A pangenome reference overcomes the inherent limitation of any individual reference genome by integrating the variation present in a population. We present the Human Pangenome Reference Consortium’s (HPRC) Release 2 (HPRC2), an openly available, second phase pangenome that is an approximately fivefold expansion in genome number over HPRC Release 1 (HPRC1) and measurable improvement in genome completeness, contiguity, and accuracy. Selecting samples with a principled algorithm prioritising common variant coverage, HPRC2 contributes 460 haplotypes that together capture over 99% of common variation observed in the All of Us Research Program v8 cohort. Combining high-coverage long and ultra-long reads with modern assemblers and polishers, we produce thousands of telomere-to-telomere (T2T) chromosomes, and relative to HPRC1 halve the number of structurally unreliable regions as well as individual base errors per haplotype. We complement the assemblies with whole genome multiple alignments and gene annotations, and derive formal pangenome coordinate systems for addressing off-reference variation, demonstrating that individual human genomes contain more than one hundred thousand variants not succinctly described with respect to existing reference genomes. We also present the first matched long-read backed pantranscriptome and panepigenome at this scale, provide continuous local-ancestry estimates spanning every genome, and outline a host of new tools and applications that leverage the pangenome resource for improved genomics analysis.
Julian K. Lucas, Prajna Hebbar, Wen-Wei Liao et al.· bioRxiv· 1 citation
Background Critically ill stroke patients frequently experience dysphagia, posing challenges to adequate nutrient intake. Furthermore, these patients often remain in a prolonged state of high stress, hypermetabolism, and reduced immunity. While early enteral nutritional support is crucial, feeding intolerance remains a prevalent issue. This study evaluates the real-world impact of a refined enteral nutrition (EN) intervention on EN outcomes. Objective To investigate the effect of a refined enteral nutrition intervention on nutritional status and feeding intolerance in critically ill stroke patients. Methods This quasi-experimental study employed a pre-post design. The control group (n = 81; January–December 2022) was retrospectively enrolled, and the intervention group (n = 81; January–December 2023) was prospectively enrolled. The Control group received routine nutrition management, and the Intervention group received refined enteral nutrition management. Primary outcomes assessed included: (1) Nutritional markers: Serum albumin, hemoglobin, triceps skinfold thickness (non-paralyzed side), mid-upper arm circumference (non-paralyzed side); (2) EN intolerance incidence: Diarrhea (≥3 stools/day), vomiting, abdominal distension, elevated gastric residual volume (≥250 mL); (3) Disease severity: APACHE II score. Energy and protein targets were calculated individually (25–30 kcal/kg/day and 1.2–2.0 g/kg/day). Achievement of ≥70% of both targets was considered adequate. (4) Nutritional Risk Screening (NRS2002) and hospital length of stay were also recorded. Results Post-intervention albumin levels were significantly higher in the Intervention group (40.69 ± 1.88 g/L) compared to the Control group (38.92 ± 1.21 g/L; t = −7.147, p < 0.001), mean difference 1.77 g/L [95% CI: 1.29–2.25], Cohen’s d = 1.12, with comparable baseline values (36.97 ± 2.34 vs. 36.81 ± 1.67 g/L; p = 0.056). Post-intervention hemoglobin levels were also significantly higher in the Intervention group (114.40 ± 8.00 g/L vs. 110.57 ± 6.52 g/L; t = −3.337, p = 0.001), despite comparable baseline values (97.37 ± 9.89 vs. 99.77 ± 5.92 g/L; t = 1.870, p = 0.630). Post-intervention triceps skinfold thickness was significantly greater in the Intervention group (12.29 ± 2.08 mm vs. 11.20 ± 2.40 mm; t = −3.087, p = 0.002), with comparable baselines (9.97 ± 2.10 mm vs. 9.82 ± 2.21 mm; t = −0.448, p = 0.655). Similarly, post-intervention mid-upper arm circumference was significantly higher in the Intervention group (21.11 ± 1.47 cm vs. 19.86 ± 1.65 cm; t = −5.068, p < 0.001), with comparable baseline values (17.15 ± 1.22 cm vs. 16.99 ± 1.37 cm; t = −0.762, p = 0.447). Post-intervention NRS2002 scores were significantly lower in the Intervention group (4.56 ± 0.82 vs. 5.07 ± 0.83; p < 0.001). Moreover, the APACHE II score was significantly lower in the Intervention group (15.06 ± 2.89) than in the Control group (19.85 ± 3.36; t = 9.236, p = 0.000). In the Intervention group, 91.4% of patients achieved ≥70% of energy targets and 88.9% achieved ≥70% of protein targets, compared to 64.2% and 59.3% in the Control group, respectively (both p < 0.001). The Intervention group also had a significantly shorter hospital stay (42.22 ± 7.25 vs. 44.78 ± 5.21 days; p = 0.011). Conclusion The refined enteral nutrition intervention was associated with improved short-term nutritional status and reduced incidence of feeding intolerance in critically ill stroke patients. However, due to the quasi-experimental design historical controls, the inclusion of adjunctive therapies with unproven efficacy, and the lack of long-term outcome data (including 30-day mortality and functional recovery), categorical claims about improved prognosis cannot be made. The observed benefits may be associated with the comprehensive nursing protocol rather than the refined EN intervention alone and our findings should be interpreted as demonstrating an association rather than a causal relationship. Large-scale, multicenter randomized controlled trials are needed to confirm these findings.
Neng Huang, Cai-Ling Huo, Yu-Tong Zhu et al.· Frontiers in Neurology· 0 citations
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