bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prion protein conversion at two distinct cellular sites precedes fibrillisation
Authors: Ribes Juan , Patel Mitali , Halim Halim , Tooze Sharon , Kloehn Peter 
Published: May 2022

Abstract
The self-templating nature of prions plays a central role in prion pathogenesis and is associated with infectivity and transmissibility. Since propagation of proteopathic seeds has now been acknowledged a principal pathogenic process in many types of dementia, more insight into the molecular mechanism of prion replication is vital to delineate specific and common disease pathways. By employing highly discriminatory anti-PrP antibodies and conversion-tolerant PrP chimera, we here report that de novo PrP conversion and formation of fibril-like PrP aggregates are distinct in mechanistic and kinetic terms. De novo PrP conversion occurs within minutes after infection at two subcellular locations, while fibril-like PrP aggregates are formed exclusively at the plasma membrane, hours after infection. Phenotypically distinct pools of abnormal PrP at perinuclear sites and the plasma membrane show differences in N-terminal processing, aggregation state and amyloid formation and are linked by exocytic transport via synaptic and large-dense core vesicles.
Blood Cytology in Children with Down Syndrome
Authors: Puente Silvestre García de la , Arizmendi Karla Adney Flores , Tapia Yessica Yuliana Guerrero , Robledo Tania Tonantzin Vargas , Santiago Norma Candelaria López 
Published: May 2022

Abstract
IntroductionDown syndrome is associated with various congenital anomalies and metabolic alterations such as hematological alterations. Values for the major hematological indicators vary with age and sex, but these values have not been described for Mexican children with Down syndrome.Objective. To describe the complete blood count (CBC) values of pediatric patients with Down syndrome and report the most common non-malignant hematological alterations. Materials and Methods.The analysis includes data from 450 patients with Down syndrome, 55.5% ware males, aged 0-18 years who were patients at the Mexican National Institute of Pediatrics and whose clinical charts included CBC panel results for the period January 2008 through March 2018. Results.A total of 3438 CBC panels were analyzed with descriptive statistics to find the values and statistical dispersion of the major indicators, with percentiles, and reported separately by sex and age group. The most common non-malignant hematological alterations found were macrocytic anemia, leukopenia, lymphopenia, and thrombocytosis. There were differences in values in all three series.Conclusions. The CBC panels and hematological alterations are summarized for patients with Down syndrome.
The differentiation potential of human granulosa cells into sperm-like cells
Authors: Ghadirkhomi Elham , Maleki Masoud , ghadirkhomi Akram 
Published: May 2022

Abstract
Context: According to previous studies human-derived luteal phase granulosa cells are able to differentiate into other cell lineages, such as osteoblasts, chondrocytes and neurons. Aims: In this study we investigated the differentiation potential of these cells into sperm-like cells. Methods: First, we demonstrated the stemness of isolated GCs by flow cytometry and then we showed that granulosa cells can differentiate into advanced male germ cell lineages including spermatid-like cells in vitro. Follicular-phase GCs were cultured then induced by sheep testis tissue extract to differentiate into sperm-like cells, as evidenced by their expression of Gpr125, as well as VASA and DAZL, which are markers of different steps of Spermatogenesis.Key results: Mesenchymal stem cell markers were expressed in these cells. Spermatogenesis markers including DAZL,VASA and GPR125, were also expressed from the second week after induction. Morphological analysis of induced cells showed that Producing sperm- like cellsweresimilar to the normal sperm. Conclusions: Obtained results prove that isolated GCs are a kind of mesenchymal stem cells and have the capability to differentiate into sperm–like cells. Implications: This finding may represent a novel strategy for studying spermatogenesis in vitro or may help to improve assisted reproductive technology methods in the future.
Life history traits and biogeographic features shaped the complex evolutionary history of an iconic apex predator (Galeocerdo cuvier).
Authors: Lesturgie Pierre , Lainé Hugo , Suwalski Arnaud , Chifflet-Belle Pascaline , Delser Pierpaolo Maisano , Clua Eric , Jaquemet Sébastien , Magalon Hélène , Mona Stefano 
Published: May 2022

Abstract
Background. The tiger shark (Galeocerdo cuvier) is a large iconic marine predator inhabiting worldwide tropical and subtropical waters. So far, only mitochondrial markers and microsatellites studies have investigated its worldwide historical demography with inconclusive outcomes. Here, we assessed for the first time the genomic variability of tiger shark by Rad-sequencing 50 individuals from five sampling sites in the Indo-Pacific (IP) and one in the Atlantic Ocean (AO) to decipher the extent of the global connectivity and its demographic history. Results. Clustering algorithm, FST and an approximate Bayesian computation framework revealed the presence of two clusters corresponding to the two oceanic basins. By modelling the two-dimensional site frequency spectrum, we tested alternative isolation/migration scenarios between these two populations. We found the highest support for a divergence time of ~193,000 years before present (B.P) and an ongoing but limited asymmetric migration ~176 times larger from the IP to the AO (Nm~3.9) than vice versa (Nm~0.02). Conclusions. The two oceanic regions are isolated by a strong barrier to dispersal more permeable from the IP to the AO through the Agulhas leakage. We finally emphasized contrasting recent demographic histories for the two regions, with the IP characterized by a recent bottleneck around 2,000 years B.P. and the AO by an expansion starting 6,000 years B.P. The large differentiation between the two oceanic regions and the absence of population structure within highlight the existence of two large management units and call for future conservation programs at the oceanic rather than local scale, particularly in the Indo-Pacific where the population is declining.
Inhibitory antibacterial activity of two novel dihydroxy fatty acids and other constituents from the stem bark of Trichilia gilgiana Harms (Meliaceae)
Authors: Kengne Michael Hermann Kamdem , Talla Rostan Mangoua , Morifi Eric , Bodju Sandra Nyanda , Kemkuignou Blondelle Matio , Tata Charlotte Mungho , Melacheu Gertrude Laura Foudjo , Fotsing Marthe Carine Djuidjeu , Mmutlane Edwin Mpho , Ndinteh Derek Tantoh 
Published: May 2022

Abstract
Two novel dihydroxy-fatty acids, gilgianic acid (1), phenylgilgianic acid (2) together with four known compounds: ß-sitosterol (3), stigmasterol (4), sitosterol-3-O-ß-D-glycoside (5) and lupeol (6) were isolated from the stem bark of Trichilia gilgiana. The structures of compounds 1–6 were elucidated based on spectroscopic (1 D and 2 D NMR) and HR-ESI-MS data as well as comparison with relevant literature data. This study reports for the first time the isolation of fatty acids from the genus Trichilia. Compounds 3–6 had already been isolated from trichilia genus. The crude extract and compounds 1–5 were tested for their inhibitory effect against a panel of bacterial strains using the microdilution technique with ampicillin, nalidixic acid and streptomycin as standard drugs. The crude extract and the tested compounds were found to exhibit significant activity against Bacillus subtilis and Klebsiella aerogenes with a MIC value of 2.3 µg/mL. Compounds 3 and 5 were also found to be active against Enterococcus faecalis with a MIC value of 2.3 µg/mL.
Herb-Symptom analysis of Erchen Decoction combined Xiebai Powder prescription and its mechanism of action in treating chronic obstructive pulmonary disease
Authors: Ye Hua , He Beibei , Yu Ziwei , Feng Yifan , Wen Chuanbiao , Feng Quansheng 
Published: May 2022

Abstract
Background
In this study, Herb-Symptom analysis of Erchen Decoction combined Xiebai Powder (ECXB) prescription was conducted based on the SymMap platform, and the synergistic mechanism of this prescription in the treatment of chronic obstructive pulmonary disease (COPD) was explored by network pharmacology and molecular docking method.
Methods
The SymMap platform was used to collect information related to Traditional Chinese Medicine (TCM) symptoms and Modern Medicine (MM) symptoms prescribed by ECXB, and the “Herb-TCM Symptoms” network and “Herb-MM symptoms” network were drawn for Herb-Symptom analysis. TCMSP database was used to screen the active ingredients and corresponding targets of ECXB. GeneCards database was used to screen Chronic obstructive pulmonary disease related targets, which were mapped to the predicted targets of ECXB to obtain the action targets of ECXB in the treatment of Chronic obstructive pulmonary disease. Cytoscape software was used to construct the “Drug-ingredient-target” network. Protein-protein Interaction (PPI) network was analyzed by STRING database, and the core targets were obtained. DAVID database was used for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis.
Results
Herb-Symptom analysis showed that ECXB prescription drugs had similar symptoms with COPD patients. Network pharmacology obtained 170 active ingredients with 137 corresponding targets, and 7002 Chronic obstructive pulmonary disease action targets were obtained. 120 ECXB treating chronic obstructive pulmonary disease joint action targets were obtained by intersection mapping, among which the core targets include MAPK8, ESR1, TP53, MAPK3, JUN, RELA, MAPK1, and AKT1. The GO enrichment analysis results indicated that ECXB mainly participates in response to drug, response to nutrient levels, response to extracellular stimulus, response to oxygen levels, and other biological processes. The pathway analysis showed that ECXB treating Chronic obstructive pulmonary disease by regulating hepatitis B, pathways in cancer, TNF signaling pathway, and so on.
Conclusions
This study analyzed the medication rule of ECXB prescription in the treatment of COPD from a new perspective, and found that the symptoms of TCM treatment with ECXB prescription were similar to those of Modern medicine treatment, and that ECXB could treat COPD through multi-component, multi-target, and multi-pathway synergistic effects, providing a scientific basis for further study on the mechanism of ECXB treatment of chronic obstructive pulmonary disease. It also provides new ideas for drug development.
Evaluation and countermeasures of Chinese family doctor contracted service from the perspective of demander -- a case study of a city
Authors: Liu Songyi , Meng Wenqi , Yu Qianqian , Peng Haibo , Jiang Xiaoli , Li Zixin , Yin Wenqiang , Chen Zhongming , Ma Dongping , Sun Kui 
Published: May 2022

Abstract
Background: From the perspective of the demander, the purpose of the study is to find out the weak link of the family doctor contracted service in a city, that is, to optimize the effect of the family doctor contracted service in China.Methods: In this study, a city in Shandong Province, China was selected as the sample city. In January 2020, 1098 contracted residents (including 40.5% men and 59.5% women) from 18 primary medical institutions (including township health centers and community health centers) were selected for on-site investigation. The PCAT-AS scale revised in Chinese was used as the research tool to understand the treatment experience of contracted residents in primary medical institutions.Results: Among the four core dimensions of PCAT-AS, the score of Continuous was the highest (3.44 ± 0.58); The score of Coordinated was the lowest (3.08 ± 0.66); Among the three derived dimensions, the score of Family-centeredness was the highest (3.33 ± 0.65); The score of Culturally-competent was the lowest (2.93 ± 0.77). The PCAT scores of contracted residents with different demographic characteristics such as contracted institution, age, education level, marital status and occupation were statistically significant (P < 0.05).Conclusions: The family doctor contracted service in the city has achieved certain results. At the same time, there are still some problems, such as difficult access to outpatient services during nonworking hours and incomplete service items. It is suggested that primary medical institutions further improve their service capacity in the dimensions of Coordinated and Comprehensiveness, in order to provide better services for contracted residents.
Immune Cell Infiltration Reveals Dynamic Changes in Hypertrophic Cardiomyopathy and Heart Failure
Authors: Xu Jiachen , Liu Sijia , Wang Jiang , Lin Xiufang , Zhou Jianghua 
Published: May 2022

Abstract
Heart failure is a global public health problem, and hypertrophic cardiomyopathy is one of the pathologic processes which can develop into heart failure. The purpose of this study was to explore changes in typical pathway activity, sift and verify effective biomarkers for providing a possible way to block disease progression. The GSE32453 and GSE1145 data sets were analyzed by short time sequence expression (STEM) and CIBERSORT analysis. The module genes with high correlation were identified by co-expression network analysis (WGCNA) screening and differential analysis. The common genes were obtained by intersection analysis. The enrichment analysis of these genes and the protein interaction network (PPI) analysis were constructed. The area under the ROC (AUC) was calculated by selecting the genes with the top 100 degrees of connectivity in the PPI network, and the genes with AUC values greater than 0.99 were analyzed by intersection again in the GSE36961 and GSE2656 datasets, resulting in a T-test, and P < 0.05 was considered as a key gene. The activity of the immune-related pathway was up-regulated, and the activity of substance transport and signal transduction pathway was down-regulated. Toll and other typical pathways play an important role in disease development. Five genes, JAK2, PLCE1, CD86, MYB, and IL13RA1, were considered as biomarkers. Among the 22 immune cells, Naïve B Cells had the highest abundance, followed by Plasma cells and M2 macrophages.In the progression of HCM to HF, we identified several potential diagnostic genes and mechanisms for changes in typical pathway activity.
Spatiotemporal Risk Assessment of Agricultural Drought Disasters in Aman Rice Growing Season in Western Bangladesh
Authors: Jion Most. Mastura Munia Farjana , Kamruzzaman Mohammad , Mallick Javed , Das Samiran , I Abu Reza Md. Towfiqul 
Published: May 2022

Abstract
Agricultural drought (AGD) is among the most well-known and devastating natural disasters on the globe, wreaking havoc on rain-fed agricultural countries, including Bangladesh. The Penman-Monteith (P-M) equation and a crop coefficient model were used to assess the spatial and temporal variability of the rainfed Aman rice season in western Bangladesh between 1980 and 2017. To reveal the spatiotemporal changes in drought during the Aman rice growing phases in western Bangladesh, the crop water deficit index (CWDI) was developed for AGD evaluation. In addition, based on risk formation theory, this study intends to construct a drought disaster risk index (DDRI) for rain-fed Aman rice for various growth phases. The results revealed that the crop water deficit was found to be the lowest in the vegetative phase and the highest in the ripening phase. Among all the areas, the CWDI was highest in the Rangpur and Rajshahi regions. Drought risk was relatively higher in the late phase of the crop growing period due to high temperatures, inadequate rainfall, climatic characteristics, and geographical setting. Precipitation, evapotranspiration, and a rapidly changing climate all contributed to variations in crop water deficits in the study region. Crop yields were reduced in all sub-areas. Spatially, higher values of DDRI were observed in the northern areas of western Bangladesh. New adaptive measures and policies are essential to improve the adaptability and mitigation capacity of AGD risk. Finally, this study suggests that farm-level adaptation, cropping patterns, and drought-resistant crops should be introduced in the study region.
Iroquois homeobox gene 2 as a novel prognostic marker that dysregulated in lung adenocarcinoma
Authors: Huang Zhen , Xiao Ping , Qu Bin , Sun Lisa 
Published: May 2022

Abstract
Lung adenocarcinoma (LUAD), is one of the deadliest and most common types of cancer. Homeobox-containing genes are evolutionary conserved regulators that play important roles in embryogenesis and tumorigenesis. We discovered that seven dysregulated homeobox-containing genes with prognostic value in LUAD. Furthermore, we showed that Iroquois homeobox (IRX)2 is enriched in normal lung tissues but dysregulated in LUAD. IRX2 is an independent prognostic marker in LUAD in univariate and multivariate Cox proportional and further confirmed in Kaplan-Meier survival analyses. Furthermore, patients with long-term survival had significantly higher IRX2 expression levels in public LUAD dataset. Meanwhile, methylation level of IRX2 promoter region was increased in TCGA (The Cancer Genome Atlas) and was linked to a decreased overall survival rate in patients. The results of Gene Set Enrichment Analysis (GSEA) revealed that IRX2-related genes were enriched humoral immune and also in tumorigenesis pathways such as G2/M checkpoint and mTOR pathways. Early research suggested that IRXs play a role in lung morphogenesis, but their pathological role in LUAD is unknown. These findings suggest that IRX2 dysregulation may play a role in the development of LUAD tumors and could be used as a novel prognostic marker for LUAD patients.
Comparative Assessment of The Willems Dental Age Estimation Methods: A Chinese Population-Based Radiographic Study
Authors: Wang Jian , Fan Linfeng , Sui Meizhi , Shen Shihui , Zhou Jiaxin , Yuan Xiaoyan , Wu Yiwen , Zhong Pingping , Ji Fang , Tao Jiang 
Published: May 2022

Abstract
Objectives
The objective of the work was to assess the accuracy of the two Willems dental age estimation methods (gender-specific (Willems I) and non-gender-specific (Willems II)) in a Chinese population.
Materials and Methods
A total of 1211 oral panoramic radiographs (582 boys and 629 girls) of the Chinese Han population aged 11-to-16-year-old were collected. Dental ages (DAs) were calculated using the Willems method. Statistical significance was set at a p-value < 0.05. Age differences between chronological age (CA) and dental age were analyzed by paired t-tests and mean absolute error (MAE).
Results
The differences between CA and DA determined by the Willems I method were + 0.44 and + 0.09 years for boys and girls, respectively. When using the Willems II method, these differences were + 0.57 and − 0.09. The MAEs of the Willems I method between DA and CA were 0.95 and 1.00 years in boys and girls, respectively. For Willems II, MAEs were 1.02 and 1.00 years in boys and girls.
Conclusions
This study showed that the Willems I method was more accurate than the Willems method in the boys’ group for predicting age. While the Willems is more competitive in the girls' group. Neither method may be satisfactory for 11-to-16-year-old teenagers in Eastern China.
Microcomputed tomographic analysis of the efficiency of two retreatment techniques in removing root canal filling materials from mandibular incisors
Authors: YANG Xueqin , Wang Ye , JI Mengzhen , LI Yanyao , WANG Hao , LUO Tao , GAO Yuan , ZOU Ling 
Published: May 2022

Abstract
Objectives: The aim of this study was to evaluate the removal effect of the ProTaper Next system (PTN) combined with manual nickel-titanium Hedström (MNiTiH) files or with chloroform on root canal filling materials of mandibular incisors by microcomputed tomography (micro-CT).Materials and Methods: Sixty-four extracted human mandibular incisors were selected and assigned to two groups (n=32) based on root canal morphology investigated by micro-CT after instrumentation. Two subgroups (n=16) were formed based on two methods (PTN combined with MNiTiH or chloroform) of removing root canal filling materials. Specimens were scanned with micro-CT before and after canal instrumentation, after obturation and retreatment. The volume of residual filling materials (RFMs) and the surface area of the root canal covered by RFMs were analyzed, and the time taken for removing the filling materials and apical extrusion was recorded.Results: A smaller percentage of the volume of RFMs and less root canal surface area covered by RFMs occurred in samples in the PTN combined with MNiTiH group and with round-shaped canal incisors (P<0.05). RFMs in the apical third were significantly greater than those in the middle and coronal thirds of the root (P<0.05). Both the time taken to reach the working length and to achieve filling material removal were not significantly different in all groups (P>0.05). There was no significant difference in the extruded apical debris of different root canal forms (P>0.05), but the extruded apical debris was significantly less in samples in the PTN combined with MNiTiH groups than in samples in the PTN combined with chloroform groups (P<0.05).Conclusions: Neither of the two methods rendered root canals completely free from filling materials. Compared with PTN combined with chloroform, PTN combined with MNiTiH could remove root canal filling materials more efficiently and reduce the extruded apical debris. During root canal retreatment, the oval-root canal system presented an anatomical challenge compared to the round-canal mandibular incisor.Clinical Relevance: The ProTaper Next combined with manual nickel-titanium Hedström files could remove root canal filling materials more efficiently and reduce the extruded apical debris. The oval-root canal system presented an anatomical challenge compared to the round-canal mandibular incisors.
Combination carboplatin and nab-paclitaxel as a first-line treatment for advanced thymic carcinoma
Authors: Manaka Hiroya , Igawa Satoshi , Yamamoto Michiko , Oguri Akito , Manabe Hideaki , kasajima Masashi , Kusuhara Seiichiro , Hosotani Shinji , Nakahara Yoshiro , Sato Takashi , Fukui Tomoya , Hisashi Mitsufuji , Sasaki Jiichiro , Naoki Katsuhiko 
Published: May 2022

Abstract
Background: Thymic carcinoma is a very rare neoplasm for which no optimal chemotherapeutic regimen has been established to date. Hence, we performed this study to investigate the efficacy and safety of carboplatin plus nanoparticle albumin-bound (nab)-paclitaxel as a first-line regimen for patients with advanced thymic carcinoma.Patients and methods: We conducted this multi-institutional retrospective cohort study of patients with advanced thymic carcinoma who had received carboplatin plus nab-paclitaxel as a first-line chemotherapy between August 2013 and December 2021. Results: Twelve patients were included in this study and were subjected to efficacy and safety analysis. Their median age was 62 years (range, 47–74 years), and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1. After a median follow-up time of 19.7 months, the overall response rate was 50%; the median progression-free and overall survival times were 8.8 months and 23.3 months, respectively. Chemotherapy-related peripheral neuropathy was observed in 2 patients (16%; each with grade 1). Other toxicities were manageable, and there were no treatment-related deaths.Conclusion: Carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen showed good efficacy and safety in patients with advanced thymic carcinoma.