bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computer-aided genomic data analysis of drug-resistant Neisseria gonorrhoeae for the Identification of alternative therapeutic targets
Authors: Qasim Aqsa , Jaan Samavia , Wara Tehreem Ul , Shehroz Muhammad , Nishan Umar , Shams Sulaiman , Shah Mohibullah , Ojha Suvash Chandra 
Published: March 2023

Neisseria gonorrhoeae is an emerging multidrug resistance pathogen that causes sexually transmitted infections in men and women. The N. gonorrhoeae has demonstrated an emerging antimicrobial resistance against reported antibiotics, hence fetching the attention of researchers to address this problem. The present in-silico study aimed to find putative novel drug and vaccine targets against N. gonorrhoeae infection by the application of bioinformatics approaches. Core genes set of 69 N. gonorrhoeae strains was acquired from complete genome sequences. The essential and non-homologous metabolic pathway proteins of N. gonorrhoeae were identified. Moreover, different bioinformatics databases were used for the downstream analysis. The DrugBank database scanning identified 12 novel drug targets in the prioritized list. They were preferred as drug targets against this bacterium. A viable vaccine is unavailable so far against N. gonorrhoeae infection. In the current study, two outer-membrane proteins were prioritized as vaccine candidates via reverse vaccinology approach. The top lead B and T-cells overlapped epitopes were utilized to generate a chimeric vaccine construct combined with immune-modulating adjuvants, linkers, and PADRE sequences. The top ranked prioritized vaccine construct (V7) showed stable molecular interaction with human immune cell receptors as inferred during the molecular docking and MD simulation analyses. Considerable response for immune cells was interpreted by in-silico immune studies. Additional tentative validation is required to ensure the effectiveness of the prioritized vaccine construct against N. gonorrhoeae infection. The identified proteins can be used for further rational drug and vaccine designing to develop potential therapeutic entities against the multi-drug resistant N. gonorrhoeae.
Protective effects of Theracurmin treatment during experimental infection of the Colombian strain of Trypanosoma cruzi at the testicular site
Authors: Pimenta Breno Luiz , Menezes Tatiana Prata , Louise Vitória , Dias Fernanda Carolina Ribeiro , Machado Bianca Alves Almeida , Ribeiro Lais , Pinto Kelerson Mauro de Castro , Talvani Andre 
Published: March 2023

IntroductionChagas’ disease is a tropical neglected illness caused by Trypanosoma cruzi and remains one of the most significant causes of morbidity and mortality in South and Central Americas. The disease is caused by a moderate to intense and persistent inflammatory response characterized by local upregulated expression and production of inflammatory mediators that favors the activation and recruitment of distinct cells of the immune system into different tissues to eliminate the parasites. Theracurmin is a curcumin’s derived formulation of nanoparticles. Its anti-inflammatory properties make this bioactive compound a mitigating factor in pathological cases after an overwhelming inflammatory response.MethodsOur research focused on the testicular investigation in 28 mice infected by 103 trypomastigote forms of Colombian strain of T. cruzi and preventively treated with Theracurmin. The mice were treated with 30 mg/Kg of Theracurmin during the period of 30 days. At the 30th day post infection animals were euthanized, and its testicles were collected to morphological and immunological assays.ResultsThe animals infected and treated with Theracurmin presented a reduction in the testicular levels of IL-15 and IL-6. The volume density (%) of the tunica propria was also higher in all infected animals, but Theracurmin decreased this parameter in the treated animals. In the intertubular area, the percentage of some intertubular components was decreased in the infected animals such as the percentage and volume of Leydig cells, connective tissue, and macrophages.DiscussionFurthermore, our data pointed to the daily use of Theracurmin in the diet as a protective element of the testicular function.
Machine learning-based analysis of risk factors for atrial fibrillation recurrence after Cox-Maze IV procedure in patients with atrial fibrillation and chronic valvular disease: A retrospective cohort study with a control group
Authors: Jiang Zenan , Song Long , Liang Chunshui , Zhang Hao , Tan Haoyu , Sun Yaqin , Guo Ruikang , Liu Liming 
Published: March 2023

ObjectivesTo evaluate the efficacy of the Cox-Maze IV procedure (CMP-IV) in combination with valve surgery in patients with both atrial fibrillation (AF) and valvular disease and use machine learning algorithms to identify potential risk factors of AF recurrence.MethodsA total of 1,026 patients with AF and valvular disease from two hospitals were included in the study. 555 patients received the CMP-IV procedure in addition to valve surgery and left atrial appendage ligation (CMP-IV group), while 471 patients only received valve surgery and left atrial appendage ligation (Non-CMP-IV group). Kaplan–Meier analysis was used to calculate the sinus rhythm maintenance rate. 58 variables were selected as variables for each group and 10 machine learning models were developed respectively. The performance of the models was evaluated using five-fold cross-validation and metrics including F1 score, accuracy, precision, and recall. The four best-performing models for each group were selected for further analysis, including feature importance evaluation and SHAP analysis.ResultsThe 5-year sinus rhythm maintenance rate in the CMP-IV group was 82.13% (95% CI: 78.51%, 85.93%), while in the Non-CMP-IV group, it was 13.40% (95% CI: 10.44%, 17.20%). The eXtreme Gradient Boosting (XGBoost), LightGBM, Category Boosting (CatBoost) and Random Fores (RF) models performed the best in the CMP-IV group, with area under the curve (AUC) values of 0.768 (95% CI: 0.742, 0.786), 0.766 (95% CI: 0.744, 0.792), 0.762 (95% CI: 0.723, 0.801), and 0.732 (95% CI: 0.701, 0.763), respectively. In the Non-CMP-IV group, the LightGBM, XGBoost, CatBoost and RF models performed the best, with AUC values of 0.738 (95% CI: 0.699, 0.777), 0.732 (95% CI: 0.694, 0.770), 0.724 (95% CI: 0.668, 0.789), and 0.716 (95% CI: 0.656, 0.774), respectively. Analysis of feature importance and SHAP revealed that duration of AF, preoperative left ventricular ejection fraction, postoperative heart rhythm, preoperative neutrophil-lymphocyte ratio, preoperative left atrial diameter and heart rate were significant factors in AF recurrence.ConclusionCMP-IV is effective in treating AF and multiple machine learning models were successfully developed, and several risk factors were identified for AF recurrence, which may aid clinical decision-making and optimize the individual surgical management of AF.
A novel saline-based occlusion tool allows for dye-less cryoballoon-based pulmonary vein isolation and fluoroscopy reduction
Authors: Rottner Laura , Obergassel Julius , Borof Katrin , My Ilaria , Moser Fabian , Lemoine Marc , Wenzel Jan-Per , Kirchhof Paulus , Ouyang Feifan , Reissmann Bruno , Metzner Andreas , Rillig Andreas 
Published: March 2023

BackgroundCryoballoon (CB)- based pulmonary vein isolation (PVI) remains guided by fluoroscopy and dye. The novel saline injection-based occlusion tool allows for pulmonary vein (PV)-occlusion assessment without the need for dye injection.AimTo compare KODEX-EPD guided CB-PVI using the novel saline injection-based workflow with conventional cryoablation for acute efficacy, fluoroscopy exposure and dye volume.MethodsConsecutive atrial fibrillation (AF)- patients undergoing CB-PVI in conjunction with KODEX-EPD (CryoEPD group) were analyzed. Patients undergoing conventional CB-PVI (Cryo group) in the same time period acted as controls.ResultsOne hundred forty patients [91/140 (65%) persistent AF] were studied. Seventy patients underwent CryoEPD procedures [64 ± 13 years, 21 (30%) female] and seventy patients underwent Cryo procedures [68 ± 10 years, 27 (39%) female].A total of 560 PVs were identified and successfully isolated. Mean procedure time was 66 ± 15 min for the CryoEPD group, and 65 ± 19 min for the Cryo group (p = 0.3). Fluoroscopy time (CryoEPD 6 ± 4 min; Cryo 13 ± 6 min, p &lt; 0.001) and dose area product (CryoEPD 193 [111; 297] cGycm2; Cryo 381 [268; 614] cGycm2, p &lt; 0.001) were lower in patients undergoing CryoEPD compared with Cryo procedures. No dye was needed in the CryoEPD group while 53 ± 18 ml dye per patient were administered for the Cryo group (p &lt; 0.001). The overall complication rate was comparable between both groups (p = 0.5).ConclusionKODEX-EPD guided AF-ablation enables dye-free CB-based PVI with reduced fluoroscopy exposure when compared to conventional CB-ablation, without differences in acute procedural outcomes or procedure duration.
Associations of levels of peripheral blood leukocyte and subtypes with type 2 diabetes: A longitudinal study of Chinese government employees
Authors: Li Ruimin , Li Ling , Liu Bibo , Luo Dan , Xiao Shuiyuan 
Published: March 2023

ObjectivesAvailable evidence suggests that type 2 diabetes (T2D) may be associated with inflammation and that leukocytes are a topical clinical, biological indicator of inflammation. This study investigates the associations between peripheral blood leukocyte and subtypes levels with T2D.MethodsA total of 5,475 individuals were included in the baseline examination from January 2018 to April 2020, with incidence data updated to April 30, 2021, and follow-up to 5,362 individuals. T2D was defined according to the Chinese guidelines for preventing and treating type 2 diabetes. Physiological and biochemical indicators, including leukocyte and subtypes, were obtained from the physical examination results of the tertiary care hospitals relied on at the cohort sites. Covariates such as demographic characteristics and lifestyle were collected by questionnaire. Binary logistic regression and Cox proportional hazard models were used to explore the correlations. Receiver Operating Characteristic (ROC) curves and time-dependent ROC curves were used to estimate the predictive diagnosis of T2D across the subtype of leukocytes.ResultsThe mean follow-up time was 12 months, and the cumulative incidence density of T2D was 4.0/1000 person-years. Cross-sectional results at baseline showed that the levels of peripheral blood leukocyte and its subtypes were higher in the T2D group than in the non-T2D group. Total leukocyte count and subtypes levels were grouped by quintile. After adjusting for age, sex, family history of diabetes, lifestyle score, and triglyceride levels, all were compared with the lowest quintile of each group. Logistic regression model results showed that the corrected OR for those with the highest quintile level of leukocyte was 2.01 (95% CI: 1.02-3.98). The longitudinal analysis showed that the adjusted HR was 8.43 (95%CI: 1.06-66.92) for those with the highest quintile level of leukocytes at baseline after controlling for the effects of the above covariates. For those with the highest quintile level of neutrophils at baseline, the adjusted HR was 5.05 (95%CI: 1.01-25.29). The leukocyte and subtypes had predictive values for T2D.ConclusionPatients with T2D have a higher level of peripheral blood leukocyte and subtypes than those without the disease. Elevated leukocyte and neutrophil counts may link to a higher risk of T2D.
High-density lipoprotein cholesterol levels is negatively associated with intertrochanter bone mineral density in adults aged 50 years and older
Authors: Yang Pei , Li DongDong , Li Xiaokang , Tan Zongbiao , Wang Huan , Niu Xiaona , Han Yang , Lian Cheng 
Published: March 2023

BackgroundHigh-density lipoprotein cholesterol (HDL-C) has long been viewed as a protective factor for cardiovascular health. Yet, higher HDL-C was not necessarily beneficial. The purpose of this study was to investigate the relationship between HDL-C levels and intertrochanter bone mineral density.MethodsThe study collected the most recent data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). Weighted multiple regression analysis was used to evaluate the relationship between HDL-C and intertrochanter BMD, and further subgroup analysis and threshold effect analysis were conducted. Finally, the relationship between HDL-C and intertrochanter BMD was analyzed by fitting smooth curves.ResultsThe study included 3,345 people ranging in age from 50 to 80. HDL-C was discovered to be negatively correlated with intertrochanter BMD (β = -0.03, 95%CI: -0.04, -0.01, P = 0.0002). In subgroup analysis, the negative correlation was found among 60-70-year-olds (β = -0.04, 95%CI: -0.06, -0.02, P = 0.0010), additionally, non-Hispanic whites (β = -0.03, 95%CI: -0.05, -0.01, P = 0.0140), and obese individuals (β = -0.03, 95%CI: -0.05, -0.01, P = 0.0146). The negative correlation, on the other hand, remained significant and consistent across genders, menstruation status, hormone usage, and long-term use of steroids. The relationship between HDL-C and intertrochanter BMD was an inverted U-shaped curve in men and hormone users, with inflection points of 1.01 mmol/L and 1.71 mmol/L, and an U-shaped curve in other Hispanic and premenopausal individuals, with inflection points of 0.96 mmol/L and 1.89 mmol/L.ConclusionsHDL-C was negatively associated with intertrochanter BMD in people over 50 years of age, non-Hispanic whites, and obesity.
A meta-analysis of obstetric and neonatal outcomes in patients after treatment of hysteroscopic adhesiolysis
Authors: Wenzhi Xu , Xin Xu , Ping Zhou , Hanglin Wu , Xiaona Lin 
Published: March 2023

IntroductionHysteroscopic adhesiolysis is widely performed in women with intrauterine adhesions. Small observational studies have reported the obstetric and neonatal outcomes, but studies with larger sample sizes are few. The aim of this study is to evaluate the obstetric and neonatal outcomes in women after hysteroscopic adhesiolysis.MethodsWe conducted a literature search in July 2022 using the PubMed, Embase, the Cochrane Library, and Web of Science databases, and finally, 32 studies (N = 3812) were included. We did a meta-analysis to estimate the prevalence of placenta-related disorders, including placenta previa, placental abruption, placenta accreta, placenta increta, and retained placenta. We also included other obstetric and neonatal outcomes like postpartum hemorrhage, ectopic pregnancy, oligohydramnios, gestational hypertension, gestational diabetes mellitus, and intrauterine growth restriction. The results were presented as odds ratios (ORs) with 95% confidence intervals (CIs) in studies with a control group, but otherwise as prevalence (%) with 95% confidence intervals (CIs).ResultsThe overall pregnancy and live birth rates were 58.97% and 45.56%, respectively. The prevalence of placenta previa differed in pregnant women who underwent hysteroscopic adhesiolysis compared with those who did not (OR, 3.27; 95% CI, 1.28-8.36). In studies without a comparative group, the pooled rate of placenta accreta was 7% (95% CI, 4-11) in 20 studies; placenta increta was 1% (95% CI, 0-4) in 5 studies; a retained placenta was 11% (95% CI, 5-24) in 5 studies; postpartum hemorrhage was 12% (95% CI, 8-18) in 12 studies; ectopic pregnancy was 1% (95% CI, 0-2) in 13 studies; oligohydramnios was 3% (95% CI, 1-6) in 3 studies; intrauterine growth restriction was 3% (95% CI, 1-8) in 3 studies; gestational hypertension was 5% (95% CI, 2-11) in 4 studies; and diabetes mellitus was 4% (95% CI, 2-7) in 3 studies.DiscussionDue to the paucity of good quality comparative data, the question of whether there is an increased prevalence of obstetric and neonatal complications in women after hysteroscopic adhesiolysis compared with the general population remains unanswered. The findings from this review will provide a basis for more well-designed studies in the future.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=364021, identifier [CRD42022364021].
Prognostic prediction and multidimensional dissections of a macrophages M0-related gene signature in liver cancer
Authors: Xu Xiaoming , Wang Jingzhi 
Published: March 2023

BackgroundLiver hepatocellular carcinoma (LIHC) is the seventh most commonly diagnosed malignancy and the third leading cause of all cancer death worldwide. The undifferentiated macrophages M0 can be induced into polarized M1 and M2 to exert opposite effects in tumor microenvironment. However, the prognostic value of macrophages M0 phenotype remains obscure in LIHC.MethodsThe transcriptome data of LIHC was obtained from TCGA database and ICGC database. 365 LIHC samples from TCGA database and 231 LIHC samples from ICGC database were finally included. Macrophages M0-related genes (MRGs) were screened by Pearson correlation analysis and univariate Cox regression analysis based on the infiltration level of Macrophages M0. LASSO regression analysis was employed to construct a prognostic signature based on MRGs, and risk scores were accordingly calculated. Then we investigated the MRGs-based prognostic signature with respects to prognostic value, clinical significance, strengthened pathways, immune infiltration, gene mutation and drug sensitivity. Furthermore, the expression pattern of MRGs in the tumor microenvironment were also detected in LIHC.ResultsA ten-MRG signature was developed and clarified as independent prognostic predictors in LIHC. The risk score-based nomogram showed favorable capability in survival prediction. Several substance metabolism activities like fatty acid/amino acid metabolism were strengthened in low-risk group. Low risk group was deciphered to harbor TTN mutation-driven tumorigenesis, while TP53 mutation was dominant in high-risk group. We also ascertained that the infiltration levels of immune cells and expressions of immune checkpoints are significantly influenced by the risk score. Besides, we implied that patients in low-risk group may be more sensitive to several anti-cancer drugs. What’s more important, single-cell analysis verified the expression of MRGs in the tumor microenvironment of LIHC.ConclusionMultidimensional evaluations verified the clinical utility of the macrophages M0-related gene signature to predict prognosis, assist risk decision and guide treatment strategy for patients with LIHC.
Melanocortin 4 receptor signaling in Sim1 neurons permits sexual receptivity in female mice
Authors: Semple Erin A. , Harberson Mitchell T. , Xu Baijie , Rashleigh Rebecca , Cartwright Tori L. , Braun Jessica J. , Custer Amy C. , Liu Chen , Hill Jennifer W. 
Published: March 2023

IntroductionFemale sexual dysfunction affects approximately 40% of women in the United States, yet few therapeutic options exist for these patients. The melanocortin system is a new treatment target for hypoactive sexual desire disorder (HSDD), but the neuronal pathways involved are unclear.MethodsIn this study, the sexual behavior of female MC4R knockout mice lacking melanocortin 4 receptors (MC4Rs) was examined. The mice were then bred to express MC4Rs exclusively on Sim1 neurons (tbMC4RSim1 mice) or on oxytocin neurons (tbMC4ROxt mice) to examine the effect on sexual responsiveness.ResultsMC4R knockout mice were found to approach males less and have reduced receptivity to copulation, as indicated by a low lordosis quotient. These changes were independent of body weight. Lordosis behavior was normalized in tbMC4RSim1 mice and improved in tbMC4ROxt mice. In contrast, approach behavior was unchanged in tbMC4RSim1 mice but greatly increased in tbMC4ROxt animals. The changes were independent of melanocortin-driven metabolic effects.DiscussionThese results implicate MC4R signaling in Oxt neurons in appetitive behaviors and MC4R signaling in Sim1 neurons in female sexual receptivity, while suggesting melanocortin-driven sexual function does not rely on metabolic neural circuits.
Anaerobic digestion of brewer’s spent grain with biochars—biomethane production and digestate quality effects
Authors: Świechowski Kacper , Rasaq Waheed A. , Syguła Ewa 
Published: March 2023

In this research, biochar (BC) made from the brewer’s spent grain at temperatures of 300, 450, and 600 °C was produced and subjected to the anaerobic digestion of the brewer’s spent grain. BC shares of 2, 5, 10, and 50% concerning total solids of the substrate were tested at three substrate-to-inoculum ratios of 0.5, 1.0, and 2.0, respectively. The anaerobic digestion process was performed at 37 °C and took 30 days. For anaerobic digestion, biomethane production was recorded and used for kinetics parameter determination according to the first-order model. After the process, process residues (digestate) were analyzed for fertilizing potential. The biomethane yield differs from 264 to 325 mL×gvs−1, while kinetics parameters were 292.7–344.7 mL×gvs−1, 0.08–0.11 d−1, and 24–42.5 mL×(gvs×d)−1, for ymax, k, and r, respectively. The main factors affecting biomethane production were substrate-to-inoculum ratio and BC share. No specific effect between BC types on biomethane yield was found. An increase in BC share from 2% to 50% concerning specific SIR results in biomethane production improvement in the range of 1.8% to 10%. The main factors affecting the quality of digestate (nutrients) were the quality of the used inoculum and the quantity of the used substrate. The research results were complex and showed that the final effect of BC supplementation depends not only on BC properties, but also on process operational parameters and the quality of the used feedstock.
Downstream fish passage at small-scale hydropower plants: Turbine or bypass?
Authors: Knott Josef , Mueller Melanie , Pander Joachim , Geist Juergen 
Published: March 2023

Introduction: Hydropower plants are frequently equipped with physical and behavioral fish protection barriers to prevent downstream moving fish from harmful turbine passage and to guide them to alternative bypasses. As not only diadromous but also potamodromous fish species migrate and inevitably have to pass hydropower plants, knowledge on corridor usage for a wide range of species is important to identify potential deficits and to improve bypass efficiency.Methods: In this study, the corridor usage of downstream moving fish (6,646 individuals from 42 species) was investigated at four small-scale hydropower plants with different concepts to prevent turbine entrainment and to bypass fish.Results: Despite existing bypasses and fine screens with 15 mm and 20 mm bar spacing to prevent turbine entrainment, a large proportion of fish (35%–88%) still passed the turbines. The mainly poor efficiency of the investigated bypasses was probably due to low discharge and unfavorable bypass location or detectability. The various bypass types were used by a different range of fish species and sizes due to species-specific behavior and differing fish communities between sites. The effectiveness of the investigated downstream corridors was positively correlated with the share of discharge.Discussion: To reduce the negative ecological impacts of hydropower plants on downstream moving fish, well-performing bypasses are required that consider not only current requirements regarding design, dimensioning and location, but also the site-specific fish community. Thus, bypasses should function for the widest possible range of species, which can be achieved through less selective bypass types such as full-depth bypasses, or a combination of different bypass systems. Moreover, less harmful turbine technologies and more effective fish protection systems need to be implemented, since fine screens with 15 mm and 20 mm bar spacing cannot prevent small-bodied fish species and juvenile fish &lt;20 cm from turbine entrainment.