BACKGROUND: The study aimed to determine the optimal pool size of ABO matched buffy coat pooled platelets (BCPP) to achieve a typical adult dose (TAD) of platelets comparable to single donor platelet concentrates (SDPC), following recent regulatory changes allowing random donor platelet concentrate (and/or buffy coat [BC]) pooling, in India. MATERIALS AND METHODS: This prospective study, done in 2024 at a tertiary hospital, included donors who met whole blood (WB) or SDPC donation criteria. WB was collected in quadruple bags and separated into red cells, plasma, and BC. BC units were pooled into groups of 4, 5, or 6 with 300 mL of ABO-matched plasma. SDPC was collected with automatic separators. The study examined four groups: BCPP, prepared from pools of four, five, or six BC units, and SDPC; 10 pools of BCPP (from three pool sizes of BC), and 10 units (SDPC) were assessed for in vitro parameters. Subsequently, conducted pilot in vivo study looked at the corrected count increment (CCI) and percentage platelet recovery (PPR) of the “optimal pool,” identified on the basis of in vitro analysis. RESULTS: The study used 150 WB and 10 SDPC donors, having no significant variations in physical, biochemical, or hematological markers across four groups. Pool-of-5 BC units met TAD standards with fewer units than pool-of-6 and produced comparable quality to SDPC. Transfusion of BCPP (pool-of-5) resulted in a CCI of 9.7 ± 4 × 10⁹/L and a PPR of 25 ± 11%. CONCLUSION: BCPP (pool-of-five BC units) provides an effective TAD, making it viable option to SDPC, with comparable quality and effectiveness.
Background: Skin ageing involves interconnected changes in extracellular matrix integrity, hydration, oxidative stress and cellular resilience. This study evaluated the efficacy and tolerability of RESET by IQ HEALTH™, a multi-ingredient oral nutraceutical, in adults with visible facial skin ageing. Methods: This prospective, open-label, single-arm clinical study enrolled healthy adults aged 35-55 years with facial skin ageing. Participants consumed one sachet daily for 60 days. Facial firmness (Cutometer R0), elasticity (Cutometer R7), and hydration [MoistureMeter SC (MMSC)] were assessed at baseline, day 30, and day 60. Participant-reported skin and wellness outcomes and tolerability were assessed descriptively. Results: Thirty-four participants-initiated supplementation and 33 completed the study. At day 60, firmness improved by 38.9%, elasticity by 8.9%, and hydration by 19.2% from baseline (all p<0.001). Significant changes were observed at day 30. At day 60, 84.9% reported firmer/tighter facial skin, 81.8% reported a younger appearance, and 90.9% reported improved moisturization and hydration. Exploratory improvements were also reported in energy, joint comfort, sleep quality, fatigue, relaxation, and muscle soreness. The product was generally well tolerated; gastrointestinal symptoms were mild and infrequent, with no serious adverse events or treatment-related discontinuations. Conclusions: Daily supplementation with RESET by IQ HEALTH™ for 60 days was associated with improvements in facial skin firmness, elasticity, and hydration, together with favourable participant-reported skin and wellness outcomes. These findings are preliminary given the single-arm, open-label design and small sample size and require confirmation in randomized, placebo-controlled studies.
Chemoenzymatic peptide synthesis offers a sustainable alternative to traditional solid-phase peptide synthesis for manufacturing therapeutic peptides such as semaglutide. However, cost-efficient industrial implementation requires enzyme immobilization to enable the catalyst recovery and continuous processing. This work presents the first demonstration of a bioinformatics-guided immobilization strategy for a peptiligase variant, successfully applied in a continuous-flow packed-bed reactor for semaglutide fragment ligation. Using computational tools, we predicted optimal immobilization sites and systematically screened covalent and noncovalent methods. EP400/SS-aldehyde emerged as the superior support, maintaining >85% of the immobilized activity after 10 reuse cycles. Translation to continuous flow revealed substrate hydrolysis as a competing side reaction at high enzyme loads. Optimization of the protein loading, to 2.5 mg/g, suppressed this unwanted reaction, achieving 95% conversion with 30 min of residence time, matching solution-phase performance. This establishes a robust framework for immobilizing peptiligases in industrial bioprocesses.
Abstract Background ECG foundation models (FMs) are emerging for screening or rule-out of left ventricular systolic dysfunction (LVSD). However, previous studies rely on multiple ECGs per patient, lack head-to-head comparisons with conventional deep learning (DL) models, and rarely report on short- and long-term reproducibility. Purpose To compare a de novo time-series FM (TSFM) with a DL model (ResNet-18) for LVSD detection (LVEF≤40%), evaluate robustness across EF thresholds and subgroups, quantify short- and long-term reproducibility, assess external generalisability and prognostic utility. Methods TSFM was pretrained on unlabeled ECG data (N=189,886 from our hospital ECG archive and MIMIC-IV) using masked pre-training and fine-tuned for LVSD classification based on ECG-echocardiogram pairs. ResNet-18 was trained under the same endpoint definition. Performance was evaluated on a held-out test set (N=10,582) and in external validation (EchoNext, N=32,660). Threshold robustness (LVEF 20-50%) was assessed without retraining by relabeling. Subgroup analyses were performed in MIMIC-IV. Across pretraining, fine-tuning, and primary evaluation, one ECG per patient was used. Test–retest reproducibility was assessed in ECG pairs with unchanged echocardiography-defined LVSD status (short-term 1–14 days, N=16,503 ECG pairs; long-term ≥365 days, N=854). Prognostic utility was assessed in patients with baseline preserved LVEF (≥50%) over 5-year follow-up. Results LVSD prevalence was 16-20% across all sets. In the test set, TSFM showed higher AUROC than ResNet-18 (0.896 [0.887-0.902] vs 0.885 [0.876-0.892]), DeLong p<0.001. AUPRC was also higher (0.695 [0.663-0.723] vs 0.646 [0.612-0.683]), permutation p=0.051. Sensitivity was 0.82 for both, while TSFM showed higher specificity (0.82 vs 0.79) and PPV (0.53 vs 0.49) with NPV 0.95 for both. TSFM maintained higher AUROC across LVEF thresholds. In MIMIC-IV subgroups, TSFM showed higher AUROC across age, sex, heart rate, rhythm, and QRS duration. Short-term agreement was 83.3% for TSFM vs 87.2% for ResNet-18 (κ 0.655 vs 0.671; Δκ p=0.0796) and long-term agreement of 76.0% vs 82.1% (κ 0.520 vs 0.612; Δκ p=0.013). In EchoNext, TSFM achieved AUROC 0.875 (0.870-0.880) vs ResNet-18 0.850 (0.844-0.857), DeLong p<0.001; AUPRC 0.640 (0.627-0.653) vs 0.592 (0.578-0.605), permutation p<0.001. In baseline preserved-EF patients, model-flagged LVSD positivity predicted subsequent LVSD over 5 years (TSFM HR 2.96 [2.44-3.58]; ResNet-18 HR 3.44 [2.79-4.25]); interaction HR 0.86 (0.65-1.14), p=0.30. Conclusions In head-to-head testing, TSFM consistently improved LVSD detection across EF thresholds, clinical subgroups and external validation, with good overall reproducibility. High NPV at the observed prevalence supports evaluation for rapid LVSD rule-out in triage, emergency, and preoperative workflows. Prognostic stratification for future LVSD seems feasible.Performance metricsLVSD prediction
