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Evaluation of the difference between automated and measured QTc intervals in children.

BACKGROUND: The corrected QT interval (QTc) is obtained through automated ECG computations or manual physician measurements. We hypothesized that differences exist in children between the measured and automated QTc intervals within and between Healthy and hypertrophic cardiomyopathy (HCM) subjects with greater differences for HCM due to structural abnormalities. METHODS: QT measurements - Bazett correction- automated (aQTc) and measured (mQTc), were extracted from the GE MUSE database for 385 Healthy pediatric (single ECG) and 208 HCM subjects (2 ECGs), stratified by age&#xa0;<&#xa0;12 and&#xa0;&#x2265;&#xa0;12&#xa0;yrs., sex, race, and ethnicity. QTc means (SD), automated and measured differences, and the difference of the differences of aQTc and mQTc were analyzed overall and by subgroups. All ECGs were read by one pediatric cardiologist with a second cardiologist reading a random subset of HCM ECGs to evaluate intraclass correlations and agreement. RESULTS: The mQTc intervals were shorter than aQTc intervals within Healthy (p&#xa0;<&#xa0;0.001) and within first HCM ECGs (p&#xa0;<&#xa0;0.001) with both aQTc and mQTc shorter in Healthy than HCM (p&#xa0;<&#xa0;0.001). The difference in these differences was significant overall using HCM ECG 1 but not HCM ECG 2. Healthy subject aQTc and mQTc intervals differed by age, sex, and race (p&#xa0;<&#xa0;0.002). HCM ECG 1 aQTc- mQTc intervals differed for age&#xa0;<&#xa0;12&#xa0;yrs., as well as by sex and race. HCM ECG 2 intervals differed only for age&#xa0;<&#xa0;12&#xa0;yrs. CONCLUSIONS: Compared to measured values, automated QTc values were significantly longer in both Healthy and HCM subjects. Automated measurements may overestimate the QTc.

Humans

Infant Dietary Patterns and Early Childhood Weight Outcomes: A Secondary Analysis from the Starting Early Program Trial.

BACKGROUND: The Starting Early Program (StEP) promotes healthy nutrition during early life and leads to healthier child weight, but whether dietary patterns contribute to weight or mediate StEP weight outcomes has not been studied. OBJECTIVES: This secondary analysis identified infant dietary patterns in StEP, determined associations between dietary patterns and child weight outcomes, and examined whether dietary patterns mediated the relationship between StEP and child weight. METHODS: Data were from 377 mother-infant dyads in a randomized trial testing the efficacy of StEP. Dietary patterns at 10 months were identified using latent class analysis. Child weights were abstracted from medical records at 12, 24, and 36 months. Associations between infant dietary patterns and weight-for-age z-score (WFAz) and likelihood of being classified as overweight (WFA &#x2265;85th percentile) were assessed using linear and logistic multivariable regression models. Mediation was used to assess intervention effects on WFAz via impacts on infant dietary patterns. RESULTS: Four classes of infant dietary patterns were identified: Breastfed-High variety, Formula fed-High variety, Formula fed-Low variety, and Mixed fed-Low variety. Compared to the Breastfed-High variety class, infants in the Formula fed-Low variety class had higher WFAz and were more likely to be classified as overweight at 24 and 36 months. Participation in StEP increased membership in Breastfed-High variety, which mediated the association between StEP and lower WFAz at 24 months. CONCLUSIONS: Infant dietary patterns were identified, and some were associated with child overweight. StEP was associated with a dietary pattern most consistent with guidelines, which mediated intervention effects on child weight.

Humans

Optimal dose and exercise modality to improve HbA1c in older adults with type 2 diabetes mellitus: a systematic review with pairwise, network, and dose-response meta-analyses.

We aimed to compare exercise modalities and evaluate dose-response relationships with glycemic control including continuous aerobic exercise (CAE), resistance training (RT), combined exercise (CE), mind-body exercise (MBE), and high-intensity interval training (HIIT) in older adults with type 2 diabetes mellitus (T2DM). Three databases were searched for randomized controlled trials of exercise interventions in older adults with T2DM reporting glycated hemoglobin (HbA1c). Pairwise, Bayesian network, and dose-response meta-analyses were conducted. Compared with control, HIIT demonstrated the largest estimated reduction (MD&#xa0;=&#xa0;-0.95%; 95% CrI&#xa0;-1.45, -0.49), followed by CE (MD&#xa0;=&#xa0;-0.59%; 95% CrI&#xa0;-0.93, -0.25), CAE (MD&#xa0;=&#xa0;-0.46%; 95% CrI&#xa0;-0.69, -0.24), MBE (MD&#xa0;=&#xa0;-0.42%; 95% CrI&#xa0;-0.76, -0.10), and RT (MD&#xa0;=&#xa0;-0.29%; 95% CrI&#xa0;-0.51, -0.08). Dose-response network meta-analyses suggested a non-linear association between overall exercise dose and HbA1c reduction, with maximal estimated benefits at approximately 704 METs-min/week with the 95% CrI excluding zero between 241 and 920 METs-min/week. HIIT demonstrated the steepest estimated dose-response relationship, but with wider credible intervals. Other exercise modalities showed more gradual dose-response patterns across their estimated effective ranges. Our findings suggest that exercise prescription for older adults with T2DM should be individualized according to exercise modality, dose, and health status.

Humans

Mapping the Molecular Evolution and Role of Wild Rice GLYIII Protein-Encoding Genes in Abiotic Stress Response.

To address the need for sustainable food production amid rapid global climate change, developing rice varieties that grow optimally even under harsh conditions is essential. An effective approach in this direction would be to harness the stress resilience traits of the crop wild relatives (CWRs) of rice. Among the various crucial stress-responsive genes, the Glyoxalase III (GLYIII) gene family is of utmost importance for its ability to detoxify the toxic glycolytic byproduct, methylglyoxal (MG), in a less energy-intensive, single-step process, as well as for its multifaceted cytoprotective role. In our study, a comprehensive genome-wide search across the Oryza genus revealed that GLYIII genes are conserved across wild rice genotypes. Their number has expanded during domestication, driven by gene duplications. Interestingly, only a few orthologous pairs showed positive selection, suggesting that the functions of most others need to be constrained and or conserved.We found that higher GLYIII activity, Total Antioxidant Capacity, endogenous glutathione (GSH) levels, and free radical scavenging activity contributes to the stress resilience of wild rices O. punctata, O. meridionalis, and O. nivara, in addition to other factors. , , . , . Our qRT-PCR analysis revealed differential expression of the OpGLYIII, OmGLYIII, and OnGLYIII genes across different developmental stages and in response to various abiotic stresses. Furthermore, we report that wild rice GLYIII proteins, specifically OpGLYIII-3, OmGLYIII-3, and OnGLYIII-5, exhibit high catalytic efficiency over a broad pH range and at higher temperatures under in vitro assay conditions. Overexpression of these proteins was found to impart substantial stress resilience to the transformed E. coli cells. These findings collectively suggest that GLYIII proteins constitute a key component of the abiotic stress response machinery in wild rice.

Oryza

A versatile reversed-phase liquid chromatography charged aerosol detection method for streamlined monitoring of QS-21 content and stability in liposomal adjuvant formulations.

Identifying and quantifying an active adjuvant along with its degradants in drug formulations is essential for ensuring the safety and efficacy of the drug product. QS-21 is a potent adjuvant that is being evaluated in several clinical trials and is currently formulated in licensed vaccines that protect against shingles, malaria, and RSV. In aqueous environments, QS-21 is subject to hydrolytic degradation that is influenced by pH and temperature, resulting in the formation of a degradant known as QS-21 Hydrolyzed Product, QS-21 HP, which can occur during manufacturing and/or prolonged storage. The intact QS-21 and QS-21 HP induce distinct immune response profiles, making it critical to monitor the degradation of QS-21 in vaccine adjuvant formulations. To date, there has been a paucity of reliable assays for QS-21, its isomers, and degradant QS-21 HP in liposomal adjuvant formulations available that can be transferred seamlessly in quality control (QC) environments. Herein, we introduce a simple and QC-friendly liquid chromatography coupled to a charged aerosol detector (LC-CAD) enabled by stationary phase screening combined with in silico method development optimization. The method exploits 2.7&#xa0;&#x3bc;m fused-core phenyl hexyl particles, ensuring its versatility in standard and ultra-high pressure LC systems. This approach demonstrates a high correlation between predicted retention time (RT) and experimental outcomes with overall &#x2206;RT&#xa0;<&#xa0;4%. In addition, this assay shows great linearity, precision, specificity, and accuracy to advance process development characterization of new vaccine formulations.

Liposomes

Effects of acute resistance exercise on prefrontal oxygenation and task-switching performance: Considerations of loading strategies and blood flow restriction.

Although acute resistance exercise (RE) has been proposed to influence cognitive flexibility and underlying neural mechanisms, it remains unclear whether these effects vary across loading strategies and whether exercise-induced prefrontal hemodynamic responses translate into cognitive outcomes. The present study examined (1) prefrontal cortex (PFC) oxygenated hemoglobin (O2Hb) responses across exercise sets and conditions, (2) the effects of low-load (LL), LL with blood flow restriction (BFR), and high-load (HL) RE on task-switching performance, and (3) whether exercise-related PFC O2Hb responses were associated with pre- to post-exercise changes in task-switching performance. Thirty physically active adults completed three randomized, counterbalanced RE conditions consisting of four sets of barbell squats. LL was performed at 30% one-repetition maximum (1RM) with and without BFR, whereas HL was performed at 70% 1RM. Cognitive flexibility was assessed pre- and post-exercise using a modified Stroop task, indexed by switch-cost reaction time (RT) and accuracy. PFC O2Hb was assessed using functional near-infrared spectroscopy during exercise and expressed as changes from the resting baseline for each set (Sets 1-4). PFC O2Hb increased across sets, rising from Set 1 to Set 3 before plateauing, with no differences observed across conditions. Switch cost RT and accuracy did not improve from pre- to post-exercise, and no differences across conditions were detected. PFC O2Hb during the final set was not associated with changes in switch cost. These findings suggest that although acute RE elicits robust increases in prefrontal hemodynamic activity, such responses may not translate into acute improvements in cognitive flexibility.

Humans

Efficacy of prescription-eligible digital health applications for depression and generalized anxiety disorder in Germany: a systematic review and meta-analysis.

In Germany, prescription-eligible digital mental health applications (DiGA) were introduced in 2020 as promising interventions to address, among others, depression and anxiety disorders, two of the most prevalent mental health conditions worldwide. Despite growing interest in DiGAs, their overall efficacy remains uncertain. This study aimed to systematically evaluate and quantify the efficacy of prescription-eligible digital interventions for depression and generalized anxiety disorder by synthesizing evidence from randomized controlled trials (19 trials; total N&#x2009;=&#x2009;4,078; pooled mean age&#x2009;=&#x2009;38.7 years, SD&#x2009;=&#x2009;12.1). Here we show that prescription-eligible digital applications for depression and generalized anxiety disorder reduce symptom severity compared with control conditions. For depression, effects were observed both immediately after the intervention (number of apps&#x2009;=&#x2009;5; k&#x2009;=&#x2009;17; SMD = -&#x2009;0.49; 95% CI -&#x2009;0.65 to -&#x2009;0.32) and at follow-up (number of apps&#x2009;=&#x2009;1; k&#x2009;=&#x2009;4; SMD = -&#x2009;0.35; 95% CI -&#x2009;0.46 to -&#x2009;0.29), while evidence for generalized anxiety disorder was limited due to a small number of available studies (number of studies&#x2009;=&#x2009;2). These findings support the integration of evidence-based digital tools into mental health treatment strategies in Germany. However, the available evidence is currently dominated by a small number of applications, particularly Deprexis, and should therefore not be interpreted as equally representative of all DiGAs currently listed for depression in Germany. The findings also highlight methodological limitations of current research and underscore the need for real-world evaluations, which address not only efficacy but also the effectiveness, content, quality and implementation.

Generalized Anxiety Disorder

GIP contributes to postprandial regulation of splanchnic blood supply in humans with type 2 diabetes: a randomised, single-blinded, placebo-controlled, crossover study.

AIMS/HYPOTHESIS: In healthy lean humans, endogenous glucose-dependent insulinotropic polypeptide (GIP) contributes significantly to the postprandial increase in arteria mesenterica superior blood flow. The vascular biology related to activation of the GIP receptor is markedly impaired in individuals with type 2 diabetes and is sometimes absent. In this population, we investigated the role of endogenous GIP on postprandial splanchnic blood flow by using the GIP receptor antagonist, GIP(3-30)NH2. The primary outcome of this study was the changes in blood flow in arteria mesenterica superior during oral glucose with or without GIP receptor antagonist infusion. METHODS: Ten participants with type 2 diabetes (age 20-80 years, BMI 20-35 kg/m2, and HbA1c >48 mmol/mol and <75 mmol/mol) were investigated in a randomised, placebo-controlled, crossover study. On four separate occasions, participants received the following treatment: oral glucose + i.v. GIP(3-30)NH2; oral glucose + i.v. saline (154 mmol/l NaCl); oral water + i.v. GIP(3-30)NH2; oral water + i.v. saline. Participants were randomly assigned to intervention groups using (random.org). Participants were unaware of allocation, while investigators were aware. No additional allocation concealment procedures were used. During all four interventions, splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus and vena portae during oral glucose (75 g) or water ingestion. The study was conducted at Rigshospitalet, Copenhagen. Liver volume and oxygenation, as well as gallbladder volume, were assessed. Blood samples were collected and analysed for insulin, C-peptide, GIP, glucagon and glucose. RESULTS: Oral glucose alone increased mean blood flow in arteria mesenterica superior by 57% (95% CI 26, 88) and this was 15% (95% CI -2, 32) lower during concomitant GIP receptor antagonist infusion, p=0.012. Infusion of GIP receptor antagonist during oral glucose treatment did also result in lower insulin secretion, C-peptide and C-peptide/glucose ratio compared with saline infusion, whereas glucagon levels and plasma glucose were unaffected. Oral water did not affect any outcomes. CONCLUSIONS/INTERPRETATION: Endogenous GIP contributes to postprandially increased splanchnic blood flow in people with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT06426823 FUNDING: This work was supported by the Novo Nordisk Foundation.

Humans

A qualitative study of cancer survivors' exercise behaviour 4 months after a telerehabilitation program.

PURPOSE: Although telerehabilitation can improve access to exercise programs for cancer survivors, it is not known if these programs lead to ongoing change in exercise habits. This study explored participant experiences of exercise 4 months after finishing specialized cancer exercise-based telerehabilitation. METHOD: A qualitative study embedded in a randomized controlled trial evaluated exercise-based cancer telerehabilitation delivered in groups. Data were collected via semistructured interviews that were audio-recorded and transcribed verbatim. Seventeen adult cancer survivors (age 21 to 80) were purposively sampled 4 months after completing exercise-based cancer telerehabilitation. Data were coded independently by two researchers and analyzed inductively within an interpretive description framework. RESULTS: The overarching theme was telerehabilitation was perceived to facilitate positive exercise intentions. Participants said they were empowered to exercise through knowledge, opportunity, and connection gained through telerehabilitation. They described acting on their positive intentions to exercise to varying degrees following telerehabilitation, depending on their context. A subtheme was that exercise was challenging in their new reality created by cancer. Comorbidities, ongoing side effects, previous exercise experience, and personal factors were considered by some to influence their ability to exercise. CONCLUSION: Telerehabilitation may facilitate positive intent to maintain exercise. Cancer survivors may need ongoing support after telerehabilitation to act on positive exercise intentions due to health-related difficulties. IMPLICATIONS FOR CANCER SURVIVORS: Participation in telerehabilitation may be a positive first step to initiate exercise, but ongoing support to maintain positive behavior changes is likely to be needed for people without previous exercise experience.

Humans

Menopause in the All of Us Research Program: a descriptive summary of electronic health record and survey response across sociodemographic characteristics.

OBJECTIVES: Menopause is a significant physiological transition with implications for health outcomes (eg, cardiometabolic disease), yet gaps remain in understanding this transition, including how menopause timing and type influence health outcomes. Large-scale cohort studies in midlife (age=40-60) females, including the All of Us Research Program (AoURP), provide opportunities to study menopause across diverse populations and data modalities. We characterized menopause-related data in AoURP, focusing on age distributions and concordance between electronic health record (EHR) diagnosis codes and survey responses. METHODS: We analyzed menopause-related surveys, EHR diagnostic codes, and genomic data among ~396,000 AoURP female participants. We summarized menopause-related variables across data sources, evaluated overlap between survey, EHR, and genomic data sets, and described age distributions overall and across sociodemographic characteristics. RESULTS: Among ~396,000 females, survey responses captured ~193,000 menopause observations, nearly seven times more than EHR diagnoses (~28,000), suggesting under-ascertainment in EHR data. Nearly all females (~99%) with an EHR menopause diagnosis reported menopause in the survey. Approximately 22,000 participants had overlapping menopause-related EHR, survey, and genomic data. Survey age patterns matched expectations, with participants predominantly <40 years reporting premenopausal status and those >60 years reporting postmenopausal status. A small subset with age >70 years (N&#x2248;1,700; 4%) reported no menopause, suggesting response or recall bias. EHR menopause codes were concentrated after age 45 years, with a notable spike at age 65. Modest differences in survey-based menopause age distributions were observed across sociodemographic characteristics (eg, race and ancestry). CONCLUSIONS: These findings inform sampling strategies, power calculations, phenotype definition, and study design for menopause research using AoURP data.

Age

Time to subsequent therapy (TTST) as an endpoint in clinical studies: development of standardized documentation of subsequent therapy through systematic literature review, expert interviews, and Delphi survey.

BACKGROUND: The endpoint Time to Subsequent Therapy (TTST) is an intermediate endpoint used in research and regulatory assessments. TTST denotes initiation of subsequent therapy and is a clearly definable, clinically relevant event for healthcare professionals. However, it has not been systematically established to which extent TTST is subjectively meaningful to patients. The objective of this study was to define TTST as a patient-relevant intermediate endpoint. METHODS: The study examined five oncological indications (breast cancer, prostate cancer, melanoma, multiple myeloma, and non-small cell lung cancer) using a systematic literature review, analysis of case report forms used in international randomized controlled trials, review of German Federal Joint Committee (G-BA) documents, semi-structured interviews and a two-stage Delphi survey with healthcare professionals, patients, and relatives. RESULTS: A total of 35 individuals participated in qualitative interviews. Most of them rated TTST as particularly significant. The Delphi Survey included 264 interviewees in round one, and 117 in round two. Patient-relevance of TTST was confirmed by 81% of respondents (95% confidence interval 76%, 85%). Nine treatment scenarios that justify TTST were identified. To capture patient-relevance, prospective collection of reasons for and consequences of therapy change are required. A checklist with standardized response formats plus free-text fields was developed: a comprehensive master checklist for flexible, complete documentation and a short version focused on therapy change-specific items. CONCLUSIONS: TTST is an intermediate endpoint whose systematic documentation of characteristics demonstrating patient-relevance can be standardized in research and clinical practice using the developed checklists.

Humans

The Animal Variant Classification Guidelines v2: An Update With New Criteria and Improved Clarifications.

The Animal Variant Classification Guidelines (AVCG) were developed to standardize and objectify the classification of putative disease-causing variants. These guidelines are sufficiently reproducible and are used to classify previously published and new disease-causing variants across species. Here, the guidelines are updated (AVCG.v2), based on a three-phase decision process. Overall, four new criteria and seven clarifying comments were added. The number of criteria has increased from 23 to 27, with three new criteria supporting pathogenicity and one new criterion supporting benign classification. Pharmacogenomic variants were determined to fall within the scope of the guidelines. These updated guidelines are being used by the Variant Pathogenicity Working Group (VPWG), part of the Animal Genetic Testing Standardization standing committee, which is a committee of elected members of the International Society for Animal Genetics (ISAG). Under the auspices of ISAG, the VPWG retrospectively classifies published putative disease-causing variants. The pathogenicity label for a variant will be presented in the variant tables of Online Mendelian Inheritance in Animals (OMIA; https://omia.org/). The AVCGv.2 criteria and recommendations were developed by the expertise of the animal genetics community and the ISAG Executive Committee through the Animal Genetics Testing Standardization Committee endorses and strongly encourages their use to evaluate the evidence supporting pathogenicity of putative disease-causing variants.

Animals

Long-Term Survey to Assess Recurrence and Complications of Surgically Treated Pleomorphic Adenoma.

OBJECTIVE(S): To (1) report on the long-term recurrence rate of surgically managed pleomorphic adenoma (PA) and (2) assess long-term surgical outcomes after parotidectomyMethods:Cross-sectional survey of all patients with a pathologic diagnosis of PA who underwent surgical management in a tertiary care center from 01/1997 to 12/2023 and had access to an electronic patient portal. Surveys were delivered via electronic patient portal or phone call with 6 questions to assess recurrence and long-term surgical outcomes. Time to first recurrence and recurrence free survival were analyzed using a Kaplan-Meier curve. RESULTS: Seven hundred-forty-five patients met inclusion criteria and received the survey, with a 56% response rate (n&#x2009;=&#x2009;420). The clinical median follow-up length was 51&#x2009;days, which extended to a median length of 6.2&#x2009;years following the survey. The median change in follow-up length was 5.37&#x2009;years (P&#x2009;<&#x2009;.001). The recurrence rate was 1% at 5&#x2009;years, with a median time to first recurrence of 7.54&#x2009;years. 13% and 9% of responders reported facial asymmetry and incisional cosmetic concerns, respectively. 33% of patients reported experiencing Frey syndrome, which increased from 5.2% of survey responders with documented Frey syndrome at their original post-operative assessment. CONCLUSION: Long-term assessment of PA outcomes confirms low recurrence rates, suggesting regular surveillance of recurrence is likely unnecessary. Complaints of Frey syndrome increased in frequency with longer term follow-up, which should be considered during patient counseling. LEVEL OF EVIDENCE: 3.

Humans

Clinical and psychological characteristics of adolescents at risk of mood disorders compared with adolescents with suicidal behavior.

Suicide is one of the leading causes of death among adolescents, yet little is understood about the biopsychosocial factors related to suicidality. The demographic, clinical, and biological characteristics of adolescents with and without psychiatric histories may help inform mechanistic approaches to treatment of mood disorders and suicidality. The 'characterizing the inflammatory profile and suicidal behavior in adolescents' and 'RAD arm of the Texas Resilience Against Depression' studies aimed to characterize the clinical and biological profiles of youth with suicidal behavior and youth at risk for mood disorders, compared to healthy adolescents (n&#xa0;=&#xa0;75 in each group). Here, we report the descriptive baseline clinical and psychological characteristics of adolescents at risk of mood disorders and those with suicidal behavior. The adolescents with suicidal behavior reported 3.53 lifetime suicidal events on average, predominantly reported moderate to very severe depression (34.7%, 24%, to 9.3%), moderate to severe anxiety (58.6%), low optimism (91.9%), and mild (39.2%) to moderate (28.4%) degree of hopelessness. The at-risk adolescents predominantly reported no depression (60%) or anxiety (68.9%), moderate optimism (50%), and a positive outlook (85.7%). Healthy adolescents predominantly reported no depression (88.3%) or anxiety (93.2%), moderate optimism (59%), and a positive outlook (87%). The adolescents with suicidal behavior and those at risk of mood disorders exhibited significantly higher irritability and borderline personality disorder features (uncorrected p&#xa0;=&#xa0;0.02 to p&#xa0;<&#xa0;0.001) and lower resilience compared to healthy adolescents. Ongoing investigations using the longitudinal clinical and biological data will help identify the immune biosignatures of suicidality in youth.

Humans

MET expression by immunohistochemistry as a biomarker in pancreatic neuroendocrine tumours.

INTRODUCTION: MET (c-MET) is a receptor tyrosine kinase implicated in numerous cancers, including pancreatic neuroendocrine tumours (pNETs), by promoting cell proliferation, survival, invasion and angiogenesis. Recognizing its oncogenic potential, there is significant interest in MET-targeted therapies for malignancies like pNETs, which often develop treatment resistance. Immunohistochemistry (IHC) has become a practical method for detecting MET overexpression in cancers. This study evaluates MET expression in pNETs by IHC and assesses its correlation with prognostic variables and survival outcomes. METHODS AND RESULTS: Tissue microarrays containing well-differentiated neuroendocrine tumours from the gastrointestinal tract were analysed. The study included 125 pNET cores from 112 patients after application of inclusion criteria. MET expression was determined using the H-score system. Different variables were assessed for H-score distribution and cross-tables. Survival analyses were conducted based on progression-free survival and overall survival. Positive MET expression was found in 83.5% of cases. Higher MET H-scores were seen in patients with lymphovascular invasion (LVI), distant metastases and higher tumour grade (P&#x2009;<&#x2009;0.05). When assessing different variables for higher MET H-scores, a significant association emerged at the 150-cut-off-point for LVI, perineural invasion, radiological evidence of progression and overall survival. For survival analysis, at a MET H-score threshold of 200, high MET expression was significantly associated with shorter progression-free survival (mean 8.7 versus 13.4&#x2009;years, P&#x2009;<&#x2009;0.05) and overall survival (mean 3.6 versus 7.7&#x2009;years, P&#x2009;<&#x2009;0.05). CONCLUSION: Elevated MET expression is linked to adverse histopathological features and worse clinical outcomes in pNET. Standardizing MET IHC evaluation is critical as anti-MET therapies develop, and identifying patients likely to benefit from these treatments remains essential.

MET protein

The Efficacy of Pharmacotherapy Intervention on Anthropometric Outcomes in Survivors of Childhood Brain Tumors: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: Many survivors of childhood brain tumors face long-term adverse health outcomes like obesity. Uncertainties surround the effect of interventions to manage obesity-related outcomes in survivors of childhood brain tumors. The goal of this updated systematic review and meta-analysis was to provide the best estimate of the treatment efficacy of pharmacotherapy intervention on anthropometric outcomes in this pediatric population. METHODS: We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, and ProQuest for articles published from January 1, 2015, to January 31, 2025. A meta-analysis was performed using the generic inverse-variance method in RevMan 5.4. Heterogeneity was assessed using the Cochrane Q test and the I2 statistic. We used the GRADE approach to determine the certainty of evidence. RESULTS: A total of six studies met the inclusion criteria: four newly identified studies published after January 1, 2015 (125 participants), and two from the previously published review (23 participants). The pooled estimate showed no significant change in body mass index z-score after intervention (mean difference&#x2009;=&#x2009;-0.02; 95% CI: -0.06 to 0.02, I2&#x2009;=&#x2009;0%; 4 studies, 94 participants; low certainty of evidence). Similar pooled effects were observed across other outcomes; however, individual studies reported significant changes in some outcomes within the treatment groups after the intervention. CONCLUSION: Pharmacological agents showed no significant change in anthropometric outcomes for survivors of childhood brain tumors. Further trials are needed to assess the efficacy of pharmacological agents and to identify subgroups most likely to benefit.

Humans

Effect of brewers' yeast or beta-glucan derived from Saccharomyces cerevisiae on breast milk supply following preterm birth: the BLOOM randomised controlled trial.

OBJECTIVE: Breast milk is the optimal source of nutrition for preterm infants; however, low breast milk production is common following a preterm birth. This study aimed to determine if taking brewers' yeast or beta-glucan improves daily expressed breast milk volume. DESIGN: Randomised, blinded, parallel, placebo-controlled trial. SETTING: Three Australian tertiary-level neonatal units. PATIENTS: Mothers with a singleton or twin pregnancy who gave birth at <34 weeks' gestation. INTERVENTIONS: Mothers were randomised within 72 hours of birth into three parallel groups in a 1:1:1 ratio to receive either brewers' yeast, beta-glucan or placebo capsules for 7&#x2009;days. MAIN OUTCOME MEASURE: Total expressed breast milk volume over a 24-hour period on day 7 of intervention. RESULTS: A total of 105 mothers underwent randomisation between August 2022 and April 2024 (36 brewers' yeast, 35 beta-glucan and 34 placebo). The adjusted mean difference in daily expressed breast milk volume was 94&#x2009;mL/day (95%&#x2009;CI -51 mL/day to 239&#x2009;mL/day) between the brewers' yeast and placebo groups and -25&#x2009;mL/day (95%&#x2009;CI -173 mL/day to 123&#x2009;mL/day) between the beta-glucan and placebo groups. Maternal side effects were similar across groups. CONCLUSION: We found no clear effect of short-term administration of brewers' yeast or beta-glucan on breast-milk production following preterm birth; both interventions were well tolerated. Given the small sample size, these findings do not rule out the possibility of a clinically meaningful benefit of brewers' yeast and suggest further research with a larger sample size may be warranted to clarify the potential clinical impact. TRIAL REGISTRATION NUMBER: ACTRN12622000968774.

Intensive Care Units, Neonatal

Illicium verum polysaccharide targets fimbriae and flagella to disrupt biofilm and inhibit multidrug-resistant Escherichia coli proliferation.

The widespread dissemination of multidrug-resistant (MDR) E. coli has led to a decrease in the efficacy of antibiotics, posing severe challenges to clinical anti-infective therapy. Owing to their safety, multitarget activities, and low risk of inducing drug resistance, plant polysaccharides represent a promising alternative strategy. In this study, an acidic polysaccharide (IVP-3) was isolated and purified from the medicinal and edible plant Illicium verum, and it was found to inhibit MDR E. coli colonization by disrupting its biofilm. The Mw of IVP-3 was determined to be 35.566&#xa0;kDa. Its backbone consists of &#x2192;4)-&#x3b1;-D-GalpA-6-OMe-(1&#x2192;, &#x2192;4)-&#x3b1;-D-GalpA-(1&#x2192;, &#x2192;4)-&#x3b2;-D-Galp-(1&#x2192;, and &#x2192;3,4)-&#x3b1;-D-GalpA-(1&#xa0;&#x2192;&#xa0;residues, whereas the branched chain is composed of &#x3b1;-L-Araf-(1&#xa0;&#x2192;&#xa0;5)-&#x3b1;-L-Araf-(1&#xa0;&#x2192;&#xa0;attached to the O-5 position of &#x2192;2,5)-&#x3b1;-L-Araf-(1&#x2192;, which is further linked to the O-3 position of the backbone. Mechanistically, IVP-3 disrupts the structure of fimbriae and flagella, inhibits bacterial motility, effectively prevents initial biofilm adhesion, and eradicates preformed mature biofilms. Additionally, IVP-3 damages cell membrane integrity, disrupts the proton motive force, and induces energy metabolism disorder, efflux pump inhibition, and oxidative stress, ultimately leading to bacterial lysis. This study provides a theoretical basis for the development of natural antibacterial agents targeting MDR E. coli biofilms and for the high-value utilization of Illicium verum.

Biofilms