bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Decade of Molecular Preimplantation Genetic Diagnosis of 350 Blastomeres for Beta-Thalassemia Combined with HLA Typing, Aneuploidy Screening and Sex Selection in Iran
Authors: Keshvar Yeganeh , Sabeghi Solmaz , Sharifi Zohreh , Fatemi Kiyana Sadat , Fouladi Panti , Khah Shahrzad Younesi , Rahiminejad Faezeh , Joudaki Atefeh , Amini Masoume , Bagherian Hamideh , Novin MarefatGhaffari , Movahedin Mansoureh , Mojbafan Marzieh , Zeinali Sirous 
Published: December 2021

Abstract
Background: Preimplantation genetic diagnosis (PGD) has been developed to detect genetic disorders before pregnancy which is usually done on blastomeres biopsied from 8-cell stage embryos obtained from in vitro fertilization method (IVF).Here we report molecular PGD results for diagnosing of beta thalassemia (beta-thal) which are usually accompanied with evaluating chromosomal aneuploidies, HLA typing and sex selection.Methods: In this study, haplotype analysis was performed using short tandem repeats (STRs) in a multiplex nested PCR and the causative mutation was detected by Sanger sequencing.Results: We have performed PGDs on 350 blastomeres from 55 carrier couples; 142 blastomeres for beta-thal only, 75 for beta-thal and HLA typing, 76 for beta-thal in combination with sex selection, and 57 for beta-thal and aneuploidy screening. 150 blastomeres were transferable, 15 pregnancies were happened, and 11 babies born.We used 6 markers for beta-thal, 36 for aneuploidy screening, 32 for sex selection, and 35 for HLA typing. To our knowledge combining all these markers together and the number of STR markers are much more than any other studies which have ever done.Conclusions: PGD is a powerful diagnostic tool for carrier couples who desire to have a healthy child and wish to avoid medical abortion.
Evaluation of Postsurgical Stability And Condylar Morphology In Skeletal Class II Patients With Condylar Resorption Following Orthognathic Surgery
Authors: Wang Minjiao , Zhao Hanjiang , Wang Xiangyu , Qian Yifeng , Yu Hongbo , Shen Steve GF 
Published: December 2021

Abstract
Background: To retrospectively evaluate postsurgical stability and condylar morphology for skeletal class II malocclusion patients with condylar resorption (CR) treated with orthognathic surgery.Methods: Thirty-five patients treated with combined orthodontic and orthognathic surgery between 2014 and 2018 were enrolled in this retrospective study. CT scans were acquired preoperatively (T0), 2–7 days after surgery (T1), and 1 year postoperatively (T2). The amount of mandibular advancement, postsurgical relapse, condylar morphology and joint spaces were analysed respectively. Statistical analysis was performed using R, version 3.4.3 (R Development Core Team 2010).Results: The average mandibular advancement and counter-clockwise rotation were 5.51 mm and -2.82 degrees respectively. The average relapse was 1.08 mm (19.6% of the advancement) and 1.13 degrees. The condylar volume showed a postoperative reduction of 161.86 mm3(13.7% of initial condylar volume). AJS increased after surgery and gradually returned to its original state, while SJS and PJS decreased and remained stable. Surgical advancement of B point was significantly correlated with skeletal relapse. The optimal cut-off values were as follows: MP-FH (40.75°); ramus height (51.125 mm); SJS (1.63 mm); surgical displacement (4.72 mm); CCR (-4.3°); AJSC (1.07 mm).Conclusions: Skeletal class II patients with CR have a high risk of postsurgical condylar resorption, which was most related to nonsurgical risk factors such as gender(female) and condylar angle. Condylar had moved posteriorly to the concentric position after surgery and remained quite stable through the 1-year follow-up. Preoperative skeletal patterns such as lower ramus height and surgical procedures such as larger advancement of the mandible were closely associated with sagittal relapse of the mandible.
Design and Transition of an Emergency E-Learning Pathology Course for Medical Students Evaluation of a Novel Course Concept
Authors: Holzmann-Littig Christopher , Jedlicska Nana , Wijnen-Meijer Marjo , Liesche-Starnecker Friederike , Schmidt-Bäse Karen , Weimann Katja , Konukiewitz Björn , Schlegel Jürgen 
Published: December 2021

Abstract
Background
Around the world, medical schools emergency-created countless e-learning offerings during the COVID-19 pandemic to provide instruction despite the pandemic. The question now is how to capitalize on this momentum of digitization and how to harness the medical e-learning content created for the future. We have analyzed the transition of a pathology course to show what needs to be considered during such a transition.
Methods
In the summer semester of 2020, the pathology course at the Technical University of Munich was completely converted to an asynchronous online course. This content was adapted in winter 2021 and incorporated into a flipped classroom concept in which research skills were trained at the same time.
Results
Screencasts and lecture recordings were the most popular asynchronous teaching formats. Students reported developing a higher interest in pathology and research through group work. The amount of content was very challenging for some students.
Conclusion
Flipped classroom formats are a viable option when using the pre-existing contents. We recommend checking the contents for technical and didactic quality and optimizing them if necessary. Content on research skills can be combined very well with clinical teaching content.
Evaluation of The 10 Warning Signs In Immunodeficient Patients: Additional Suggestions
Authors: Eldeniz Fadime Ceyda , Gül Yahya , Yorulmaz Alaattin , Güner Şükrü Nail , Keles Sevgi , Reisli İsmail 
Published: December 2021

Abstract
Objective: Ten warning signs of primary immunodeficiency (PID) were suggested by the Jeffrey Modell Foundation (JMF), to increase physician awareness of PID. These warning signs have not yet been evaluated for patients with secondary immunodeficiency (SID). This study investigated whether the 10 warning signs used for the diagnosis of PID are sufficient for the diagnosis of SID, and explored the possibility of additional signs.Methods: This prospective study was conducted between June and December 2020. The mothers of 162 patients with PID and SID, and mothers of 200 healthy children, were asked to complete a questionnaire about family and personal history in addition to the warning signs of PID developed by the JMF. A JMF score was created by giving one point for each “Yes” answer for the 10 warning signs of PID. Medical records of the patients were evaluated for possible additional warning signs for PID and SID. Results: The JMF scores of the PID (3.36 ± 1.65) and SID (3.72 ± 1.12) groups were significantly higher than the scores of the control group (0.34 ± 0.61) (p < 0.05). A sign for immunological evaluation in two patients without warning signs in the PID group was found to be chronic diarrhea. In addition to the 10 JMF warning signs, we found that consanguinity and a family history of tuberculosis were statistically significant in our PID group, compared with the SID and control groups. Conclusions: The JMF warning signs are important for early diagnosis of PID. Our study showed that these signs may also be used for the early diagnosis of SID in patients and, according to our results, in addition to the 10 JMF signs for PID, parental consanguinity, chronic diarrhea, and a family history of tuberculosis may also be considered warning signs for the early diagnosis of PID.
Cholesterol Sensor SCAP Contributes to Sorafenib Resistance by Regulating Autophagy in Hepatocellular Carcinoma
Authors: Li Danyang , Yao Yingcheng , Rao Yuhan , Huang Xinyu , Wei Li , You Zhimei , Zheng Guo , Hou Xiaoli , Su Yu , Varghese Zac , Moorhead John F , Chen Yaxi , Ruan Xiong Z 
Published: December 2021

Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most malignant tumors and the fourth leading cause of cancer-related death worldwide. Sorafenib is currently acknowledged as a standard therapy for advanced HCC. However, acquired resistance substantially limits the clinical efficacy of sorafenib. Therefore, further investigations of the associated risk factors are highly warranted.Methods: We analysed a group of 78 HCC patients who received sorafenib treatment after liver resection surgery. The expression of SCAP and its correlation with sorafenib resistance in HCC clinical samples were determined by immunohistochemical analyses. Overexpression and knockdown approaches in vitro were used to characterize the functional roles of SCAP in regulating sorafenib resistance. The effects of SCAP inhibition in HCC cell lines were analysed in proliferation, apoptosis, and colony formation assays. Autophagic regulation by SCAP was assessed by immunoblotting, immunofluorescence and immunoprecipitation assays. The combinatorial effect of a SCAP inhibitor and sorafenib was tested using nude mice.Results: Hypercholesterolemia was associated with sorafenib resistance in HCC treatment. The degree of sorafenib resistance was correlated with the expression of the cholesterol sensor SCAP and consequent deposition of cholesterol. SCAP is overexpressed in HCC tissues and hepatocellular carcinoma cell lines with sorafenib resistance, while SCAP inhibition could improve sorafenib sensitivity in sorafenib-resistant HCC cells. Furthermore, we found that SCAP-mediated sorafenib resistance was related to decreased autophagy, which was connected to decreased AMPK activity. A clinically significant finding was that lycorine, a specific SCAP inhibitor, could reverse acquired resistance to sorafenib in vitro and in vivo.Conclusions: SCAP contributes to sorafenib resistance through AMPK-mediated autophagic regulation. The combination of sorafenib and SCAP targeted therapy provides a novel personalized treatment to enhance sensitivity in sorafenib-resistant HCC.
Novel Biomarker NEDD1 and Its Analysis in Hepatocellular Carcinoma
Authors: Ding Xiaopeng , Yu Jiahao , Shi Xin , Li Kangwei , Ma Shuoyi , Ren Pengwei , Xuan Guoyun , Han Ying , Zhou Xinmin 
Published: December 2021

Abstract
Background: NEDD1 (NEDD1 Gamma-Tubulin Ring Complex Targeting Factor) plays a crucial impact in regulating cell cycle and the development of scirrhous gastric cancer. However, the role of NEDD1 hasn’t been reported in hepatocellular carcinoma (HCC) so far. The aim of this research is to explore the role of NEDD1 on the development and prognosis of HCC. Methods: HCC-related data were download from The Cancer Genome Atlas (TCGA) database. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene set enrichment analysis (GSEA) were conducted by the LinkedOmics database. Results: The expression of NEDD1 has significant difference between tumor and adjacent normal tissues in HCC (P＜0.01). We also found that NEDD1 was an independent risk factor in HCC patients (HR 1.643, 95%CI 1.125–2.398; P = 0.01). The study also demonstrated that NEDD1 expression was significantly relevant to the expression of several immune checkpoint genes, including CTLA-4, PD-L1 and PD-1. GSEA revealed that Cell cycle, MicroRNAs in cancer and Ribosome pathways were significantly enriched in NEDD1 overexpression phenotype. By integrating NEDD1 with other relevant factors, we constructed the prognostic nomogram to help the improvement of the prognosis for patients with HCC. The data from the International Cancer Genome Consortium (ICGC) database were used as an independent external validation of our prognostic model. Conclusion: The expression level of NEDD1 was negatively correlated to the prognosis of HCC patients and it may be a promising therapeutic target of HCC, which probably be able to predict the efficacy of immunotherapy for HCC patients.
Nicotinamide Riboside Promotes Mfn2-mediated Mitochondrial Fusion in Diabetic Hearts through the SIRT1-PGC1α-PPARα Pathway
Authors: Hu Lang , Guo Yanjie , Song Liqiang , Wen He , Sun Nan , Wang Ying , Qi Bingchao , Liang Qi , Geng Jing , Liu Xuteng , Fu Feng , Li Yan 
Published: December 2021

Abstract
Background: Myocardial dysfunction is associated with an imbalance in mitochondrial fusion/fission dynamics in patients with diabetes. However, effective strategies to regulate mitochondrial dynamics in the diabetic heart are still lacking. This study investigated whether Nicotinamide riboside (NR) supplementation protects against diabetes-induced cardiac dysfunction by regulating mitochondrial fusion/fission and further explored the underlying mechanisms.Methods: Obese diabetic (db/db) and lean control (db/+) mice were each given NR oral supplementation in this study. NAD+ Content was determined in mice hearts and primary neonatal cardiomyocytes. Cardiac function was detected by echocardiography. Mitochondrial dynamics were analyzed by transmission electron microscopy in vivo and by confocal microscopy in vitro. Results: Here, we show an evident decrease in NAD+ level and mitochondrial fragmentation in the hearts of leptin receptor-deficient diabetic (db/db) mouse model. NR supplementation significantly increased NAD+ content in the diabetic heart tissues. Furthermore, NR treatment increased Mfn2 expression, promoted mitochondrial fusion, suppressed oxidative stress, reduced cardiomyocyte apoptosis and consequently improved cardiac function in db/db mice. In neonatal primary cardiomyocytes cultured in a high-glucose/high-fat medium, NR treatment also promoted mitochondrial fusion, suppressed mitochondria-derived ROS production and reduced cardiomyocyte apoptosis, which were all reversed when Mfn2 was knocked down. Mechanistically, chromatin immunoprecipitation (ChIP) and luciferase report assay analysis revealed that PGC1α and PPARα interdependently regulated Mfn2 transcription by binding to its promoter region. NR treatment elevated NAD+ levels and activated SIRT1, resulting in the deacetylation of PGC1α and promoting the transcription of Mfn2. Furthermore, the inhibition of SIRT1, PGC1α or PPARα blunted the positive effects of NR supplementation on Mfn2 expression and mitochondrial fusion. Conclusion: NR attenuates the development of diabetes-induced cardiac dysfunction by promoting mitochondrial fusion through the SIRT1-PGC1α-PPARα pathway, with PGC1α and PPARα being the interdependent co-regulatory factors for Mfn2. The promotion of mitochondrial fusion via oral supplementation of NR may be a potential strategy for delaying cardiac complications in patients with diabetes.
Gravida Serum POSTN and PAPPA as the Potential Biomarkers for Fetal Congenital Heart Disease Based on Quantitative and Qualitative Proteomics
Authors: Xia Yi , Cheng Lin , Duan Jie , Ma Jianhong , Liu Juan , Lu Dan , Zhang Yuanzhen 
Published: December 2021

Abstract
Background: Fetal congenital heart disease is the most common congenital defect worldwide. It has some missed diagnoses and a lack of disease biomarkers. We aim to seek objective biomarkers for noninvasive prenatal diagnosis of fetal congenital heart disease to reduce the missed diagnosis and explore its mechanism,Methods: This study used data-independent acquisition and parallel reaction monitoring to explore potential protein biomarkers that co-exist in gravida serum and fetal amniotic fluid. Moreover, logistic regression and ROC curve to establish the diagnostic model of fetal congenital heart disease potential biomarkers and molecular biology experiments were performed to validate proteomics results and explore the mechanism. Results: Proteomics and bioinformatics results show that 12 proteins co-exist in gravida serum and amniotic fluid. We identified POSTN and PAPPA in GS as candidate biomarkers and established the diagnostic model with a sensitivity of 100%, a specificity of 95% and the AUC value of 0.968 to diagnose congenital heart disease. In addition, the results of ELISA, IHC, and RT-PCR were consistent with those of proteomics. Moreover, POSTN may involve in fetal congenital heart disease through the TGF-beta signaling pathway. Conclusion: It is the first time to find that POSTN and PAPPA in GS are related to fetal congenital heart disease, contributing to developing a novel noninvasive prenatal method to diagnose fetal congenital heart disease and reduce congenital disabilities.
Cyclic Experiments and Global Buckling Design of Steel-Angles-Assembled Buckling-Restrained Braces
Authors: Tong Jing-Zhong , Zhang En-Yuan , Guo Yan-Lin , Yu Chao-Qun 
Published: December 2021

Abstract
Compared with traditional BRB, the steel-angles-assembled buckling-restrained brace (SAA-BRB) is an innovative BRB with light-weight, accurate control of the geometrical dimensions, easy installation and convenient disassembly. The SAA-BRB is composed of an external restraining system and a cruciform-sectional inner core. The external restraining system is assembled by four steel angles with the connection of high-strength bolts, and the spacers are installed between the inner core and the restraining system. In this study, the hysteretic behavior of SAA-BRB was investigated by experiments and finite element (FE) simulations. Firstly, three SAA-BRB specimens with different restraining ratios were tested under cyclic loads to investigate the hysteretic performance. It was found that all specimens exhibited stable responses and satisfactory energy-dissipating capabilities during the whole loading process. Then, a refined FE model was established, and its validity in predicting the hysteretic responses of SAA-BRB was verified by the experiments. Moreover, based on the yielding criteria of the outmost fiber for the restraining member section, a design formula for the restraining ratio requirements to avoid global buckling of the SAA-BRB was deduced. Finally, extensive parametric analysis was conducted to verify the accuracy of the design formula by changing the geometric dimensions (the restraining ratio) of models. It was found that the proposed formula for the restraining ratio requirement could lead to a conservative prediction with reasonable accuracy, thus providing valuable references for global buckling design of SAA-BRBs in engineering practice.
Performance of the BinaxNOW COVID-19 Antigen Rapid Diagnostic Test for the Detection of SARS-CoV-2
Authors: Gonzalez Fernando A Ocampo , Moore Nicholas M 
Published: December 2021

Abstract
Background: Diagnosis of COVID-19 disease primarily relies on nucleic acid amplification tests (NAAT) that amplify and detect viral RNA in specimens. These methods are expensive and time consuming. Antigen-based rapid diagnostic tests can substantially decrease turnaround time.Methods: We analyzed paired anterior nares swabs collected from symptomatic patients and asymptomatic healthcare workers being tested COVID-19. One swab was used for a direct RDT and the results were compared to NAAT.Results: 89 paired specimens were evaluated. The positive percent agreement (PPA) for the antigen RDT was 68.2%, and the negative percent agreement (NPA) was 98.5%. Despite a low PPA, the Κ statistic was 0.733 indicating substantial agreement with the NAAT result. The median cycle number in paired specimens with concordant results was significantly lower than in discordant specimens (21.3 versus 32.3; P=0.003).Conclusions: The RDT showed modest PPA and high NPA when compared to NAAT. The quick TAT and use of an inexpensive test more frequently could be useful in settings in which results from NAAT testing is delayed.
Statin Therapy May Be Associated with Reduced Mortality Risk of Sepsis Patients: A Retrospective Study from the MIMIC-IV Database
Authors: Shi Jian , Zhou Shiyu , Chen Kerong , Dai Xingui , Li Lulan , Chen Zhongqing , Wu Feng , An Shengli , Zeng Zhenhua 
Published: December 2021

Abstract
BackgroundIt is controversial whether statin therapy is beneficial for sepsis patients. A large retrospective cohort study was conducted to evaluate the association between statin therapy and mortality in sepsis patients.MethodsAdult (≥18 years) sepsis patients were enrolled and divided into two groups: the statin group and the no-statin group. Data including demographic features, vital signs, laboratory tests, and comorbidities from MIMIC-IV v1.0 were extracted. Delirium was assessed via the Confusion Assessment Method for the ICU (CAM-ICU). Ninety-day mortality, 28-day mortality and the incidence of delirium after statin therapy were evaluated using multivariable logistic analysis, the PSM model and subgroup analysis based on univariate analysis. ResultsIn univariate analysis and multivariable logistic analysis, statin therapy showed a significant association with both reduced 28-day and 90-day mortality (90-day mortality: OR 0.58, 95% CI: 0.46-0.72, p<0.001; 28-day mortality: OR 0.47, 95% CI: 0.37-0.60, p<0.001), while no relationship was found between statin therapy and delirium (OR 0.92, 95% CI: 0.49-1.72, p=0.787). In further PSM model and subgroup analyses or sensitivity analysis, consistent results were shown. ConclusionStatin therapy is significantly associated with 28-day and 90-day mortality without decrease in the incidence of delirium.
The Correlation Between Novel Survival-related Alternative Splicing Signature and Prognostic Prediction and Immune Microenvironment in Clear Cell Renal Cell Carcinoma
Authors: Jian Wengang , Wang Gang , Yu Yipeng , Cai Licheng , Yu Yongchun , Xue Wei , Wang Tengda , Meng Yuyang , Xia Zhinan , Yao Wenhao , Zhang Cheng 
Published: December 2021

Abstract
BackgroundAlthough extensive researches related alternative splicing (AS) as the prognostic markers of patients in cancers, which remains unknown in clear cell renal cell carcinoma (ccRCC), especially in immunotherapy. Therefore, a novel survival-associated AS signature was established to predict prognosis of patients and explored its correlation with immune cell infiltration or immune checkpoint expression to explain the phenomenon of resistance to immunotherapy in ccRCC.Methodsccording to AS data, clinical information and gene expression data in ccRCC, overall survival-related AS events was identified and further the AS-related prognostic risk model established by LASSO regression and multi-Cox regression analysis was evaluated by Kaplan-Meier survival analysis, the ROC curves and a nomogram model. Then we clarified the biological processes and pathways by GSEA, and further measured the immune cell infiltration by ESTIMATE, CIBERSORT and ssGSEA. Finally we analysed the clinical features and immune features of different parental genes, and quested the splicing factors regulating riskScore-related AS events by Spearman correlation analysis.ResultsWe obtained the most significant 5 AS events, including C4orf19|69001|AT, UACA|31438|AP, FAM120C|89237|AT, TRIM16L|39629|AP and SEC31A|100881|ES, to establish the prognostic risk model, and further illustrated the stability and importance of the riskScore prognostic signatures. Then we found that in high risk group, most of the top 10 GO enrichments and the KEGG pathway were closely related to the immunity, and the higher immune cell infiltration, and higher expression of classic immune checkpoints such as PD1 and CTLA4. In addition, 6 different parental genes were obtained, including C4orf19, ARHGAP24 DNASE1L3, P4HA1, SLC39A14 and TAF1D. These 6 genes could not be the independent prognostic signatures, but the expression of these genes was closely related to immune cells infiltration and the expression of immune checkpoints. Finally, we got aberrant 52 splicing factors regulating riskScore-related AS events.ConclusionOur study discovered that overall survival-related AS events mediated by aberrant splicing factors can be constructed a prognostic risk model to predict prognosis of patiens and utilized to index the situation of immune cell infiltration and immune checkpoint expression that impact tumor immune microenvironment in ccRCC.