bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative transcriptome analysis of the main beam and brow tine of sika deer antler provides insights into the molecular control of rapid antler growth
Authors: Yao Baojin , Wang Chaonan , Zhou Zhenwei , Zhang Mei , Zhao Daqing , Bai Xueyuan , Leng Xiangyang 
Published: September 2020

Abstract
Background
Deer antlers have become a valuable model for biomedical research due to the capacities of regeneration and rapid growth. However, the molecular mechanism of rapid antler growth remains to be elucidated. The aim of the present study was to compare and explore the molecular control exerted by the main beam and brow tine during rapid antler growth.

Methods
The main beams and brow tines of sika deer antlers were collected from Chinese sika deer (Cervus nippon) at the rapid growth stage. Comparative transcriptome analysis was conducted using RNA-Seq technology. Differential expression was assessed using the DEGseq package. Functional Gene Ontology (GO) enrichment analysis was accomplished using a rigorous algorithm according to the GO Term Finder tool, and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis was accomplished with the R function phyper, followed by the hypergeometric test and Bonferroni correction. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to verify the RNA levels for differentially expressed mRNAs.

Results
The expression levels of 16 differentially expressed genes (DEGs) involved in chondrogenesis and cartilage development were identified as significantly upregulated in the main beams, including transcription factor SOX-9 (Sox9), collagen alpha-1(II) chain (Col2a1), aggrecan core protein (Acan), etc. However, the expression levels of 17 DEGs involved in endochondral ossification and bone formation were identified as significantly upregulated in the brow tines, including collagen alpha-1(X) chain (Col10a1), osteopontin (Spp1) and bone sialoprotein 2 (Ibsp), etc.

Conclusion
These results suggest that the antler main beam has stronger growth capacity involved in chondrogenesis and cartilage development compared to the brow tine during rapid antler growth, which is mainly achieved through regulation of Sox9 and its target genes, whereas the antler brow tine has stronger capacities of endochondral bone formation and resorption compared to the main beam during rapid antler growth, which is mainly achieved through the genes involved in regulating osteoblast and osteoclast activities. Thus, the current research has deeply expanded our understanding of the intrinsic molecular regulation displayed by the main beam and brow tine during rapid antler growth.
A surveillance method to identify patients with sepsis from electronic health records in Hong Kong: a single centre retrospective study
Authors: Liu Ying Zhi , Chu Raymond , Lee Anna , Gomersall Charles David , Zhang Lin , Gin Tony , Chan Matthew T. V. , Wu William K. K. , Ling Lowell 
Published: September 2020

Abstract
Background
Currently there are only two population studies on sepsis incidence in Asia. The burden of sepsis in Hong Kong is unknown. We developed a sepsis surveillance method to estimate sepsis incidence from a population electronic health record (EHR) in Hong Kong using objective clinical data. The study objective was to assess our method’s performance in identifying sepsis using a retrospective cohort. We compared its accuracy to administrative sepsis surveillance methods such as Angus’ and Martin’s methods.

Method
In this single centre retrospective study we applied our sepsis surveillance method on adult patients admitted to a tertiary hospital in Hong Kong. Two clinicians independently reviewed the clinical notes to determine which patients had sepsis. Performance was assessed by sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) of Angus’, Martin’s and our surveillance methods using clinical review as “gold standard.”

Results
Between January 1 and February 28, 2018, our sepsis surveillance method identified 1352 adult patients hospitalised with suspected infection. We found that 38.9% (95%CI 36.3–41.5) of these patients had sepsis. Using a 490 patient validation cohort, two clinicians had good agreement with weighted kappa of 0.75 (95% CI 0.69–0.81) before coming to consensus on diagnosis of uncomplicated infection or sepsis for all patients. Our method had sensitivity 0.93 (95%CI 0.89–0.96), specificity 0.86 (95%CI 0.82–0.90) and an AUC 0.90 (95%CI 0.87–0.92) when validated against clinician review. In contrast, Angus’ and Martin’s methods had AUCs 0.56 (95%CI 0.53–0.58) and 0.56 (95%CI 0.52–0.59), respectively.

Conclusions
A sepsis surveillance method based on objective data from a population EHR in Hong Kong was more accurate than administrative methods. It may be used to estimate sepsis population incidence and outcomes in Hong Kong.

Trial registration
This study was retrospectively registered at clinicaltrials.gov on October 3, 2019 (NCT04114214).
D6 blastocyst transfer on day 6 in frozen-thawed cycles should be avoided: a retrospective cohort study
Authors: Xu Huiling , Qiu Shumin , Chen Xiaojing , Zhu Suqin , Sun Yan , Zheng Beihong 
Published: September 2020

Abstract
Background
There is no definitive evidence about the suitable timing to transfer blastocysts formed and cryopreserved on day 6 (D6 blastocysts) in frozen-thawed embryo transfer (FET) cycles. This study aimed to investigate the suitable timing to transfer D6 blastocysts in FET cycles and to identify factors affecting clinical pregnancy rate (CPR) and early miscarriage rate (EMR) in FET cycles with blastocysts.

Methods
This retrospective cohort study included 1788 FET cycles with blastocysts. There were 518 cycles with D6 blastocysts, and 1270 cycles with blastocysts formed and cryopreserved on day 5 (D5 blastocysts) (D5 group). According to the blastocyst transfer timing, the cycles with D6 blastocysts were divided into cycles with D6 blastocysts transferred on day 5 (D6-on-D5 group, 103 cycles) and cycles with D6 blastocysts transferred on day 6 (D6-on-D6 group, 415 cycles). The chi-square test, independent t-test or Mann-Whitney test, and logistic regression analysis were used for data analysis.

Results
The CPR and implantation rate (IR) were significantly higher in the D6-on-D5 group than in the D6-on-D6 group (55.3% vs. 37.3%, 44.8% vs. 32.6%, P < 0.01). The CPR and IR were significantly higher in the D5 group than in the D6-on-D5 group (66.0% vs. 55.3%, 62.1% vs. 44.8%, P < 0.05), and the EMR was significantly lower in the D5 group than in the D6-on-D5 group (11.2% vs. 21.1%, P < 0.05). Logistic regression analysis demonstrated that transfer D6 blastocysts on day 5, instead of day 6, could significantly increase the CPR (odds ratio[OR]: 2.031, 95% confidence interval (CI): 1.296–3.182, P = 0.002). FET cycles with D6 blastocysts transferred on day 5 had a higher EMR than those with D5 blastocysts (OR: 2.165, 95% CI: 1.040–4.506, P = 0.039). Hormone replacement therapy (HRT) cycles exhibited a higher EMR than natural cycles (OR: 1.953, 95% CI: 1.254–3.043, P = 0.003), while no difference was observed in the CPR (P > 0.05).

Conclusions
These results indicate that the suitable timing to transfer D6 blastocysts in FET cycles may be day 5, and D6 blastocyst transfer on day 6 in FET cycles should be avoided. D6 blastocysts transfer and HRT cycles may be associated with a higher EMR.
Standardized herbal extract PM014 alleviates fine dust-induced lung inflammation in mice
Authors: Lee Ye-Seul , Min Daeun , Park Seon-Young , Lee Junyoung , Bae Hyunsu 
Published: September 2020

Abstract
Background
Fine dust penetrates deep into the human alveoli, and the fine dust accumulated in the bronchus and lungs can directly trigger various respiratory diseases. PM014 (HL301) is the herbal extract derived from the herbal medicine Chung-Sang-Bo-Ha-Tang which is used for the treatment of lung diseases.

Methods
To evaluate the effect of PM014 on the lung inflammation induced by fine dust, this study investigated inflammatory responses in the lung upon pm10 exposure by examining the infiltration of inflammatory cell profiles from bronchial alveolar lavage fluid (BALF), lung histology, and production of pro-inflammatory cytokines measured by RT-PCR and ELISA.

Results
PM014-treated mice exhibited reduced lung tissue damage and inflammatory cell infiltration. Bronchoalveolar lavage fluid (BALF) analysis showed significant decrease in the population of total cells, macrophages, eosinophils, and neutrophils in PM014-treated mice. PM014 treatment downregulated the pro-inflammatory cytokine expressions including IL-1b, IL-8, IL-6, TNF-alpha, IL-21 and IL-17. ELISA analysis also showed reduced production of IL-1b, IL-6 and IL-17 in PM014-treated mice.

Conclusion
PM014 suppressed the pm10-induced inflammatory response in mice. This study shows that PM014 is a possible therapeutic agent for lung inflammation induced by fine dust.
Bayesian variable selection for high dimensional predictors and self-reported outcomes
Authors: Gu Xiangdong , Tadesse Mahlet G , Foulkes Andrea S , Ma Yunsheng , Balasubramanian Raji 
Published: September 2020

AbstractBackgroundThe onset of silent diseases such as type 2 diabetes is often registered through self-report in large prospective cohorts. Self-reported outcomes are cost-effective; however, they are subject to error. Diagnosis of silent events may also occur through the use of imperfect laboratory-based diagnostic tests. In this paper, we describe an approach for variable selection in high dimensional datasets for settings in which the outcome is observed with error.MethodsWe adapt the spike and slab Bayesian Variable Selection approach in the context of error-prone, self-reported outcomes. The performance of the proposed approach is studied through simulation studies. An illustrative application is included using data from the Women’s Health Initiative SNP Health Association Resource, which includes extensive genotypic (>900,000 SNPs) and phenotypic data on 9,873 African American and Hispanic American women.ResultsSimulation studies show improved sensitivity of our proposed method when compared to a naive approach that ignores error in the self-reported outcomes. Application of the proposed method resulted in discovery of several single nucleotide polymorphisms (SNPs) that are associated with risk of type 2 diabetes in a dataset of 9,873 African American and Hispanic participants in the Women’s Health Initiative. There was little overlap among the top ranking SNPs associated with type 2 diabetes risk between the racial groups, adding support to previous observations in the literature of disease associated genetic loci that are often not generalizable across race/ethnicity populations. The adapted Bayesian variable selection algorithm is implemented in R. The source code for the simulations are available in the Supplement.ConclusionsVariable selection accuracy is reduced when the outcome is ascertained by error-prone self-reports. For this setting, our proposed algorithm has improved variable selection performance when compared to approaches that neglect to account for the error-prone nature of self-reports.
The association between frailty and severe disease among COVID-19 patients aged over 60 years in China: a prospective cohort study
Authors: Ma Yao , Hou Lisha , Yang Xiufang , Huang Zhixin , Yang Xue , Zhao Na , He Min , Shi Yixin , Kang Yan , Yue Jirong , Wu Chenkai 
Published: September 2020

Abstract
Background
The coronavirus disease 2019 (COVID-19) has been a pandemic worldwide. Old age and underlying illnesses are associated with poor prognosis among COVID-19 patients. However, whether frailty, a common geriatric syndrome of reduced reserve to stressors, is associated with poor prognosis among older COVID-19 patients is unknown. The aim of our study is to investigate the association between frailty and severe disease among COVID-19 patients aged ≥ 60 years.

Methods
A prospective cohort study of 114 hospitalized older patients (≥ 60 years) with confirmed COVID-19 pneumonia was conducted between 7 February 2020 and 6 April 2020. Epidemiological, demographic, clinical, laboratory, and outcome data on admission were extracted from electronic medical records. All patients were assessed for frailty on admission using the FRAIL scale, in which five components are included: fatigue, resistance, ambulation, illnesses, and loss of weight. The outcome was the development of the severe disease within 60 days. We used the Cox proportional hazards models to identify the unadjusted and adjusted associations between frailty and severe illness. The significant variables in univariable analysis were included in the adjusted model.

Results
Of 114 patients, (median age, 67 years; interquartile range = 64–75 years; 57 [50%] men), 39 (34.2%), 39 (34.2%), and 36 (31.6%) were non-frail, pre-frail, and frail, respectively. During the 60 days of follow-up, 43 severe diseases occurred including eight deaths. Four of 39 (10.3%) non-frail patients, 15 of 39 (38.5%) pre-frail patients, and 24 of 36 (66.7%) frail patients progressed to severe disease. After adjustment of age, sex, body mass index, haemoglobin, white blood count, lymphocyte count, albumin, CD8+ count, D-dimer, and C-reactive protein, frailty (HR = 7.47, 95% CI 1.73–32.34, P = 0.007) and pre-frailty (HR = 5.01, 95% CI 1.16–21.61, P = 0.03) were associated with a higher hazard of severe disease than the non-frail.

Conclusions
Frailty, assessed by the FRAIL scale, was associated with a higher risk of developing severe disease among older COVID-19 patients. Our findings suggested that the use of a clinician friendly assessment of frailty could help in early warning of older patients at high-risk with severe COVID-19 pneumonia.
Different hypothermic and cerebral perfusion strategies in extended arch replacement for acute type a aortic dissection: a retrospective comparative study
Authors: Dong Song-Bo , Xiong Jian-Xian , Zhang Kai , Zheng Jun , Xu Shang-Dong , Liu Yong-Min , Sun Li-Zhong , Pan Xu-Dong 
Published: September 2020

Abstract
Background
The optimal hypothermic level in total arch replacement with stented elephant trunk implantation for acute type A aortic dissection (aTAAD) has not been established, and the superiority of unilateral or bilateral cerebral perfusion remains a controversial issue. Therefore, we evaluated the application of moderate hypothermic circulatory arrest (MHCA) with a core temperature of 29 °C and bilateral selective antegrade cerebral perfusion in aTAAD treated by total arch replacement with stented elephant trunk implantation.

Methods
From July 2019 to January 2020, 25 aTAAD patients underwent total arch replacement with stented elephant trunk implantation via MHCA (29 °C) and bilateral selective antegrade cerebral perfusion (modified group). Thirty-six patients treated by the same procedure with MHCA (25 °C) and unilateral selective antegrade cerebral perfusion during this period were selected as controls.

Results
There were no differences between the two groups of patients in terms of age, sex, incidence of hypertension, malperfusion, and pericardial effusion, although the incidence of cardiac tamponade was higher in the modified group (control 2.8%, modified 20%; P = 0.038). The lowest mean circulatory arrest temperature was 24.6 ± 0.9 °C in the control group, and 29 ± 0.8 °C in the modified group (P <  0.001). In-hospital mortality was 4.9% (3/61) for the entire cohort (control 8.3%, modified 0; P = 0.262). The incidence of permanent neurologic deficit was 4.9% (control 8.3%, modified 0; P = 0.262). There were no significant differences in the occurrence of temporary neurological deficit, renal failure, and paraplegia between groups. The rate of major adverse events in the modified group was lower (30.6% vs. 4%, P = 0.019). A shorter duration of ventilation and ICU stay was identified in the modified group, as well as a reduced volume of drainage within the first 48 h and red blood cell transfusion.

Conclusions
The early results of MHCA (29 °C) and bilateral selective antegrade cerebral perfusion applied in total arch replacement with stented elephant trunk implantation for aTAAD were acceptable, providing similar inferior cerebral and visceral protection compared with that of the conventional strategy. A higher core temperature may account for the shorter duration of ventilation and ICU stay, as well as a reduced volume of drainage and red blood cell transfusion.
IFN-α confers epigenetic regulation of HBV cccDNA minichromosome by modulating GCN5-mediated succinylation of histone H3K79 to clear HBV cccDNA
Authors: Yuan Ying , Yuan Hongfeng , Yang Guang , Yun Haolin , Zhao Man , Liu Zixian , Zhao Lina , Geng Yu , Liu Lei , Wang Jiapei , Zhang Huihui , Wang Yufei , Zhang Xiao-dong 
Published: September 2020

AbstractBackgroundHepatitis B virus covalently closed circular DNA (HBV cccDNA) is assembled by histones and non-histones into a chromatin-like cccDNA minichromosome in the nucleus. The cellular histone acetyltransferase GCN5, displaying succinyltransferase activity, is recruited onto cccDNA to modulate HBV transcription in cells. Clinically, IFN-α is able to repress cccDNA. However, the underlying mechanism of IFN-α in the depression of cccDNA mediated by GCN5 is poorly understood. Here, we explored the effect of IFN-α on GCN5-mediated succinylation in the epigenetic regulation of HBV cccDNA minichromosome.ResultsSuccinylation modification of the cccDNA minichromosome has been observed in HBV-infected human liver-chimeric mice and HBV-expressing cell lines. Moreover, histone H3K79 succinylation by GCN5 was identified in the system. Interestingly, the mutant of histone H3K79 efficiently blocked the replication of HBV, and interference with GCN5 resulted in decreased levels of HBV DNA, HBsAg, and HBeAg in the supernatant from de novo HBV-infected HepaRG cells. Consistently, the levels of histone H3K79 succinylation were significantly elevated in the livers of HBV-infected human liver-chimeric mice. The knockdown or overexpression of GCN5 or the mutant of GCN5 could affect the binding of GCN5 to cccDNA or H3K79 succinylation, leading to a change in cccDNA transcription activity. In addition, Southern blot analysis validated that siGCN5 decreased the levels of cccDNA in the cells, suggesting that GCN5-mediated succinylation of histone H3K79 contributes to the epigenetic regulation of cccDNA minichromosome. Strikingly, IFN-α effectively depressed histone H3K79 succinylation in HBV cccDNA minichromosome in de novo HepG2-NTCP and HBV-infected HepaRG cells.ConclusionsIFN-α epigenetically regulates the HBV cccDNA minichromosome by modulating GCN5-mediated succinylation of histone H3K79 to clear HBV cccDNA. Our findings provide new insights into the mechanism by which IFN-α modulate the epigenetic regulation of HBV cccDNA minichromosome.
Unusual and delayed presentation of chronic uterine inversion in a young woman as a result of negligence by an untrained birth attendant: a case report
Authors: Garg Priyanka , Bansal Romi 
Published: September 2020

Abstract
Background
Uterine inversion is a rare but known complication following parturition and may prove fatal due to neurogenic shock or postpartum hemorrhage if not corrected immediately. The incidence is variable, occurring in 1 in 2000 to 1 in 50,000 deliveries, as reported in the past. Nowadays, the incidence is declining due to better antenatal care and increasing institutional deliveries. However, in a developing country such as India, due to cultural and financial reasons, most of the deliveries are still being conducted by untrained birth attendants (“dais”) who have sparse knowledge of oxytocic drugs. Hence, proper education and training should be imparted to the traditional birth attendants and local village health practitioners about the management of labor, placental delivery, timely diagnosis, and proper management of uterine inversion to avoid this grave complication. We report this case because only a limited number of such cases have been reported so far with delayed presentation of chronic uterine inversion 8 months after delivery as a result of the negligence of an untrained birth attendant.

Case presentation
We report a case of a patient with chronic uterine inversion presenting 8 months after childbirth as a result of ignorance at the time of delivery. A 22-year-old P1L1 (Para 1 Live 1) Asian woman of Punjabi ethnicity presented to our institute with a progressively increasing painless vaginal mass along with blood-stained vaginal discharge for the last 6 months and progressive dyspareunia (pain during intercourse) for the last 5 months that had worsened with time. She had experienced a full-term normal vaginal delivery at home 8 months earlier with the assistance of an untrained birth attendant (dai). Her history revealed that she had an unduly prolonged second stage of labor and was given aggressive fundal pressure due to inadequate bearing-down efforts and had collapsed after delivery but was managed conservatively by an untrained birth attendant. A provisional diagnosis of chronic uterine inversion was made on the basis of vaginal findings of a globular mass protruding from the cervix and approaching the vagina with thinning of the cervix around the mass, forming a tight constriction ring, in addition to ultrasound findings. The patient’s condition was corrected surgically using Haultain’s approach. She had a satisfactory outcome and was discharged symptom-free.

Conclusion
Awareness of this complication with timely diagnosis and prompt management can significantly minimize maternal morbidity and mortality, especially in a low- and middle-income country such as India, where 70–80% of deliveries still occur in a rural setting with untrained birth attendants.
Synovial membrane mesenchymal stem cells: past life, current situation, and application in bone and joint diseases
Authors: Li Na , Gao Jinfang , Mi Liangyu , Zhang Gailian , Zhang Liyun , Zhang Na , Huo Rongxiu , Hu Junping , Xu Ke 
Published: September 2020

AbstractMesenchymal stem cells (MSCs) can be isolated from not only bone marrow, but also various adult mesenchymal tissues such as periosteum, skeletal muscle, and adipose tissue. MSCs from different tissue sources have different molecular phenotypes and differentiation potential. Synovial membrane (SM) is an important and highly specific component of synovial joints. Previous studies have suggested that the synovium is a structure with a few cell layers thick and consists mainly of fibroblast-like synoviocytes (FLS), which forms a layer that lining the synovial membrane on the joint cavity and synovial fluid through cell-cell contact. In recent years, studies have found that there are also mesenchymal stem cells in the synovium, and as an important part of the mesenchymal stem cell family, it has strong capabilities of cartilage forming and tissue repairing. This article reviews the sources, surface markers, subtypes, influencing factors, and applications in inflammatory joints of synovial membrane mesenchymal stem cells (SM-MSCs) in recent years, aiming to clarify the research status and existing problems of SM-MSCs.