Nevin Manimala

Front Genet. 2023 Nov 23;14:1286561. doi: 10.3389/fgene.2023.1286561. eCollection 2023.

ABSTRACT

Polygenic risk score (PRS) predictions often show bias toward the population of available genome-wide association studies (GWASs), which is typically of European ancestry. This study aimed to assess the performance differences of ancestry-specific PRS and test the implementation of multi-ancestry PRS to enhance the generalizability of low-density lipoprotein (LDL) cholesterol predictions in the East Asian (EAS) population. In this study, we computed ancestry-specific and multi-ancestry PRSs for LDL using data obtained from the Global Lipid Genetics Consortium, while accounting for population-specific linkage disequilibrium patterns using the PRS-CSx method in the United Kingdom Biobank dataset (UKB, n = 423,596) and Taiwan Biobank dataset (TWB, n = 68,978). Population-specific PRSs were able to predict LDL levels better within the target population, whereas multi-ancestry PRSs were more generalizable. In the TWB dataset, covariate-adjusted R ² values were 9.3% for ancestry-specific PRS, 6.7% for multi-ancestry PRS, and 4.5% for European-specific PRS. Similar trends (8.6%, 7.8%, and 6.2%) were observed in the smaller EAS population of the UKB (n = 1,480). Consistent with R ² values, PRS stratification in EAS regions (TWB) effectively captured a heterogenous variability in LDL blood cholesterol levels across PRS strata. The mean difference in LDL levels between the lowest and highest EAS-specific PRS (EAS_PRS) deciles was 0.82, compared to 0.59 for European-specific PRS (EUR_PRS) and 0.76 for multi-ancestry PRS. Notably, the mean LDL values in the top decile of multi-ancestry PRS were comparable to those of EAS_PRS (3.543 vs. 3.541, p = 0.86). Our analysis of the PRS prediction model for LDL cholesterol further supports the issue of PRS generalizability across populations. Our targeted analysis of the EAS population revealed that integrating non-European genotyping data with a powerful European-based GWAS can enhance the generalizability of LDL PRS.

PMID:38075701 | PMC:PMC10704094 | DOI:10.3389/fgene.2023.1286561

Front Genet. 2023 Nov 23;14:1285274. doi: 10.3389/fgene.2023.1285274. eCollection 2023.

ABSTRACT

Objective: According to the 2020 data from the World Health Organization (WHO), cancers stand as one of the foremost contributors to global mortality. Revealing novel cancer risk factors and protective factors is of paramount importance in the prevention of disease occurrence. Studies on the relationship between chemokines and cancer are ongoing; however, due to the coordination of multiple potential mechanisms, the specific causal association remains unclear. Methods: We performed a bidirectional Mendelian randomization analysis to explore the causal association between serum chemokines and pan-carcinoma. All data is from the GWAS catalog and IEU Open GWAS database. The inverse-variance weighted (IVW) method is primarily employed for assessing the statistical significance of the findings. In addition, the significance threshold after the multiple hypothesis test (Bonferroni) was 0.0013, and the evidence of a potential association was considered if the p-value < 0.05, but remained greater than Bonferroni’s threshold. Results: The results indicate that CCL1 (odds ratio, OR = 1.18), CCL2 (OR = 1.04), CCL8 (OR = 1.36), CCL14 (Colorectal, OR = 1.08, Small intestine, OR = 0.77, Lung, OR = 1.11), CCL15 (OR = 0.85), CCL18 (Breast, OR = 0.95, Prostate, OR = 0.96), CCL19 (Lung, OR = 0.66, Prostate, OR = 0.92), CCL20 (Lung, OR = 0.53, Thyroid, OR = 0.76), CCL21 (OR = 0.62), CCL22 (OR = 2.05), CCL23 (OR = 1.31), CCL24 (OR = 1.06), CCL27 (OR = 1.49), CCL28 (OR = 0.74), CXCL5 (OR = 0.95), CXCL9 (OR = 3.60), CXCL12 (Breast, OR = 0.87, Small intestine, OR = 0.58), CXCL13 (Breast, OR = 0.93, Lung, OR = 1.29), CXCL14 (Colon, OR = 1.40) and CXCL17 (OR = 1.07) are potential risk factors for cancers. In addition, there was a reverse causal association between CCL1 (OR = 0.94) and CCL18 (OR = 0.94) and breast cancer. Sensitivity analysis results were similar. The results of the other four MR Methods were consistent with the main results, and the leave-one-out method showed that the results were not driven by a Single nucleotide polymorphism (SNP). Moreover, there was no heterogeneity and pleiotropy in our analysis. Conclusion: Based on the two-sample MR Analysis method, we found that chemokines might be upstream factors of cancer pathogenesis. These results might provide new insights into the future use of chemokines as potential targets for cancer prevention and treatment. Our results also provide important clues for tumor prevention, and changes of serum chemokine concentration may be recognized as one of the features of precancerous lesions in future clinical trials.

PMID:38075694 | PMC:PMC10702354 | DOI:10.3389/fgene.2023.1285274

Front Genet. 2023 Nov 24;14:1215493. doi: 10.3389/fgene.2023.1215493. eCollection 2023.

ABSTRACT

Introduction: The selection of antiseizure medication usually requires a trial-and-error process. Our goal is to investigate whether genetic markers can predict the outcome of perampanel (PER) use in patients with epilepsy. Method: The studied participants were selected from our previous epilepsy genetics studies where whole exome sequencing was available. We reviewed the medical records of epilepsy patients older than 20 years old treated with PER. The outcome of PER treatment included the response to PER, the occurrence of any adverse drug reaction (ADR), the presence of behavior ADR, and the ability to adhere to PER for more than 1 year. We investigated the association between the rare variants of the glutamate receptor genes and the outcomes of PER use. Result: A total of 83 patients were collected. The gene group burden analysis showed that enriched genetic variants of the glutamate receptor gene group were statistically significantly associated with the occurrence of ADR, while the glutamate ionotropic receptor delta type subunit had a nominal association with the occurrence of ADR. The gene collapse analysis found that GRID1 had a nominal association with the occurrence of ADR and GRIN3A had a nominal association with the occurrence of behavior ADR. However, these nominal associations did not remain statistically significant once adjusted for multiple testing. Discussion: We found that enriched rare genetic variants of the glutamate receptor genes were associated with the occurrence of ADR in patients taking PER. In the future, combining the results of various pharmacogenetic studies may lead to the development of prediction tools for the outcome of antiseizure medications.

PMID:38075685 | PMC:PMC10704178 | DOI:10.3389/fgene.2023.1215493

Chem Sci. 2023 Nov 21;14(47):13908-13914. doi: 10.1039/d3sc04466a. eCollection 2023 Dec 6.

ABSTRACT

Surface intermediate species and oxygen vacancy-assisted mechanism over CeO₂ catalyst in the direct dimethyl carbonate (DMC) synthesis from carbon dioxide and methanol are suggested by means of transient spectroscopic methodologies in conjunction with multivariate spectral analysis. How the two reactants, i.e. CO₂ and methanol, interact with the CeO₂ surface and how they form decisive surface intermediates leading to DMC are unraveled by DFT-based molecular dynamics simulation by precise statistical sampling of various configurations of surface states and intermediates. The atomistic simulations and uncovered stability of different intermediate states perfectly explain the unique DMC formation profile experimentally observed upon transient operations, strongly supporting the proposed oxygen vacancy-assisted reaction mechanism.

PMID:38075668 | PMC:PMC10699564 | DOI:10.1039/d3sc04466a

Data Brief. 2023 Nov 14;51:109805. doi: 10.1016/j.dib.2023.109805. eCollection 2023 Dec.

ABSTRACT

Most seaplanes used for aircraft operations in territorial waters are classified into three main types, namely floatplanes, flying boats, and amphibians. Among these, the floatplane stands out as it replaced its landing gear with two floating pontoons, known as the catamaran floater, on which the fuselage rests. Therefore, this research presented a data article on resistance testing to predict force and moment along the x, y, and z axes for a 1:10 scale model of the catamaran floater. Test data encompassed variations in trim angles 0°, -1°, and -2°, and speed ranging from 1 to 6 m/s. The results of the resistance testing are presented in the form of descriptive statistics and shown through two graphs. The first graph described the relationship between the catamaran floater’s speed and the corresponding force generated. The second graph illustrated the correlation between the catamaran floater’s speed and moment generated.

PMID:38075614 | PMC:PMC10700570 | DOI:10.1016/j.dib.2023.109805

J Trop Med. 2023 Nov 30;2023:2289552. doi: 10.1155/2023/2289552. eCollection 2023.

ABSTRACT

OBJECTIVE: Malaria during pregnancy is a priority area for malaria research and control as pregnant women represent a high risk group for severe malaria, and the presentation of malaria during pregnancy varies according to the level of transmission in the area; so the aim of this study is to determine the prevalence rates of malaria parasite among pregnant women attending to Saudi Kassala Teaching hospital in Kassala state, 2022.

METHODS: A cross-sectional study was carried out in Saudi Kassala Teaching hospital in Kassala State. This study involved one hundred and eighty-five blood samples collected from pregnant women who was then examined by using blood films and ICT for malaria, and the data were collected by a structured questionnaire and analyzed using SPSS version 21.

RESULTS: The prevalence of malaria among pregnant women was 2.2% (95% CI: 0.006-0.054). There was no significant difference among the different age groups with respect to the prevalence of malaria (P value = 0.483). The prevalence of malaria in rural residency was 2.2%, and this was significantly more common than the urban residency (P value = 0.021). When compared across the gestational trimesters, there was no significant difference between them (P value = 0.518). The number of gravidity is not related to malaria infection (P value = 0.737). The presence of symptom compliant of malaria during pregnancy does not suggest the presence of malaria (P value = 0.152). No difference was found between the different educational levels with respect to the prevalence of malaria (P value = 0.362). The result showed that there was 1 (0.5%) negative result in ICT which was positive in blood film for malaria (BFFM) and there were 3 (1.6%) positive malaria parasites by both methods in all 185 samples with statistically insignificant differences (P = 0.703).

CONCLUSION: Plasmodium falciparum was only species detected in this study. Malaria among pregnant women was more prevalent in rural areas. However, other factors such as age, gestational age, gravidity, and educational level do not affect the prevalence of malaria in pregnant women. The presence of symptomatic compliant of malaria during pregnancy does not suggest the presence of malaria. The use of ICT or BFFM has similar diagnostic outcome for malaria in pregnancy.

PMID:38075586 | PMC:PMC10703523 | DOI:10.1155/2023/2289552

World J Clin Cases. 2023 Nov 26;11(33):7980-7986. doi: 10.12998/wjcc.v11.i33.7980.

ABSTRACT

BACKGROUND: Postpartum depression (PPD) is a common psychological disease among puerperal women, and postpartum pelvic floor dysfunction is a common disease among pregnant women. The occurrence of postpartum pelvic floor dysfunction will increase the incidence of PPD.

AIM: To explore the therapeutic effect of integrated traditional Chinese and Western medicine nursing combined with electrical stimulation of pelvic floor muscles and the rectus abdominis on PPD.

METHODS: From April 2020 to January 2022, 100 parturients with a rectus abdominis muscle separation distance > 2.0 cm who underwent reexamination 6 wk after delivery at our hospital were selected as the research subjects. According to the random number table method, the patients were divided into either an observation group (n = 50) or a control group (n = 50). There was no significant difference in the general data between the two groups (P > 0.05). Both groups were treated by electrical stimulation. The observation group was additionally treated by integrated traditional Chinese and Western medicine nursing. A self-designed Depression Knowledge Questionnaire was used to evaluate the awareness of knowledge on depression in all patients 3 wk after intervention. The Hamilton Depression Scale (HAMD) was used to evaluate the depression before intervention and 1 wk and 3 wk after intervention, and the Morisky Medication Adherence Scale (MMAS-8) was used to evaluate the medication compliance. SPSS19.0 was used for statistical analyses.

RESULTS: The rate of awareness of knowledge on depression in the observation group was significantly higher than that of the control group (P < 0.05). The scores of MMAS-8 were comparable between the two groups before intervention (P > 0.05), but were significantly higher in the observation group than in the control group at 1 wk and 3 wk after intervention (P < 0.05). The HAMD scores were comparable between the two groups before intervention (P > 0.05), but were significantly lower in the observation group than in the control group at 1 wk and 3 wk after intervention (P < 0.05).

CONCLUSION: Integrated traditional Chinese and Western medicine nursing combined with electrical stimulation of pelvic floor muscles and the rectus abdominis is effective in the treatment of postpartum depression and worthy of clinical promotion.

PMID:38075581 | PMC:PMC10698394 | DOI:10.12998/wjcc.v11.i33.7980

World J Clin Cases. 2023 Nov 26;11(33):8003-8012. doi: 10.12998/wjcc.v11.i33.8003.

ABSTRACT

BACKGROUND: The recovery time of hand wounds is long, which can easily result in chronic and refractory wounds, making the wounds unable to be properly repaired. The treatment cycle is long, the cost is high, and it is prone to recurrence and disability. Double layer artificial dermis combined with autologous skin transplantation has been used to repair hypertrophic scars, deep burn wounds, exposed bone and tendon wounds, and post tumor wounds.

AIM: To investigate the therapeutic efficacy of autologous skin graft transplantation in conjunction with double-layer artificial dermis in treating finger skin wounds that are chronically refractory and soft tissue defects that expose bone and tendon.

METHODS: Sixty-eight chronic refractory patients with finger skin and soft tissue defects accompanied by bone and tendon exposure who were admitted from July 2021 to June 2022 were included in this study. The observation group was treated with double layer artificial dermis combined with autologous skin graft transplantation (n = 49), while the control group was treated with pedicle skin flap transplantation (n = 17). The treatment status of the two groups of patients was compared, including the time between surgeries and hospital stay. The survival rate of skin grafts/flaps and postoperative wound infections were evaluated using the Vancouver Scar Scale (VSS) for scar scoring at 6 mo after surgery, as well as the sensory injury grading method and two-point resolution test to assess the recovery of skin sensation at 6 mo. The satisfaction of the two groups of patients was also compared.

RESULTS: Wound healing time in the observation group was significantly longer than that in the control group (P < 0.05, 27.92 ± 3.25 d vs 19.68 ± 6.91 d); there was no significant difference in the survival rate of skin grafts/flaps between the two patient groups (P > 0.05, 95.1 ± 5.0 vs 96.3 ± 5.6). The interval between two surgeries (20.0 ± 4.3 d) and hospital stay (21.0 ± 10.1 d) in the observation group were both significantly shorter than those in the control group (27.5 ± 9.3 d) and (28.4 ± 17.7 d), respectively (P < 0.05). In comparison to postoperative infection (23.5%) and subcutaneous hematoma (11.8%) in the control group, these were considerably lower at (10.2%) and (6.1%) in the observation group. When comparing the two patient groups at six months post-surgery, the excellent and good rate of sensory recovery (91.8%) was significantly higher in the observation group than in the control group (76.5%) (P < 0.05). There was also no statistically significant difference in two point resolution (P > 0.05). The VSS score in the observation group (2.91 ± 1.36) was significantly lower than that in the control group (5.96 ± 1.51), and group satisfaction was significantly higher (P < 0.05, 90.1 ± 6.3 vs 76.3 ± 5.2).

CONCLUSION: The combination of artificial dermis and autologous skin grafting for the treatment of hand tendon exposure wounds has a satisfactory therapeutic effect. It is a safe, effective, and easy to operate treatment method, which is worthy of clinical promotion.

PMID:38075574 | PMC:PMC10698399 | DOI:10.12998/wjcc.v11.i33.8003

J Endocr Soc. 2023 Nov 27;8(1):bvad148. doi: 10.1210/jendso/bvad148. eCollection 2023 Dec 1.

ABSTRACT

BACKGROUND: Although thyroid eye disease (TED) can impact social and psychological well-being, the epidemiological evidence of TED is lacking in Japan.

METHODS: Nationwide claims databases provided by JMDC Inc. and Medical Data Vision Co., Ltd. and national population statistics are used. Three TED definitions ranging from a strict definition only including a TED diagnosis to a broad definition including a TED diagnosis and considering ocular symptoms are considered. The proportion of patients by severity and disease activity are estimated based on definitions that would allow identification of those patients within the claims data.

RESULTS: The incidence rate per 100 000 person-years ranged from 7.3 to 11.1 for the strict and broad TED definitions, respectively. For fiscal year 2020 (April 2020 to March 2021) the prevalence rate ranged between 24.65 (strict TED) and 37.58 (broad TED) per 100 000 persons. These correspond to 25 383 and 38 697 patients for the strict and broad TED definitions, respectively. Regardless of the definition used, a predominance of female patients was observed, and the highest burden of the disease was seen in the age group of 35 to 59. Mild and inactive forms of TED were predominant (about 85% and 74%, respectively).

CONCLUSION: The incidence and prevalence of TED in Japan were 7.3 to 11.1 per 100 000 person-years and 24.65 to 37.58 per 100 000 persons, respectively. The robust results of this database study add valuable real-world evidence on the incidence and prevalence of TED in Japan.

PMID:38075564 | PMC:PMC10701629 | DOI:10.1210/jendso/bvad148

J Endocr Soc. 2023 Nov 28;8(1):bvad145. doi: 10.1210/jendso/bvad145. eCollection 2023 Dec 1.

ABSTRACT

OBJECTIVE: To evaluate potential improvements in the diagnosis of thyroid nodules when conventional ultrasound (US) is combined with contrast-enhanced US (CEUS).

METHODS: We recruited 515 participants with 323 malignant and 192 benign nodules, who underwent both US and CEUS examinations at 8 different medical centers in China between October 2020 and October 2021. We assessed the malignancy of thyroid nodules in US using the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TIRADS). Diagnostic criteria for US and US + CEUS were developed by investigators based on evaluations of sonographic features. Using multivariate logistic regression and receiver operating characteristic (ROC) analysis, we compared diagnostic performance between the 2 methods based on criteria identified by investigators and via statistical models.

RESULTS: On the basis of diagnostic criteria identified by investigators, we measured statistically significant differences in area under the curve (AUC) values between ACR TIRADS (0.83) and CEUS TIRADS (0.87; P < .001). On the basis of diagnostic regression models, we found statistically significant differences in AUC values between US (0.76) and US + CEUS (0.84; P = .001). Models based on US + CEUS outperformed those based on US alone (Akaike information criterion of 347.7 and significant improvement in integrated discrimination). These results were confirmed by similar analyses applied to a validation cohort.

CONCLUSION: The accuracy of conventional US for differentiating between benign and malignant thyroid nodules can be improved by combining this approach with CEUS.

PMID:38075563 | PMC:PMC10699741 | DOI:10.1210/jendso/bvad145