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Comparative Efficacy of Tirzepatide Versus Semaglutide for Weight Loss in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis of Head-to-Head Studies.

This systematic review and meta-analysis aimed to compare&#xa0;the efficacy and safety of tirzepatide versus semaglutide for weight reduction in adults with overweight or obesity. We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with &#x2265;&#x2009;24&#x2009;weeks of follow-up. The primary outcome was percentage weight change from baseline. Secondary outcomes included absolute weight change, weight-loss thresholds, HbA1c and safety outcomes. Ten studies including 41&#x2009;381 participants were analysed. Tirzepatide was associated with greater percentage weight reduction than semaglutide (MD -4.28 percentage points; 95% CI -5.28 to -3.28; p&#x2009;<&#x2009;0.00001) and greater absolute weight loss (MD -4.43&#x2009;kg; 95% CI -5.56 to -3.30; p&#x2009;<&#x2009;0.00001). Tirzepatide was also associated with a higher likelihood of achieving &#x2265;&#x2009;10%, &#x2265;&#x2009;15% and &#x2265;&#x2009;20% weight loss, with no difference at &#x2265;&#x2009;5%. HbA1c reduction was greater with tirzepatide (MD -0.29%; p&#x2009;=&#x2009;0.0002). Subgroup analyses by study design and type 2 diabetes status yielded consistent findings. There was no significant difference in treatment discontinuation due to adverse events (RR 1.28; p = 0.54), whereas serious adverse events were more frequent with tirzepatide (RR 1.83; p&#x2009;=&#x2009;0.007). Overall and gastrointestinal adverse events were similar between groups. Tirzepatide was associated with greater weight reduction, greater glycaemic benefit and a higher likelihood of achieving weight-loss thresholds than semaglutide, but with a higher risk of serious adverse events.

Humans

Evolution of Precision Oncology, Personalized Medicine, and Molecular Tumor Boards.

With multiple molecular targeted therapies available for patients with cancer that correspond to a specific genetic alteration, the selection of the best treatment is essential to ensure therapeutic efficacy. Molecular tumor boards (MTBs) play a key role in this process to deliver personalized medicine to patients with cancer in a multidisciplinary manner. Historically, personalized medicine has been offered to patients with advanced cancer, but the incorporation of molecular targeted therapies and immunotherapy into the perioperative setting requires clinicians to understand the role of the MTB. Evidence is accumulating to support feasibility and survival benefit in patients treated with matched therapy.

Humans

Ultra-high-field 7T MRI reveals neural abnormalities of attention networks in relation to cognitive impairment in hypertension.

Hypertension is a significant risk factor for cognitive impairment (CI), yet the corresponding neural network abnormalities remain underexplored. In this study, we examined the associations among global and domain-specific cognitive dysfunction, neuroimaging measures, and blood pressure in a subgroup of hypertensive patients with CI (N&#xa0;=&#xa0;41) from a randomized controlled trial who underwent ultra-high-field 7&#xa0;T MRI. Structural atrophy related to CI was localized to regions overlapping the attention networks. Both whole-brain and within-network dysfunction of the attention networks were associated with worse global cognitive performance. Notably, hyperconnectivity within key attention network hubs, including the right anterior insula and posterior intraparietal sulcus, was associated with declined processing speed in hypertensive patients, mediating the association between pulse pressure and processing speed. These findings provide new insights into the neural pathophysiology of hypertension-related CI and suggest potential network-based targets for intervention.

Magnetic Resonance Imaging

Comparative in silico analysis of Apis mellifera immune responses to Varroa destructor and Tropilaelaps mercedesae: Common and mite-specific molecular signatures.

Parasitic mites Varroa destructor and Tropilaelaps mercedesae represent major threats to global honey bee (Apis mellifera) health and productivity, yet comparative molecular insights into host responses remain limited. To address this, we systematically compiled published studies (2015-2025) reporting genes associated with honey bee interactions with V. destructor (11 studies, 87 genes), T. mercedesae (4 studies, 35 genes), and hygienic behavior (6 studies, 44 genes). Gene identifiers were harmonized to the Amel_HAv3.1 genome assembly, yielding three non-redundant sets: 64 Varroa-associated, 34 Tropilaelaps-associated, and 44 hygienic behavior-associated genes. Venn analysis identified 10 overlapping genes (including A0A088A8D5, A0A088ADL8, ABAE_APIME, Def1, Def2, Gapdh, HYTA_APIME, Imd, LOC726783, and Vg), suggesting conserved defense mechanisms, while 41 and 24 genes were uniquely associated with Varroa and Tropilaelaps, respectively. Enrichment analyses revealed Varroa-responsive genes were enriched in immune processes, chitin catabolism, and signaling pathways (Toll/Imd, MAPK, Wnt). Tropilaelaps-associated genes were enriched for antibacterial defense and stress response, with Toll/Imd signaling as the sole significantly enriched pathway. Overlapping genes reinforced core innate immunity activation. Protein-protein interaction network centrality analysis identified key hub genes: Def1, HYTA_APIME, ABAE_APIME, PPO, Imd, PGRP-LC, Vg for Varroa; and ACPH1_APIME, MRJP1, Vg, LOC726783 for Tropilaelaps. Results demonstrate that, despite differences in mite biology, honey bees show a conserved immune response against both parasites, centered on antibacterial defense, humoral immunity, and activation of the Toll/Imd pathway. Although limited by the in-silico nature and research asymmetries reflecting Tropilaelaps' emergence, this curated resource establishes a comprehensive framework for elucidating shared and distinct molecular defense mechanisms. Ultimately, this approach prioritizes diagnostic markers and candidate genes for functional validation and breeding strategies to enhance colony resilience against mite&#x2011;driven disease globally.

Animals

Efficacy and Safety of Elagolix Versus Dienogest for Treatment of Moderate-to-Severe Endometriosis Pain: A Phase III, Multicentric, Double-Blind, Active-Controlled, Non-Inferiority Study.

OBJECTIVE: To compare the efficacy, safety and tolerability of elagolix with dienogest in women with moderate-to-severe endometriosis-associated pain. DESIGN: A multicentre, double-blind, double-dummy, randomised, parallel-group, active-controlled, non-inferiority phase III study. SETTING: Nineteen clinical centres across India. STUDY POPULATION: Women (18-49&#x2009;years) diagnosed with endometriosis and experiencing moderate-to-severe pain. METHODS: Participants were randomised (1:1) to receive oral elagolix (150&#x2009;mg once daily) or dienogest (2&#x2009;mg once daily) for 24&#x2009;weeks. OUTCOME MEASURES: The primary outcome was change in endometriosis-related pain (Numeric Rating Scale [NRS]) from baseline to Day 85. Secondary outcomes included changes in NRS (Day 169), dysmenorrhoea, non-menstrual pelvic pain (NMPP) scores (Days 85 and 169), rescue medication use, patient global impression of change (PGIC), adverse events and bone mineral density. RESULTS: Of 340 patients screened, 230 were randomised (115 per group). At Day 85, both arms showed similar reductions in NRS pain scores with a treatment difference of 0.04 (95% CI: -0.3, 0.37) [p&#x2009;=&#x2009;0.9747] demonstrating non-inferiority as upper 95% CI was below pre-specified margin of 1.5. At Day 169, both arms showed comparable improvements in overall pain, dysmenorrhoea and NMPP from baseline (p&#x2009;=&#x2009;0.9372, p&#x2009;=&#x2009;0.8884, and p&#x2009;=&#x2009;0.9616, respectively). Rescue medication use and PGIC were comparable between treatment arms. Adverse event incidence was similar (elagolix: 14.8%; dienogest: 19.1%), with no serious TEAEs or discontinuations. No significant bone mineral density changes were observed. CONCLUSIONS: Elagolix demonstrated non-inferiority to dienogest with an acceptable safety and tolerability profile, supporting its use in managing endometriosis-associated pain. TRIAL REGISTRATION: ClinicalTrials.gov identifier: CTRI/2023/01/049292.

Humans

SBUF-SMUF: On the path to the optimum hemofiltration technique in pediatric cardiopulmonary bypass: A randomized clinical trial.

BACKGROUND: Hemofiltration during pediatric cardiopulmonary bypass (CPB) is essential to mitigate hemodilution, inflammatory responses, and postoperative complications. Conventional ultrafiltration (CUF) is widely practiced, but novel methods such as subzero balanced ultrafiltration combined with simple modified ultrafiltration (SBUF-SMUF) may offer superior outcomes. OBJECTIVE: To compare the clinical efficacy and safety of CUF versus SBUF-SMUF in pediatric patients undergoing open-heart surgery. METHODS: In this prospective randomized, outcome-assessor-blinded clinical trial, 80 pediatric patients with congenital heart disease were allocated to either CUF (n = 40) or SBUF-SMUF (n = 40) during CPB. Baseline demographics, intraoperative characteristics, fluid balance, blood product utilization, and postoperative outcomes were assessed. Statistical analysis was conducted using independent t-tests, Chi-square tests, and Fisher's exact tests. Statistical significance was defined as a two-tailed p-Value of less than 0.05. RESULTS: Demographic and preoperative variables were comparable between groups. Mean fluid balance was significantly positive in the CUF group (+192.1 &#xb1; 178.8 mL) but negative in the SBUF-SMUF group (-105.0 &#xb1; 78.9 mL, p < 0.001). The SBUF-SMUF group required significantly less intraoperative PRBC (141.7 &#xb1; 70.2 vs. 261.0 &#xb1; 68.8 mL, p < 0.001) and postoperative FFP transfusion (2% vs. 10%, p = 0.020). Post-bypass hematocrit levels were higher (31.2% vs. 27.3%, p = 0.001) and extubation occurred earlier in the SBUF-SMUF group (1.05 &#xb1; 1.03 vs. 2.27 &#xb1; 2.37 days, p = 0.006). No significant differences were observed in potassium levels or incidence of acute kidney injury. CONCLUSION: The SBUF-SMUF technique is safe, effective, and superior to CUF in optimizing fluid balance, reducing blood product utilization, and facilitating earlier extubation in pediatric cardiac surgery. No additional risk of oliguria or electrolyte imbalance was observed compared to CUF. Its simplicity and reproducibility support its consideration as a standard approach in pediatric CPB.

Humans

Multisensory stimulation for promoting development and preventing morbidity in preterm infants.

RATIONALE: Multisensory stimulation is a structured, developmentally appropriate intervention that provides simultaneous or sequential stimulation of two or more senses (e.g. tactile, auditory, visual, or vestibular) in a controlled and non-stressful manner, with the aim of supporting early neurodevelopment in preterm infants. It has the potential to enhance physiological regulation in preterm infants by stabilizing key functions, such as respiratory patterns, heart rate, and oxygen saturation; reducing the need for respiratory support; and improving feeding performance and sleep regulation. Targeted multisensory interventions have also been associated with improved neurodevelopmental outcomes, including enhanced psychomotor development and visual function. OBJECTIVES: To assess the benefits and harms of multisensory stimulation compared to any single sensory intervention or standard care on major neurodevelopmental disability, mortality, and growth in preterm infants. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Emcare, CINAHL, Epistemonikos, two trial registries, and conference abstracts up to 28 November 2025. We checked reference lists of included trials, and systematic reviews on sensory interventions. ELIGIBILITY CRITERIA: We included 18 randomized controlled trials (RCTs) comparing multisensory stimulation in preterm infants with no intervention (placebo or standard care), and one RCT comparing multisensory stimulation with single-sense stimulation (tactile stimulation). OUTCOMES: Our critical outcomes were major neurodevelopmental disability at 18 to 24 months: cerebral palsy (CP), developmental delay, intellectual impairment, blindness, sensorineural deafness; death during initial hospitalization; and total weight gain (grams), assessed at discharge. When comparing multisensory stimulation with single-sense intervention, we also included weight gain during the intervention, an outcome added during the post-hoc analysis. Important outcomes were duration of hospital stay, of NICU stay, and of respiratory support; and time until full oral feeding. RISK OF BIAS: We used the Cochrane tool, RoB 2. SYNTHESIS METHODS: We conducted meta-analyses using fixed-effect models to calculate risk ratios (RR) for dichotomous data, and mean differences (MDs) for continuous data, each with its 95% confidence intervals (CIs). We assessed statistical heterogeneity by calculating the I2 statistic when we included more than two trials in a meta-analysis. We evaluated the certainty of evidence using GRADE. INCLUDED STUDIES: We included 19 trials (1554 newborn infants): 18 studies compared multisensory stimulation with standard care; one compared multisensory stimulation with single-sensory stimulation (tactile). In 10 studies, the primary aim was to assess the neurobehavioral outcomes of multisensory stimulation on preterm neo-nates. The other nine studies aimed to assess the impact of multisensory stimulation on weight gain during the intervention, weight gain until hospital discharge, length of neonatal intensive care unit (NICU) stay, length of hospital stay, time until full oral feeding, length of respiratory support, or a combination. In the abstract we report results for the critical outcomes only. We identified 13 ongoing studies. Four studies are awaiting assessment. SYNTHESIS OF RESULTS: Multisensory stimulation compared to standard care No studies reported on these major neurodevelopmental disabilities, assessed at 18 to 24 months' corrected age (CA): developmental delay, intellectual impairment, blindness, or sensorineural deafness. One study reported on rates of CP at 12 months of age. The evidence is very uncertain about the effect of multisensory stimulation on CP (RR 0.67, 95% CI 0.28 to 1.58; I&#xb2; not applicable; 1 study, 18 participants; very low-certainty evidence). The evidence suggests that multisensory stimulation may result in little to no difference in death during initial hospitalization (RR 0.97, 95% CI 0.54 to 1.73; I&#xb2; not applicable; 1 study, 395 participants; low-certainty evidence). Multisensory stimulation may increase total weight gain prior to discharge (MD 72.67, 95% CI 68.23 to 77.12; I&#xb2; = 0%; 3 studies, 474 participants; low-certainty evidence). Multisensory stimulation compared to single-sense (tactile) stimulation No studies reported on major neurodevelopmental disability, assessed at 18 to 24 months' CA, or death during initial hospitalization. The evidence is very uncertain about the effect of multisensory stimulation compared to tactile stimulation on weight gain during the intervention (MD -175.00, 95% CI -376.60 to 26.60; I&#xb2; not applicable; 1 study, 20 participants; very low-certainty evidence). The certainty of the evidence was low to very low across outcomes, primarily due to risk of bias, imprecision from small sample sizes and wide CIs, and in some cases, inconsistency. The evidence base was also limited by the lack of reporting of relevant outcomes and reliance on surrogate outcomes or shorter follow-up periods. AUTHORS' CONCLUSIONS: The available evidence on multisensory stimulation in preterm infants is limited and of low to very low certainty. No included studies reported on major neurodevelopmental disabilities at 18 to 24 months' CA, which represented a critical outcome for this review. Evidence regarding the effect of multisensory stimulation on CP is very uncertain, as it is based on a single small study reporting a surrogate outcome at 12 months. Multisensory stimulation may result in little to no difference in mortality during the initial hospitalization. It may increase total weight gain prior to discharge. However, the clinical significance of this finding is uncertain, particularly given the low certainty of the evidence and the multifactorial nature of growth in preterm infants. The evidence is very uncertain about the effect of multisensory stimulation compared to single-sense (tactile) stimulation on weight gain during the intervention. The only included study did not report major neurodevelopmental disabilities at 18 to 24 months' CA, mortality during the initial hospitalization, or total weight gain prior to discharge, which represented the critical outcomes for this review. Overall, the current evidence does not allow firm conclusions about the effectiveness of multisensory stimulation in promoting development or preventing morbidity in preterm infants. Future studies on multisensory stimulation should use more rigorous designs, larger samples, and report interventions using the template for intervention description and replication (TIDieR) checklist to ensure transparency. They should also report essential outcomes, such as neonatal death, major neurodevelopmental disabilities, length of hospital and NICU stay, time to full oral feeding, duration of respiratory support, and weight gain, to better assess the long&#x2011;term effects of multisensory stimulation in preterm infants. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol available via DOI: 10.1002/14651858.CD016073.

Humans

Systematic evaluation of one-dimensional-to-two-dimensional near-infrared spectroscopy transformations with deep learning for quantifying coconut sap adulteration.

Near-infrared (NIR) spectroscopy have limitations when combined with deep learning (DL) algorithms because they rely on low-dimensional datasets. Therefore, we investigated the potential of transforming one-dimensional (1D) NIR spectra into two-dimensional (2D) spectrograms using synchronous and asynchronous techniques and the continuous wavelet transform (CWT) and their effectiveness by integrating with DL for detecting adulteration in coconut sap. NIR spectra (12,500-4000&#xa0;cm-1) were collected from binary mixtures (0%-100%;w/w). The performance of all DL (convolutional neural networks-CNN, AlexNet and ResNet) models was compared with that of partial least squares (PLS). The models were ranked in the mentioned order based on their performances: 2D-CWT&#xa0;>&#xa0;2D-asynchronous > 2D-synchronous > 1D/2D-PLS. The important features of the best model can be explained and visualized using gradient-weighted-class-activation-mapping. The findings highlight that the 1D-to-2D NIR data transformation combined with DL is a highly robust approach because it addresses the feature representation gap in NIR data and effectively captures the spatial-spectral correlations.

Spectroscopy, Near-Infrared

From human papillomavirus (HPV) infection to HPV-associated cancers in systemic lupus erythematosus: A systematic review and Meta-analysis.

OBJECTIVE: The current cervix-focused screening paradigm in systemic lupus erythematosus (SLE) may underestimate extra-cervical anogenital cancer risk. This meta-analysis aimed to quantify the risk of human papillomavirus (HPV) infection and HPV-associated cancers in SLE patients. METHODS: A comprehensive search was conducted in PubMed (2010), Embase (2010), and Cochrane Library (2010) to August 8, 2025. Odds Ratios (ORs) and Standardized Incidence Ratios (SIRs) with 95% Confidence Intervals (CIs) were calculated. The study protocol was registered with PROSPERO (CRD420251122192). RESULTS: SLE was associated with significantly increased odds of HPV infection (OR&#xa0;=&#xa0;4.12, 95% CI 2.03, 8.32). We further assessed the risk of HPV-associated malignancies in SLE patients. SLE patients exhibited substantially elevated risks across multiple HPV-associated cancers (SIR&#xa0;=&#xa0;1.90, 95% CI 1.51, 2.38). The risk of cervical cancer was more than doubled (SIR&#xa0;=&#xa0;2.25, 95% CI 1.75, 2.89). Notably, even higher risks were observed for extra-cervical anogenital cancers, namely vulvar/vaginal cancers (SIR&#xa0;=&#xa0;5.60, 95% CI 3.71, 8.43). CONCLUSIONS: SLE is associated with elevated risks of HPV infection and a broad spectrum of HPV-associated cancers. Subgroup analyses suggested that cyclophosphamide use, multiple sexual partners, and Asian populations may constitute higher-risk subgroups. These findings highlight the need for additional prospective evidence to better characterize HPV-associated cancer risks in SLE patients.

Humans

Association between prenatal exposure to tetrachloroethylene and adverse birth outcomes: Systematic review and meta-analysis.

BACKGROUND: Tetrachloroethylene (PCE) is a ubiquitous chlorinated solvent with documented placental transfer. Despite widespread environmental and occupational exposure, no prior systematic review has synthesized evidence on prenatal PCE exposure and adverse birth outcomes. METHODS: We conducted a systematic review and meta-analysis of observational studies. PubMed, Web of Science, PsycINFO, EMBASE, and CINAHL were searched from inception to July 13, 2026. Eligible studies reported associations between prenatal PCE exposure (drinking water or inhalation) and adverse birth outcomes. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ) criteria. Random-effects meta-analyses were performed using risk ratios (RRs) with 95% confidence intervals (CIs), with Knapp-Hartung adjustments and Paule-Mandel &#x3c4;2 estimation. RESULTS: Twenty one studies (1987-2023) met inclusion criteria. Prenatal PCE exposure was associated with spontaneous abortion (8 studies; RR&#x202f;=&#x202f;1.28, 95% CI 1.00-1.63; I2&#x202f;=&#x202f;64.2%). Analyses of stillbirth, central nervous system defects, oral clefts, neural tube defects, preterm birth, low birthweight, and small-for-gestational-age (SGA) yielded positive but statistically non-significant pooled estimates. The certainty of evidence ranged from very low to low across outcomes (GRADE). CONCLUSIONS: Prenatal PCE exposure may be associated with spontaneous abortion, particularly at higher exposure levels, and with SGA. Findings support ongoing regulatory efforts to limit PCE in occupational and environmental settings, particularly for pregnant individuals. Future prospective studies with biological monitoring and confounder-adjusted designs are needed.

Tetrachloroethylene

A Randomized Clinical Trial to Compare Moxifloxacin Versus Azithromycin for the Treatment of Mycoplasma genitalium: The FARTHEST Study.

BACKGROUND: Mycoplasma genitalium (MG) is increasingly characterized by high rates of macrolide and fluoroquinolone resistance. International guidelines recommend resistance-guided therapy; however, access to genotypic testing is limited, and randomized trial evidence is lacking. We assessed the efficacy of moxifloxacin and azithromycin without resistance assays. METHODS: This monocentric, open-label, superiority, randomized controlled trial enrolled adults with MG infection detected by multiplex PCR, randomized 1:1 to receive moxifloxacin 400 mg daily for 10 days or azithromycin 500 mg daily for 6 days. A test of cure was performed &#x2265;28 days after treatment completion. The primary endpoint was microbiological cure in the intention-to-treat (ITT) and per-protocol (PP) populations. Subgroup analyses assessed symptomatic versus asymptomatic infections, doxycycline exposure, re-treatment, and sexual behavior. RESULTS: Among 358 randomized participants, 87.0% of those treated with moxifloxacin and 61.2% of those treated with azithromycin achieved microbiological cure in the ITT analysis (absolute risk difference 25.8%, 95% CI 16.5, 35.2). The superiority of moxifloxacin was confirmed in the ITT and PP populations. Moxifloxacin remained superior across most subgroups, whereas azithromycin showed comparable efficacy only among heterosexual individuals. Doxycycline coadministration did not improve outcomes. Both regimens were well tolerated, with only one case of discontinuation. CONCLUSIONS: Moxifloxacin demonstrated superior efficacy compared to azithromycin for treating MG infection in the absence of resistance testing. These randomized data support the use of moxifloxacin as a first-line option when resistance assays are unavailable and may inform treatment strategies.

Humans

Metabolomic Responses to Oral Glucose Tolerance Test and Hyperinsulinemic-euglycemic Clamp in CKD.

BACKGROUND: The oral glucose tolerance test (OGTT) captures integrated physiological responses involving intestinal glucose absorption, incretin signaling, and endogenous insulin secretion, whereas the hyperinsulinemic-euglycemic clamp (clamp) isolates insulin-mediated glucose uptake. Comparing plasma metabolomic responses to these two challenges may identify processes specific to intestinal nutrient delivery and how they vary in CKD. METHODS: Targeted plasma metabolomics was performed in 59 adults without diabetes (39 with CKD [eGFR <60 mL/min/1.73 m2] and 20 controls) from the Study of Glucose and Insulin in Renal Disease (SUGAR). Each participant underwent a 75-g OGTT and clamp approximately one week apart. Eighty-eight plasma metabolites were quantified at fasting and during each challenge. Metabolite levels were log-transformed and normalized using Systematic Error Removal Using Random Forest (SERRF). Metabolites were classified using adjusted regression slopes relating OGTT and clamp responses. RESULTS: The mean (SD) age and eGFR were 64 (13) years and 54 (26) mL/min/1.73 m2, respectively, and 41% were female. In the overall cohort, OGTT and clamp induced broad plasma metabolic changes, with 63 (72%) and 76 (86%) metabolites significantly altered from fasting, respectively. Seventy-three metabolites (83%) demonstrated a significant relationship between OGTT and clamp responses. Of these, 22 (25%) exhibited true concordance and 51 (58%) demonstrated similar directional changes but differed in magnitude. A total of 15 (17%) metabolites were discordant or non-corresponding, of which only three were discordant. The non-corresponding metabolites were enriched in amino acid metabolism. Eleven metabolites (13%) demonstrated differential responses between OGTT and clamp by CKD status, involving amino acid and glucose metabolism pathways. CONCLUSIONS: Metabolomic responses to OGTT and clamp were largely directionally concordant but differed in magnitude, with attenuation during OGTT. Discordant metabolites were rare, while non-corresponding metabolites were confined to amino acid pathways. CKD modified OGTT-clamp correspondence for metabolites involved in amino acid and glycolytic metabolism.

Journal Article

Pharmacokinetic and Pharmacodynamic Bio-Similarity of ADL-018 to Innovator Omalizumab: A Randomized Study in Healthy Adults.

Bioequivalence and safety of ADL-018, an omalizumab biosimilar, were compared with United States-licensed omalizumab (US-OMA) and European Union-approved omalizumab (EU-OMA), both approved for allergies. Healthy adults were randomized (1:1:1) to receive a dose of ADL-018, US-OMA, or EU-OMA (150 mg/mL). Pharmacokinetic (PK) parameters, including AUC(0-last), AUC(0-&#x221e;), and Cmax, were considered equivalent if 90% CIs of geometric mean ratios (GMRs) were within predefined equivalence margin (0.80-1.25) using ANCOVA model. Other PK parameters, pharmacodynamics (PD) (free/total immunoglobulin E [IgE]), immunogenicity, and safety were compared. Overall, 306 participants (n&#xa0;=&#xa0;102 per arm) were dosed; 287 completed the study. Equivalence of primary PK parameters was confirmed for pairwise comparisons, with 90% CIs within the predefined margin (GMRs of ADL-018 vs US-OMA: AUC(0-last)-1.08, AUC(0-&#x221e;)-1.07, Cmax-1.05; GMRs of ADL-018 vs EU-OMA: AUC(0-last)-1.06, AUC(0-&#x221e;)-1.06, Cmax - 1.05; and GMRs of US-OMA vs EU-OMA: AUC(0-last)-0.99, AUC(0-&#x221e;)-0.99, Cmax-1.00). PK/PD parameters were comparable across arms. Increase in total IgE (AUEC &#x223c;30,000 to 35,000 h IU/mL) and decrease in free IgE (AUEC &#x223c;29,000 to 35,000 h IU/mL) were comparable across arms. Similar incidence of adverse events across arms (treatment-emergent adverse events: ADL-018, n&#xa0;=&#xa0;6; US-OMA, n&#xa0;=&#xa0;5; EU-OMA, n&#xa0;=&#xa0;4) was observed. ADL-018 demonstrated PK/PD equivalence and comparable safety profile to reference omalizumab.

Humans

Online-delivered eye movement desensitization and reprocessing treatment for adults with post-traumatic stress disorder due to multiple traumas: a non-concurrent multiple baseline design.

Background: No controlled studies incorporating randomization have been conducted to investigate the effectiveness of online eye movement desensitization and reprocessing (EMDR) treatment, despite its use in clinical practice.Objective: This study evaluated the effect of online EMDR treatment in adults aged 18-65&#xa0;years with post-traumatic stress disorder (PTSD) resulting from multiple traumas.Method: A multiple baseline single-case experimental design (n&#x2009;=&#x2009;21) was employed. Participants were patients with PTSD due to multiple traumas, recruited from a mental healthcare institution in the Netherlands. They were randomly assigned to baseline phases of 2, 3.5, or 5.5 weeks. After this, participants received 10 weekly online EMDR sessions. The primary outcome was the total score on an adapted version of the PTSD Checklist for DSM-5 (PCL-5), which was administered twice a week during baseline and intervention phases, and once 12 weeks after the end of the intervention phase. We performed visual analysis and calculated the improvement rate difference (IRD) for each individual separately to determine whether online EMDR was effective. We also performed a paired t-test and calculated Cohen's d for pretreatment and post-treatment comparisons, and pretreatment versus follow-up to evaluate effects at the group level.Results: Visual analysis and IRD scores showed that the treatment was effective for 15 participants, with effect sizes ranging from small to very large. The mean scores on the PCL-5 at group level decreased significantly over time between pretreatment and post-treatment (Mdiff&#x2009;=&#x2009;23.6, Cohen's d&#x2009;=&#x2009;1.34, 95% CI 0.74-1.93), as well as between pretreatment and follow-up (Mdiff&#x2009;=&#x2009;27.2, Cohen's d&#x2009;=&#x2009;1.62, 95% CI 0.95-2.27).Conclusion: Most participants showed a reduction in symptoms following the start of the online EMDR. Furthermore, at the group level there was a significant and clinically relevant reduction in symptoms over time. This provides preliminary evidence for the effectiveness of online EMDR treatment.

Humans

Functional Reading Activities to Motivate and Empower: Maintenance of Reading Outcomes for Young Adults With Intellectual and Developmental Disabilities Following a Randomized Controlled Trial.

PURPOSE: This study examined whether the effects of Functional Reading Activities to Motivate and Empower (FRAME), a functional, strategy-based reading comprehension intervention for young adults with intellectual and developmental disabilities (IDDs), were maintained 6 months following the completion of the intervention and explored participants' perceptions of the intervention's feasibility, relevance, and perceived impact. METHOD: Participants were 44 young adults with IDDs (ages 18-26 years) who participated in a previously reported randomized controlled trial (FRAME participants: n = 23; controls: n = 21). Trial outcomes were assessed via telepractice at pretest, posttest, and 6-month follow-up. Six-month maintenance analyses focused on outcomes that demonstrated significant posttest group differences: use of (a) reading comprehension strategies (proximal) and (b) reading comprehension questions (distal). Participant perceptions (social validity) were collected post-intervention from FRAME participants using a structured interview protocol with closed- and open-ended items. RESULTS: At the 6-month follow-up, FRAME participants demonstrated sustained but reduced improvements in strategy use relative to controls (p = .040). Between-groups differences were not maintained for reading comprehension questions (p = .091). Participants reported high acceptability and perceived relevance of FRAME, with qualitative themes reflecting perceived improvements in comprehension, self-improvement, and increased independence. CONCLUSION: Findings suggest that FRAME supports sustainable gains in reading comprehension strategy use and is perceived as meaningful and feasible for young adults with IDDs, although additional supports may be needed to promote sustained improvements in distal comprehension outcomes. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.33307218.

Humans

Sexual selection purges mutation load, but not overall genetic diversity, decreasing vulnerability to extinction.

Theory suggests sexual selection will enhance population viability by purging deleterious alleles. However, direct genomic evidence for this fundamental idea is scarce and contradictory. We combined long-term experimental evolution with whole-genome resequencing to directly test how sexual selection affects mutation load, genomic divergence, and extinction risk in small populations (maximum Ne = 40) of Tribolium castaneum. After 156 generations, populations evolving under strong sexual selection carried substantially fewer deleterious alleles than populations under weak sexual selection, based on both individual-level estimates of missense and nonsense variants and population-level Rxy analyses, indicating more efficient purging of deleterious alleles. In contrast, nucleotide diversity and runs of homozygosity were similar across treatments, indicating that purging acted most strongly on deleterious variation, and that reduced mutation load in these small populations under strong sexual selection was not explained by demographic effects. Importantly, population-level mutation load estimates best explained extinction risk under inbreeding, directly linking sexual selection to purging and population viability. Genome scans of high and low sexual selection populations revealed peaks of divergence, which included genes involved in courtship, sex discrimination, and seminal fluid proteins. Our results provide direct genomic evidence that sexual selection can reduce mutation load without eroding standing genetic diversity and thus adaptive potential, while driving adaptive divergence in reproductive traits. This beneficial purging may help explain the widespread prevalence of sexual reproduction in nature despite inherent costs and have important ramifications as to how we manage populations of conservation concern.

Animals

"Clinical efficacy and expression of antimicrobial resistance genes after using a novel herbal mouthwash compared to chlorhexidine: A Randomised controlled trial in generalised gingivitis patients".

OBJECTIVES: Chlorhexidine, the gold-standard mouthwash, has several disadvantages, like promotion of antimicrobial resistance. Herbal mouthwashes are emerging as alternatives to chlorhexidine. However, its impact on antimicrobial resistance remains unclear. The aim of the study was to compare the clinical efficacy and the expression of antimicrobial resistance genes of chlorhexidine with a novel herbal mouthwash. DESIGN: Sixty patients with generalised gingivitis were randomly assigned to two groups using block randomisation. After professional mechanical plaque removal patients were instructed to use either chlorhexidine or a novel herbal mouthwash (patented composition) for two weeks. Tetracycline resistance (tetM) and macrolide efflux (mefI) gene expression in subgingival plaque were analysed using real-time polymerase chain reaction. Intragroup comparisons were performed with a paired t-test and Wilcoxon signed-rank test for parametric and nonparametric data. Intergroup comparisons employed unpaired t-test, chi-square test, and Mann-Whitney test. RESULTS: A significant reduction in bleeding, plaque, pocket depth and and patient reported outcomes were noticed in both groups. But reduction in plaque was more significant in chlorhexidine group. tetM and mefI genes significantly upregulated in the chlorhexidine group, while it was downregulated with herbal mouthwash (fold change 1.79&#x202f;&#xb1;&#x202f;0.74 and 0.60&#x202f;&#xb1;&#x202f;0.43 for tetM, and 1.83&#x202f;&#xb1;&#x202f;0.87 and 0.51&#x202f;&#xb1;&#x202f;0.44 for mefI). However, patients' perception of taste, freshness, and overall satisfaction was better in the chlorhexidine group. CONCLUSIONS: The increased expression of antimicrobial resistance genes following chlorhexidine use warrants careful consideration. Herbal mouthwash is an effective, safer alternative with comparable clinical benefits and less impact on antimicrobial resistance.

Humans

Transcriptomic responses to developmental temperature in two field-collected Spodoptera exigua populations from Korea.

The beet armyworm, Spodoptera exigua, is a polyphagous insect whose development and seasonal occurrence are strongly influenced by temperature. However, transcriptomic responses to developmental thermal regimes remain insufficiently characterized in field-collected populations. In this study, we compared two Korean field-collected populations of S. exigua: a Haenam population collected in May and initially maintained at 15&#xa0;&#xb1;&#xa0;1&#xa0;&#xb0;C (HN), and a Jeju population collected in July and initially maintained at 27&#xa0;&#xb1;&#xa0;1&#xa0;&#xb0;C (JJ). F1 larvae from each population were reared under three fluctuating developmental temperature regimes: low (15-21&#xa0;&#xb0;C), middle (21-27&#xa0;&#xb0;C), and high (27-33&#xa0;&#xb0;C), followed by RNA-seq analysis. Differential expression analysis revealed population-associated variation in transcriptomic responses across developmental temperatures. HN exhibited a larger number of differentially expressed genes under the high-temperature regime, suggesting stronger transcriptomic sensitivity to elevated developmental temperature. Functional enrichment analyses identified population-associated differences in pathways related to heat response, oxidative metabolism, cytoskeletal organization, cuticle-associated processes, lipid metabolism, and immune-related functions. In JJ, heat-response and cuticle-related expression patterns were more prominent under warmer developmental conditions, whereas HN showed broader changes in stress- and metabolism-associated pathways under high temperature. Overall, this study provides a comparative transcriptomic analysis of two field-collected S. exigua populations under different developmental temperature regimes and identifies RNA-seq-based molecular response patterns associated with population-specific thermal response profiles.

Animals