Nevin Manimala

BMC Med Genomics. 2026 May 12. doi: 10.1186/s12920-026-02386-7. Online ahead of print.

ABSTRACT

BACKGROUND: Genome-wide association analyses (GWASs) have identified numerous genetic variants associated with type 2 diabetes, but the utility of polygenic risk scores (PRSs) derived from these associations for predicting future incident diabetes remains uncertain. We analyzed utility of PRSs to predict incident diabetes in longitudinal studies, consisting of African Americans (AfrAm) and European Americans (EurAm) from the publicly available dbGAP resource.

METHODS: Data consisted of 3,886 AfrAm and 17,345 EurAm with GWAS data, who were initially without diabetes; there were 688 incident diabetes cases in AfrAm and 2,304 in EurAm. Strength of association was assesed by the hazard ratio (HR), while ability to discriminate between those who did and did not develop diabetes was assessed by change in the C statistic (ΔC), and ability to correctly reclassify diabetes risk was assessed by the net reclassficiation information (NRI). Decision curve analysis was used to model potential benefits of using the PRS to select individuals for a preventive intevention across a range of thresholds for implementation.

RESULTS: Among the 8 PRSs evaluated, PGS002308 (1.2 M variants, from a multi-ancestry GWAS) provided the best performance. With adjustment for age, sex, parental history of diabetes, body mass index (BMI) and fasting glucose levels, the HR was 1.50 per 5000 risk alleles (95% confidence interval, 1.41-1.60). The NRI was 0.313 (0.229-0.397) and ΔC was 0.010 (0.007-0.014). In comparison, NRI was 0.401 (0.338-0.464) for BMI and 0.257 (0.188-0.327) for serum lipid levels. The PRS provided a 5.9% (1.6-10.4) improvement in area under the decision curve. For most measures of predictive utility there was little heterogeneity between AfrAm and EurAm. In contrast, measures of predictive utility were stronger in younger, than in older, individuals.

CONCLUSIONS: PRSs for type 2 diabetes, as currently constructed, provide utility for clinical prevention purposes that is similar to that provided by commonly used clinical predictors; utility is likely greater in younger than in older individuals. Further studies of diabetes risk assessment and those that aim to determine optimal target populations for diabetes prevention efforts would be strengthened by incorporating PRSs.

PMID:42120982 | DOI:10.1186/s12920-026-02386-7

Asian J Endosc Surg. 2026 Jan-Dec;19(1):e70311. doi: 10.1111/ases.70311.

ABSTRACT

PURPOSE: Laparoscopic cholecystectomy is common, but bile duct injury occurs in 0.3% of cases. Moderate to severe cholecystitis increases operative difficulty, and subtotal cholecystectomy is recommended as a preventive procedure. This study evaluated the outcomes of reconstituting subtotal cholecystectomy for cholecystitis at our institution.

METHODS: We retrospectively analyzed 2707 patients who underwent cholecystectomy between January 2010 and December 2022. Of these, 109 patients underwent reconstituting subtotal cholecystectomy. Patients were classified into a laparoscopic group (36 cases) and an open conversion group (73 cases). Short- and long-term outcomes were compared.

RESULTS: No bile duct injuries or operation-related deaths occurred. The laparoscopic group had significantly less blood loss and a shorter postoperative hospital stay. In almost all open conversion cases, the gallbladder stump was closed with sutures, whereas stapler closure was mainly used laparoscopically. Three cases of retained stone cholecystitis occurred in the laparoscopic stapler group, whereas no cases occurred in the laparoscopic suture group or open conversion group.

CONCLUSIONS: Laparoscopic reconstituting subtotal cholecystectomy is an acceptable surgical approach; however, retained stone-related complications require particular attention when stapled stump closure is performed, as the stump closure method may be more closely associated with these complications than the surgical approach.

PMID:42120958 | DOI:10.1111/ases.70311

J Chem Theory Comput. 2026 May 12. doi: 10.1021/acs.jctc.5c01985. Online ahead of print.

ABSTRACT

Fold-switching metamorphic protein sequences defy the classical “one sequence – one fold” paradigm. The ability of metamorphic proteins to reversibly switch between distinct folds make them attractive de novo protein engineering candidates since they can function as environment-sensitive molecular switches. However, the underlying thermodynamic design principles that drive their fold-switching behavior is poorly understood. Gaining insights into the molecular driving forces leading to fold switching behavior is crucial for the rational design of new metamorphic proteins based molecular switches, sensors and stimulus responsive nanomaterials. In this study, we perform a detailed thermodynamic analysis of a designed fold-switching protein [Solomon et al. PNAS 2023, 120 (4), e2215418120] that transitions between a 3α fold and α/β fold upon changes in temperature. We use an efficient advanced sampling molecular simulation based free energy calculation approach called Confine-Desolvate-Convert-Solvate-Release (CDCSR), which subjects the protein through the complete range of thermodynamic cycle and deconvolutes the enthalpic and entropic driving forces at each stage of the cycle. We find that while 3α fold is stabilized at low temperatures by enthalpic contributions from favorable water-water and protein-water interactions, the transition to the α/β fold at high temperatures is driven by the gain of entropy from the release of ordered water molecules surrounding the 3α fold. Our study elucidates the molecular driving forces governing temperature-induced fold-switching behavior and provides a rigorous statistical thermodynamic framework that can help in the design and engineering of future synthetic and functional metamorphic proteins. Significance: Recent success in the de novo protein design for molecular function is powered by the transformative AI methods and interpreted using the classical wisdom from the Physics-based modeling approaches. Stimuli-sensitive fold switching proteins that can take multiple shapes based on environmental factors are the next frontier in de novo protein engineering. In this work, we unravel the thermodynamic driving forces behind a recently designed temperature-sensitive artificial protein and provide a physics-based framework to understand the design principles leading to fold switching behavior. Our work complements the ongoing AI methods that are being explored to unravel the hidden evolutionary embeddings inherent in fold-switching proteins and also highlights the importance of thinking in terms of entropy-based design principles for natural systems.

PMID:42120955 | DOI:10.1021/acs.jctc.5c01985

Int J Dent Hyg. 2026 May 12. doi: 10.1111/idh.70087. Online ahead of print.

ABSTRACT

AIM: This study aimed to compare the clinical and biochemical effectiveness of using an oral irrigator (OI) and an interdental brush (IB) during fixed orthodontic treatment.

METHODS: A total of 30 patients with fixed orthodontic treatment were included in the study. All participants were randomly divided into two equal groups: patients using OI (OI-group) and patients using IB (IB-group). The patients were followed regularly; clinical evaluations were performed at 4 different times (baseline, 2nd, 4th, and 8th weeks), and gingival crevicular fluid samples were collected simultaneously. Total and concentration levels of IL-1β, IL-10, MMP-1, and MMP-8 from the collected gingival crevicular fluid samples were evaluated by the ELISA method. Clinical and biochemical differences that occurred at different times between the two groups were statistically examined.

RESULTS: The GI and BOP values at the 8th week (p < 0.001) and PI values at the 2nd (p = 0.004), 4th (p = 0.003), and 8th weeks (p < 0.001) were found to be statistically lower in the OI-group. Total IL-1β values in the 2nd week (p = 0.016), and total MMP-8 values in the 4th (p = 0.006) and 8th weeks (p = 0.01) were statistically lower in the OI-group. There were no significant differences in MMP-1 and IL-10 values between the groups at any time interval of the study (p > 0.05).

CONCLUSION: This study demonstrated that the use of an oral irrigator in conjunction with a toothbrush resulted in lower levels of gingival inflammation markers and plaque compared to an interdental brush in patients undergoing fixed orthodontic treatment, suggesting that the oral irrigator served as a beneficial tool for supporting periodontal health during orthodontic treatment.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05562986.

PMID:42120952 | DOI:10.1111/idh.70087

Am J Health Syst Pharm. 2026 May 12:zxag132. doi: 10.1093/ajhp/zxag132. Online ahead of print.

ABSTRACT

PURPOSE: To assess the comprehensive workflow and time and motion activities associated with hospital pharmacy and nursing staff for a cephalosporin antibiotic in 3 different marketed formulations: (1) a formulation prepared by traditional compounding, (2) a dual-chamber IV bag stored with prefilled diluent in the upper chamber and powdered drug in the lower chamber, and (3) a standard diluent container with an integrated drug vial adaptor that allows for drug admixture after connection to a single-dose powdered drug vial.

METHODS: The study was conducted at 3 hospital locations from a single hospital network located in Arkansas. Study procedures were assessed by direct observations of pharmacists, pharmacy technicians, and nurses. Sequences and durations of tasks were observed to identify and document the actual time for each task.

RESULTS: Approximately 402 observational hours of data collection occurred, with more than 100 formulated doses observed per formulation, with 98.6% overall study confidence. Use of the dual-chamber IV bag formulation resulted in a 63% decrease in labor time compared to traditional compounding. When comparing the dual-chamber IV bag formulation to the standard diluent formulation, there was about a 22% decrease in labor time. Based on the number of process steps, use of the dual-chamber formulation resulted in approximately 54% fewer opportunities for error versus traditional compounding and 35% fewer opportunities for error than use of the standard diluent formulation.

CONCLUSION: Independent descriptive statistical analysis verified that the dual-chamber IV bag cephalosporin antibiotic formulation is a faster, simpler-to-use drug administration platform and associated with less chance of formulation and dosing errors.

PMID:42120928 | DOI:10.1093/ajhp/zxag132

Sci Rep. 2026 May 12. doi: 10.1038/s41598-026-49630-9. Online ahead of print.

ABSTRACT

This study adopted single-factor tests integrated with response surface methodology (RSM) based on Box-Behnken design (BBD) to improve and optimize the microwave-assisted extraction (MAE) technique for protein extraction from perilla meal. Four major parameters (material-liquid ratio, extraction pH, microwave power, microwave time) were screened and evaluated in preliminary trials, and their favorable ranges were determined as 1:15, 8-10, 400 W and 120 s, respectively. On this basis, BBD was employed to further refine three core variables: extraction pH, microwave power, and microwave time, and a quadratic regression model was constructed. Analysis of variance verified the model was statistically significant and highly reliable (F = 30.48, p < 0.0001), with a satisfactory goodness-of-fit. A distinct synergistic interaction between extraction pH and microwave power toward protein yield was detected, whereas interactive impacts between microwave time and the other two variables were not significant. The magnitude of influence on protein yield followed: microwave time > microwave power > extraction pH. The model predicted a peak protein yield of 31.3276% under the optimized conditions: pH 10.02, 398.63 W, 115.45 s. Validation experiments yielded an actual yield of 30.9309 ± 0.1036% (n = 3), which closely matched the predicted value, confirming the precision and industrial applicability of the model. This work established a high-efficiency MAE protocol for perilla meal protein and supplied a scientifically sound and scalable technical foundation for industrial application and high-value valorization of this underused plant protein resource.

PMID:42120921 | DOI:10.1038/s41598-026-49630-9

Sci Rep. 2026 May 12. doi: 10.1038/s41598-026-52546-z. Online ahead of print.

ABSTRACT

Wildlife-vehicle collisions (WVCs) are a global biodiversity threat impacting most terrestrial vertebrates and posing scientific, economic and conservation challenges. Research on WVC is nevertheless geographically uneven, and large-scale multi-taxon studies are scarce. We analysed data from the Polish Roadkill Observation System, a nationwide volunteer-based programme recording WVC carcasses across all terrestrial vertebrates. Based on 28,709 casualties recorded during 2000-2022, we examined the mortality patterns in vertebrate classes and some correlates of WVCs distribution. In total, 205 species were identified, representing 55% of Poland’s terrestrial vertebrate fauna, including 16% of threatened species. The approximate proportion of roadkilled mammals, amphibians, birds and reptiles was 8:8:5:1; mammals and amphibians are thus the most frequently reported vertebrates on Polish roads by citizen scientists. Reports of multiple casualties concerned mostly amphibians and reptiles, and were often associated with protected areas. Regression models revealed that observed roadkill was positively correlated with body mass and carcass persistence but not with species distribution range in Poland. Prominent seasonal patterns were also evident, with peak mortality occurring in warm seasons and coinciding with taxon-specific phenological events. Our study demonstrates the value of citizen-science data for identifying nationwide patterns of WVCs, while also highlighting the need to move beyond opportunistic observations toward a nationally coordinated, systematic survey to generate more accurate and policy-relevant estimates.

PMID:42120920 | DOI:10.1038/s41598-026-52546-z

Sci Rep. 2026 May 12. doi: 10.1038/s41598-026-50326-3. Online ahead of print.

ABSTRACT

Urbanisation-environment interactions are increasingly non-linear, yet traditional Coupling Coordination Degree (CCD) frameworks often rely on static, linear assumptions that fail to capture complex feedback loops. This study proposes an integrated framework combining CRITIC-weighted CCD assessment with interpretable machine learning (Random Forest and XGBoost) to decode the co-evolution of urbanisation and ecological integrity. Taking Malaysia, a country characterised by rapid expansion and high spatial disparity-as a critical case study, we utilized multi-source remote sensing and longitudinal statistics across 16 states. Our XGBoost model (Test R² ≈ 0.87) outperformed traditional regressions, confirming significant non-linear and dynamic coupling effects. By applying SHAP (SHapley Additive exPlanations), we moved beyond mere prediction to identify the sustainability “tipping points” within the system. Key findings reveal: (1) a distinct spatial decoupling in northern and east-coast regions; (2) a “hump-shaped” threshold effect for built-up expansion where coordination peaks before declining; and (3) the critical role of forest/water assets as non-linear ecological buffers. These results demonstrate that sustainable transitions depend more on spatial structure and asset management than on income growth alone. This interpretable AI-CCD framework provides a scalable, evidence-based toolkit for low- and middle-income countries to navigate the trade-offs between development and ecological preservation.

PMID:42120893 | DOI:10.1038/s41598-026-50326-3

Sci Data. 2026 May 12. doi: 10.1038/s41597-026-07347-4. Online ahead of print.

ABSTRACT

Significant improvements in sequencing technologies have allowed the development of more contiguous genome assemblies in many plant species. The pea genome is characterized by its richness in repeated elements and its long and complex centromeres. This makes its assembly challenging. In this paper, we present an improved version of the genome sequence of the French cultivar ‘Caméor’. This sequence was obtained by combining Nanopore and PacBio long-read sequencing, Hi-C contact maps and Bionano maps. The assembly of centromeres was refined using a combination of FISH and ultra-long Nanopore read analyses. Overall, the new Cameor_v2 genome assembly is a highly continuous pea genome assembly with small total gap size and a large contig N50. In this version, the orientation of chromosomes was revised according to internationally accepted karyotype rules. Gene annotation statistics indicated a high completeness of gene sequences, with most gene sequences with 3′ and 5′ UTR. This genome assembly with its associated data constitute a useful resource for pea genetics, comparative mapping and functional genomics.

PMID:42120873 | DOI:10.1038/s41597-026-07347-4

Eur J Epidemiol. 2026 May 13. doi: 10.1007/s10654-026-01396-0. Online ahead of print.

ABSTRACT

BACKGROUND: The poor performance of the UK in reducing mortality compared to many other high-income countries following the 2008 financial crisis have been extensively studied, with particular attention to deaths of despair at working ages. However, longer-term trends in the differences in working-age mortality between the UK and peer countries have not been systematically investigated.

METHODS: We compared trends (1990-2019) in age-standardised mortality rates at age 25-49 years in the UK and its constituent parts (England and its 9 standard regions, Wales, Scotland, Northern Ireland) with those of 21 peer countries.

FINDINGS: Between 1990 and 2019 the UK went from having relatively low mortality rates at age 25-49 years compared to its peers to having one of the highest. This reflects both the better progress made by many other countries in reducing mortality rates as well as an absolute increase in the UK from 2013. Against the counter-factual that rates in the UK followed the median of the comparator countries (2001-2019) this resulted in 3.1 million excess years of life lost. The divergence in mortality of the UK with its peers was apparent from 1990 and was observed for all constituent parts of the UK and English regions. External cause mortality accounted for much of the divergence in rates between 2001 and 2019 (69% women; 78% men), as did the overlapping categories of drug-related deaths (42%; 28%) and suicides (17%; 20%). Alcohol-related deaths made only a small contribution.

INTERPRETATION: The divergence in mortality rates at ages 25-49 years in the UK from peer countries was already apparent from 1990, pre-dating the austerity policies two decades later. Nevertheless, austerity may well have exacerbated this longer-term deterioration in the UKs position. The fact that all areas of the UK showed deterioration relative to peer countries indicates that this is a national problem.

PMID:42120865 | DOI:10.1007/s10654-026-01396-0