISO; n = 12) or the sucrose group (CON; n = 11) in a double-blind controlled trial. Participants consumed gummies containing isomaltulose or sucrose immediately after each hole (12.1 g carbohydrate per hole; total carbohydrate intake: 217.5 g). Primary outcomes were salivary stress markers [cortisol, testosterone, and dehydroepiandrosterone sulfate (DHEAS)] levels. Secondary outcomes included interstitial glucose concentration measured via continuous glucose monitoring, subjective assessments (i.e. sleepiness, relaxation, and concentration), and golf performance (18-hole score). Between-group comparisons at each time point were conducted using planned Welch's t-tests. RESULTS: No significant between-group differences were observed for 18-hole score (p = 0.38) or mean interstitial glucose concentration (p = 0.20). However, exploratory analyses revealed distinct hormonal variations; salivary DHEAS and testosterone levels were higher in the ISO group during the latter half of the round (p < 0.05), whereas both declined in the CON group. Regarding glycemic variability, the ISO group demonstrated a more stable glucose profile with a medium effect size for lower standard deviation (ISO: 14.7 ± 1.9 vs. CON: 16.7 ± 4.6 mg/dL; d = 0.58), although this difference was not significant. Conversely, subjective outcomes diverged; the CON group reported significantly greater subjective arousal (wakefulness and relaxation) (p < 0.01) relative to the ISO group. CONCLUSIONS: In conclusion, continuous intake of isomaltulose-containing gummies during an 18-hole golf round was associated with differences in selected physiological markers, including DHEAS and testosterone concentrations. However, these findings were not accompanied by improvements in objective golf performance outcomes compared with sucrose-containing gummies. Isomaltulose may influence glycemic dynamics and hormonal responses during prolonged golf play; however, the practical significance of these effects remains exploratory. Further studies with larger sample sizes and appropriate repeated-measures frameworks are needed to determine whether such physiological changes translate into meaningful performance or recovery benefits.

Humans↗

PubMed2026

Hierarchical modeling of tumor subtypes in cell lines using large-scale genomic datasets.

Cancer cell lines (CLs) are widely used to study tumor biology and drug response, yet their translational relevance is often limited by inaccurate subtype annotations. Existing CL-tumor matching approaches are frequently constrained by flat classification schemes, weak subtype definitions, and the exclusion of normal tissue references, leading to potential confounding of tumor-specific and tissue-of-origin signals. To address these limitations, a hierarchical classification (HC) framework is presented in which CLs are aligned with patient tumors across biological resolutions, from organ to molecular subtype. Gene expression profiles from 802 CLs, 5,612 tumors from The Cancer Genome Atlas (TCGA) , and 8,939 non-cancerous tissues were integrated to separate oncogenic signals from tissue-specific signals. Node-specific features were selected using maximum relevance minimum redundancy, and balanced accuracies of 89% in cross-validation and 75%, and 80% on external datasets were achieved. Through the framework, 43 CLs were reassigned, and clinically relevant underrepresented subtypes were identified.

cancer cell lines↗

PubMed2026

Telmisartan-based monotherapy and combination regimens for blood pressure control in adults with hypertension: a systematic review, meta-analysis, and GRADE assessment.

PURPOSE: To evaluate the efficacy, safety, and certainty of evidence for telmisartan-based antihypertensive regimens in adults with hypertension. METHODS: This systematic review and meta-analysis followed PRISMA 2020. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL were searched from inception to 2026. Eligible studies enrolled adults with hypertension and compared telmisartan monotherapy or telmisartan-containing combinations with placebo, usual care, non-telmisartan antihypertensive agents, or alternative telmisartan-based regimens. Continuous outcomes were pooled as mean differences (MDs) and dichotomous outcomes as risk ratios (RRs), both with 95% confidence intervals (CIs), using random-effects models, with additional subgroup analyses conducted by comparator type. Risk of bias was assessed using RoB 2, and certainty of evidence was evaluated using GRADE. RESULTS: Twenty-five included reports (24 unique trials, since two reports present secondary outcomes from the same underlying trial) involving 6,521 participants were included, spanning placebo-controlled, usual-care-controlled, active-comparator, and telmisartan-combination-versus-telmisartan-monotherapy designs. Telmisartan-based therapy significantly reduced office systolic blood pressure (MD - 6.39 mm Hg; 95% CI - 7.86 to - 4.93; low certainty) and office diastolic blood pressure (MD - 4.88 mm Hg; 95% CI - 6.67 to - 3.09; low certainty), although the magnitude of effect was comparator-dependent. Based on only two trials, 24-h ambulatory systolic blood pressure (MD - 7.16 mm Hg; 95% CI - 10.61 to - 3.72) and ambulatory diastolic blood pressure (MD - 4.42 mm Hg; 95% CI - 6.36 to - 2.48) were reduced with moderate certainty. Telmisartan-based regimens improved blood pressure response (RR 1.68; 95% CI 1.31 to 2.16; moderate certainty) but not blood pressure control achievement (RR 1.44; 95% CI 0.92 to 2.24; very low certainty). Overall adverse events, dizziness, and headache were comparable (very low to low certainty), while edema was less frequent with telmisartan-based therapy (RR 0.33; 95% CI 0.15 to 0.73; moderate certainty). CONCLUSION: Telmisartan-based regimens, particularly fixed-dose and multidrug combinations, effectively reduce office and ambulatory blood pressure and improve blood pressure response, with broadly comparable short-term safety and less edema. These effect sizes are comparator-dependent, and certainty of evidence for absolute blood pressure control achievement and for major adverse events is very low; heterogeneity, limited long-term data, and a predominance of Asian-population trials warrant cautious interpretation pending larger, higher-quality, and more geographically diverse confirmatory studies.

Humans↗

PubMed2026

Integrated transcriptomic and metabolomic analysis of fluoride tolerance-related pathways and differentially expressed genes in silkworm strain XSKD.

XueSong KD (XSKD) silkworm strain exhibits prominent fluoride tolerance, yet the underlying molecular mechanisms of fluoride tolerance remains unclear. In the present study, fourth-instar pre-molting XSKD silkworms were used as experimental materials for integrated transcriptomic and untargeted metabolomic analyses. In total, 572 differentially expressed genes and 90 differential metabolites were screened. GO enrichment and KEGG enrichment based on the hypergeometric distribution model revealed that 13-Hydroxy-9Z,11E-octadecadienoic acid (13-(S)-HODE) acts as the core differential metabolite, which is significantly enriched in the linoleic acid metabolism pathway. Within this pathway, LOC101737302 and CYP338A1 display opposite expression trends and show correlations with pathway metabolites. Based on multi-omics data, this study preliminarily characterizes the lipid metabolic response under fluoride stress, providing omics dataset support for further in-depth exploration of the molecular mechanism of fluoride tolerance in silkworms.

Animals↗

PubMed2026

The science of Arabic coffee (Qahwa): from phytochemistry and nutritional profile to health benefits and safety evaluation.

Arabic coffee (Qahwa), a traditional beverage widely consumed in the Middle East, has attracted increasing scientific attention due to its distinctive phytochemical composition and associated health effects. This review provides an integrated analysis of Qahwa's nutritional profile, focusing on its key bioactive constituents, including chlorogenic acids, caffeine, diterpenes (cafestol and kahweol), and phenolic compounds. These constituents contribute to a range of biological activities, notably antioxidant, anti-inflammatory, hepatoprotective, and metabolic regulatory effects. The influence of technological variables, including roasting degree, brewing method, and bean origin, on the chemical composition and functional properties is critically examined. Safety concerns, particularly acrylamide formation and mycotoxin contamination, are also discussed. Although emerging data support Qahwa's potential as a functional beverage, further research is required to clarify dose-response relationships, synergistic interactions, and long-term health outcomes. This work highlights Qahwa as a promising candidate for food and nutraceutical applications, warranting standardized compositional profiling and toxicological evaluation.

Humans↗

PubMed2026

Syndemics, violence and injury: exploring historical relationships between infectious disease epidemics and violent crime in South Africa.

This paper explores historical and contemporary intersections between mass-mortality epidemics and violent crime in South Africa, focusing on four major epidemics - Spanish Flu, tuberculosis, HIV, and Covid-19. The study integrates epidemiological data and contextual historical information such as crime statistics, archival records, and secondary scholarship to explore whether epidemic-driven mortality crises are associated with subsequent changes in violence and injury profiles. With the possible exception of gendered violence, the study finds little evidence that earlier epidemics directly contributed to rapid or sustained increases in violent crime, despite causing substantial adult mortality and long-term social and economic disruption. A comparison between epidemic and socio-economic profiles strongly suggests that the significant increases in violent crime recorded after the Covid-19 pandemic are highly localised, and may be more strongly related to lockdown responses, including alcohol restrictions, rather than the effects of disease itself.

Humans↗