bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi-discipline phenotyping platform for late-onset Alzheimer’s disease employed on a novel, humanized APOEε4.Trem2*R47H mouse model
Authors: Kotredes Kevin , Oblak Adrian , Pandey Ravi , Lin Peter , Garceau Dylan , Williams Harriet , Uyar Asli , O'Rourke Rita , O'Rourke Sarah , Ingraham Cynthia , Bednarczyk Daria , Belanger Melisa , Cope Zackary , Foley Kate , Logsdon Benjamin , Mangravite Lara , Rizzo Stacey Sukoff , Territo Paul , Carter Gregory , Lamb Bruce , Howell Gareth , Sasner Michael 
Published: January 2021

Abstract
Background: Late-onset Alzheimer’s Disease (AD) (LOAD) is the most common neurodegenerative disease. Despite extensive efforts to understand disease progression there are currently no approved disease modifying interventions to delay or reverse neurodegeneration caused by AD. Repeated failures in human trials, despite promising preclinical results in amyloidogenic mouse models, highlight the need for animals that better model human AD. MODEL-AD (Model organism development and evaluation for late-onset AD) are identifying and integrating disease-relevant, humanized gene sequences identified from public AD data repositories to create more translatable mouse models relevant to AD.Methods: Strong risk factors for LOAD, APOEε4 and Trem2*R47H, were expressed alone or in combination on a congenic C57BL/6J (B6) background, in cohorts of mice established on multiple sites and aged to between 4-24 months. A deep phenotyping approach was employed to assess phenotypes relative to human AD. Results: The LOAD1 mouse strain, expressing humanized APOEε4 and Trem2*R47H alleles, was designed to elucidate the disease state of animals expressing the two strongest genetic risk factors of LOAD at endogenous levels. Robust analytical pipelines measured behavioral, transcriptomic, metabolic, and neuropathological phenotypes in cross-sectional cohorts for progression of disease hallmarks at all life stages. In vivo PET/MRI neuroimaging revealed regional alterations in glycolytic metabolism and vascular perfusion. Transcriptional profiling by RNA-Seq of brain hemispheres identified sex and age as the main sources of variation between genotypes including age-specific enrichment of AD-related processes. Similarly, age, but not genotype, was the strongest determinant of behavioral change. In the absence of mouse amyloid plaque formation, many of the hallmarks of AD were not observed in this strain. However, these two alleles together form a sensitized, background strain which will serve as a platform for the characterization of additional genetic and environmental LOAD risk factors. Conclusions: Comprehensive phenotyping provided key insights into genetic and environmental effects aimed at modeling human disease, critical to understand the complex intergenic interactions and subsequent molecular signaling cascades. The data provided by these assays are important for understanding the relative contributions of subsequent risk factors amended to LOAD1.
Storage Management and Wastage of Reproductive Health Medicines in Public Health Facilities of West Wollega Zone, Ethiopia: Mixed Study
Authors: Kebede Oliyad , Tilahun Gizachew , Feyissa Desalegn 
Published: January 2021

Abstract
Background: Keeping proper storage conditions at health facilities is important to reduce pharmaceutical wastage caused by environmental factors. The expiration of medicines at the health facilities led to wastage of potentially life-saving drugs and unnecessary expenditure on the disposal of those expired medicines. Therefore, the aim of this study was to assess pharmaceutical stores and wastage of reproductive health medicines due to expirationMethod: A facility-based descriptive cross-sectional quantitative and qualitative study was conducted using a checklist, structured and semi-structured questionnaires.Results: Among 23 health facilities assessed, 17 (73.91%) (4(100%) hospitals and 13(68.42%) health centers) fulfilled desirable storage conditions. The total value of reproductive health medicines wasted due to expire in surveyed facilities was 357,920.52 ETB (12,323.81 US dollars) and the Percentage of Stock Wasted due to Expiration was 8.04%. Levonorgestrel 0.75mg tablet contributed highest percentage to expired medicines.Conclusion: Pharmaceutical stores in hospitals had equipment and furniture, fulfilled desirable storage conditions, whereas, significant number of the health centers’ medical store did not comply with the recommended storage conditions. Challenges of store management identified were poor infrastructure, administrative challenges, and shortage of human resource. Stock wasted due to expiration was high and the contributing challenge was non-need-based supply. So Ethiopian pharmaceutical Supply Agency should supply reproductive health medicines based on need and concerned government bodies should avail pharmaceutical store infrastructures, hire professionals, and follow health facilities administrations.
Ultrasound-Guided Microwave Ablation for Benign Thyroid Nodules: A Retrospective Analysis of Safety and Efficacy Factors
Authors: Xia Baoying , Yu Boyang , Wang Xiaofei , Ma Yu , Liu Feng , Gong Yanping , Zou Xiuhe , Lei Jianyong , Su Anping , Wei Tao , Zhu Jingqiang , Lu Qiang , Li Zhihui 
Published: January 2021

Abstract
ObjectiveMicrowave ablation (MWA) is a minimally invasive technique for the treatment of benign thyroid nodules. The purpose of this study was to evaluate the efficacy and safety of ultrasound-guided microwave ablation in the treatment of benign thyroid nodules, and to provide reference for future clinical work.MethodsThis study retrospectively analyzed the patients who received ultrasound-guided microwave ablation for benign thyroid nodules in our hospital from October 2018 to March 2020. A total of 214 patients were included in the study. We assessed thyroid volume changes (represented by volume reduction ratio VRR) , the serum levels of triiodide thyroid hormone (T3), thyroxine (T4) and thyrotropin (TSH) and complications after MWA treatment.ResultsThere were a total of 306 nodules in 214 patients, including 183 (85.51%) females and 31 (14.49%) males. The median diameter and volume of the nodule were 33mm and 8.01ml. The volume reduction ratio（VRR）at 1 month, 3 months, 6 months and 12 months were 40.79%, 60.37%, 74.59% and 85.60%, respectively.（P<0.05) In addition, initial nodular volume were the influencing factors of volume reduction ratio.Conclusions﻿Ultrasound-guided MWA is effective and safe in the treatment of benign thyroid nodules. In addition, it has little damage to surrounding tissues and no effect on thyroid function. Especially for the initial small volume of nodules, treatment is better. Therefore, ultrasound-guided thyroid MWA can be used as one of the main clinical treatment methods for benign thyroid nodules.
Medical Education Research Trends, 1989–2018: A Bibliometric and Social Network Analysis
Authors: Li Yanjun , Huang Desheng , Guan Peng , Liu Chunhe , zhang Jin , Bi Fangfang , Yu Hong , Yang Qing 
Published: January 2021

Abstract
Background We are now in the third generation of medical education reform. To fully grasp this transformation, we need to identify the field’s knowledge structure. This study conducted a bibliometric analysis to discover the general publication statue during the last three decades (1989–2018) with an eye for identifying prolific institutions, core journals, international collaboration, and the evolution of key themes.Methods We retrieved 15,329 papers from the Web of Science Core Collection database that were published between 1989 and 2018 , and we analysed them to determine prolific institutions, core journals, institutional collaboration statue, and hot spots of research. R studio, SciMAT, and VOSviewer were jointly applied. For a better understanding of thematic evolution in the field, we split the study period into three sub-periods with equal time spans.Results We discovered that, worldwide, scholars are increasingly attracted to research on medical education. Medical Education is the most prolific journal in the field. While the US publishes an overwhelming proportion of the most relevant papers, articles published by the UK are, on average, most frequently cited. We identify five key research centres based on the most prolific academic institutions, and our analysis of relevant collaborations reveals that international collaboration is common. The hottest themes during each sub-period are revealed and how they evolve across different time spans are also detected.Conclusions This bibliometric study identifies the scientific structure of medical education research over the past three decades. Ultimately, it may help scholars identify new topics and future research challenges in this field and, moreover, highlight meaningful evidence for policymakers in the field of medical teaching innovation.
Kaempferol and Its Glycoside Derivatives as Modulators of Etoposide Activity in HL-60 Cells
Authors: Kluska Magdalena , Juszczak Michał , Żuchowski Jerzy , Stochmal Anna , Woźniak Katarzyna 
Published: January 2021

Abstract

Kaempferol is a polyphenol found in a variety of plants. Kaempferol has antitumor properties by affecting proliferation and apoptosis of cancer cells. We investigated whether kaempferol and its glycoside derivatives: kaempferol 3-O-[(6-O-E-caffeoyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D -glucuropyranoside (P2), kaempferol 3-O-[(6-O-E-p-coumaroyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P5) and kaempferol 3-O-[(6-O-E-feruloyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P7) isolated from aerial parts of Lens culinaris Medik. affect the antitumor activity of etoposide in HL-60 cells. We analyzed the effect of kaempferol and its derivatives on cytotoxicity, DNA damage, apoptosis, cell cycle progression and free radicals induced by etoposide. We also studied the impact of kaempferol and its derivatives on the expression of HO-1 and Nrf-2 genes in HL-60 cells. We demonstrated that kaempferol increases the sensitivity of HL-60 cells to etoposide but does not affect apoptosis induced by this drug. Kaempferol also reduces the level of free radicals generated by etoposide. Unlike kaempferol, some of its derivatives reduce the apoptosis of HL-60 cells (P2 and P7) and increase the level of free radicals (P2 and P5) induced by etoposide. Our results indicate that kaempferol derivatives may have an opposite effect on the action of etoposide in HL-60 cells compared to kaempferol.
Epigenetic Changes in Equine Embryos After Short-term Storage at Different Temperatures
Authors: Gastal Gustavo Desire Antunes , Scarlet Dragos , Melchert Maria , Ertl Reinhard , Aurich Christine 
Published: January 2021

Abstract

Background: In embryos subjected to assisted reproductive techniques, epigenetic modifications may occur that can influence embryonic development and establishment of pregnancy. In horses, the storage temperature during transport of fresh embryos before transfer is a major concern. The aim of this study was to determine the effects of two storage temperatures (5˚C and 20˚C) on equine embryos, collected at day 7 after ovulation and stored for 24 hours, on the following characteristics: (i) morphological and histological development; (ii) expression of candidate genes associated with embryo growth and development, maternal recognition of pregnancy, methylation, and apoptosis; and (iii) gene-specific and global-DNA methylation. Embryos (n=80) were collected from Haflinger mares (n=15) on day 7 (n=60) or day 8 (n=20) after ovulation and assigned to 4 groups: day 7 control (E7F, fresh); day 7, stored for 24h at 5°C (E5C); day 7, stored for 24h at 20°C (E20C); and day 8 control (E8F, fresh 24h time control). The embryos and the storage medium from all groups were analyzed for: (i) medium temperature, pH, and lipid peroxidation (malondialdehyde; MDA), (ii), embryo morphology, mRNA expression, and DNA methylation (immunohistochemistry and gene-specific DNA methylation). Results: Temperature during storage (E5C and E20C) did not affect embryo size (382±47 and 553±99 µm, respectively). There were no changes in pH and MDA accumulation irrespective of group. The relative mRNA abundance of specific genes related to growth and development (POU5F1, SOX2, NANOG), maternal recognition of pregnancy (CYP19A1, PTGES2), DNA methylation (DNMT1, DNMT3A, DNMT3B), and apoptosis (BAX) in the E5C and E20C were either up or downregulated (P<0.05) when compared to controls (E7F and E8F). The global methylation status, even as 5mC and 5hmC immune expression were similar among treatment groups. The specific genes ESR1, NANOG, and DNMT1 were hypomethylated (P<0.001) in E20C embryos when compared to E8F (advanced stage). Conclusions: Therefore, our study demonstrates for the first time the gene-specific and global-DNA methylation status of fresh equine embryos collected on days 7 and 8 after ovulation. In addition, short-term storage, regardless of temperature, modified gene expression and methylation of genes involved in embryo development and may therefore compromise embryo viability and development after transfer.
Ferroptosis regulator genes are a favorable biomarker for hepatocellular carcinoma
Authors: He Yongfei , Zhao Shuqi , Wei Zhongliu , Zhou Xin , Liang Tianyi , Wei Yongguang , Han Chuangye , Peng Tao 
Published: January 2021

Abstract
BackgroundIn this study, we comprehensively analyzed the relationship between ferroptosis regulator genes (FRGs) and prognosis of hepatocellular carcinoma (HCC), determined the prognostics value of FRGs, established a prediction model, and explored the relationship with immunotherapy for HCC.MethodsThe mRNA transcriptional levels and clinical information of HCC were obtained from The Cancer Genome Atlas (TCGA) database. The 24 FRGs were combined with the differential expression genes (DEGs) of HCC for further analysis. The prognostics values of differential FRGs via the construction of model and validation by the Cox regression analysis.ResultThere were three genes (CARS1, FANCD2, and SLC7A11) were identified as independent risk factors for HCC, and a predictive model was constructed based on CARS1, FANCD2, and SLC7A11. The model showed that the low-risk group HCC patients with a more prolonged overall survival (OS) than the high-risk group (P=0.001). The high-risk group with higher expression of FRGs than the low-risk group. Finally, the relations between FGEs and immune infiltration showed that CARS1, FANCD2, and SLC7A11 had a positive relationship with macrophage infiltration. From these, three genes might be the potential therapeutic targets.ConclusionOur study indicated that CARS1, FANCD2, and SLC7A11 might have potential value for therapeutic strategies as practical and reliable prognostic tools for HCC.
Prevalence of PTSD Symptoms Among Psychiatric Patients During the COVID-19 Pandemic
Authors: Tang Lirong , Gao Yue , Qi Shuangyi , Cui Jie , Zhou Li , Feng Yi 
Published: January 2021

Abstract
Background: The outbreak of the COVID-19 pandemic has caused extensive public health concern and posed great challenges to the medical services, including the mental health concern for psychiatric patients who were one of neglected groups. The current study aimed to assess the prevalence and risk factors of post-traumatic stress disorder (PTSD) symptoms among psychiatric patients in China during the pandemic. Method: Self-reported questionnaires were distributed to psychiatric patients in several psychiatric hospitals in Beijing China from 28 April to 30 May 2020. The socio-demographic information and psychiatric symptoms such as PTSD, anxiety and depressive symptoms were collected by using The Impact of Event Scale- Revised (IES-R), the 7-item Generalized Anxiety Disorder Scale (GAD-7) and the 9-item Patient Health Questionnaire depression scale (PHQ-9). Multivariate regression was used to analysis the related factors for PTSD symptoms. Results: 1,055 psychiatric patients were included in the final sample. The prevalence of PTSD symptoms was 41.3%. Risk factors for PTSD symptoms and its subscales included old age, high risk perception, symptoms of anxiety, symptoms of depression. Conclusions: The prevalence of PTSD symptoms is high among psychiatric patients during the COVID-19 pandemic in China. We call for more concern and PTSD interventions to relieve the psychological stress of psychiatric patients during the pandemic.
A New Tool to Assess Quality of life in Patients with Idiopathic Pulmonary Fibrosis or Non-Specific Interstitial Pneumonia *
Authors: Kirsten Detlef , Vries Ulrike de , Costabel Ulrich , Koschel Dirk , Bonella Francesco , Günther Andreas , Behr Jürgen , Claussen Martin , Schwarz Stefan , Prasse Antje , Kreuter Michael 
Published: January 2021

Abstract
Background: Quality of life (QoL) is significantly impaired in patients with pulmonary fibrosis, however reliable tools to assess QoL are still missing. We thus aimed to develop a new questionnaire called QPF to measure QoL in patients with fibrotic idiopathic interstitial pneumonias (IIP). Methods: As part of a multi-center validation study in a pre-post design, 200 patients with idiopathic pulmonary fibrosis (IPF) or idiopathic non-specific interstitial pneumonia (iNSIP) filled in the questionnaire at 2 measurement time points with an interval of 6 months. Cross-validation was carried out with the St. Georges Respiratory Questionnaire (SGRQ). Results: The alpha of the QPF-total score and its subscales range from .858 to .616 and can be rated as good. In contrast to the SGRQ, the QPF was able to detect a change in the patient's mood ("Condition" scale) in the course of treatment. This could be due to the SGRQ being a condition specific measure but also due to the greater amount of items, especially those with a job-related theme, which are not relevant for the sample examined. The questionnaire can be used to evaluate treatment response more appropriately, by collecting data on physical performance and general behaviour. Conclusion: This newly developed questionnaire maps the special needs of the patients well and is superior to the SGRQ. The QPF is suitable for screening as well as for supplementing the medical history and for monitoring the course of disease in fibrotic IIPs.
Lateral ﬂow biosensor combined with loop-mediated isothermal ampliﬁcation for detection of legionella pneumophila.
Authors: Jiang Luxi , Li Xiaomeng , Gu Rumeng , Shi Ziling , Song Meijun , Huang Xiaojun , Mu Deguang 
Published: January 2021

Abstract
Legionella pneumophila ( L. pneumophila ) is the most pathogenic species of Legionella , which can cause Legionella disease. It can cause pneumonia, or Pontiac fever. In severe cases, it can lead to respiratory failure and kidney failure, with a high fatality rate. Here, a novel molecular diagnosis method, a loop-mediated isothermal ampliﬁcation coupled with lateral flow biosensor (LFB) method (LAMP-LFB) was successfully established and evaluated for the identification of L. pneumophila . A set of 6 primers was designed specifically based on the L. pneumophila -specific gene mip. The optimized time and temperature conditions for the LAMP was 50 min and 64◦C respectively. The minimum concentration that can be detected by this method was 100fg. Using the protocol, we could observe the LAMP amplification within 2min by LFB. The whole process, including the preparation of DNA (20 min), LAMP reaction (50 min) and results reporting (2 min), could be finished within 75 min. Among 50 alveolar lavage fluid samples, 5(10%) were L. pneumophila -positive by the LAMP-LFB, and the diagnostic accuracy was 100% when compared to the culture method. While only 4 samples were positive using PCR method.
In a word, the LAMP-LFB assay is a rapid, sensitive and specific detection method that can detect Legionella pneumophila , and it can be used as a new molecular method for the detection of target pathogens in water, environmental and clinical samples.
Initial engagement and persistence of health risk behaviors through adolescence: longitudinal findings from urban South Africa
Authors: Kowalski Alysse , Addo O. Yaw , Kramer Michael R , Martorell Reynaldo , Norris Shane A , Waford Rachel N , Richter Linda M , Stein Aryeh 
Published: January 2021

Abstract
Background:Little is known about longitudinal patterns of adolescent health risk behavior initial engagement and persistence in low- and middle-income countries. Methods: Birth to Twenty Plus is a longitudinal birth cohort in Soweto-Johannesburg, South Africa. We used reports from Black African participants on cigarette smoking, alcohol, cannabis, illicit drug, and sexual activity initial engagement and adolescent pregnancy collected over 7 study visits between ages 11 and 18 y. We fit Kaplan-Meier curves to estimate behavior engagement or adolescent pregnancy, examined current behavior at age 18 y by age of first engagement, and performed a clustering analysis to identify patterns of initial engagement and their sociodemographic predictors. Results:By age 13 y, cumulative incidence of smoking and alcohol engagement were each >21%, while the cumulative incidence of other behaviors and adolescent pregnancy were <5%. By age 18 y (15 y for cannabis), smoking, alcohol, and sexual activity engagement estimates were each >65%, cannabis and illicit drug engagement were each >16%; adolescent pregnancy was 31%. Rates of engagement were higher among males. Current risk behavior activity at age 18 y was generally unrelated to age of initial engagement. We identified three clusters reflecting low, moderate, and high-risk patterns of initial risk behavior engagement. One-third of males and 17% of females were assigned to the high-risk cluster. Sociodemographic factors were not associated with cluster membership.Conclusions:Among urban dwelling Black South Africans, risk behavior engagement across adolescence was common and clustered into distinct patterns of initial engagement which were unrelated to the sociodemographic factors assessed. Patterns of initial risk behavior engagement may inform the timing of primary and secondary public health interventions and support integrated prevention efforts that consider multiple behaviors simultaneously.