bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clonal hematopoiesis of indeterminate potential, DNA methylation, and risk for coronary artery disease
Authors: Uddin Md Mesbah , Nguyen Ngoc Quynh , Yu Bing , Brody Jennifer , Pampana Akhil , Nakao Tetsushi , Fornage Myriam , Bressler Jan , Sotoodehnia Nona , Weinstock Josh , Honigberg Michael , Nachun Daniel , Bhattacharya Romit , Griffin Gabriel , Chander Varuna , Gibbs Richard , Rotter Jerome , Liu Chunyu , Baccarelli Andrea , Chasman Daniel , Whitsel Eric , Kiel Douglas , Murabito Joanne , Boerwinkle Eric , Ebert Benjamin , JAISWAL SIDDHARTHA , Floyd James , Bick Alexander , Ballantyne Christie , Psaty Bruce , Natarajan Pradeep , Conneely Karen 
Published: March 2022

Abstract
Age-related changes to the epigenome are well-documented, especially the pattern of genome-wide DNA methylation (DNAm) changes observed in blood. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the age-related acquisition and expansion of leukemogenic mutations in hematopoietic stem cells (HSCs), is associated with blood cancer and coronary artery disease (CAD). Epigenetic regulators DNMT3A and TET2 are the two most frequently mutated CHIP genes. Here, we present results from an epigenome-wide association study for CHIP in 582 Cardiovascular Health Study participants, with replication in 2655 Atherosclerosis Risk in Communities Study participants. We show that DNMT3A and TET2 CHIP have distinct and directionally opposing genome-wide DNAm association patterns consistent with their regulatory roles, albeit both promoting self-renewal of HSCs. Mendelian randomization analyses indicate that a subset of DNAm alterations for these two leading CHIP genes may promote the risk for CAD.
Cryo-EM structures reveal the activation and substrate recognition mechanism of human enteropeptidase
Authors: Huang Haojie , Li Zhaoshen , Yang Xiaoli , Ding Zhanyu , Peng Lisi , Song Qiuyue , Cui Fang , Zhang Deyu , Xia Chuanchao , Li Keliang , Yin Hua , Li Shiyu 
Published: March 2022

Abstract
The enteropeptidase (EP) initiates the intestinal digestion by proteolytic processing of trypsinogen, generating catalytic active trypsin. The dysfunction of EP will cause a series of pancreatic diseases, the most severe of which is acute necrotizing pancreatitis. However, the molecular mechanism of EP activation and substrate recognition remain elusive due to the lack of structural information, hampering the structure-based research of EP and even further EP-targeted drug design. Here we report cryo-EM structures of human EP in multiple states, covering the functional cycle spanning from inactive to active state and eventually to the substrate binding state, with the inactive core region reached an atomic 2.7-Å-resolution. The heavy chain of EP exhibits a clamping configuration with the CUB2 domain serving for substrate recognition. The N-terminus of light chain induces the surface loop remodeling from inactive to active conformation, resulting in a highly dynamic and active EP. Then the heavy chain performs like a hinge to ensure the flexibility of light chain for substrate recruitment and subsequent cleavage. Our study provides structural insights of EP remodeling and heavy chain dynamics while performing enzymatic function, facilitating our understanding of the pathogenies of EP-related pancreatitis and the EP-targeted treatment of pancreatitis.
Obese mammary tumour-bearing mice are highly sensitive to doxorubicin-induced hepatotoxicity
Authors: Sedeman Megan , Christowitz Claudia , de Jager Louis , Engelbrecht Anna-Mart 
Published: March 2022

Abstract
Background: Breast cancer is a major health burden for women, worldwide. Lifestyle-related risk factors, such as obesity and being overweight, have reached epidemic proportions and contributes to the development of breast cancer. Doxorubicin (DXR) is a chemotherapeutic drug commonly used to treat breast cancer, and although effective, may cause toxicity to other organs. The mechanisms and effects of DXR on hepatic tissue, and the contributing role of obesity, in breast cancer patients are poorly understood. The aim of this study was therefore to investigate the effects of doxorubicin on hepatic tissue in an obese tumour-bearing mouse model. Methods: A diet-induced obesity (DIO) mouse model was established, where seventy-four three-week-old female C57BL/6 mice were divided into two main groups, namely the high fat diet (containing 60% kcal fat) and standard diet (containing 10% kcal fat) groups. After eight weeks on their respective diets, the DIO phenotype was established, and the mice were further divided into tumour and non-tumour groups. Mice were subcutaneously inoculated with E0771 triple negative breast cancer cells in the fourth mammary gland and received three doses of 4 mg/kg DXR (cumulative dosage of 12 mg/kg) or vehicle treatments via intraperitoneal injection. The expression levels of markers involved in apoptosis and alanine aminotransferase (ALT) were compared by means of western blotting. To assess the pathology and morphology of hepatic tissue, haematoxylin and eosin staining was performed. The presence of fibrosis and lipid accumulation in hepatic tissues were assessed with Masson’s trichrome and Oil Red O staining, respectively. Results: Our western blot results indicated that a significant increase in the ratio of cleaved caspase-8 and caspase-8 protein expression was observed in the standard diet tumour-bearing mice treated with DXR compared to the high fat diet tumour-bearing mice treated with DXR. Microscopic examination of liver tissue showed significant changes in the high fat diet tumour-bearing mice treated with DXR, consisting of macrovesicular steatosis, hepatocyte ballooning and lobular inflammation, compared to the standard diet tumour-bearing mice treated with DXR and the control group (standard diet mice). These changes are the hallmarks of non-alcoholic fatty liver disease, associated with obesity.Conclusion: Our results suggest that DXR activated the extrinsic apoptotic pathway in tumour-bearing mice on the standard diet. The histopathological findings indicated that DXR caused significant hepatic parenchymal injury in the obese tumour-bearing mouse model. Hepatotoxicity is aggravated in obesity as an underlying co-morbidity. It has been shown that obesity is associated with poor clinical outcomes in patients receiving neo-adjuvant chemotherapy treatment regimens.
Intraventricular hemorrhage prediction in premature neonates in the era of hemodynamics monitoring:a prospective cohort study
Authors: Farag Marwa , Gouda Mohamed Hazem , Almohsen Ali Mohamed Abd , Khalifa Mohammed Attia 
Published: March 2022

Abstract
Purpose Unstable hemodynamics and prematurity are the main players in IVH development. Our objective was the use of SVCF, LVO and RVO, and ACA Doppler measures in prediction of IVH in the first week of life in preterm infant ≤ 32 weeks.Method Prospective cohort Study in NICU of the Maternity university hospital is presented. Of 147 patients, 132 infants born ≤32 weeks GA were enrolled in the study. 127 completed the study till 7th day of life. Infants were scanned for ACA-RI using transfontanellar ultrasound, and SVC flow, LVO, and RVO using FE in the first 24 hours after birth. Patients had another two scans on DOL3 and7 to detect IVH development. Results Low SVCF and high ACA-RI significantly increased the risk of IVH using logistic regression models with (OR, 3.16; 95%Cl, 1.19 – 8.39; P0.02) and (OR, 1.64; 95%Cl, 1.10 – 2.44;P0.02),respectively. Low SVCF and high ACA-RI significantly increased risk of catastrophic IVH P 0.025 and 0.023, respectively. Combined use Low SVCF < 55 ml/kg/min and ACA-RI > 0.75 is predictor of IVH with sensitivity 40.8% and 82.1% specificity. This work was registered in clinical trial.gv no NCT05050032ConclusionsThere are strong relations between both low SVC flow and high ACA-RI and IVH development in premature neonates ≤32 weeks, with more significance towards catastrophic IVH. Admission RSS and LVO are the strongest factors affecting SVC flow. PDA size (mm/kg) and CRT were significantly associated with high ACA-RI. Theses finding helps in more understanding of pathophysiological factors affecting central perfusion that might affect the longer term neurodeveopmental outcome.
The prevalence and risk factors for anxiety/depression in patients with connective tissue disease (CTD) associated interstitial lung diseases (ILDs)
Authors: Liao Jun-Zhe , qi Min , Zhu Min , Luo Feng-Ming 
Published: March 2022

Abstract
Background
Connective tissue disease(CTD) associated interstitial lung diseases (ILDs) is a common chronic disease. Given that anxiety and depression are prevalent in patients with chronic diseases, this study aimed to explore the prevalence of anxiety/depression in CTD-ILD patients, and identify its associated risk factors.
Methods
This study is based on the ICE study (Interstitial lung disease in West China Hospital: a 24-month prospective Cohort in the real world). The anxiety and depression symptoms were evaluated in CTD-ILD patients using Hamilton Anxiety/Depression Rating Scale (HAM-A/D), respectively. Demographic data, clinical symptoms, pulmonary function, and radiological data were collected. Multivariate analysis was performed to identify the independent risk factors of anxiety/depression in CTD-ILD patients.
Result
A total of 118 patients with CTD-ILD were enrolled. Among them, 66 patients (55.93%) with anxiety symptoms (HAM-A > 7), 55 patients (46.61%) with depression symptoms (HAM-D > 8), while 51patients (43.22%) with both anxiety and depression symptoms. Muscle soreness (OR = 3.451, 95% CI: 1.147–10.384, P = 0.028) is significantly associated with anxiety. And muscle soreness (OR = 4.337, 95% CI: 1.43–13.154, P = 0.01), Raynaud's phenomenon (OR = 4.264, 95% CI: 1.355–13.424, P = 0.013), and lower FVC% predicted (OR = 1.768, 95% CI: 1.152–2.714, P = 0.018) are significantly associated with depression. Besides, muscle soreness (OR = 4.737, 95% CI: 1.451–15.463, P = 0.010), lower FVC% predicted (OR = 1.649, 95% CI: 1.067–2.549, P = 0.024) and more severe dyspnea scaled by mMRC score (OR = 1.725, 95% CI: 1.075–2.769, P = 0.024) were associated with comorbid depression and anxiety.
Conclusion
Anxiety and depression were common in CTD-ILD patients. Impaired respiratory physiology (reduced FVC% predicted, dyspnea) and CTD related symptoms (Raynaud's phenomenon and muscle soreness) were risk factors for anxiety and depression in CTD-ILD patients, which emphasize the importance of focusing on the management of psychological disorders in CTD-ILD patients.
Evaluating the effects of CMIP6 model uncertainty on extreme flows of the Caspian Hyrcanian forest watersheds by BMA method
Authors: Lotfirad Morteza , Adib Arash , Riyahi Mohammad Mehdi , Jafarpour Mohammad 
Published: March 2022

Abstract
This paper investigates the climate change effects on the hydrological and meteorological parameters of the Navrood Basin (a Caspian Hyrcanian forest watershed) in the north of Iran. Outputs of seven CMIP6 GCMs (Tmin, Tmax, and precipitation) under two scenarios, SSP2-4.5 and SSP5-8.5, were utilized. This study considered the historical period (1994 to 2014), the near future (2025 to 2049), the middle future (2050 to 2074), and the far future (2075 to 2099). The EDCDFm and MBA methods were used for bias correction of the outputs of GCMs and combine GCMs, respectively. The LARS-WG model was used for statistical downscaling. The IHACRES model calculated the runoff. The annual Tmin under SSP2-4.5 and SSP5-8.5 will increase 1.04 °C and 1.25 °C in the near future, 1.55 °C and 2.48 °C in the middle future and, 2.09 °C and 4.11 °C in the far future, respectively. The annual Tmax under SSP2-4.5 and SSP5-8.5 will increase 1.59 °C and 1.38 °C in the near future, 1.98 °C and 3.02 °C in the middle future and, 2.58 °C and 4.94 °C in the far future, respectively. The annual precipitation (PCP) under SSP2-4.5 and SSP5-8.5 will increase 6.81% and 7.11% in the near future, 6.15% and 4.43% in the middle future, 8.63% and 6.58% in the far future, respectively. Finally, the annual runoff under SSP2-4.5 and SSP5-8.5 will increase 16.3% and 15.4% in the near future, 14.8% and 10.6% in the middle future and, 19.2% and 15.1% in the far future, respectively.
Development and Characterization of Novel Hybrid Materials Formed from ZnO-SiO2-Modified and Polyaniline for Organic Dyes Adsorption and Electrochemical Supercapacitor Applications
Authors: Benchikh Imen , Lahreche Saadia , Benmimoun Youcef , Benyoucef Abdelghani 
Published: March 2022

Abstract
Polyaniline (PANI) coated ZnO-SiO2 based hybrid material was prepared successfully by in-situ polymerization method and the product was analyzed by XPS, XRD, TEM, UV-vis, TGA, FTIR and BET techniques. According to these characterization results, ZnO were successfully incorporated with SiO2 and PANI matrix was also supported on ZnO–SiO2. The optical band gap was calculated from the Tauc’s plot it has been found 2.89 eV. The development of a PANI@ZnO–SiO2 is a new way to achieve better adsorption efficacy for Congo Red (CR) and Methylene Blue (MB) dyes in aqueous solutions due to the engineered excellent porous structure, which was 83.82 and 71.19 mg.g− 1, respectively. Moreover, this work reports also an extensive study of the effect of the SiO2 on the electrochemical performance of hybrid material based on ZnO and PANI employing cyclic voltammetry. It was found that the perfect stability, which can be sustained during a longtime of the galvanostatic charge-discharge (GCD) operation. The results reveal a superior cycling stability, with 90.1% capacitance retention after 1500 cycles.
MicroRNA-140-5p was involved in osteonecrosis of the femoral head by inhibiting osteogenic diffentiation and migration of hBMSCs
Authors: Hui Pu-Sheng , Qi Jia-Yi , Cao Chun-hao , Rong Xiao-Feng 
Published: March 2022

Abstract
Background: Osteonecrosis of the femoral head (ONFH) is a common but intractable disease and usually leads to disability. The unclear mechanism caused the trouble in diagnosis and early therapy of ONFH. Methods: We downloaded and analyzed the traumatic ONFH miRNA expression profile GSE89587. Then western blotting, PCR, alkaline phosphatase staining, wound healing assay and alizarin red S staining was used to investigate the effect of the selected miR-140-5p on human bone marrow-derived stem cells (hBMSCs). Furthermore, the relationship between miR-140-5p and BMP2 was detected by WB and we also used a siRNA of BMP2 to study whether silencing miR-140-5p could mitigate the damage caused by BMP2 interference.Results: 6 up-regulated miRNAs and 12 down-regulated miRNAs were identified and an upregulated miR-140-5p was selected for the downstream experiments. The further experiments showed that miR-140-5p upregulation in hBMSCs inhibited the expression of collagen type 1, OCN, and BMP2, reduced the ALP activity, mineralization, and migration ability of hBMSCs. In addition, inhibition of BMP2 inhibited osteogenesis of hBMSCs by regulating the BMP2-SMAD1/5/9-RUNX2 axis, while silencing miR-140-5p promoted osteogenesis of hBMSCs by regulating the BMP2-SMAD1/5/9-RUNX2 axis. Our study showed that miR-140-5p may be an emerging and valuable target for studying the mechanism of ONFH.
Delineating Mycobacterium abscessus population structure and transmission employing high-resolution core genome multilocus sequence typing
Authors: Diricks Margo , Merker Matthias , Wetzstein Nils , Kohl Thomas , Niemann Stefan , Maurer Florian 
Published: March 2022

Abstract
Mycobacterium abscessus (Mab) is an emerging multidrug-resistant nontuberculous mycobacterium that causes a wide spectrum of infections and has caused several local outbreaks worldwide. To facilitate standardized prospective molecular surveillance, we established a novel core genome multilocus sequence typing (cgMLST) scheme. Over 2000 isolates of Mab, covering all subspecies and main dominant circulating clones as well as extra-pulmonary outbreak strains and sequential isolates of chronically infected cystic fibrosis patients, were used to validate the scheme and set genetic distance thresholds to delineate transmission events and global population structure. Most global clonal complexes previously classified using cgSNP were confirmed by our cgMLST approach, and also correlated well with traditional 7-loci MLST sequence types. 99% of pairwise comparisons between epidemiologically linked isolates were below 25 alleles and 90% below 10 alleles. These thresholds can be used for initial cluster analysis and to guide further epidemiological investigations. Overall, the scheme will help to unravel the apparent global spread of certain clonal complexes and as yet undiscovered transmission routes.
Insilco Analysis of Anti-malarial drug resistant genes of Plasmodium falciparum 3D7 to understand its expression
Authors: Waktole Gemechis , Donghee Cho 
Published: March 2022

Abstract
Malaria is one amongst the foremost necessary infectious diseases that threaten 1/2 the world’s population. Federal Democratic Republic of Ethiopia is among countries with a high protozoan infection burden. Plasmodium falciparum is that the commonest (64%) reason for Malaria infection in Federal Democratic Republic of Ethiopia whereas P. vivax accounts for the remaining cases (34%). Despite various advances in malaria infection management methods, the disease still kills innumerable kids worldwide, principally in desert African countries and protozoan infection still remains a serious public pathological state in Federal Democratic Republic of Ethiopia. Analyzing parasite biology has monumental potential to help each effort at elimination additionally as international efforts toward wipeout. Therefore, this study is aimed to in atomic number 14 analysis of regulative parts like CpG islands, transcription factors (TFs) and their corresponding binding sites (TFBSs) concerned within the regulation of organic phenomenon of Plasmodium falciparum 3D7 isolates drug-resistant genes. during this analysis, 9 drug resistance touching cistron secret writing sequences, on the market within the NCBI information with the beginning sequence at the start of the sequence and solely useful genes (protein-coding) were deliberated. consequently, the promoter prediction by neural network promoter prediction result showed Plasmodium falciparum 3D7 drug resistance touching genes have 1–6 toxic shock syndrome and 5 common candidate motifs (MPfI, MPfII, MPfIII, MPfIV, and MPfV) were known. The study indicates the poor incidence of CpG islands in each cistron body and promoter regions which can have an effect on the access of the promoter region of genes to their transcription factors, therefore touching their expression. In general, this in silico analysis of cistrons secret writing for Plasmodium falciparum drug resistance touching genes can be useful to feature data concerning the molecular knowledge and collateral to spot gene regulative parts within the promoter regions.
CarpeDiem: Exploring health pillars to define a holistic recommender system to accomplish a sutainable change in lifestlye habits
Authors: Migliorelli Carolina , Ros-Freixedes Laura , Gómez-Martínez Meritxell , Orte Silvia 
Published: March 2022

Abstract
To live longer, healthier, and more active, people at any age have to follow simple and clear suggestions that cover the 3 main pillars of health: physical activity, nutrition, and sleeping. Unfortunately, due to the intrinsic (e.g., daily-life habits) and extrinsic (e.g., environmental change) factors, people are far to have a healthy life and, thus, there is an increase of chronic diseases, mental disorders, and premature death. This paper presents the approach followed in CarpeDiem, an IoT-based system focused on self-management as a way to engage and empower citizens in order to improve their quality of life and to allow a better follow-up of their own health. The CarpeDiem self-management system is intelligent and autonomous, and it is aimed at monitoring physical-and sleeping-activity, nutrition, as well as environmental data and lifestyle habits, with the final goal of providing personalized recommendations and nudges to foster behaviour change towards healthier behaviours. CarpeDiem system currently designed to provide individual recommendations in each one of the domains. However, there is increasing evidence that these three pillars influence each other. Subsequently, the final goal of the application is to assemble the information provided by the three pillars together and supply holistic recommendations to the users to induce a meaningful and enduring change in their behaviours. The purpose of this study is to analyze the existing associations between the three mentioned pillars, by using data from a previous pilot and current state of the art, to later design intelligent recommendations capable of producing lasting behavioural changes in the user’s community.
Towards robust in vivo quantification of oscillating biomagnetic fields using Rotary Excitation based MRI
Authors: Gram Maximilian , Albertova Petra , Schirmer Verena , Blaimer Martin , Gamer Matthias , Herrmann Martin J. , Nordbeck Peter , Jakob Peter 
Published: March 2022

Abstract
Spin-lock based functional magnetic resonance imaging (fMRI) has the potential for direct spatially-resolved detection of neuronal activity and thus may represent an important step for basic research in neuroscience. In this work, the corresponding fundamental effect of Rotary EXcitation (REX) is investigated both in simulations as well as in phantom and in vivo experiments. An empirical law for predicting optimal spin-lock pulse durations for maximum magnetic field sensitivity was found. Experimental conditions were established that allow robust detection of ultra-weak magnetic field oscillations with simultaneous compensation of static field inhomogeneities. Furthermore, this work presents a novel concept for the emulation of brain activity utilizing the built-in MRI gradient system, which allows REX sequences to be validated in vivo under controlled and reproducible conditions. Via transmission of Rotary EXcitation (tREX), we successfully detected magnetic field oscillations in the lower nano-Tesla range in brain tissue. Moreover, tREX paves the way for the quantification of biomagnetic fields.
Development of multi-epitope chimeric antigens for scrub typhus diagnostics and vaccines: An in-silico investigation
Authors: Namsa Nima D , Dolley Anutee , Goswami Himanshu Ballav , Dowerah Dikshita , Dey Upalabdha , Kumar Aditya , Sharma Debashree Saikia , Hmuaka Vanlal , Mukhopadhyay Rupak , Kundu Debasree , Varghese George M. , Doley Robin , Deka Ramesh , Saharia Niruprabha 
Published: March 2022

Abstract
Scrub typhus is a zoonotic bacterial disease caused by Orientia tsutsugamushi and accounts for up to 20% of common febrile illnesses and hospitalizations. The main obstacle to vaccine development is the lack of identification of relevant immunodominant antigens that stimulate broad-spectrum immune responses, including antibody, CD4 + T cells, and CD8 + T cells production. We examined the 56-kDa type-specific cell membrane surface protein (TSA56) and ScaA as candidates for developing vaccine and diagnostic assays using an in-silico approach. We predicted 35 linear and 29 conformational immunogenic B-cell epitopes and 51 non-overlapping strong binders of MHC class I and 27 for MHC class II T-cell epitopes in the conserved and variable regions of TSA56. We used this information to design effective multi-epitope vaccine constructs that are predicted to stimulate cross-protective immunity. Furthermore, the epitope-based vaccine constructs showed antigenic, non-allergenic, and interferon gamma-inducing properties, as predicted by online servers. We cloned the chimeric gene into a pET-15b plasmid vector and successfully expressed the histidine-tagged recombinant antigen in an Escherichia coli expression system. The findings the present study provide a platform for validations of the predicted epitopes and chimeric antigens for designing effective epitope-based vaccine candidates and serological diagnostic assays against scrub typhus.