bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALS-associated mutation disturbs amyloid fibril formation of TIA-1 prion-like domain
Authors: Inaoka Daigo , Miyata Tomoko , Makino Fumiaki , Ohtani Yasuko , Ekari Miu , Kobayashi Ryoga , Imamura Kayo , Kodama Takashi , Yoshida Norio , Kato Takayuki , Namba Keiichi , Tochio Hidehito , Sekiyama Naotaka 
Published: June 2023

Abstract
T-cell intracellular antigen-1 (TIA-1) is a key component of stress granules with an intrinsically disordered region called the prion-like domain (PLD). TIA-1 PLD forms phase-separated droplets that subsequently transition into amyloid fibrils. However, the structural basis of TIA-1 PLD amyloid fibril formation has not been elucidated. We investigated the amyloid fibril structure of TIA-1 PLD using cryo-electron microscopy and found structural features that ensure the reversibility of the fibrils, including a kinked backbone conformation, a polar zipper, and a proline-mediated cross-b structure. We also determined the amyloid fibril structure with the amyotrophic lateral sclerosis (ALS)-associated G355R mutation and found that G355R disrupts the tight conformation surrounding G355 in the wild-type fibril structure, resulting in destabilized and delayed amyloid fibril formation. The structural disturbance of amyloid fibril formation by G355R may contribute to the pathogenesis of ALS.
Estimation of Bio-energy Potential in Northwestern India Using Crop Residue
Authors: Meena Seeta Ram , Meena Guman Singh 
Published: June 2023

Abstract

Northwestern India is mainly agrarian produced around 384.25MT/year crop residue out of that 116 MT/year burnt in the field and released lot of pollutants such as CO2, CO, CH4, NOx, NMVOC, PM2.5, PM10 and other which contribute to climate change. In present paper, Introduction of energy and bioenergy in India, estimation of crop residue and bioenergy potential for each state of North-West India is discussed. India generates around 620.27 MT/year crop residues. Northwestern India alone produced 384.25 Mt/year or 62% of India crop residues. Bio-energy potential for northwestern India is 6657.29 PJ per year. States having higher bio-energy potentials are (1) Uttar Pradesh (2020.45 PJ per year), (2) Maharashtra (962.74 PJ per year), (3) Punjab (935.54 PJ per year), (4) Gujarat (598.4 PJ per year) (5) Haryana (610.94 PJ per year), (6) Rajasthan (578.59 PJ per year).The total power demand of India in 2018 was 1212 Twh and bio-fuel potential of northwestern India is 832.16 Twh, which can be satisfy around 68.66 percentage power demand of India annually.
Novel algorithms for improved detection and analysis of fluorescent signal fluctuations
Authors: Stopper Gebhard , Caudal Laura C. , Rieder Phillip , Gobbo Davide , Stopper Laura , Felix Lisa , Everaerts Katharina , Bai Xianshu , Rose Christine R. , Scheller Anja , Kirchhoff Frank 
Published: June 2023

Abstract
Fluorescent dyes and genetically encoded fluorescence indicators (GEFI) are common tools for visualizing concentration changes of specific ions and messenger molecules during intra- as well as intercellular communication. Using advanced imaging technologies, fluorescence indicators are a prerequisite for the analysis of physiological molecular signaling. Automated detection and analysis of fluorescence signals requires to overcome several challenges, including correct estimation of fluorescence fluctuations at basal concentrations of messenger molecules, detection and extraction of events themselves as well as proper segmentation of neighboring events. Moreover, event detection algorithms need to be sensitive enough to accurately capture localized and low amplitude events exhibiting a limited spatial extent. Here, we present two algorithms (PBasE and CoRoDe) for accurate baseline estimation and automated detection and segmentation of fluorescence fluctuations.
Development of Entrustable Professional Activities for Entry-level Dietitians in Taiwan
Authors: Huang Meng-Chuan , Kuo Su-E , Chin Huei-Min , Chang Hui-Ping , Chang Chiao-I , Yang Chih-Wei 
Published: June 2023

Abstract
Background Entrustable professional activities (EPAs) successfully link competencies with everyday practice in the training of health care professionals. Herein, we report on the nationwide development of EPAs and the competencies of entry-level dietitians receiving postgraduate clinical training programs.Methods The consensus process comprised three phases. The approach involved identifying core tasks for entry-level dietitians, holding national workshops and obtaining feedback from experts to form EPA drafts, and conducting a consensus meeting to construct EPAs framework and EPA/competency domain matrix. A total of 101 nutritionists or dietitian educators from teaching hospitals nationwide participated in the workshops (n = 101). Among the participants, experts (n = 31) were invited to join the competency-based medical education taskforce of Taiwan Dietitian Association (TWDA), provide feedback on drafted EPAs, and attend the consensus meeting using the nominal group technique (NGT). During NGT, any proposal for changes of the drafted EPAs or competencies, including adding, removing, and amending, had to be seconded by an additional expert before being further discussed sufficiently and voted on, with rates of agreement of consensus reached being set at ≥ 50%.Results We reached a consensus on seven core EPAs for entry-level dietitians. Each EPA was mapped to specific tasks and corresponding core competencies by developing an EPA/competency matrix. Among the seven EPAs, three were related to clinical nutrition care, two were related to the provision of dietetic services, one was related to group education on disease-specific nutrition, and one was related to nutrition care in the residential long-term care of the teaching hospital.Conclusions Development of the seven core EPAs as well as the EPA/competency matrix was accomplished by a solid consensus process that would offer goals for the expected progression and augment competency-based training for entry-level dietitians. Future study will be needed to test feasibility of implementing training and assessment of the core EPAs and their efficacy in teaching hospitals of Taiwan.
Corticosteroids for hospitalized patients with severe/critical COVID-19: a retrospective study in Chongqing, China
Authors: Zhuang Rongjuan , Xia Hongli , Xu Li , Li Anmao , Liu Zhiqiang , Chen Jiacheng , Zong Kaican , Peng Hailang , Liu Bin , Wu Huizi , Huang Lan , Yang Hongwei , Luo Chun , Luo Chen , Yin Yuting , Guo Shuliang 
Published: June 2023

Abstract
Background
To estimate the association between the administration of corticosteroids and all-cause mortality of hospitalized patients with severe/critical Corona Virus Disease 2019 (COVID-19).
Methods
We conducted this study at six tertiary hospitals in the area of Chongqing, China. Clinical records from all consecutive adult subjects admitted with SARS-CoV-2 infection from 1 November 2022 to 20 January 2023 were retrospectively reviewed. In-hospital and 28-day mortality were analyzed before and after propensity score matching (PSM). Logistic regression model and cox regression model was used to further examine the relationship between corticosteroid treatment and the risk of mortality.
Results
A total of 406 severe and critically ill COVID-19 patients were included in this study. They were divided into the corticosteroids group (231, 56.9%) and non-corticosteroids group (175, 43.1%) according to corticosteroids use (0.5-1mg/kg/d methylprednisolone or any corticosteroid at equivalent dose, no more than 10 days). Corticosteroid treatment did not reduce in-hospital mortality in overall cohorts (36.4% vs.28.0%) and matched cohorts (32.5% vs.34.5%). Univariate analysis showed that the 28-day mortality in the corticosteroids group was significantly higher than that in the non-corticosteroids group [hazard ratio (HR), 0.706; 95% CI, 0.507–0.983; p = 0.039] in the overall population. When the multivariate analysis was further used to control confounders, the results showed that corticosteroids were not associated with improved 28-day mortality (HR, 1.121; 95% CI, 0.641–1.959; p = 0.689). With PSM, similar results were obtained with univariate and multivariate analysis.
Conclusions
Corticosteroids in hospitalized patients with severe/critical COVID-19 did not reduce mortality in the overall population.
Individualized brain radiomics-based network tracks distinct subtypes and abnormal patterns in prodromal Parkinson’s disease
Authors: Hua Lin , Huang Canpeng , Gao Fei , Yuan Zhen 
Published: June 2023

Abstract
Individuals in the prodromal phase of Parkinson’s disease (PD) exhibit significant heterogeneity and can be divided into distinct subtypes based on clinical symptoms, pathological mechanisms, and brain network patterns. However, little has been done regarding the valid subtyping of prodromal PD, which hinders the early diagnosis of PD. Therefore, we aimed to identify the subtypes of prodromal PD using the brain radiomics-based network and examine the unique patterns linked to the clinical presentations of each subtype. Individualized brain radiomics-based network was constructed for normal controls (NC; N = 110), prodromal PD patients (N = 262), and PD patients (N = 108). Data-driven clustering approach using the radiomics-based network was carried out to cluster prodromal PD patients into higher-/lower-risk subtypes. Then, the dissociated patterns of clinical manifestations, anatomical structure alterations, and gene expression between these two subtypes were evaluated. Clustering findings indicated that one prodromal PD subtype closely resembled the pattern of NCs (N-P; N = 159), while the other was similar to the pattern of PD (P-P; N = 103). Significant differences were observed between the subtypes in terms of multiple clinical measurements, neuroimaging for morphological changes, and gene enrichment for synaptic transmission. Identification of prodromal PD subtypes based on brain connectomes and a full understanding of heterogeneity at this phase could inform early and accurate PD diagnosis and effective neuroprotective interventions.
Identification of super-enhancers regulatory network mediates the pathogenesis of hyperlipidemia
Authors: Hu Yingying , Xu Run , Feng Jing , Zhang Qingwei , Zhang Lifu , Chen Ximing , Du Menghan , Chen Zhouxiu , Liu Xin , Zhang Yong 
Published: June 2023

Abstract
Hyperlipidemia (HLP) is a prevalent metabolic disorder and a significant risk factor for cardiovascular disease. According to recent discoveries, super-enhancers (SEs) play a role in the increased expression of genes that encode important regulators of both cellular identity and the progression of diseases. However, the underlying function of SEs in the development of HLP is still unknown. We performed an integrative analysis of H3K27ac ChIP-seq data and RNA-seq data obtained from liver tissues of mice under a low-fat diet (LFD) and high-fat diet (HFD) from the GEO database. The rank ordering of super enhancers algorithm was employed for the computation and identification of SEs. A total of 1877 and 1847 SEs were identified in the LFD and HFD groups, respectively. The SE inhibitor JQ1 was able to potently reverse lipid deposition and the increased intracellular triglyceride and total cholesterol induced by oleic acid (OA), indicating that SEs are involved in regulating lipid accumulation. Among the identified SEs, 278 were considered as HFD-specific SEs (HSEs). Gene Ontology and KEGG pathway enrichment analysis of HSEs-associated genes revealed that they are mainly involved in lipid metabolism and transcription regulation. Tsku was a highly ranked HSEs-associated differentially expressed genes. JQ1 reversed the elevated Tsku mRNA level induced by OA treatment, whereas there was no significantly change with JQ1 alone. The results above indicate that the HSE regulatory network is involved in the pathogenesis of HLP, suggesting that it could be a promising target for future treatments for HLP.
Aspartate-β-hydroxylase as a promising prognostic and therapeutic biomarker for HBV-positive hepatocellular carcinoma
Authors: Li Jingtao , Wang Zongwen , Ren Xiaohang , Zhu Qiankun , Zhang Yao , Ma Shuoheng , Liu WenYu , Zeng Shicong , Zhai Bo 
Published: June 2023

Abstract
BACKGROUND: Hepatitis B virus (HBV) is a key factor in the development of hepatocellular carcinoma (HCC). However, effective treatments to improve prognosis are still lacking. Aspartate plays a critical role not only in tumor cell proliferation, invasion, and migration, but also in the tumor immune microenvironment. A deeper understanding of the cellular and molecular mechanisms of HBV-positive HCC in terms of the role of aspartate-related genes may contribute to the development of targeted methods for prevention and treatment.
Methods: Transcriptomic data and clinical information on HCC samples from TCGA, GEO, and ICGC databases were obtained for assessing prognosis and variable genetic information. We collected a total of 79 clinical samples, including 66 cases of HBV-positive HCC and 13 cases of HBV-negative HCC, along with corresponding clinical information. Subsequently, ASPH immunohistochemical staining was performed on the samples, enabling the analysis of ASPH expression and its prognostic implications for the patients. In vitro, we demonstrated the effect of ASPH expression on malignant progression of HCC by examining the proliferation, invasion, and migration of various hepatocellular carcinoma cell lines. Transcriptomic data were analyzed to confirm potential mechanisms and validated by western blotting and immunohistochemical staining.
Results: Clinical prognostic models can influence the prognosis of HBV-positive HCC patients. ASPH acts as an independent factor affecting prognosis in HBV-positive HCC patients, but not in HBV-negative cases. In vitro, knockout of ASPH inhibited the proliferation, invasion and migration of tumor cells, while its overexpression exhibited a promoting effect. Mechanistically, ASPH demonstrates a close correlation with disulfidoptosis and tumor immunity. Notably, we have identified ASPH can regulate the expression of SLC7A11, NCKAP1, and mTOR. Moreover, the expression of ASPH can be associated with the infiltration of immune cells in tumor tissues.
Conclusions: Our research established the optimal model to predict the prognosis of HBV-positive HCC patients. Furthermore, we demonstrated that ASPH plays a critical role in the prognosis, immunological microenvironment, and drug sensitivity of HBV-positive HCC patients. Disulfidoptosis and tumor immunity are possible mechanisms of ASPH function.
Groundwater potential zones Modeling using GIS, remote sensing, and AHP Method in the Guigou basin, Morocco
Authors: Hairchi Khalid El , Brahim Youssef Ben , Saadi Omar , Ouiaboub Lahcen , Limame Abdelhak , Nouayti Abderahim , Nouayti Nourdine 
Published: June 2023

Abstract
This study aims to model the groundwater storage areas in the Guigou basin using Geographic Information System (GIS), Remote Sensing (RS) and AHP methods. Eight thematic maps of lithology, slope, rainfall, rock fracture, Fractional impervious surfaces, LU/LC, soil and drainage were respectively classified and weighted and then used to create the map of potential groundwater storage areas. The results have shown that the area of Medium, high, and very high potential zones make up 66.38%, 11.43%, and 0.048% of the total, respectively, while medium and low potential zones make up 22.14% and 0.002% of the total. The obtained results have been validated with 51 wells in the study area. It indicates a clear correlation between the groundwater potential zones and the wells depth, This relationship between depth and location of drilled wells is particularly clear; in fact, the majority of shallow wells are found in places with high potential, whilst the majority of deep wells are found in areas with low potential.
Recommendation via Entering a Human Conversation
Authors: Galitsky Boris , Ilvovsky Dmitry 
Published: June 2023

Abstract
We propose a novel way of the conversational recommendation where instead of asking user questions to acquire her preferences, the recommender tracks her conversations with other people, including customer support agents (CSA) and joins the conversation only when there is something important to recommend and the time is correct to do so. Building a recommender that joins a human conversation (CRS), we propose information extraction, discourse and argumentation analyses, as well as dialogue management techniques to compute a recommendation for a product and service that is badly needed by the customer, as inferred from the conversation. A special case of such conversations is considered where the customer raises his problem with a CSA in an attempt to resolve at, along with receiving a recommendation for a product with features addressing this problem. Performance of CRS is evaluated in a number of human-human and human-chatbot dialogues and demonstrates that CRS is efficient and less intrusive way to provide high relevance and persuasive recommendations.
Determination of Groundwater Potential Zones on the Eastern Slope of Mount Cameroon using Geospatial Techniques and Seismoelectric Method
Authors: Njumbe Lionel Junior Ngome , Lordon Anatole Eugene Djieto , Agyingi Christopher M. 
Published: June 2023

Abstract
In complex hard-rock terrain where the population suffers from water scarcity, the use of site-specific single-method surface geophysical survey to prospect for groundwater is a common practice. However, this has not completely solved the problem of drilling dry wells. To combat this failure, geospatial data and the analytical hierarchy process (AHP) are being used as supporting techniques to increase the chance of success. This study had the aim of generating groundwater potential zones (GWPZ) map of the complex strato-volcanic terrain of Buea by integrating geospatial techniques, AHP and the seismoelectric method. Six factors influencing groundwater recharge were used to define the groundwater potential zones. Via the AHP and weighted overlay methods, five classes of groundwater potential zones were delineated: very poor, poor, moderate, good, and very good. More than half of the study area has good to very good groundwater potential. Lastly, the GWPZ model is validated with an iso-conductivity map from a seismoelectric survey and existing static water level data. The iso-conductivity map revealed four main conductivity zones that correlate positively with the GWPZ map. The northwestern part of the study area is characterised by moderate groundwater potential, poor formation conductivity and dry boreholes. There is an uneven distribution of groundwater and variable water table depth in the area. The results of this study are very encouraging, and the integrated approach used has proven to be efficient in determining groundwater potential zones in complex volcanic terrain.
Apixaban and Clopidogrel in a fixed-dose combination: Formulation and in vitro evaluation
Authors: Al-Shami Ni'meh , Naseef Hani , Kanaze Feras 
Published: June 2023

Abstract

Fixed-dose combination (FDC) products represent a novel, safe, and cost-effective formulation. Combined use of anticoagulant and antiplatelet medications is common among comorbid cardiovascular patients. This study aimed to formulate FDC tablets for Apixaban and Clopidogrel, as prophylaxis and treatment of thrombo-embolic events. FDC tablets were developed by combining small tablets of Immediate-Release (IR) Clopidogrel 75 mg and Extend-Release (ER) Apixaban 5 mg through direct compression and wet granulation. Particularly, Apixaban tablets were developed using design expert software, and various types and concentrations of polymers were entered. For Clopidogrel tablets, various diluents were used to develop the formulation. Then, the dissolution profile for each formula was studied. Finally, the optimized formulations were encapsulated within hard gelatin capsules. Apixaban formulation followed zero-order with super case Ⅱ transport mechanism as the dominant mechanism of drug release. The Apixaban drug release rate was affected by the type and concentration of the polymers in the formulation (P < 0.05). As the HPMC concentration was increased, Apixaban release was retarded. For, Clopidogrel, the formulated tablets with spray-dried lactose filler and sodium stearyl fumarate lubricant were found to be stable with good properties. In conclusion, the optimum formulation yielded IR of Clopidogrel and ER of Apixaban for 24 hours with the desired in vitro drug dissolution.
Cognitive impairment is induced by BDNF-TrkB signaling mediating synaptic damage and reduction of amino acid neurotransmitters in heart failure rats
Authors: Wang Lei , Lu Ziwen , Teng Yu , Pan Weibing , Li Yang , Su Sha , Chang Jingling , Zhao Mingjing 
Published: June 2023

AbstractBackground Heart failure (HF) is often accompanied by cognitive impairment (CI). Yet, the underlying molecular mechanism is still not fully understood. Methods A HF model was prepared by ligation of the anterior descending coronary artery of the rat for 8 weeks. Echocardiography and morris water maze were performed to evaluate cardiac and cognitive function. Electron microscopy was conducted to quantify postsynaptic density (PSD) thickness, length, and cleft width of synapses. Thirteen neurotransmitters were detected by high-performance liquid chromatography, and proteins associated with the BDNF-TrkB pathway were determined by Western blot. The intervention of BDNF siRNA in fetal rat cortical neurons was chosen for further validation of the BDNF-TrkB pathway. Results HF rats passed through the original platform position in the probe trials fewer times and took more time and distance to reach the platform in the reversal phase compared with Sham rats; also, they had reduced thickness and length of PSD and increased synaptic cleft width. Expression of BDNF, TrkB, PSD95, and VGLUT1 was significantly decreased in HF rats brain. In addition, compared with Sham rats, amino acids were significantly reduced with no changes in the acetylcholine and monoamine neurotransmitters. Further examination showed that the number of synaptic bifurcation and the expression of BDNF, TrkB, PSD95, and VGLUT1 were all decreased in the neurons that interfered with BDNF-siRNA compared with those in the negative control neurons. Conclusions These data suggest that CI in HF is regulated by BDNF-TrkB signaling, mediating synaptic damage and reduction of amino acid neurotransmitters.