bluuebunny/crossref_metadata_2025 huggingface dataset:
Menstrual Hygiene Management Practice among Adolescent Girls: An Urban-Rural Comparative Study in Rajshahi Division, Bangladesh
Authors: Ha Md. Abu Tal , Alam Md. Zakiul
Published: December 2020

Introduction:Adolescence is a critical period characterized by significant physical, emotional, cognitive and social changes, and monthly occurrence of menstruation of adolescent girls. Despite being an inevitable natural event, most of the societies consider menstruation and menstrual blood as taboo and impure that prevents many adolescent girls from proper education and information which force them to develop their ways of managing the event. In this study, we attempted to explore the pattern of menstrual hygiene management practice, the urban-rural differences of the practice, and the determinants of the practice among adolescent girls in Rajshahi division, Bangladesh.Methodology:Using a cross-sectional study design with systematic random sampling, we collected data from 589 adolescent girls (aged 14–19 years) from Rajshahi division of Bangladesh. We employed bivariate and multinomial logistic regression analysis.Findings:We found significant differences in menstrual hygiene management practice among adolescent girls between urban and rural areas. Only 37.9% continuously used sanitary pad. Among the cloth users, nearly two-third reused cloths and about 56% of them used water and soap to wash these cloths. About 49% changed menstrual absorbent and 44% washed their genitalia three times a day. About 41% used water only to wash genitalia, and 55% buried sanitary materials under soil after using. Around 22% of the girls practiced terrible, 63.3% fair, and 14.7% proper menstrual management. Multinomial logistic regression found that the place of residence, family size, wealth quintile, parents’ education, and social connectivity was the significant determinant of menstrual hygiene management practice.Conclusion:Although there are some cases of sanitary pad use, still menstrual hygiene management is unhealthy in most cases. The continuous flow of sanitary pads at affordable cost, change in existing social norms about menstruation and proper education, information and services are essential for achieving health-related SDG goals.
Single-Cell Manifold Preserving Feature Selection (SCMER)
Authors: Chen Ken , Liang Shaoheng , Mohanty Vakul , Dou Jinzhuang , Qi Miao , Huang Yuefan , Müftüoğlu Muharrem , Ding Li , Peng Weiyi
Published: December 2020

A key challenge in studying organisms and diseases is to detect rare molecular programs and rare cell populations (RCPs) that drive development, differentiation, and transformation. Molecular features such as genes and proteins defining RCPs are often unknown and difficult to detect from unenriched single-cell data, using conventional dimensionality reduction and clustering-based approaches. Here, we propose a novel unsupervised approach, named SCMER, which performs UMAP style dimensionality reduction via selecting a compact set of molecular features with definitive meanings. We applied SCMER in the context of hematopoiesis, lymphogenesis, tumorigenesis, and drug resistance and response. We found that SCMER can identify non-redundant features that sensitively delineate both common cell lineages and rare cellular states ignored by current approaches. SCMER can be widely used for discovering novel molecular features in a high dimensional dataset, designing targeted, cost-effective assays for clinical applications, and facilitating multi-modality integration.
fMRI-Based Machine Learning Analysis of Neural Substrates of Pediatric Anxiety: Temporal Pole and Emotional Face-Responses.
Authors: Sawalha Jeffrey , Yousefnezhad Muhammad , Selvitella Alessandro , Cao Bo , Greenshaw Andrew , Greiner Russell
Published: December 2020

A prominent cognitive aspect of anxiety is dysregulation of emotional interpretation of facial expressions, associated with neural activity from the amygdala and prefrontal cortex. We report machine learning analysis of fMRI results supporting a key role for a third area, the temporal pole (TP) for childhood anxiety in this context. This finding is based on differential fMRI responses to emotional faces (e.g. angry versus fearful faces) in children with one or more of generalized anxiety, separation anxiety, and social phobia (n = 22) compared with matched controls (n = 23). In our machine learning model, the right TP distinguished anxious from control children (accuracy = 81%). Involvement of the TP as significant for neurocognitive aspects of pediatric anxiety is a novel finding worthy of further investigation.
Climate vulnerability scenario of the agri-fishery communities in the Bicol River Basin, Philippines
Authors: Laureta Ricky , Regalado Ric Ryan , Cruz Ermar De La
Published: December 2020

This paper investigated the vulnerability of the agriculture sector and rural agri-fishery livelihoods in the Bicol River Basin (BRB) in the Philippines to projected changes in climate. The geographical characteristics of the BRB features eight major sub-basins or watersheds consisting of Libmanan-Pulantuna, Ragay Hills, Thiris, Naga-Yabo, Pawili River, Waras-Lalo, Naporog, and Quinali. The study adopted the Climate Risk Vulnerability Assessment (CRVA) which employed geospatial modelling through the use of geographic information systems (GIS) data, briefly, a number of indicators which are presumed to affect vulnerability were used including exposure, sensitivity, and adaptive capacity which were aggregated to provide an index of vulnerability. These components were integrated and modelled using GIS by identifying exposure to natural hazards, assessing the sensitivity of major crops to climate variations using ecological model (MaxEnt) under high emission climate scenario (RCP8.5), and identifying key aspects of adaptive capacity. Additionally, we also analyzed the perception of stakeholders towards vulnerability using participatory approaches. This enabled us to identify areas of exposure and vulnerability, and pointed areas of greatest need for strengthened adaptive capacity and risk management. Our findings suggested that majority of the towns in the north and central portions of the BRB will largely experience increased vulnerability, particularly, in the Thiris sub-basin including some parts of Ragay Hills, Waras-Lalo and the northwestern Libmanan-Pulantuna sub-basins. On the contrary, the entire Quinali sub-basin in the south revealed to have the lowest vulnerability index. The information derived from the study can be utilized to reinforce local-based climate policies.
Transcriptome Analysis of the Effect of Diosgenin on Autoimmune Thyroiditis in A Rat Model
Authors: Zhang Chengfei , Qin Lingling , Sun Boju , Wu You , Zhong Fengying , Wu Lili , Liu Tonghua
Published: December 2020

Transcriptomics was used to analyze the protective effect of diosgenin on autoimmune thyroiditis (AIT) in rats and its possible mechanism. Forty AIT model rats were established following high iodine induction and injection of porcine thyroglobulin adjuvant into Lewis rats. AIT-model rats were treated with an oral gavage(diosgenin) for 8 weeks. The concentrations of T3, T4, FT3, FT4, TSH, TRAb, TPOAb and TgAb in rat serum were detected. The unilateral thyroid lobes of rats were detected by transcriptomes, RT-qPCR (S100A9, PKA, Creb, Epac, and Rap1 mRNA), and Immunohistochemistry (cAMP, PKA, and Creb). The results showed that the expression of serum T3, T4, FT3, FT4, TSH, TgAb, and TPOAb in the high-dose group was greater than that in the low and middle-dose groups. And compared with the AIT-model group, the relative expression of cAMP, PKA and Creb mRNA and protein increased, S100A9 mRNA decreased in the diosgenin groups. To sum up, diosgenin can improve the expression of T3, T4, FT3, FT4, and TSH in AIT model rats, and decrease the concentrations of TRAb, TgAb and TPOAb, which may be related to activation of the cAMP/PKA/Creb pathway and downregulating the expression of S100A9 gene.
Transcriptomic analysis of breast cancer patients sensitive and resistant to chemotherapy: Looking for overall survival and drug resistance biomarkers
Authors: Barrón-Gallardo Carlos , García-Chagollán Mariel , Morán-Mendoza Andrés , Delgadillo-Cristerna Raúl , Martínez-Silva María , Aguilar-Lemarroy Adriana , Jave-Suárez Luis
Published: December 2020

Neoadjuvant chemotherapy is one important therapeutic strategy for breast cancer with the drawback of resistance development. Chemotherapy has adverse effects that combined with resistance could contribute to lower overall survival. This work aimed to evaluate the molecular profile of patients who received neoadjuvant chemotherapy to discover differentially expressed genes (DEGs) that could be used as biomarkers of chemotherapy response and overall survival. Breast cancer patients who received neoadjuvant chemotherapy were enrolled in this study and according to their pathological response were assigned as sensitive or resistant. To evaluate DEGs, GO, KEGG, and protein-protein interactions, RNAseq information from all patients was obtained by next-generation sequencing. A total of 1985 DEGs were found and KEGG analysis indicated a great number of DEGs in metabolic pathways, pathways in cancer, cytokine-cytokine receptor interactions, and neuroactive ligand-receptor interactions. A selection of 73 DEGs was used further for an analysis of overall survival using the METABRIC study. Seven of those DEGs correlated with overall survival, of them the sub-expression of C1QTNF3, CTF1, OLFML3, PLA2R1, PODN and the over expression of TUBB and TCP1 were found in resistant patients and related to patients with lower overall survival.
Impact of Pre-Existing Depression in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention; A Nationwide Cohort Study
Authors: Park Jangho , Park Sangwoo , Kim Yong-Giun , Ann Soe Hee , Park Hyun Woo , Suh Jon , Roh Jae-Hyung , Cho Young-Rak , Han Seungbong , Park Gyung-Min
Published: December 2020

The impact of pre-existing depression on mortality in individuals with established coronary artery disease (CAD) remains unclear. We evaluate the clinical implications of pre-existing depression in patients who underwent percutaneous coronary intervention (PCI). Based on National Health Insurance claims data in Korea, patients without a known history of CAD who underwent PCI between 2013 and 2017 were enrolled. The study population was divided into patients with angina (n=50,256) or acute myocardial infarction (AMI; n=40,049). The primary endpoint, defined as all-cause death, was compared between the non-depression and depression groups using propensity score matching analysis. After propensity score matching, there were 4,262 and 2,346 matched pairs of patients with angina and AMI, respectively. During the follow-up period, there was no significant difference in the incidence of all-cause death in the angina (hazard ratio [HR] of depression, 1.013; 95% confidence interval [CI]: 0.893-1.151) and AMI (HR, 0.991; 95% CI: 0.865-1.136) groups. However, angina patients less than 65 years of age with depression had higher all-cause mortality (HR, 1.769; 95% CI: 1.240-2.525). In Korean patients undergoing PCI, pre-existing depression is not associated with poorer clinical outcomes. However, in younger patients with angina, depression is associated with higher all-cause mortality.
Defining GP Practices from an Urban Versus Rural Perspective: The Case of Czechia
Authors: Šídlo Luděk , Bělobrádek Jan
Published: December 2020

BackgroundThis study is an attempt to demonstrate the potential for classifying GP practices in Czechia along an urban versus rural dimension and to compare the structure of areas thus defined with the OECD territorial typology. The aim is to ascertain whether a general approach to distinguishing regions is transferrable and could be used to define GP practices in Czechia. MethodsIn this study two variants are considered using data supplied to the authors by the largest health insurance company in Czechia, using geographical information systems. The results were then compared with the OECD regional typology, in which areas are classified as predominantly urban, intermediate, and predominantly rural. ResultsThe two GP practice typologies were then found to correspond closely to the OECD typology, but the most recent variant is more suitable. A high degree of similarity was evident in the categorisation of urban regions, and therefore practices, and slightly less so in the rural type areas. The most problematic aspect is defining the intermediate type, which has its own peculiarities and has to be considered within the wider context. ConclusionsDespite some structural differences, we can state that the main thinking behind the OECD typology is transferrable and can be used to determine urban versus rural healthcare providers, especially primary care ones. Nonetheless, the results point to further research avenues, especially on how to best to define the intermediate category so greater accuracy can be achieved in determining the resulting urban versus rural polarity.
Associations between occupational therapy students’ academic performance and their study approaches and perceptions of the learning environment
Authors: Bonsaksen Tore , Magne Trine , Stigen Linda , Gramstad Astrid , Åsli Lene , Mørk Gry , Johnson Susanne , Carstensen Tove
Published: December 2020

Background: Relationships between students’ academic performance and their employed study approaches have been studied extensively. However, research using study approaches and learning environment factors as concurrent predictors of academic performance is sparse. There is a need to disentangle the potentially interrelated influences of individual and contextual factors on students’ academic performance. Objective: This study aimed to increase the understanding of the associations between occupational therapy students’ academic performance, and their approaches to studying and perceptions of the learning environment. Method: A cross-sectional study was designed, and 174 first-year students completed the Approaches and Study Skills Inventory for Students and the Course Experience Questionnaire, in addition to background information. Data on grades were collected from the data registries of each education institution, and associations were analyzed by multiple linear regression. Results: None of the learning environment scales were associated with grades. Adjusting for all variables, better exam results were associated with being female (β = 0.22, p < 0.01) and having higher scores on strategic approach (β = 0.31, p < 0.001) and lower scores on surface approach (β = -0.20, p < 0.01). Conclusion: The study suggests that students with a desire for obtaining good grades ought to use strategic study behaviors and avoid using surface approach behaviors. While it is important to ensure good quality of the learning environment for a variety of reasons, the learning environment did not contribute significantly to explain the students’ academic performance.
Open Clinical Trial of the Use of Antioxidants and Pentoxifylline as Coadjuvant Measures to Standard Therapy to Improve Prognosis of Patients with Pneumonia and Septic Shock due to Covid-19
Authors: Chavarria Adrián , Vázquez Rafael Ricardo , Cherit José Guillermo , Bello Héctor , Suastegui Humberto , Castañeda Lidia , Estrada Gabriela , Valdez Fabián , Marcos Omar , Orozco Huitzilihuitl , Pech Linaloe , Velasco Ricardo , Lans Verónica , Torres Israel , López Maria Elena
Published: December 2020

Background: SARS-CoV-2 infection produces pneumonia with pulmonary alveolar collapse and in some cases sepsis and septic shock. There is no specific treatment for COVID-19. Vitamin C (Vit C), Vitamin E (Vit E), N-acetylcysteine (NAC) and Melatonin (MT) increase the intracellular content of GSH, kidnap free radicals and protect DNA, proteins in the cytosol and lipids of cell membranes. Pentoxifylline (Px) has anti-inflammatory activities. Methods: Here we evaluate the effect of Vit C, Vit E, NAC, and MT plus Px in COVID-19 patients with moderate and severe pneumonia. 110 patients of either sex were included. They were divided into five groups with 22 patients each. Group 1 received Vit C+Px, group 2 Vit E+Px, group 3 NAC+Px, group 4 MT+Px, and group 5 only Px. Oxidative stress markers as Lipid peroxidation levels, evaluation of total antioxidant capacity and nitrites were evaluate by spectrophotometry, and by ELISA assay IL-6 levels. Results: The antioxidant therapy improved the survival scores including SOFA, Apache II, SAPS II, COVIDGRAM and GCS. OS markers in plasma such as LPO (p≤0.04) and TAC (p≤0.03) decreased in COVID-19 patients administered with antioxidants. There was an increase of IL-6 (p≤0.01) and decreases of CRP (p≤0.01) and PCT (p≤0.05) in COVID-19 patients when entering the hospital and the different antioxidants reversed this alteration at the end of the hospital stay. Conclusions: This study confirms the presence of OS in COVID-19 patients. The results suggest that the treatment with antioxidant supplements such as Vit C, E, NAC, and MT plus Px could contribute to the deceleration of the aggressive and lethal development COVID-19. There is evidence that antioxidants in moderate doses decrease inflammation and control of OS; therefore, their use as an adjuvant therapy to improve prognosis is confirmed. The antioxidant therapy can be effective in this pandemia since it improves all of the survival scores including SOFA, Apache II, SAPS II, COVIDGRAM, GCS by lowering the LPO, IL-6, CRP, PCT and increasing systemic TAC.
Psychological and Physiological Stress and Burnout Among Maternity Providers in A Rural County in Kenya: Individual and Situational Predictors
Authors: Afulani Patience , Ongeri Linnet , Kinyua Joyceline , Temmerman Marleen , Mendes Wendy Berry , Weiss Sandra
Published: December 2020

Background: Stress and burnout among healthcare workers has been recognized as a global crisis needing urgent attention. Yet few studies have examined stress and burnout among healthcare providers in sub-Saharan Africa, and even fewer among maternity providers who work under very stressful conditions. To address these gaps, we examined self-reported stress and burnout levels as well as stress-related physiologic measures of these providers, along with their potential predictors. Methods: Participants included 101 maternity providers (62 nurses/midwives, 16 clinical officers/doctors, and 23 support staff) in western Kenya. Respondents completed Cohen’s Perceived Stress Scale, the Shirom-Melamed Burnout scale, and other sociodemographic, health, and work-related items. We also collected data on heart rate variability (HRV) and hair cortisol levels to assess stress-related physiologic responses to acute and chronic stress respectively. Multilevel linear regression models were computed to examine individual and work-related factors associated with stress, burnout, HRV, and cortisol level. Results: 85% of providers reported moderate stress and 11.5% high stress. 65% experienced low burnout and 19.6% high burnout. Average HRV (measured as the root mean square of differences in intervals between successive heart beats: RMSSD) was 60.5 (SD=33.0) and mean cortisol was 38.6 (SD=44.3). Greater satisfaction with life accomplishments was associated with reduced stress (𝛽=-2.83; CI=-5.47; -0.18), while motivation to work excessively (over commitment) was associated with both increased stress (𝛽=-0.61 CI: 0.19, 1.03) and burnout (𝛽=2.05, CI=0.91, 3.19). Female providers had higher burnout scores compared to male providers. Support staff had higher HRV than other providers and providers under 30 years of age had higher HRV than those 30 and above. Although no association between cortisol and any predictor was statistically significant, the direction of associations was consistent with those found for stress and burnout. Conclusions: Most providers experienced moderate to high levels of stress and burnout. Individuals who were more driven to work excessively were particularly at risk for higher stress and burnout. Higher HRV of support staff and providers under age 30 suggest their more adaptive autonomic nervous system response to stress. Given its impact on provider wellbeing and quality of care, interventions to help providers manage stress are critical.
Mid-term Outcomes of Valve-sparing Aortic Root Replacement Versus the Bentall Procedure for Middle-aged Chinese Patients with Acute DeBakey I Aortic Dissection: A Single-center Retrospective Study.
Authors: Wu Qingsong , wang Zhisheng , Qiu Zhihuang , Shen Yue , Chen Xiaodong , Chen Xingfeng , Chen Liangwan
Published: December 2020

Background: The mid-term and long-term efficacies of valve preservation in acute DeBakey I aortic dissection(AD) are controversial. Thus, it is unclear whether middle-aged patients with acute DeBakey I AD should undergo valve-sparing procedures or the Bentall procedure in an emergency setting.Methods: This study included 213 middle-aged Chinese patients(30-60 years old) who were treated for acute DeBakey I AD between January 2009 and June 2015. The treatments involved valve-sparing aortic root replacement(VSARR)(117 patients) or the Bentall procedure(96 patients). Preoperative, intraoperative, postoperative, and follow-up data were analyzed. Echocardiography and thoracoabdominal computed tomography angiography(CTA) findings were reviewed at 3 months, 1 year, and then annually after surgery. Results: No significant differences were observed in terms of the preoperative, intraoperative, in-hospital mortality, and postoperative parameters. There were also no significant differences in aortic regurgitation(AR). However, follow-up examinations using CTA revealed that 6 patients had endoleakage at the distal end of the triple-branched stent(0/110 patients [0.0%] vs. 6/90 patients [6.7%], P=0.022). The anticoagulation-related thromboembolism/bleeding events was significantly lower in group A than in group B(0/110 patients [0.0%] vs. 11/90 patients [11.1%], P=0.001). And postoperative aortic valve re-operation rate was significantly lower in group A (1/110 patients [0.9%] vs. 8/90 patients [8.9%], P=0.020). There was no significant difference in survival during the follow-up period (log-rank P>0.05).Conclusion: For middle-aged patients with acute DeBakey I AD, VSARR were associated with a lower rate of endoleakage at the distal end of the triple-branched stent, thromboembolism/bleeding events and aortic valve re-operation(vs. the Bentall procedure) .
Equilibrium and Thermodynamic Investigation of Biosorption of Nickel from Water by Activated Carbon Made from Palm Kernel Chaff
Authors: Nnaji Chidozie , Agim Edward , Mama Cordelia , Emenike PraiseGod , Ogarekpe Nkpa
Published: December 2020

Novel biosorbents were derived from a waste product of palm kernel oil extraction known a palm kernel chaff (PKC). One portion of the PKC was carbonized in a furnace and then activated chemically while the other half was activated without carbonization. Both were designated as CPKC and UPKC respectively. The two biosorbents so produced were then used to conduct batch equilibrium sorption studies at 30 ºC, 35 ºC and 40 ºC and pH 3.0 and 9.0. The Koble-Corrigan, Dubinin-Radushkevich and the Freundlich isotherms fitted the experimental data very well with R2 values of 0.97 to 1.0, 0.95 to 1.0 and 0.96 to 1.0 respectively. The linear type II Langmuir isotherm performed much better (0.96 ≤ R2 ≤ 1.0) than the nonlinear isotherm. The maximum sorption capacity was obtained as 120.6 mg/g using CPKC at pH 9.0 and 35ºC. The values of Langmuir separation coefficient (0.022 ≤ RL≤0.926) show that the sorption of nickel to PKC is favourable. The most favourable sorption condition was found for CPKC at pH 9 and temperature of 40 ºC. The values of sorption energy (8.21 ≤ E ≤ 14.27) and the isosteric heat of sorption (-133.09≤∆Hx≤-17.92) indicate that the mode of sorption is mostly ion exchange. Thermodynamic parameters also show that the process is exothermic and entropy-driven.
Thermostable Adenosine 5’-Monophosphate Phosphorylase from Thermococcus kodakarensis forms catalytically active inclusion bodies
Authors: Kamel Sarah , Walczak Miriam , Kaspar Felix , Westarp Sarah , Neubauer Peter , Kurreck Anke
Published: December 2020

Catalytically active inclusion bodies (CatIBs) produced in E. coli are an interesting but currently underexplored strategy for enzyme immobilization. They can be purified easily and used directly as stable and reusable heterogenous catalysts. However, very few examples of CatIBs that are naturally formed during heterologous expression have been reported so far. Previous studies have revealed that the adenosine 5'-monophosphate phosphorylase of Thermococcus kodakarensis (TkAMPpase) forms large soluble multimers with high thermal stability. Herein, we show that heat treatment of solubilized protein induces aggregation of active protein which phosphorolysis all natural 5’-mononucleotides. Additionally, inclusion bodies formed during the expression in E. coli were found to be similarly active with 2−6 folds higher specific activity compared to the heat-induced aggregates. Interestingly, differences in the substrate preference were observed. These results show that the recombinant thermostable TkAMPpase is one of rare examples of naturally formed CatIBs.
Construction and Characterization of EGFP Reporter Plasmid Harboring Putative Human RAX Promoter for in Vitro Monitoring of Retinal Progenitor Cells Identity
Authors: Atefi Atefeh , kojouri Pendar Shojaei , Karamali Fereshteh , Irani Shiva , Esfahani Mohammad Hossein Nasr
Published: December 2020

Background: In retinal degenerative disease, progressive and debilitating conditions result in deterioration of retinal cells and visual loss. In human, retina lacks the inherent capacity for regeneration. Therefore, regeneration of retinal layer from human retinal progenitor cells (hRPCs) is a challenging task and restricted in vitro maintenance of hRPCs remains as the main hurdle. Retina and anterior neural fold homeobox gene ( RAX ) play critical roles in developing retina and maintenance of hRPCs. In this study, for the first time regulatory regions of human RAX gene with potential promoter activity were experimentally investigated. Results: For this purpose, after in silico analysis of regulatory regions of human RAX gene, the expression of EGFP reporter derived by putative promoter sequences was first evaluated in 293T cells and then in hRPCS derived from human embryonic stem cells. The candidate region ( RAX -3258bp) showed the highest EGFP expression in hRPCs. This reporter construct can be used for invitro monitoring of hRPC identity and verification of an efficient culture medium for maintenance of these cells. Conclusions: Furthermore, our findings provide a platform for better insight into regulatory regions of human RAX gene and molecular mechanisms underlying its vital functions in retina development.
Existence of a Single Population of Hilsa Shad (Tenualosa Ilisha) With Low Genetic Variation in Bangladesh Waters Revealed by Cross-Species Gene Enrichment Method 
Authors: Sarker Anirban , Naher Habibon , Huang Junman , Sarker Kishor , Yin Guoxing , Baki Mohammad , Li Chenhong
Published: December 2020

Tenualosa ilisha is a popular anadromous and significant trans-boundary fish. For sustainable management and conservation of this fish, drawing an appropriate picture reflecting population status of this species is very essential based on their all-strategic habitats in Bangladesh. In this study, 139 samples from 18 sites were collected and cross-species gene enrichment method was applied to discover the exact population status of the fish. Like most of the Clupeiforms, nucleotide diversity and variation of this shad were very low. Population differences between most of the locations were low and not significant. However, P values of a few locations were significant (P< 0.05) but their pairwise FST values were very poor, which is inadequate to recognize any local populations. Structure analysis, PCA and maximum likelihood IQtree all indicated the presence of a single population in the Bangladesh water with some admixture individuals, which may contain partial genes from other populations. In the ML IQtree and Network, most of the individuals were mixed without showing any precise grouping, which might due to their highly migratory nature. Fishes from special type of habitats, e.g., haors, small coastal rivers etc. were not unique and no genetic differences between migratory cohorts were found.
The First Detection of a [C II] 158μm Emitter Associated with a Strong OI Absorber at the End of the Reionization Epoch
Authors: Wu Yunjing , Cai Zheng , Neeleman Marcel , Finlator Kristian , Kanekar Nissim , Zhang Shiwu , Prochaska Jason , Wang Ran , Fan Xiaohui , Keating Laura , Wang Feige , Yang Jinyi , Hennawi Joseph , Wang Junxian
Published: December 2020

The physical and chemical properties of the circumgalactic medium (CGM) at z ≳ 6 have been studied successfully through the absorption in the spectra of background Quasi-Stellar Objects (QSOs) 1–3. One of the most crucial questions is to investigate the nature and location of the source galaxies that give rise to these early metal absorbers4–6. Theoretical models suggest that momentum-driven outflows from typical star-forming galaxies can eject metals into the CGM and the intergalactic medium (IGM), with the projected separation between absorbers and galaxies expected to range from 5 to 50 proper kpc at z=5–6 7–10. Deep, dedicated surveys have searched for Lyα emission associated with strong CIV absorbers at z ≈ 6, but only a few Lyα emitter candidates have been detected. Interpreting these detections is moreover ambiguous because Lyα is a resonant line11–13, raising the need for complementary techniques for detecting absorbers’ host galaxies. Here, using Atacama Large Millimeter Array (ALMA), we report, for the first time, the [C II] 158µm emission and the far-infrared dust continuum associated with a strong low-ionization absorber, O I, at z = 5.978. The [C II] luminosity is 73 million solar luminosities, corresponding to a dark matter halo mass of 100 billion solar masses. This is one to two orders of magnitude more massive than typical values predicted from cosmological simulations9, 16.
Factor Graph-aggregated Heterogeneous Network Embedding for Disease-gene Association Prediction
Authors: He Ming , Huang Chen , Liu Bo , Wang Yadong , Li Junyi
Published: December 2020

Background Exploring the relationship between disease and gene is of great significance for understanding the pathogenesis of disease and de-veloping corresponding therapeutic measures. The prediction of dis-ease-gene association by computational methods accelerates the pro-cess.Results Many existing methods cannot fully utilize the multi-dimen-sional biological entity relationship to predict disease-gene association due to multi-source heterogeneous data. This paper proposes Fac-torHNE, a factor graph-aggregated heterogeneous network embedding method for disease-gene association prediction, which captures a vari-ety of semantic relationships between the heterogeneous nodes by fac-torization. It produces different semantic factor graphs and effectively aggregates a variety of semantic relationships, by using end-to-end multi-perspectives loss function to optimize model. Then it produces good nodes embedding to prediction disease-gene association.Conclusions Experimental verification and analysis show FactorHNE has better performance and scalability than the existing models. It also has good interpretability can be extended to large-scale biomedical net-work data analysis.
Asymmetric Three-Component Olefin Dicarbofunctionalization Enabled by Photoredox and Copper Dual Catalysis
Authors: Xiao Wen-Jing , Wang Peng-Zi , Gao Yuan , Huan Xiao-Die , Chen Jun , Chen Jia-Rong
Published: December 2020

An intermolecular, enantioselective three-component radical vicinal dicarbofunctionalization reaction of olefins enabled by merger of radical addition and cross-coupling using photoredox and copper dual catalysis is presented here. Key to the success of this protocol relies on chemoselective addition of acyl and cyanoalkyl radicals, generated in situ from the redox-active oxime esters by a photo-catalytic N-centered iminyl radical-triggered C-C bond cleavage event, onto the alkenes to form new carbon radicals. Single electron metalation of such newly formed carbon radicals to TMSCN-derived L1Cu(II)(CN)2 complex leads to asymmetric cross-coupling. This three-component process proceeds under mild conditions, and tolerates a diverse range of functionalities and synthetic handles, leading to valuable optically active β–cyano ketones and alkyldinitriles, respectively, in a highly enantioselective manner (> 60 examples, up to 97% ee).
Genotype-by-environment Interaction in Holstein Heifer Fertility Traits using Single-step Genomic Reaction Norm Models
Authors: Shi Rui , Brito Luiz , Liu Aoxing , Luo Hanpeng , Chen Ziwei , Liu Lin , Guo Gang , Mulder Herman , Ducro Bart , Linden Aart van der , Wang Yachun
Published: December 2020

Background: The effect of heat stress on livestock production is a worldwide issue, where animal performance is influenced by exposure to high environmental temperatures, indicating the existence of possible genotype-by-environment interactions (G´E). The main objectives of this study were to (1) detect the time periods in which heifer fertility traits are more sensitive to the exposure to high environmental temperature and/or humidity, (2) investigate G´E due to heat stress in heifer fertility traits, and (3) identify genomic regions associated with heifer fertility and heat stress in Holstein cattle. Results: Phenotypic records for three heifer fertility traits (i.e., age at first calving, interval from first to last service, and conception rate at the first service) were collected, from 2005 to 2018, for 56,998 Holstein heifers raised in 15 herds in the Beijing area (China). By integrating environmental data including hourly air temperature and relative humidity, the critical periods in which the heifers are more sensitive to heat stress were defined as <=30 days before the first service for age at first calving and interval from first to last service, or 10 days before and <= 60 days after the first service for conception rate. Using reaction norm models, significant G´E was detected for all three traits regarding both environmental gradients, proportion of days exceeding heat threshold and minimum temperature humidity index. Through single-step genome-wide association study, PLAG1, AMHR2, SP1, KRT8, KRT18, MLH1, and EOMES were suggested as candidate genes for heifer fertility while HCRTR1, AGRP, PC, and GUCY1B1 were for heat tolerance. Conclusions: The critical periods in which reproductive perfromances of heifers are more sensitive to heat stress are trait-dependent. Thus, detailed analysis should be conducted to determine this particular period for other fertility traits. The considerable magnitude of G´E and sire re-ranking indicates the necessity to consider G´E in breeding schemes. This will enable selection of more heat-tolerant animals with high reproductive efficiency under harsh climatic conditions. The candidate genes identified to be linked with response to heat stress provide a better understanding of the underlying biological mechanisms of heat tolerance in dairy cattle.
Precision Medicine, Developmental Plasticity and Prevention of Non-Communicable Disease
Authors: Wang Carol , Attia John , Lye Stephen , Oddy Wendy , Beilin Lawrence , Mori Trevor , Meyerkort Claire , Pennell Craig
Published: December 2020

Background: It is well established that genetics, environment, and interplay between them play crucial roles in adult disease. We aimed to evaluate the role of genetics, early life nutrition, and interaction between them, on optimal adult health. Methods: As part of a large international consortium (n~154,000), we identified 60 SNPs associated with both birthweight and adult disease. Utilising the Raine Study, we developed a birthweight polygenic score (BW-PGS) based the 60 SNPs and examined relationships between BW-PGS and adulthood cardiovascular risk factors, specifically evaluating interactions with early life nutrition. Findings: Healthy nutrition was beneficial for all individuals; longer duration of any breastfeeding was associated with lower BMI and lower Systolic Blood Pressure in those with higher BW-PGS. Interpretation: Optimal breastfeeding offers the greatest benefit to reduce adult obesity and hypertension in those genetically predisposed to high birthweight. This provides an example of how precision medicine in early life can improve adult health.
Metabolic Modeling Reveals Potential Muscle Metabolite Markers of Insulin Resistance in Newly Diagnosed Diabetic Patients
Authors: Khoshnejat Maryam , Banaei-Moghaddam Ali Mohammad , Kavousi Kaveh , Moosavi-Movahedi Ali Akbar
Published: December 2020

BackgroundType 2 diabetes mellitus (T2DM) is a challenging and globally ubiquitous metabolic disease caused by insulin resistance. Skeletal muscle is the major insulin-sensitive tissue that plays a great role in blood sugar homeostasis. Dysfunction of muscle metabolism is implicated in the disturbance of glucose hemostasis and the development of insulin resistance and T2DM. Here, we attempted to find metabolic dysregulations that are associated with the onset of T2DM. Besides, metabolite markers of T2DM were explored. MethodsWe reconstructed a human muscle-specific metabolic model and applied it to perform metabolic analysis in newly diagnosed T2DM patients. We investigated the metabolism reprogramming by using two topology-based and constraint-based approach. Moreover, we applied a machine learning method to predict potential metabolite markers of insulin resistance in muscle.ResultsOur results showed that metabolic alterations have occurred in carbohydrate, fatty acids, lipids, amino acids, and inositol phosphate metabolisms as well as pathways implicated in building extracellular matrix (ECM). Also, dysregulation of coenzyme Q10 metabolism was observed. Moreover, 13 exchange metabolites were predicted as the potential metabolite markers of insulin resistance in skeletal muscle. The efficiency of these markers in detecting insulin-resistant muscle was validated using a separate muscle gene expression data from another diabetes-related study. ConclusionIn this study, the most updated muscle-specific metabolic model was generated and successfully was validated. This model was used for the investigation of metabolic disturbances at the onset of T2DM. Our results indicated the significance of ECM metabolites in insulin resistance, and reinforce the role of coenzyme Q10 as a candidate for further research in insulin resistance and T2DM treatment. The model is freely available and can be used for other muscle metabolic studies. We also predicted metabolite markers of insulin resistance in the skeletal muscle, which can be considered for further empirical investigations.
Reverse migration under the devolved governance system in Kenya: Subsequent implications for income and occupation
Authors: Okumu Evans Taabu , Moenga Joash
Published: December 2020

Reverse migration is on a steady increase under the devolved system of governance in Kenya. The situation could be attributed to an array of triggers such as; the ongoing rural development programmes, backdrop of non-availability of livelihood and job opportunities in the city. Upon return to the rural areas, it could be perceived that the returnees encounter some socio-economic shocks, which tend to impact their income and career. To ascertain the impact, we use a binomial probit model to estimate the probability of income and occupational change. We postulate that harsh encounters in the city inspire those with savings, newly acquired entrepreneurial acumen, and land to migrate out of the city and exploit rural job opportunities. Study participants were people that had moved from Nairobi to their rural counties. Using snowball sample selection, we obtained 49 adult participants mean age = 41years, SD = 15.95, female 48%, employed 68%, married 59%, and 29% educated up to university Results found that significance for career and income changes varies across participants socio-economics status or demographics. For instance, those aged 35–59 years (r2 = 0.399, ME = 0.421); land size greater than 2.5 acres (r2 = 0.507, ME = 0.473) and postgraduate degree (r2 = 0.513, ME = 0.591) had significant income increment. For 60 + years (r2=-0.369, ME=-0.312), primary-leavers (r2=-0.459, ME=-0.226) had significant decrease in income upon return. Conversely, females (r2 = 0.326, ME = 0.348), and migrants aged 60 + years (r2 = R2 = 0.797, ME = 0.651) were more prone to career change; all at .01 significance level. Attributes such as marital status, age 25-34yrs, secondary or college-level education are weak income or career change determinants. We conclude that rural land size, more than 2.5acres was a significant incentive for reverse migration, since the likelihood of shifting to agriculture and establishing a robust livelihood source and income after assigning other dummy variables, and setting the baseline at two years was evident across groups.
Evaluation of Risk Mitigation Measures for People With Substance Use Disorders to Address the Dual Public Health Crises of COVID-19 and Overdose in British Columbia: A Mixed-Methods Study Protocol.
Authors: Nosyk Bohdan , Slaunwhite Amanda , Urbanoski Karen , Hongdilokkul Natt , Palis Heather , Lock Kurt , Min Jeong E , Zhao Bin , Card Kiffer G , Barker Brittany , Meilleur Louise , Burmeister Charlene , Thomson Erica , Beck-McGreevy Phoenix , Pauly Bernie
Published: December 2020

BackgroundThe COVID-19 pandemic was preceded by an ongoing overdose crisis and linked to escalating drug overdose deaths in British Columbia (BC). At the outset of these dual public health emergencies, the BC government announced interim Risk Mitigation Guidance (RMG) that permitted prescribing medication alternatives to substances, including opioids, alcohol, stimulants, and benzodiazepines, an intervention sometimes referred to as ‘Safe Supply’. This protocol outlines the approach for a study of the implementation of RMG and its impacts on COVID-19 infection, drug-related and systemic harms, continuity of care for people with substance use disorder, as well as their behavioural, psychosocial, and well-being outcomes.MethodsWe conduct a parallel mixed-method study that involves both analysis of population-level administrative health data and primary data collection, including a 10-week longitudinal observational study (target n=200), a cross-sectional survey (target n=200), and qualitative interviews (target n=60). We have implemented a participatory approach to this evaluation, partnering with people with lived or living experience of substance use, as well as researchers and public health decision-makers across the province. Linked population-level administrative databases will analyze data from a cohort of BC residents with an indication of substance use disorder between 1996 and 2000. We will conduct a high-dimensional propensity score matching and marginal structural modeling to construct a control group and assess the impact of RMG dispensation receipt on a collaboratively-determined set of primary and secondary outcomes.DiscussionThis study constitutes the first formal evaluation of a province-wide program providing regulated pharmaceutical alternatives to the toxic drug supply. The study features an integrated knowledge translation approach, including communications with people with lived/living experience of substance use and consortium meetings with various stakeholders. Supported by the unique research context in BC, our selected mixed method study design will provide an exceptionally strong evidence base to judge not only the impact of the initial implementation of RMG, but also critical evidence on the implementation of the program, which can be used to adapt its future iterations if deemed successful.
NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway
Authors: Zhong Chaoqin , Wang Ruiqing , Hua Mingqiang , Zhang Chen , Han Fengjiao , Xu Miao , Yang Xinyu , Li Guosheng , Hu Xiang , Sun Tao , Ji Chunyan , Ma Daoxin
Published: December 2020

Background: NLRP3 inflammasome has been reported to be associated with the pathogenesis of multiple solid tumors. However, the role of NLRP3 inﬂammasome in acute myeloid leukemia (AML) remains unclear. Methods: NLRP3 inflammasome expression in AML bone marrow samples was investigated via quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays and further determined in a cohort of AML bone marrow via Western blot analysis. Cell proliferation and flow cytometry assays were performed to confirm the roles of NLRP3 in AML proliferation, cell cycle regulation, and apoptosis. A mouse model with up-regulated NLRP3 expression was constructed by lentiviral transfection and a model with down-regulated expression was established by hematopoietic stem cell transplantation.Results: NLRP3 inflammasome is over-expressed and highly activated in AML bone marrow leukemia cells, which is correlated with poor prognosis. The activation of NLRP3 inflammasome in AML cells promotes leukemia cells proliferation, inhibits apoptosis and increases resistance to chemotherapy, while inactivation of NLRP3 by caspase-1 or NF-κB inhibitor shows leukemia-suppressing effects. Bayesian networks analysis and cell co-culture tests further suggests that NLRP3 inflammasome acts through IL-1β but not IL-18 in AML. Knocking down endogenous IL-1β or anti-IL-1β antibody inhibits leukemia cells whereas IL-1β cytokine enhances leukemia proliferation. In AML murine model, up-regulation of NLRP3 increases the leukemia burden in bone marrow, spleen and liver, and shortens the survival time; furthermore, knocking out NLRP3 inhibits leukemia progression. Conclusions: Collectively, all these evidences demonstrated that NLRP3 inflammasome promotes AML progression in an IL-1β dependent manner, and targeting NLRP3 inflammasome may provide a novel therapeutic option for AML.
Dickkopf-1 Promotes Angiogenesis by Upregulating VEGF Receptor 2-mediated mTOR/p70S6K Signaling in Hepatocellular Carcinoma
Authors: Seo Sang Hyun , Cho Kyung Joo , Park Hye Jung , Kim Hyemi , Lee Hye Won , Kim Beom Kyung , Park Jun Yong , Kim Do Young , Ahn Sang Hoon , Kim Seung Up
Published: December 2020

Background: The expression of Dickkopf-1 (DKK1), a negative regulator of the Wnt/β-catenin signaling pathway, is upregulated in hepatocellular carcinoma (HCC). Here, we investigated the tumorigenic and angiogenic potential of DKK1 in HCC.Methods: Stable cell lines were established using the clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9)-based DKK1 knock-out system in Hep3B cells and the tetracycline-based DKK1 inducible system in Huh7 cells. Multicellular tumor spheroids (MCTSs) were cultured using Hep3B stable cells. We also employed xenografts generated using Hep3B stable cells and transgenic mouse models established using hydrodynamic tail vein injection.Results: The angiogenic potential increased in HUVECs treated with CM from Huh7 stable cells with high DKK1 expression and Hep3B wild-type cells. There was an increase in the phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and p70 S6 kinase (p70S6K), which are downstream proteins of VEGFR2-mediated mTOR/p70S6K signaling. MCTSs generated using Hep3B wild-type cells promoted compact spheroid formation and raised expression of CD31 and epithelial-mesenchymal transition (EMT) markers, compared to the controls (all P<0.01). Xenograft tumors generated using Hep3B cells with DKK1 knock-out (n=10) exhibited slower growth than, the controls (n=10) and the expression of Ki-67, VEGFR2, CD31 and EMT markers decreased (all P<0.05). In addition, forced DKK1 expression with HRAS in transgenic mouse livers (n=5) resulted in the formation of more tumors and increased expression of Ki-67, VEGFR2, CD31, and fibronectin, compared to the controls (n=5) (all P<0.05).Conclusions: Our findings indicate that DKK1 facilitates angiogenesis and tumorigenesis by upregulating VEGFR2-mediated mTOR/p70S6K signaling in HCC.