bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic engineering of Escherichia coli for efficient production of L-5-hydroxytryptophan from sugars
Authors: Zhang Zhen , Yu Zichen , Wang Jinduo , Yu Yifa , Li Lanxiao , Sun Pengjie , Fan Xiaoguang , Xu Qingyang 
Published: August 2022

Abstract
Background
5-hydroxytryptophan (5-HTP), the direct biosynthetic precursor of the neurotransmitter 5-hydroxytryptamine, has been shown to have unique efficacy in the treatment of a variety of disorders, including depression, insomnia, and chronic headaches, and is one of the most commercially valuable amino acid derivatives. However, microbial fermentation for 5-HTP production continues to face many challenges, including low titer/yield and the presence of the intermediate L-tryptophan (L-Trp), owing to the complexity and low activity of heterologous expression in prokaryotes. Therefore, there is a need to construct an efficient microbial cell factory for 5-HTP production.
Results
We describe the systematic modular engineering of wild-type Escherichia coli for the efficient fermentation of 5-HTP from sugars. First, a xylose-induced T7 RNA polymerase-PT7 promoter system was constructed to ensure the efficient expression of each key heterologous pathway in E. coli. Next, a new tryptophan hydroxylase mutant was used to construct an efficient tryptophan hydroxylation module, and the cofactor tetrahydrobiopterin synthesis and regeneration pathway was expressed in combination. The L-Trp synthesis module was constructed by modifying the key metabolic nodes of tryptophan biosynthesis, and the de novo synthesis of 5-HTP was achieved. Finally, the NAD(P)H regeneration module was constructed by the moderate expression of the heterologous GDHesi pathway, which successfully reduced the surplus of the intermediate L-Trp. The final engineered strain HTP11 was able to produce 8.58 g/L 5-HTP in a 5-L bioreactor with a yield of 0.095 g/g glucose and a maximum real-time productivity of 0.48 g/L/h, the highest values reported by microbial fermentation.
Conclusions
In this study, we demonstrate the successful design of a cell factory for high-level 5-HTP production, combined with simple processes that have potential for use in industrial applications in the future. Thus, this study provides a reference for the production of high-value amino acid derivatives using a systematic modular engineering strategy and a basis for an efficient engineered strain development of 5-HTP high-value derivatives.
Sex difference in the association of the triglyceride glucose index with obstructive coronary artery disease
Authors: Lu Ya-Wen , Tsai Chuan-Tsai Tsai , Chou Ruey-Hsing , Tsai Yi-Lin , Kuo Chin-Sung , Huang Po-Hsun , Lin Shing-Jong 
Published: August 2022

Abstract
Background
Insulin resistance is associated with cardiovascular disease in nondiabetic patients. The triglyceride-glucose (TyG) index, incorporating serum glucose and insulin concentrations, is a surrogate insulin resistance marker. We investigated its association with obstructive coronary artery disease (CAD) and sex differences therein.
Methods
Patients with stable angina pectoris requiring invasive coronary angiography between January 2010 and December 2018 were enrolled. They were divided into two groups according to TyG indices. Two interventional cardiologists diagnosed obstructive CAD by angiography review. Demographic characteristics and clinical outcomes were compared between groups.
Results
Relative to lower indices, patients with higher (≥ 8.60) TyG indices had higher BMIs and more prevalent hypertension, diabetes, and elevated lipid profiles [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, triglycerides, fasting plasma glucose]. Higher TyG indices increased women’s obstructive CAD risk after adjustment for age; smoking; BMI; hypertension; congestive heart failure; stroke; diabetes; LDL; estimated glomerular filtration rate; and statin, antiplatelet agent, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use (adjusted odds ratio 2.15, 95% confidence interval 1.08–4.26, p = 0.02). No sex difference was found for diabetic patients.
Conclusion
Higher TyG indices significantly increased the obstructive CAD risk, overall and for non-diabetic women. Larger-scale studies are needed to confirm our findings.
Associated factors with mortality in people living with HIV in Ziguinchor, Southern-region, Senegal: about 804 cases
Authors: Diallo Kalilou , Wembulua Bruce Shinga , Sarr Généviève D , Diallo Khadidiatou , Kane Yaya , Diatta Ansoumana , Manga Noel Magloire 
Published: August 2022

Abstract
Background: The effectiveness and increasingly easy access to highly active antiretroviral treatment (ART) have contributed to a considerable drop in HIV-related mortality. However, the mortality of adults in people living with HIV (PLHIV) remains overall higher than in the population in general. The objective of this study was to determine the associated factors with the occurrence of death in (PLHIV) followed in Ziguinchor , in order to improve the care of these patients in our context.Patients and method: This was a cross-sectional, descriptive and analytical study on cohorts of PLHIV followed in the health districts of Ziguinchor during 5 years. All PLHIV, aged 15 and beyond, regularly followed on antiretroviral treatment during the study period in those health districts were included.Results: We included 804 patients, women represented 597 (74.25%), i.e. a sex ratio (F/M) of 2.88. The average age was 45.61 ± 13.01 years with extremes from 15 to 96 years. The 46-60 age group was the most represented, 297 (36.94%). 286 patients (35.58%) were diagnosed at stages 3 and 4 of WHO. 82.34% were infected with HIV1. HIV2 was found in 122 (15.17%) patients and the dual profile in 20 cases (2.49%). The average CD4 count was 327±295/mm3 with extremes from 1 to 2156/mm3. Two hundred and thirteen patients (40.73%) had a CD4 count below 200/mm3 and 117 patients (22.37%) had a CD4 count above 500/mm3. Antiretroviral treatment was initiated in 791 patients (98.38%). The antiretroviral regimen combined 2 NRTIs (nucleoside reverse transcriptase inhibitor) with 1 NNTI (non-nucleoside reverse transcriptase inhibitor) in 82.71% of cases. The average length of follow-up was 3.22±1.33 years (range 1 to 6 years). In multivariate analysis, the occurrence of death was associated with age greater than 65 years (p = 0.027), treatment duration < 12 months (p 0.005), delay in ARV treatment (CD4 at baseline less than 500 cells/mm3 (p=0.001) and high viral load greater than 1000 copies/mL (p=0.000) at baseline).Conclusion: Strengthening screening, early initiation of ART, strengthening the therapeutic arsenal of antiretrovirals, are the main factors to be taken into consideration in order to reduce mortality in HIV-infected patients.
Enhanced delivery of low-dose of aducanumab via FUS in 5xFAD mice, an AD model
Authors: Kong Chanho , Yang Eun-Jeong , Shin Jaewoo , Park Junwon , Kim Si-Hyun , Chang Won Seok , Lee Changhan , Kim Hyunju , Kim Hye-Sun , Chang Jin Woo 
Published: August 2022

Abstract
BackgroundAducanumab (Adu), which is a human IgG1 monoclonal antibody that targets oligomer and fibril forms of beta-amyloid (Aβ), has been reported to reduce amyloid pathology and improve impaired cognition after the administration of a high dose (10 mg/kg) of the drug in Alzheimer’s disease (AD) clinical trials. The purpose of this study is to investigate the effects of a lower dose of Adu (3mg/kg) with enhanced delivery via focused ultrasound (FUS) in an AD mouse model.MethodsThe FUS with microbubbles opened the blood-brain barrier of the hippocampus for the delivery of Aducanumab. Combined therapy of FUS and Aducanumab was performed three times in total and each treatment was performed biweekly. Y-maze test, Brdu labeling, immunohistochemical experimental methods were employed in this study. In addition, RNA sequencing and ingenuity pathway analysis were employed to investigate gene expression profiles in the hippocampi of experimental animals.ResultsThe combined treatment with FUS markedly increased the delivery of Adu into the brain by approximately 8.1 times in the brains. The combined treatment significantly restored cognitive impairment and decreased the level of amyloid plaques in the hippocampi of 5xFAD mice compared with Adu or FUS alone. The combined treatment with FUS and Adu increased reactive microglia and astrocytes associated with amyloid plaques in the hippocampi of 5xFAD mice. Furthermore, RNA sequencing identified 4 enriched canonical pathways such as phagosome formation, neuroinflammation signaling, CREB signaling and reelin signaling was altered in the hippocami of 5xFAD given the combined treatment. ConclusionIn conclusion, the enhanced delivery of a low dose of Aducanumab via FUS decreased amyloid deposits and restored cognitive function. This study provides better insight into establishing a solid therapeutic strategy for the treatment of AD as well as other neurodegenerative diseases.
Holocene Records of Large Palaeoearthquake events from the Brahmaputra valley in the proximity of the Eastern Himalayan Syntaxis and Environmental Impacts
Authors: Bhadran Arun , Duarah B.P. , Girishbai Drishya , Raza Mohammed Atif , Mero Avi , Lahon Sandeep , A.L. Achu , Gopinath Girish 
Published: August 2022

Abstract
The Eastern Himalayan Syntaxis (EHS) and associated tectonic plate boundaries have caused two great earthquakes within hundred years and more than fifteen strong earthquakes (from eighteen centuries) in the foredeep Brahmaputra Basin. These earthquakes are generally considered blind, owing to the deficiency of surface rupture. Further, the lack of instrumental and historical archives elicits palaeo-seismological proxies for future seismic hazard assessment. The present study area is confined to the rapidly growing Dibrugarh City, lies on left bank of Brahmaputra and bounded by EHS in northeast, Main Frontal Thrust (MFT) in North, Naga Thrust (NT) in Southeast and Mishmi Thrust (MT) in east. This tectonically active area witnessed dreadful damages during the 1950 great Assam earthquake (Mw = 8.4), the largest continental ever recorded event. In this study, palaeoseismological evidence such as sand dyke and sand blow from different levels of the river terraces in and around Dibrugarh City has been dated using optically stimulated luminescence (OSL) methodology to understand the ages of the causative event. The optical dates from the palaeoliquefacton features indicate multiple episodic events ca. 888 ± 63 yrs, ca. 934 ± 63 yrs & ca. 989 ± 83 yrs. On the other hand, an age of ca. 11.3 ± 0.7 ka, early Holocene has been obtained from a neotectonic scarp indicates the crustal shortening time during MFT orogeny. Further, the empirical back-calculation of the complex geometry of the palaeoliquefaction feature facilitated in determining the causative earthquake magnitude and PGA, which is first of its kind from northeast of India. Back-calculation indicates, the magnitude of the earthquake might be range from 6.2-7.4Mw with PGA ~ 0.5-0.6g. The overlapping of palaeointensity lines /isoseismic lines from the empirical calculation, ESI and 1950 earthquake indicate the effect of multiple episodes of earthquake and vulnerability in Eastern Himalayan foothill areas. This study is of immense importance considering the seismic hazard potential in the eastern Himalaya and its surroundings and inadequate instrumentally recorded earthquake database.
The prevalence and social determinants of Intimate partner violence and its association with children under 5 morbidity and mortality in Afghanistan; An implication for global advocacy and women’s rights
Authors: Dadras Omid , Dadras Mohammad Yasin , Nakayama Takeo 
Published: August 2022

Abstract
Background
Limited knowledge exists concerning the prevalence and drivers of IPV against Afghan women and its association with child morbidity and mortality; thus, further studies are warranted.
Methods
A cross-sectional study, using the data from Afghanistan Demographic and Health Survey (ADHS) conducted in 2015. To estimate the prevalence and associated sociodemographic factors, the analysis was restricted to the women aged 15–49 years who were selected for the IPV module in ADHS 2015 (n = 24070). To estimate the morbidity and mortality of children and its association with IPV, the children born in the past 5 years to married women aged 15–49 years who were selected for the IPV module were included (n = 22927). The significant level was set at 0.05.
Results
More than half of the Afghan women aged 15–49 years experienced IPV in the past year. Illiteracy (OR = 1.69; 95%CI: 1.19–2.39), living in rural areas (OR = 1.47; 95%CI: 1.19–1.82) being from the Pashtun, Tajik, Uzbak, and Pashai ethnic backgrounds were associated with a higher risk of IPV exposure. In general, the likelihood of child mortality within the first five years was higher among children born to mothers exposed to IPV, particularly physical and sexual even after adjustment for sociodemographic inequalities, the number of antenatal care, and marriage age. In addition, the odds of diarrhea, acute respiratory infection, and fever in the past two weeks were significantly higher among the children of victimized mothers in both adjusted and unadjusted models. Moreover, low birth weight and small birth size were more likely to be observed among the children of a mother who either experienced sexual or physical violence.
Conclusion
The findings emphasized the elevated risk of morbidity and mortality among children under 5 born by mothers aged 15–49 years who were exposed to IPV in Afghanistan. A high rate of spousal violence was also observed among Afghan women driven mainly by illiteracy, particularly in rural areas. This calls for immediate action, formulating interventions and protective measures to reduce IPV against Afghan women by engaging all stakeholders. First and foremost could be incorporating IPV screening, as an important predictor of child morbidity and mortality, into maternity and child care programs in Afghanistan.
Successive variational mode decomposition and blind source separation based on salp swarm optimization for bearing fault diagnosis
Authors: tawfik thelaidjia , Thelaidjia Tawfik , Chetih Nabil , Moussaoui Abdelkrim , Chenikher Salah 
Published: August 2022

Abstract
In this paper we are interested in developing a new approach that combines successive variational mode decomposition and blind source separation based on salp swarm optimization for bearing fault diagnosis. Firstly, vibration signals are pre-processed using successive variational mode decomposition to increase the signal-to-noise ratio. Then, the dynamic time warping algorithm is adopted to select the most effective modes which will be considered as mixture signals. In the second step we apply salp swarm algorithm (SSA) for estimating the de-mixing matrix to extract independent components from mixture signals. However, SSA suffers from the problem of population diversity. Consequently, it offers somewhat different independent sources at every execution of the program. To overcome this shortcoming, the SSA based source estimation will be executed several times with different ranges of initial positions. Then, a fuzzy C-mean algorithm is introduced to select the reliable independent components. The suggested method is tested based on two experiments and compared with other blind source algorithms based on Bat and particle swarm optimization (PSO) algorithms. The obtained results demonstrate the effectiveness of the suggested method in recovering reliable independent components and extracting fault frequency of bearings.
Prognostic nomogram for acute pancreatitis after percutaneous biliary stent insertion in patients with malignant obstruction
Authors: Xu Chen , Gu Yiming , Zhou Weizhong , Liu Sheng , Shi Haibin 
Published: August 2022

Abstract
Objective: This study aimed to develop and validate a nomogram to predict the risk of pancreatitis after percutaneous transhepatic biliary stenting (PTBS) in patients with malignant biliary obstruction (MBO).Materials and methods: We enrolled 314 patients who underwent PTBS for MBO from March 2016 to July 2021 in this retrospective study. We used univariate analysis to identify potential risk factors, while a multivariate logistic regression model was employed to establish a nomogram for predicting the risk of pancreatitis. The discrimination and calibration of the nomogram were evaluated by estimating the area under the receiver operator characteristic curve (AUC) and by bootstrap resampling and visual inspection of the calibration curve. The clinical utility of the nomogram was assessed using decision curve analysis (DCA).Results: After the procedure, 41 (13.1%) patients developed pancreatitis. Based on multivariate logistic regression analysis, young age (OR = 2.57, 95% CI 1.16 to 5.69), stent insertion across the papilla (OR = 6.47, 95% CI 2.66 to 15.70), and visualization of the pancreatic duct (OR = 15.40, 95% CI 6.07 to 39.03) were associated with an elevated risk of pancreatitis. Importantly, the performance of the nomogram was satisfactory, with an identical AUC (0.807, 95% CI 0.730 to 0.883) and high-level agreement between predicted and observed probabilities as suggested in calibration curves. The DCA curve subsequently confirmed the clinical utility.Conclusion: A predictive nomogram for pancreatitis after PTBS in patients with MBO was successfully established in the present study.
NCAPG promotes proliferation of epithelial ovarian cancer by activating the NF-κB and AKT/mTOR pathways
Authors: Wang Sixue , Li Zeying , Yi Mingyu , Jiang Li , Zhang Tingting , Fang Xiaoling , Wang Xi 
Published: August 2022

Abstract
Objective
Dysregulation of nonstructural maintenance of chromosome condensin I complex subunit G (NCAPG) in ovarian cancer might be associated with tumor progression, while the mechanistic roles of NCAPG in epithelial ovarian cancer (EOC) are still unclear. In this research, we aimed to elucidate the potential role and molecular basis of NCAPG in EOC.
Methods
We identified differentially expressed genes (DEGs) between EOC and normal tissues based on five Gene Expression Omnibus (GEO) datasets (GSE18520, GSE54388, GSE9891, GSE63885 and GSE40595) and The Cancer Genome Atlas (TCGA) database. A protein–protein interaction (PPI) network was established to evaluate the relationship between the DEGs and to screen hub genes. The expression levels of the hub genes were further validated through the Human Protein Atlas (HPA) databases. Additionally, the prognostic values of the hub genes were evaluated by the Kaplan‒Meier plotter. Furthermore, the expression of NCAPG, the most remarkable hub gene in EOC, was examined by qRT‒PCR, immunohistochemistry (IHC), and western blotting. A2780 and SKOV3 cell lines were stably transfected with lentivirus to build knockdown and overexpression cell lines. CCK8, clone formation, transwell, and flow cytometry assays were used to evaluate the migratory and proliferation potential of EOC cells. Transcriptome profiling analysis was used to reveal the mechanism by which NCAPG regulated the epithelial-mesenchymal transition (EMT) of EOC. Finally, the mechanistic roles of NCAPG were examined through in vitro and in vivo experiments.
Results
Our findings demonstrated that NCAPG expression was enhanced in EOC tissues compared to normal ovarian tissues and was associated with poor prognosis. NCAPG could facilitate the proliferation, invasion, and migration of EOC cells through the EMT mechanism. Mechanistically, NCAPG could activate the NF-κB and AKT/mTOR pathways to regulate the EMT process of EOC.
Conclusion
Overall, our investigation revealed NCAPG as an important candidate oncogene in EOC. Targeting NCAPG could be a novel treatment with the potential to act as an EOC biomarker.
Association Between Visceral Adipose Tissue and Glomerular Hyperfiltration in Adolescents: A Cross-Sectional Study
Authors: Yang Yong-Chang , Zhao Jing-Ying , zhao Cheng-Guang 
Published: August 2022

Abstract
Background: Glomerular hyperfiltration is an early indicator of obesity-related glomerular disease. However, in adolescents, there are no quantifiable indicators of obesity and glomerular hyperfiltration. This study investigates the association between visceral adipose tissue and glomerular hyperfiltration in adolescents.Methods: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES; 2011–2018), and adolescents aged 12–17.99 were included. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) formed the independent variables while estimated glomerular filtration rate (eGFR) acted as the dependent variable. Their association was assessed using unadjusted and multifactorial multiple linear regression analyses, as well as subgroup and interaction analyses.Results: Multivariate regression analysis revealed that VAT was positively associated with eGFR and glomerular hyperfiltration among adolescents. The incidence of glomerular hyperfiltration increased by 99% in boys and 56% in girls per 100 g of VAT increase. Additionally, VAT and eGFR exhibited a linear relationship in both boys (β = 5.63, p < 0.001) and girls (β = 2.72, p < 0.001).Conclusions: In US adolescents aged 12–17.99, VAT was positively correlated with eGFR and glomerular hyperfiltration.
Endangered elasmobranchs visit specific reef sites in southern Mozambique.
Authors: Murie Calum , Oliver Simon , Mychek-Londer Justin , Lebrato Mario , Dicken Matt , Gavard Livia , Brown James , Lawrence Andrew 
Published: August 2022

Abstract
Delineating the spatial ecology of elasmobranchs is an important precursor to their effective management. Establishing long-term patterns in the habitat use of several threatened species can focus management to yield increased conservation benefits. We completed 738 transects on 16 reef sites off the coast of southern Mozambique to record encounters with elasmobranch species and 12 environmental and spatiotemporal parameters (location, time, day, tide and range, cloud cover, visibility, lunar phase, temperature, current strength, and direction, transect duration). The influence of the measured parameters on the visit frequencies of nine regularly (> 20 / year) encountered elasmobranch species (Carcharhinus amblyrhynchos, Triaenodon obesus, Stegastoma tigrinum, Neotrygon kuhlii, Himantura jenkinsii, Taeniura meyeni, Mobula kuhlii, Mobula alfredi, Mobula birostris) were estimated using multivariate models. All species, bar H. jenkinsii, frequented specific reef sites. Counts were generally highest in summer. Three species (M. birostris, M. kuhlii, S. tigrinum) counts peaked in winter. T. obesus and M. alfredi tended to frequent reefs during high tides, M. kuhlii during slack tides, N. kuhlii during low tides and C. amblyrhynchos when the tidal range was high. Counts of M. alfredi were highest during full moons and M. kuhlii during full, half, and new moons. Non-Metric Multidimensional Scaling (NMDS) indicated that species responses to the measured parameters grouped taxonomically. Environmental influences resulted in daily, monthly, and seasonal patterns of reef use. Our results indicate that specific elasmobranch species routinely congregate on specific reef sites and that management of these sites could promote several threatened populations.