Nevin Manimala

Commun Biol. 2025 Jan 4;8(1):10. doi: 10.1038/s42003-024-07445-2.

ABSTRACT

Single cell studies have transformed our understanding of cellular heterogeneity in disease but the need for fresh starting material can be an obstacle, especially in the context of international multicenter studies and archived tissue. We developed a protocol to obtain high-quality cells and nuclei from dissected human skeletal muscle archived in the preservative Allprotect® Tissue Reagent. After fluorescent imaging microscopy confirmed intact nuclei, we performed four protocol variations that compared sequencing metrics between cells and nuclei enriched by either filtering or flow cytometry sorting. Cells and nuclei (either sorted or filtered) produced statistically identical transcriptional profiles and recapitulated 8 cell types present in skeletal muscle. Flow cytometry sorting successfully enriched for higher-quality cells and nuclei but resulted in an overall decrease in input material. Our protocol provides an important resource for obtaining high-quality single cell genomic material from archived tissue and to streamline global collaborative efforts.

PMID:39755918 | DOI:10.1038/s42003-024-07445-2

Ophthalmol Ther. 2025 Jan 4. doi: 10.1007/s40123-024-01083-x. Online ahead of print.

ABSTRACT

INTRODUCTION: This study compared the clinical outcomes of allogenic cultured limbal epithelial transplantation (ACLET) and cultivated oral mucosal epithelial transplantation (COMET) in the management of limbal stem cell deficiency (LSCD).

METHODS: Forty-one COMET procedures in 40 eyes and 69 ACLET procedures in 54 eyes were performed in the Corneoplastic Unit of Queen Victoria Hospital, East Grinstead. Data were examined for demographics, indications, ocular surface stability, absence of epithelial defect, ocular surface inflammation, visual outcomes, and intra- and postoperative complications.

RESULTS: Kaplan-Meier analysis showed that patients in the ACLET group with longer follow-up had a significantly higher graft survival rate (81.7%, n = 56) than the COMET group (60.7%, n = 25) and the difference was statistically significant (p = 0.01). In the COMET group, there was no statistically significant improvement in the visual acuity (VA) while in the ACLET group there was statistically significant improvement in the final VA. Elevated intraocular pressure (IOP) developed in 9 eyes (22.0%) in the COMET group and in 18 eyes (26.1%) in the ACLET group; infection developed in 4 eyes (9.8%) in the COMET group and in 10 eyes (14.5%) in the ACLET group; and perforation or melting happened in 4 eyes (9.8%) in the COMET group and in 1 eye (1.4%) in the ACLET group. Postoperative immunosuppression complications were noted in 9 eyes (13.0%) in the ACLET group. No graft rejection was observed in either group.

CONCLUSION: Both ACLET and COMET are effective therapeutic procedures for managing advanced and bilateral cases of LSCD. Although COMET has lower graft survival rate than ACLET, it does not mandate systemic immunosuppression therapy to protect against potential graft rejection.

PMID:39755899 | DOI:10.1007/s40123-024-01083-x

Arch Dermatol Res. 2025 Jan 4;317(1):166. doi: 10.1007/s00403-024-03600-1.

ABSTRACT

Observational studies have shown that the risk of developing herpes zoster (HZ) increases with the use of statins. However, there are many confounding factors in observational studies. Therefore, our Mendelian randomization (MR) study aimed to explore the causal role of lipids in HZ and to assess the causal impact of lipid-lowering drug targets on HZ risk. Our study used low-density lipoprotein (LDL) as a biomarker, and MR analysis was applied to study the effects of genetic inhibition of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR, targeted by statins), Niemann-Pick C1-like 1 (NPC1L1, targeted by ezetimibe), and proprotein convertase subtilisin/kexin type 9 (PCSK9, targeted by, e.g., alirocumab) on the risk of HZ. Second, we analyzed the overall effect of different lipid traits, including LDL, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs), on the HZ. Finally, we analyzed the causal association between cardiovascular disease (CVD) and HZ. The primary MR analysis employed the inverse variance weighted (IVW) approach, which MR supplemented‒Egger, weighted median and weighted mode methods. In addition, we performed sensitivity analysis to assess the robustness of the results and the presence of bias. Heterogeneity and pleiotropy analyses were performed to ensure the accuracy of the results. Genetically modified HMGCR inhibition was significantly associated with an increased risk of HZ (OR: 2.02, per standard deviation reduction in LDL; 95% CI 1.05-3.90; P = 0.035, P(BH) = 0.0525 < 0.1). Moreover, genetically proxied PCSK9 inhibition was associated with a reduced risk of HZ (OR: 0.58, per standard deviation reduction in LDL; 95% CI 0.42-0.80; P = 0.001, P(BH) = 0.003 < 0.1). Sensitivity analysis did not provide statistical evidence of bias from pleiotropy or genetic confounding. No robust association was found for NPC1L1 inhibition. No significant effect of lipid traits or CVD on HZ risk was found. Our findings did not support dyslipidemia and CVD as causal factors for HZ. Among the three lipid-lowering drug targets, HMGCR inhibition (targeted by statins) was associated with an increased risk of HZ, and PCSK9 is a promising candidate drug target in HZ. These findings have important implications for understanding the pathogenesis of HZ and for the development of new therapeutic strategies.

PMID:39755897 | DOI:10.1007/s00403-024-03600-1

Langenbecks Arch Surg. 2025 Jan 4;410(1):24. doi: 10.1007/s00423-024-03568-6.

ABSTRACT

OBJECTIVES: The objective of this web-based study is to analyze the attributes of bariatric surgery cases ensuing health implications. Additionally, the study seeks to delve into the factors influencing post-bariatric psychological evaluations and the impact of various bariatric surgeries on weight loss and psycho-social assessment scores for patients who had undergone bariatric surgeries within a specific bariatric surgery center in Egypt between January 2017 and January 2024.

METHODS: An analytical cross-sectional study recruited 411 adults who had undergone different bariatric procedures by the same surgical team. We collected the data using a validated self-administered questionnaire that included the Body Image Scale (BIS), the Rosenberg Self-Esteem Scale (RSES), the quality-of-life score (QOLS), and the modified General Patient Satisfaction Score after Bariatric Surgeries (GSABS).

RESULTS: The most commonly performed bariatric surgery was sleeve gastrectomy (SG), accounting for 82.7% of the procedures. The majority of the patients (78%) were female, with a mean age of 35.8. Among the participants, 32.4% reported experiencing complications, and 21.2% of those individuals were still experiencing complications at the time of assessment. The BIS had a mean score of 16.54 ± 6.27, indicating an average body image perception. The RSES yielded a mean score of 20.11 ± 4.63, indicating average self-esteem, while the GSABS had a mean score of 8.08 ± 2.39, indicating an overall average level of patient satisfaction. No statistically significant differences were found between the various types of bariatric surgeries in terms of total body weight loss percentage, excess body weight loss percentage, or the timing of the intervention. However, increased time intervals from surgeries noted a significant reduction in the BIS.

CONCLUSION: The majority of patients who underwent SG and Roux-en-Y gastric bypass (RYGB) surgeries exhibited high GSABS scores. SG patients also had high BIS scores. However, all other interventions showed normal GSABS and BIS scores. All types of surgeries resulted in normal RSES and QOLS. Furthermore, the BIS score increases with the intervention’s recentness, but it significantly decreases after the second-year post-surgery. Conversely, the older the timing of the intervention, the higher the RSES score after surgery.

PMID:39755894 | DOI:10.1007/s00423-024-03568-6

Sci Rep. 2025 Jan 4;15(1):808. doi: 10.1038/s41598-024-85063-y.

ABSTRACT

We have adopted the classification Read-Across Structure-Activity Relationship (c-RASAR) approach in the present study for machine-learning (ML)-based model development from a recently reported curated dataset of nephrotoxicity potential of orally active drugs. We initially developed ML models using nine different algorithms separately on topological descriptors (referred to as simply “descriptors” in the subsequent sections of the manuscript) and MACCS fingerprints (referred to as “fingerprints” in the subsequent sections of the manuscript), thus generating 18 different ML QSAR models. Using the chemical spaces defined by the modeling descriptors and fingerprints, the similarity and error-based RASAR descriptors were computed, and the most discriminating RASAR descriptors were used to develop another set of 18 different ML c-RASAR models. All 36 models were cross-validated 20 times with a fivefold cross-validation strategy, and their predictivity was checked on the test set data. A multi-criteria decision-making strategy – the Sum of Ranking Differences (SRD) approach-was adopted to identify the best-performing model based on robustness and external validation parameters. This statistical analysis suggested that the c-RASAR models had an overall good performance, while the best-performing model was also a c-RASAR model (LDA c-RASAR model derived from topological descriptors, with MCC values of 0.229 and 0.431 for the training and test sets, respectively). This model was used to screen a true external data set prepared from the known nephrotoxic compounds of DrugBankDB, demonstrating good predictivity.

PMID:39755865 | DOI:10.1038/s41598-024-85063-y

Environ Sci Pollut Res Int. 2025 Jan 4. doi: 10.1007/s11356-024-35826-x. Online ahead of print.

ABSTRACT

Climate change significantly impacts the risk of eutrophication and, consequently, chlorophyll-a (Chl-a) concentrations. Understanding the impact of water flows is a crucial first step in developing insights into future patterns of change and associated risks. In this study, the Statistical DownScaling Model (SDSM)-a widely used daily downscaling method-is implemented to produce downscaled local climate variables, which serve as input for simulating future hydro-climate conditions using a hydrological model. The vulnerability of water quality, particularly Chl-a concentrations in the Latyan Dam and Tehranpars Water Treatment Plant (TWTP) is assessed through six fuzzy regression models under three scenarios: RCP2.6, RCP4.5, and RCP8.5. Projections indicate an increase in minimum temperatures for the Jajrood watershed ranging from 92 to 93%. Seasonal forecasts suggest significant precipitation during the dry season. The HYMOD model predicts increases in streamflow of approximately 97%, 90%, and 92% by 2050 under RCP2.6, RCP4.5, and RCP8.5, respectively, indicating a heightened risk of flooding that poses economic, health, and environmental concerns. Among the six fuzzy regression models, FGR1, FGR3, and FGR4 demonstrated the most favorable results in modeling Chl-a output from the TWTP. In conclusion, while Chl-a concentrations in the effluent of the TWTP are only slightly influenced by climate change, the effects on streamflow patterns are significant. These findings highlight serious future water quality challenges and increased vulnerability of water resources due to climate change.

PMID:39755861 | DOI:10.1007/s11356-024-35826-x

Acta Parasitol. 2025 Jan 4;70(1):3. doi: 10.1007/s11686-024-00968-y.

ABSTRACT

BACKGROUND: Intestinal parasitic infections are a significant public health concern, especially among food handlers, who can transmit these infections to the public through food preparation and handling. This systematic review and meta-analysis aimed to determine the pooled prevalence and associated factors of intestinal parasitic infections among food handlers in the East African region.

METHODS: A systematic review and meta-analysis on intestinal parasitic infections among food handlers involved a comprehensive search across various databases, including Scopus, PubMed, ScienceDirect, Google Scholar, and the institution’s library registers. Forty relevant articles were identified and analyzed using STATA Software version 17.0. Sensitivity analysis, publication bias assessment with Egger’s test, and the Trim-and-fill meta-analysis for bias adjustment were conducted. Heterogeneity across the studies was assessed using Cochran’s Q statistic and I² statistics, and subgroup analysis computed for significant heterogeneity (I² value ≥ 50%). A random effect model was used to determine the pooled prevalence of intestinal parasitic infections.

RESULTS: The pooled prevalence of intestinal parasitic infections among food handlers was 32.27% (95% CI 27.90-36.65). The most prevalent parasites were Entamoeba histolytica/dispar 20.83% (95% CI 13.66-28%), Ascaris lumbricoides 13.84% (95% CI 10-17.68%), Giardia lamblia 8.55% (95% CI 6.03-11.06%), and hookworm 6.43% (95% CI 3.93-8.93%). Using a common knife for cutting raw meat (AOR = 2.27, 95% CI 1.21-4.31), food handler’s untrimmed fingernails (AOR = 2.14, 95% CI 1.50-2.78), and no hand washing practices with soap after using the toilet (AOR = 2.25, 95% CI 1.33-3.18) were associated with higher rates of intestinal parasitic infections among food handlers.

CONCLUSIONS: Parasitic infections among food handlers were found to be significantly prevalent. Factors contributing to this high prevalence included food handlers’ untrimmed fingernails, poor hand hygiene practices, and using a shared knife for chopping various food items, including raw meat. These findings emphasize the need for proper personal hygiene and sanitation practices among food handlers to prevent transmitting parasitic infections to consumers.

PMID:39755837 | DOI:10.1007/s11686-024-00968-y

Cancer Causes Control. 2025 Jan 4. doi: 10.1007/s10552-024-01950-9. Online ahead of print.

ABSTRACT

PURPOSE: Historical redlining, a 1930s-era form of residential segregation and proxy of structural racism, has been associated with breast cancer risk, stage, and survival, but research is lacking on how known present-day breast cancer risk factors are related to historical redlining. We aimed to describe the clustering of present-day neighborhood-level breast cancer risk factors with historical redlining and evaluate geographic patterning across the US.

METHODS: This ecologic study included US neighborhoods (census tracts) with Home Owners’ Loan Corporation (HOLC) grades, defined as having a score in the Historic Redlining Score dataset; 2019 Population Level Analysis and Community EStimates (PLACES) data; and 2014-2016 Environmental Justice Index (EJI) data. Neighborhoods were defined as redlined if score ≥ 2.5. Prevalence quintiles of established adverse and protective breast cancer factors relating to behavior, environment, and socioeconomic status (SES) were used to classify neighborhoods as high-risk or not. Factor analysis grouped factors into domains. Overall and domain-specific scores were calculated for each neighborhood according to historical redlining status. Percent difference in score by historical redlining was used to assess differences in average scores, with Wilcoxon-Mann-Whitney test used to estimate significance. Kappa statistic was used to estimate concordance between historical redlining status and high-risk status. Heatmaps of scores were created to compare spatial clustering of high-risk factors to historical redlining.

RESULTS: We identified two domains: (1) behavior + SES; (2) healthcare. Across the US, redlined neighborhoods had significantly more breast cancer factors than non-redlined (redlined neighborhoods = 5.41 average high-risk factors vs. non-redlined = 3.55 average high-risk factors; p < 0.0001). Domain-specific results were similar (percent difference for redlined vs. non-redlined: 39.1% higher for behavior + SES scale; 23.1% higher for healthcare scale). High-scoring neighborhoods tended to spatially overlap with D-grades, with heterogeneity by scale and region.

CONCLUSION: Breast cancer risk factors clustered together more in historically redlined neighborhoods compared to non-redlined neighborhoods. Our findings suggest there are regional differences for which breast cancer factors cluster by historical redlining, therefore interventions aimed at redlining-based cancer disparities need to be tailored to the community.

PMID:39755825 | DOI:10.1007/s10552-024-01950-9

Sci Rep. 2025 Jan 4;15(1):747. doi: 10.1038/s41598-024-84986-w.

ABSTRACT

The preservation of the original configurations of root canals during endodontic preparation is crucial for treatment success. Nickel-titanium (NiTi) rotary systems have been refined to optimize canal shaping while minimizing iatrogenic errors. This study aimed to evaluate and compare the shaping efficacy of the novel R-Motion (RM) and the established WaveOne Gold (WG) systems using micro-computed tomography (micro-CT). Twenty-four mesial canals of 12 double-rooted extracted mandibular first molars were randomly assigned to either the RM or WG groups, with the mesiobuccal (MB) and mesiolingual (ML) canals allocated accordingly. Root canals were prepared following the manufacturer’s protocols. In the RM group, crown-down technique up to a 25/0.06 taper was employed. For the WG group, the preparation was completed with a WG primary file (25/0.07 taper). Specimens were scanned using micro-CT scans before and after instrumentation to establish baseline and post-instrumentation datasets. The following parameters were evaluated, and values were calculated to compare the shaping ability of the two files: percentage of untouched canal walls, changes in surface area, canal volume, dentin thickness, canal angulation, structure model index, canal transportation, and centering ability ratio. Data were analyzed using IBM SPSS Statistics for Windows, Version 23.0 (IBM Corp., Armonk, NY), with a statistical significance set at P ≤ 0.05. Micro-CT analysis demonstrated comparable untouched canal surface areas and changes in surface area and volume between both RM and WG systems. Both systems effectively straightened canal curvature without significant differences in canal angulation. The RM files exhibited a statistically lower reduction in dentin thickness, indicating better preservation of structural integrity. Both RM and WG files displayed similar effective shaping abilities. However, RM caused less dentin removal and canal transportation. Thus, RM is recommended for its ability to balance effective canal shaping with structural preservation in a conservative manner.

PMID:39755800 | DOI:10.1038/s41598-024-84986-w

Sci Rep. 2025 Jan 4;15(1):837. doi: 10.1038/s41598-024-85047-y.

ABSTRACT

Benign paroxysmal vertigo (BPV) is a common cause of dizziness, and some patients are comorbid with psychiatric disorders such as depression, requiring intervention with antidepressants. However, the causal association between BPV, depression and antidepressants has not been clearly established. We used two-sample bidirectional Mendelian randomization (MR) to analyze the causal association between BPV, depression, and antidepressants. From a Finnish database, 43,280 patients with depression and 329,192 controls, and 106,785 patients with antidepressants and 88,536 controls were selected. Independent single nucleotide polymorphisms (SNPs) for depression and antidepressants were used as instrumental variables (IVs) with genomic significance (p < 5 × 10^-8). Similarly, genome-wide association study (GWAS) data for BPV were selected from a Finnish database consisting of 8280 cases and 359,094 controls. Afterwards, a two-sample MR study was performed using R’s Two Sample MR and MR-PRESSO software packages. The multiplicity and heterogeneity of the data, as well as the effect of individual SNPs on the results were investigated. The main statistical analyses were weighted median, weighted mode, MR-Egger and weighted inverse variance weighting (IVW) for random effects. Finally, we identified associations between BPV, antidepressants and depression. Four outliers (rs3773087, rs4619804, rs62099231, rs7192848) were found to be associated with depression. After removing the outliers, the statistics showed no heterogeneity (p > 0.05) and horizontal pleiotropy (p > 0.05). Antidepressants were also found to have a random effect IVW (β = 0.440; p = 9.692 × 10^-6; OR = 1.553; 95% CI 1.278-1.887). The inverse MR random effects IVW results showed a causal association between BPV and antidepressants (β = 0.051; p = 0.045; OR = 1.052; 95% CI 1.001-1.1066). In conclusion, there was a significant causal association between antidepressants and BPV at the genetic level. Clinicians should pay attention to patients with BPV combined with depressive disorders and develop timely interventions.

PMID:39755797 | DOI:10.1038/s41598-024-85047-y