Tag: nevin manimala

Genome Res. 2024 Jul 22:gr.279207.124. doi: 10.1101/gr.279207.124. Online ahead of print.

ABSTRACT

SNP heritability, the proportion of phenotypic variation explained by genotyped SNPs, is an important parameter in understanding the genetic architecture underlying various diseases and traits. Methods that aim to estimate SNP heritability from individual genotype and phenotype data are limited by their ability to scale to Biobank-scale datasets and by the restrictions in access to individual-level data. These limitations have motivated the development of methods that only require summary statistics. While the availability of publicly accessible summary statistics makes them widely applicable, these methods lack the accuracy of methods that utilize individual genotypes. Here we present a SUMmary statistics-based Randomized Haseman-Elston regression (SUM-RHE), a method that can estimate the SNP heritability of complex phenotypes with accuracies comparable to approaches that require individual genotypes, while exclusively relying on summary statistics. SUM-RHE employs Genome-Wide Association Study (GWAS) summary statistics and statistics obtained on a reference population, which can be efficiently estimated and readily shared for public use. Our results demonstrate that SUM-RHE obtains estimates of SNP heritability that are substantially more accurate compared to other summary statistic methods and on par with methods that rely on individual-level data.

PMID:39038848 | DOI:10.1101/gr.279207.124

BMJ. 2024 Jul 22;386:q1614. doi: 10.1136/bmj.q1614.

NO ABSTRACT

PMID:39038829 | DOI:10.1136/bmj.q1614

J Natl Cancer Inst. 2024 Jul 23:djae145. doi: 10.1093/jnci/djae145. Online ahead of print.

ABSTRACT

BACKGROUND: Ovarian cancer is among the leading causes of gynecologic cancer-related death. Past ovarian cancer screening trials using combination of cancer antigen 125 testing and transvaginal ultrasound failed to yield statistically significant mortality reduction. Estimates of ovarian cancer sojourn time-that is, the period from when the cancer is first screen detectable until clinical detection-may inform future screening programs.

METHODS: We modeled ovarian cancer progression as a continuous time Markov chain and estimated screening modality-specific sojourn time and sensitivity using a Bayesian approach. Model inputs were derived from the screening arms (multimodal and ultrasound) of the UK Collaborative Trial of Ovarian Cancer Screening and the Prostate, Lung, Colorectal and Ovarian cancer screening trials. We assessed the quality of our estimates by using the posterior predictive P value. We derived histology-specific sojourn times by adjusting the overall sojourn time based on the corresponding histology-specific survival from the Surveillance, Epidemiology, and End Results Program.

RESULTS: The overall ovarian cancer sojourn time was 2.1 years (posterior predictive P value = .469) in the Prostate, Lung, Colorectal and Ovarian studies, with 65.7% screening sensitivity. The sojourn time was 2.0 years (posterior predictive P value = .532) in the United Kingdom Collaborative Trial of Ovarian Cancer Screening’s multimodal screening arm and 2.4 years (posterior predictive P value = .640) in the ultrasound screening arm, with sensitivities of 93.2% and 64.5%, respectively. Stage-specific screening sensitivities in the Prostate, Lung, Colorectal and Ovarian studies were 39.1% and 82.9% for early-stage and advanced-stage disease, respectively. The histology-specific sojourn times ranged from 0.8 to 1.8 years for type II ovarian cancer and 2.9 to 6.6 years for type I ovarian cancer.

CONCLUSIONS: Annual screening is not effective for all ovarian cancer subtypes. Screening sensitivity for early-stage ovarian cancers is not sufficient for substantial mortality reduction.

PMID:39038822 | DOI:10.1093/jnci/djae145

Cancer Treat Res Commun. 2024 Jul 11;40:100835. doi: 10.1016/j.ctarc.2024.100835. Online ahead of print.

ABSTRACT

INTRODUCTION: Single nucleotide polymorphisms (SNPs) have been identified as prognostic markers that can influence the response to chemotherapy and, ultimately, the outcome of the disease. The objective of this study is to investigate the association between the rs1045485 and rs4880 variants and breast cancer.

METHODS: Ninety-nine cases and 81 healthy individuals (over 60 years old) were recruited from Iranian population. Genotyping of the rs1045485 and rs4880 polymorphisms was determined using the PCR-RFLP molecular method. The obtained results were then evaluated using the SPSS 23.0, odds ratios (ORs) with 95 % confidence intervals (95 %CIs).

RESULTS: The average age of the subjects was 50.17± 1.8 years, with age ranging from 40 to 76 years. Additionally, more patients were in stage and grade 2 of the disease. Furthermore, 51.73 %, 53.24 % and 41.48 % of patients tested positive for ER, PR and HER2 status, respectively. The odds ratios of the genotypes studied for each of the two variants were not statistically significant. Additionally, all models (dominant, codominant, recessive and over dominant) also indicated that this difference was not significant (p > 0.05). Investigation of the association between the CASP8rs1045485 and SOD2 rs4880 variants with clinicopathological status were not revealed a significant relationship. The Hardy-Weinberg test showed that the evaluated population was balanced (p > 0.05).

CONCLUSION: In the studied models of both polymorphisms, no significant correlation was found between the genotypes and the conditions of estrogen, progesterone and Her2 receptors, as well as the stage and grade of the disease.

PMID:39038402 | DOI:10.1016/j.ctarc.2024.100835

Musculoskelet Sci Pract. 2024 Jul 11;73:103144. doi: 10.1016/j.msksp.2024.103144. Online ahead of print.

ABSTRACT

BACKGROUND: Some patients with low back pain (LBP) also report radiating leg pain which is a prognostic factor for poorer clinical outcomes. We aimed: 1) to compare the baseline characteristics of patients with LBP with – (LBP + leg pain) and without radiating leg pain (LBP – alone); 2) to investigate whether patients with LBP + leg pain show similar post-treatment outcomes as compared to LBP – alone, after participation in an exercise and patient education program, i.e. the GLA:D Back program.

METHODS: The patient sample included 3508 patients in the GLA:D Back program between March 2018 and August 2022. The outcomes were mean changes in LBP intensity, back-related activity limitation, self-efficacy and fear of movement measured from baseline to 3, 6 and 12 months. Baseline characteristics were compared with descriptive statistics, and linear mixed models were used to estimate group differences in changes from baseline to 3-, 6- and 12 months.

RESULTS: 1915 (55%) of the patients were in the group LBP- alone and 1593 (45%) in the LBP + leg pain. The LBP + leg pain group displayed higher STarT back classification (greater risk of chronicity) compared to the LBP-alone. The LBP + leg pain group showed almost similar improvements in all outcomes compared to LBP – alone after the GLA:D Back program.

CONCLUSION: In long-lasting (chronic) LBP patients, the LBP + leg pain group improved to the same extent as LBP – alone regarding LBP intensity, disability, and fear of movement following an exercise and patient education program, GLA:D Back.

PMID:39038395 | DOI:10.1016/j.msksp.2024.103144

Comput Methods Programs Biomed. 2024 Jul 17;255:108328. doi: 10.1016/j.cmpb.2024.108328. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Patch-Clamp recordings allow for in depth electrophysiological characterization of single cells, their general biophysical properties as well as characteristics of voltage- and ligand-gated ionic currents. Different acquisition modes, such as whole-cell patch-clamp recordings in the current or voltage clamp configuration, capacitance measurements or single channel recordings from cultured cells as well as acute brain slices are routinely performed for these purposes. Nevertheless, multipurpose transparent and adaptable software tools to perform reproducible state-of-the-art analysis of multiple experiment types and to manage larger sets of experimental data are currently unavailable.

METHODS: Biophysical Essentials (BPE) was developed as an open-source full stack python software for transparent and reproducible analysis of electrophysiological recordings. For validation, BPE results were compared with manually analyzed single-cell patch-clamp data acquired from a human in vitro nociceptor-model and mouse dorsal root ganglia neurons.

RESULTS: While initially designed to improve time consuming and repetitive analysis steps, BPE was further optimized as a technical software solution for entire workflow processing including data acquisition, data preprocessing, normalization and visualization and of single recordings up to stacked calculations and statistics of multiple experiments. BPE can operate with different file formats from different amplifier systems and producers. An in-process database logs all analysis steps reproducible review and serves as a central storage point for recordings. Statistical testing as well as advanced analysis functions like Boltzmann-fitting and dimensional reduction methods further support the researchers’ needs in projects involving electrophysiology techniques.

CONCLUSIONS: BPE extends beyond available patch-clamp specific, open source – and commercial analysis tools in particular because of reproducible and sharable analysis workflows. BPE enables full analysis from raw data acquisition to publication ready result visualizations – all within one single program. Thereby, BPE significantly enhances transparency in the analytical process of patch-clamp data analysis. BPEs function scope is completely accessible through an easy-to-use graphical user interface eliminating the need for programing language proficiency as required by many community patch-clamp analysis frameworks and algorithms.

PMID:39038390 | DOI:10.1016/j.cmpb.2024.108328

J Hazard Mater. 2024 Jul 17;477:135254. doi: 10.1016/j.jhazmat.2024.135254. Online ahead of print.

ABSTRACT

Land-based microplastics (MPs) are considered the primary source of MPs in aquatic environments, with runoff being a major pathway for their transfer from soil to surface water. However, the transportation characteristics of MPs via agricultural surface runoff remain unclear. In this study, we investigated the occurrence and emission characteristics of MPs in agricultural surface runoff under various short-term fertilizer applications and natural rainfall events using laser direct infrared imaging analysis (LDIR). MPs from fertilizers and soils co-migrated with the agricultural runoff. The abundance and concentration of MPs in runoff were 145.90 ± 22.48-2043.38 ± 89.51 items·L^-1 and 39.17 ± 21.94-523.04 ± 47.85 µg·L^-1, respectively. Small and low-density MPs, such as polyethylene (PE), chlorinated polyethylene (CPE), and polyurethane (PU) in film/fragment form with 20-50 µm exhibited a higher mobility. No statistical differences were observed in the distribution of runoff MPs with the application of different fertilizers. There was a significant positive relationship between runoff MP abundance and rainfall intensity. The annual emission load in this study area was 116.73 g·hm^-2, indicating that the transportation of MPs via agricultural surface runoff cannot be ignored. This study is conducive to understanding the migration behavior of MPs in soil-water environments in a better manner.

PMID:39038379 | DOI:10.1016/j.jhazmat.2024.135254

Altern Ther Health Med. 2024 Jul 19:AT10280. Online ahead of print.

ABSTRACT

OBJECTIVE: The study aimed to investigate the factors influencing the efficacy of Shenqi Yanshen Granule in ameliorating proteinuria among nephrotic syndrome patients in renal function stages 1-3.

METHODS: 100 patients with nephrotic syndrome and renal function stages 1-3, treated at our hospital from May 2021 to March 2023 were enrolled. All patients received Shenqi Yanshen granule treatment. The patients were divided into the control group (n = 68, with proteinuria reduction of ≥50%) and the observation group (n = 32, with proteinuria reduction of <50% or increased proteinuria) at 24 hours after treatment. Clinical data, proteinuria levels at 24 hours after treatment, renal function indices, and mean blood pressure were statistically compared. The efficacy of Shenqi Yanshen Granule in treating proteinuria and factors influencing the efficacy was assessed using multiple logistic regression.

RESULTS: The observation group had a higher average age and duration of disease compared to the control group (P < .05). Upon treatment, proteinuria decreased in both groups (P < .05), with higher levels in the observation group than in the control group. Post-treatment, serum creatinine levels decreased and GFR increased in the control group (P < .05), while the serum creatinine level increased and GFR decreased in the observation group (P < .05). Mean blood pressure decreased in both groups post-treatment (P < .05). The observation group exhibited lower rates of remarkable and effective outcomes and higher rates of general effective and ineffective outcomes (P < .05). Logistic regression analysis highlighted age, severity of nephropathy, underlying conditions, lifestyle, and pre-treatment proteinuria as significant factors influencing the impact of Shenqi Yanshen Granule on proteinuria in patients with nephrotic syndrome (P < .05).

CONCLUSION: Shenqi Yanshen Granule proves to be a potent intervention for reducing proteinuria in patients with nephrotic syndrome. Notably, age and disease severity emerge as pivotal determinants of drug efficacy.

PMID:39038363

Altern Ther Health Med. 2024 Jul 19:AT10653. Online ahead of print.

ABSTRACT

OBJECTIVE: This work explored the relationship between nosocomial infection-related factors and inflammatory factors after total hip replacement (THA).

METHODS: A total of 296 THA patients treated in the Zhejiang hospital from 2018 to 2022 were analyzed retrospectively. Clinical data of the patients were collected, and the nosocomial infection rate, infection site, infectious pathogen, related risk factors, and postoperative follow-up were statistically analyzed. Disease types included avascular necrosis of the femoral head, osteoarthritis, and femoral neck fracture. The troponin (Tn), blood routine, blood types, heparin-binding protein (HBP), thyroid function, thromboelastogram (TEG), brain natriuretic peptide (BNP), bone metabolism-related markers, glycosylated hemoglobin (GHb), and other indicators in three types of patients before and after surgery were analyzed.

RESULTS: 37 cases (12.5%) had necrosis of the femoral head, 105 cases had osteoarthritis (35.47%), and femoral neck fracture was observed in 154 cases (52.03%). The main infection sites were the respiratory tract, urinary tract, deep incision, and tissue infection. There were 8 pathogenic bacteria strains, including gram-positive and gram-negative bacteria. The BNP content in plasma was highly decreased after treatment [RR: 0.353 (95% CI: 0.234-0.533), P < .001]. HBP in patients with postoperative infection was notably higher than that in patients without infection [RR: 0.241 (95% CI: 0.161-0.361), P < .001]. The blood glucose of both the diabetic group and the non-diabetic group was remarkably decreased after surgery [RR: 0.367 (95% CI: 0.233-0.461), P < .001]. The level of triiodothyronine (T3) showed a downward trend, while both tetraiodothyronine (T4) and thyroid stimulating hormone (TSH) were at normal levels. There were 15 cases of postoperative loosening, 6 cases of femoral shaft loosening, and 9 cases of acetabulum loosening.

CONCLUSION: THA can regulate and maintain the balance of inflammatory cytokines, and taking preventive measures against risk factors can effectively reduce nosocomial infection, which is of great significance in improving the quality of medical treatment.

PMID:39038357

Altern Ther Health Med. 2024 Jul 19:AT9413. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effect of auricular point pressing with beans combined with three-step analgesic therapy on cancer pain.

METHODS: Sixty patients with cancer admitted to The Ganzhou Cancer Hospital from January to December 2021 were selected and randomly divided into experimental and control groups. The control group received three-step pain relief and routine care, while the experimental group was treated with auricular point acupressure combined with three-step analgesic therapy. The pain intensity was assessed by a numerical rating scale (NRS) at 0, 24, 48, and 72 h after treatment, and the incidence of adverse reactions was recorded.

RESULTS: The NRS score of the experimental group was lower than that of the control group (Ftreatment = 105.521, P = .001). The difference in NRS scores before and 24, 48, and 72 h after treatment was statistically significant (Ftime = 335.521, P = .001). The number of eruption pain cases in the experimental group and the control group was found to be statistically significant (χ2 = 10.767, P = .001), and the occurrence of eruption pain in the control group was more severe than that in the experimental group (Z = -4.472, P = .001). The incidence of adverse reactions in the experimental and control groups was 3.33% and 30.00%, respectively, and the difference was statistically significant (χ2 = 12.738, P = .001).

CONCLUSION: The combination of auricular point pressing and three-step ladder analgesic therapy can significantly improve the pain of cancer patients.

PMID:39038354