bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eleven Mutations in Six Genes Causing Abnormal Sperm Morphology: A Case Series
Authors: Zhong Chongfu , Liu Shengjing , Wang Yong , Shi Zhuozhuo , Liu Fengrui , Gao Zhaowang 
Published: August 2021

Abstract
Objective: Infertility has become a major health problem worldwide, approximately 10%–15% of male infertility cases can be attributed to genetic mutations. However, the genetic factors contributing to male infertility remain largely unknown. This study aimed to identify genetic mutations associated with morphological abnormalities in sperm.Methods: In this study, we assessed the semen parameters of 60 patients with sperm morphological abnormalities by semen analysis, and subsequently performed targeted next-generation sequencing (NGS) to identify gene mutations. Results: Of the 60 cases of male infertility, 8 individuals (13%) were identified as carrying genetic mutations. In brief, patient 1 carried two heterozygous mutations of SUN5, including c.1066C>T and c.638delC; Patient 2 and Patient 3 had a 109.73 kb homozygous deletion on chromosome 12 in DPY19L2; patient 4 presented two heterozygous mutations (c.1670_1671delinsTT and c.255_258del) of DPY19L2; patient 5 carried a homozygous variant c.1159+1G>A of CCDC40; patient 6 had a heterozygous mutation c.38_43del in the SEPT12 gene; patient 7 had two heterozygous mutations in DNAH1 (c.10060_10061insATCT and c.12278T>C), and patient 8 presented two heterozygous mutations of CFAP43 (c.3658C>T and c.823del). Conclusions: We identified gene mutations associated with sperm morphological abnormalities in a series of male infertility cases. Eight of sixty individuals were identified as carrying gene mutations. Genetic mutations of SUN5, DPY19L2, CCDC40, SEPT12, DNAH1, and CFAP43 might be responsible for male infertility. Our study expanded the landscape of gene mutations related to sperm morphological abnormalities, which might provide new insights into the genetics underlying male infertility.
Mre11-Rad50 oligomerization promotes DNA double-strand break repair
Authors: Kissling Vera , Reginato Giordano , Bianco Eliana , Kasaciunaite Kristina , Tilma Janny , Cereghetti Gea , Lee Sung Sik , Guérois Raphaël , Seidel Ralf , Cejka Petr , Peter Matthias 
Published: August 2021

Abstract
The conserved Mre11-Rad50 (MR) complex is crucial for the detection, signaling, end tethering and processing of DNA double-strand breaks (DSBs). While it was known for decades that MR foci formation at DSBs accompanies repair, the underlying molecular assembly mechanisms and functional implications remained unclear. Combining pathway reconstitution in electron microscopy, biochemical assays and genetic studies, we show that S. cerevisiae MR oligomerizes via a conserved Rad50 beta-sheet to higher-order assemblies, which bind DNA with positive cooperativity. We designed Rad50 point mutants with enhanced or disrupted MR oligomerization, and demonstrate that MR oligomerization facilitates foci formation, DNA damage signaling and repair in vivo. MR oligomerization does not affect its exonuclease activity but drives endonucleolytic cleavage at multiple sites on the 5'-terminated DNA strand near DSBs. Interestingly, mutations in the human Rad50 beta-sheet are linked to hereditary cancer predisposition and our findings might provide new insights into their potential role in chemoresistance.
Perioperative protocol to reduce blood transfusions in ankylosing spondylitis patients undergoing total hip arthroplasty
Authors: Huang Yu , Huang Xiao , Li Fulin , Huang Wenwen , Yin Dong 
Published: August 2021

Abstract
Introduction: Although tranexamic acid (TXA) can reduce bleeding during total hip arthroplasty (THA), the amount of perioperative bleeding is greater in patients with ankylosing spondylitis (AS); So blood management is more challenging. Patient Blood Management (PBM) program can improve AS patients care and reduce health costs in THA. The purpose of this study is to assess the effects of PMB program on allogeneic transfusion rate, length of hospital stay(LOS), hospitalization expenses and adverse events.
Methods : We conducted a retrospective observational study of patients with AS who underwent THA. All patients were treated with tranexamic acid before and after operation. Our PBM program included preoperative evaluation, preoperative acute normovolemic hemodilution and intraoperative recovery autotransfusion. We compared results between the group of patients before and the one after the PBM program implementation.
Result: We included 68 as patients who underwent total hip arthroplasty before PBM program from January 2013 to December 2015 (group A) and 84 as patients who underwent total hip arthroplasty after PBM program from January 2016 to December 2019 (group B). In the comparison of intraoperative blood transfusion volume, intraoperative blood transfusion rate and total blood transfusion rate between the two groups, the group B was significantly lower than the group A (P ≤ 0.05); The length of stay and hospitalization expenses of the group B were lower than the group A (P ≤ 0.05). No adverse events were recorded.
Conclunsions: Our PMB program can reduce allogeneic blood transfusion, hospital stay and hospitalization expenses, without risking patients to higher number of com- plications in AS patients undergoing THA.
eIF6 Promotes Inﬂammatory Macrophage Phenotype, Foam Cell Formation and Atherosclerosise
Authors: Zheng Junnian , Chen Renjin , Xian Xuemei , Zhan xiaoqiang , Chang Jiajia , Yuan Honghua , Chen Quangang , Han Xufeng , Chen Yang , Zhu Yuhua , Wang Zhenzhen 
Published: August 2021

Abstract
Background：Atherosclerosis is a chronic inflammatory disease, caused by accumulation of lipid-laden and inflammatory macrophages in the artery wall. Understanding its molecular mechanisms and developing novel therapeutic targets to promote atherosclerotic regression is an important clinical goal.Methods : ApoE-/- and eIF6+/-/ApoE-/- mice were fed Western diet (WD) for 16 weeks. Molecular biology technology were performed to analyze the differences between them.Results: The mechanism by which Eukaryotic initiation factor 6 (eIF6) affects macrophages and atherosclerosis remains to be elucidated. Western blotting and real-time polymerase chain reaction (PCR ) analysis indicated significantly higher expression levels of eIF6 than those in the control in RAW264.7 cells induced by Lipopolysaccharide (LPS) and Interleukin-4 (IL4). We constructed eIF6+/-/ApoE-/- mice, the hematoxylin (HE) and Oil Red O staining analysis indicated that these mice showed a significant decrease in atherosclerotic lesion formation increased anti-inﬂammatory cell content in aortas, and reduced necrotic core content compared with ApoE-/- mice on a western diet for 16 weeks. eIF6 deficiency suppressed foam cell formation and promoted the anti-inﬂammatory macrophage phenotype in primary macrophages. More anti-inflammatory populations were observed in blood and atherosclerotic aortas of eIF6+/- ApoE-/- mice by flow cytometry. Immunofluorescent staining analysis obtained the same results.Conclusions: eIF6 deficiency protects against atherosclerosis by promoting the anti-inﬂammatory macrophage phenotype and reducing macrophage uptake of low-density lipoprotein (LDL), indicating that new insight into eIF6 may reveal a potential novel therapeutic target for the resolution of inflammation in atherosclerosis.
Prognosis of Pancreatic Cancer in Hamadan, Iran (2008-2018): A case Series Study
Authors: Khanlarzadeh Elham , Nazari Saman , Ghobakhloo Mehdi , Ranjbar Hossein , Nazari Sasan 
Published: August 2021

Abstract
Background: The present study aimed to determine the prognosis of pancreatic cancer from 2008 to 2018 in Hamadan, Iran. A case series study was conducted retrospectively at Beheshti Hospital in Hamadan, Iran. Methods: A total of 409 cases that had been diagnosed with pancreatic cancer from 2008 to 2018 were assessed. The variables included age, gender, pathological type, location involved, early symptoms, metastasis, prognosis and treatments, was extracted from the files and recorded in checklist. Data were analyzed by using SPSS/20 software. Results: The mean of age was 66.23±13.06 year. The most frequent of pancreatic cancers was Adenocarcinomas (66.7%). The highest frequency of early symptoms was jaundice (53.1%) and weight loss (12.7%). The highest frequency of pancreatic cancer lesions was more in the head of pancreas (68.7%). Most patients had metastasis at the beginning of diagnosis (82.3%). Most metastases were in liver (31.5%) and peritoneum (25.2%). The prognosis of the pancreatic cancer is significantly related to the lesion location and the consumption of alcohol, cigarettes and substance abuse (p <0.05), but it wasn’t correlated with age, sex and pathological type (p> 0.05). The 1-year and 5-year survival rates were (22.3%) and (9.5%), respectively. The lowest and the highest in 5-year survival rate were (7.8%) and (18.8%) in adenocarcinoma and carcinoma type. Conclusion: More preventive considerations were found to be beneficial among this population.
Effects of Exogenous Regulation of Ethylene and Abscisic Acid on Grain-Filling and Endosperm PCD of Wheat Under Drought Stress After Anthesis
Authors: Li Chao , Zhang Xiangchi , Guo Wenting , Fu Kaiyong , Li Cheng , Li Chunyan 
Published: August 2021

Abstract
Although studies have shown that grain-filling and programmed cell death of wheat endosperm are affected by drought stress, which is closely related to ethylene and abscisic acid.The mechanism of ethylene and abscisic acid regulate grain-filling and endosperm PCD under drought stress is remains unclear. In this study, we regulated the production of ethylene and abscisic acid in wheat grains under drought stress at filling stage by chemicals. The results showed that spraying ethylene synthesis inhibitor enhanced endosperm cell viability, delayed nuclear deformation, and decreased ACC content. Compared with the CK, the CN significantly decreased the DNA hydrolase activity and significantly increased the DNA content. In addition, the CN treatment reduced the expression of four genes related to ethylene receptors (ers1, ers2 etr1, etr2) and increase the expression of dad1. Under CN treatment, the process of endosperm PCD was delayed, the duration of high grouting rate was prolonged, and the grain weight was increased, in contrast, the opposite result was obtained after spraying abscisic acid synthesis inhibitor. The production of abscisic acid and ethylene in grains determines the fate of endosperm cells. A new model of artificial regulation of abscisic acid and ethylene, delaying endosperm PCD process and increasing grain weight under post-anthesis drought was proposed.
Increased Testicular Insulin-like Growth Factor 1 is Associated with Gonadal Activation by Recombinant Growth Hormone in Immature Rats
Authors: Xu Yang , Han Chang Yong , Park Mi Jung , Gye Myung Chan 
Published: August 2021

Abstract
To understand the mechanism of precocious sexual maturation following prepubertal growth hormone (GH) therapy, the effects of recombinant human GH (rhGH) on the kisspeptin-gonadotropin-releasing hormone-luteinizing hormone (GnRH-LH) system in the hypothalamus-pituitary axis, systemic and testicular insulin-like growth factor-1 (IGF1), spermatogenesis and Leydig cell steroidogenesis, and circulating testosterone levels were examined in immature rats. Following daily injection of rhGH (1 or 2 IU/kg) from postnatal day (PND) 21 to PND 23 or 30, testicular steroidogenic pathway genes and spermatogenesis marker genes mRNA levels, the number and size of HSD17B(+) Leydig cells, and blood testosterone levels in the rhGH rats were significantly higher than those of controls on PNDs 24 and 31. Hypothalamic Kiss1 and Gnrh1 mRNA in the rhGH rats were significantly higher than those in the controls on PND 24, indicating early activation of hypothalamic kisspeptin-GnRH neurons by rhGH. Hypothalamic Igf1 mRNA levels in rhGH rats were significantly higher than those in the controls on PND 24 but significantly lower than those in controls on PND 31. Testicular Igf1 mRNA levels were significantly higher in rhGH rats than in the controls on PNDs 24 and 31 whereas liver Igf1 mRNA levels and circulating IGF1 levels were not. In progenitor Leydig cells, rhGH significantly increased the Igf1 and steroidogenic pathway genes mRNA levels and the testosterone production. Therefore, local increases in testicular IGF1 might be an important mediator of gonadal activation via steroidogenic activation of Leydig cells in immature rats given rhGH.
The Diagnostic Journey of Genetically Defined Neurodevelopmental Disorders
Authors: Simon Juliana , Hyde Carly , Saravandapandian Vidya , Wilson Rujuta , DiStefano Charlotte , Besterman Aaron , Jeste Shafali 
Published: August 2021

Abstract
Background

The development of advanced genetic technologies has resulted in rapid identification of genetic etiologies of neurodevelopmental disorders (NDDs) and has transformed the classification and diagnosis of various NDDs. However, diagnostic genetics has far outpaced our ability to provide timely medical counseling, guidance, and care for patients with genetically defined NDDs. These patients and their caregivers present with an unmet need for care coordination across multiple domains including medical, developmental, and psychiatric care, and for educational resources and guidance from care professionals. After a genetic diagnosis is made, families also face several barriers in access to informed diagnostic evaluations and medical support.
Methods

As part of Care and Research in Neurogenetics (CARING), a multidisciplinary clinical program for children and adults with neurogenetic disorders, we conducted qualitative clinical interviews about the diagnostic journey of families. This included the overall timeline to receiving diagnoses, experiences before and after diagnosis, barriers to care, and resources that helped them to navigate the diagnostic process.
Results

A total of 37 interviews were conducted with parents of children ages 16 months to 33 years. Several key themes were identified: 1) delays between initial caregiver observations of developmental delays and formal developmental or genetic diagnoses; 2) practical barriers to clinical evaluation and care, including long wait times for an appointment, lack of insurance coverage, availability of local evaluations, transportation difficulties, and native language differences; 3) the importance of being part of a patient advocacy group to help navigate the diagnostic journey; and (4) unique challenges faced by adults (18 years or older).
Conclusions

Families of children with complex neurodevelopmental and genetic disabilities face numerous challenges in finding adequate medical care and services for their child. They experience considerable delays in receiving timely diagnoses and face significant barriers that further delay the process of receiving access to services needed for the child’s continued care. The gaps indicated in this study speak to the need for more comprehensive coordination of care for patients with intellectual and developmental disabilities, as well as the development of systematic, disorder-specific resources both for providers and families in order to improve patient outcomes.
Effects of Steel Fibers (SF) and Ground Granulated Blast Furnace Slag (GBBS) on Recycle Aggregate Concrete
Authors: Ahmad Jawad , Aslam Fahad 
Published: August 2021

Abstract
Recycle aggregate is one of the good options to use in concrete as coarse aggregate which results environmental benefits as well as sustainable development. However, recycle aggregate cause reduction in concrete performance. One the other hand, the removal of industrial waste would be considerably decreased if it could be incorporated in cement concrete production. One of these possibilities is the substitution of the cement by slag, which enhance concrete poor properties of recycle aggregate concrete as well as provides to the decrease of cement consumption, reducing carbon dioxide productions, while resolving a waste management challenge. Furthermore, steel fiber was also added to hance the tensile capacity of recycle aggregate concrete. The main goal of this study is to investigate the characteristics of concrete using Ground granulated blast-furnace slag (GGBS) as binding material on recycle aggregate fibers reinforce concrete (RAFRC). Mechanical performance was assessed through compressive strength and split tensile strength, while durability aspects was study through water absorption, acid resistance and dry shrinkage. The results detected from the different experiments depict that replacement of Ground granulated blast-furnace slag (GGBS) enhance mechanical performance as well as durability aspects of the recycle aggregate fibers reinforce concrete (RAFRC).
WITHDRAWN: In Vitro Study On The Potential Fungicidal Effects of Atorvastatin In Combination With Some Azole Drugs Against Multidrug Resistant Candida Albicans
Authors: Mahmoud Dina Ezzat Mahmoud , Faraag Ahmed Hassan Ibrahim , El-Wafa Wael Mohamed Abu 
Published: August 2021

Abstract
The resistance of Candida albicans to azole drugs represents the great global challenge. This study investigates the potential fungicidal effects of atorvastatin (ATO) combinations with fluconazole (FLU), itraconazole (ITR), ketoconazole (KET) and voriconazole (VOR) against thirty-four multidrug-resistant (MDR) C. albicans using checkerboard and time-kill methods. Results showed that 94.12% of these isolates were MDR to ≥ two azole drugs, whereas 5.88% of them were susceptible to azole drugs. The tested isolates exhibited high resistance rates to FLU (58.82%), ITR (52.94%), VOR (47.06 %) and KET (35.29 %), whereas only three representative (8.82%) isolates were resistant to all tested azoles. Remarkably, the inhibition zones of these isolates were increased at least two-fold with the presence of ATO, which interacted in a synergistic (FIC index ≤ 0.5) manner with tested azoles. In silico docking study of ATO and the four azole drugs were performed against the Lanosterol 14-alpha demethylase enzyme (ERG11) of C. albicans. Results showed that the mechanism of action of ATO against C. albicans is similar to that of azole compounds, with docking score (-4.901) lower than azole drugs (> - 5.0) due to the formation a single H-bond with Asp 225 and a pi-pi interaction with Thr 229. Importantly, ATO combinations with ITR, VOR and KET achieved fungicidal effects (≥ 3 Log10 cfu/ml reduction) against the representative isolates, whereas a fungistatic effect (≤ 3 Log10 cfu/ml reduction) was observed with FLU combination. Thus, the combination of ATO with azole drugs could be promising options for treating C. albicans infection.
Clinical Performance of Lithium Disilicate Glass-Ceramic Onlays For The Treatment of Tooth Defects
Authors: Chen Shujiang , Lu Meng , Zhu Zhimin , Chen Wenchuan C. 
Published: August 2021

Abstract
BackgroundThe aim of this study was to assess the clinical performance of lithium disilicate glass-ceramic onlays for the treatment of tooth defects and to evaluate the clinical performance and whether they are worth more extensive use as that of the full crown. MethodsPatients who received treatment by lithium disilicate glass-ceramic onlays at the Western China Hospital of Stomatology were recalled after 1~4 years. The clinical performance and patients’ satisfaction of onlays for various tooth defects, cracked or uncracked teeth and endodontically treated or vital teeth were retrospectively evaluated with a combination of modified United States Public Health Service Criteria and questionnaire survey. Statistical analysis was performed by using the chi-squared test, Kaplan–Meier analysis and Log-rank test (a = 0.05) where appropriate. ResultsA total of 154 patients with 166 onlays were recalled for clinical examination. Of the 166 onlays examined, 65 (39.19%) were occlusal onlays, 92 (55.42%) were proximal-occlusive onlays and 9 (5.42%) were buccal-or lingual-occlusal onlays. The clinical performance of O and PO onlays was not significantly different (P > 0.05), according to USPHS Criteria. Kaplan-Meier analysis showed that the 4-year survival rate of O and PO onlays was 95.4% and 97.8%, respectively while there was no failure happened in buccal-or lingual-occlusal onlays. Log- rank test showed that the kinds of defects/onlays, tooth vitality and tooth crack had no influence on the survival rate (P > 0.05). The overall satisfaction rate was more than 98%.ConclusionsThis medium-term analysis indicated that lithium disilicate glass-ceramic onlays achieved satisfactory clinical performance for the restoration of different tooth defects. The survival rate of onlays was comparable to that of full crown. Different kinds of tooth defects, tooth vitality and tooth crack did not influence performance.Trial registrationThe study was approved by the Medical Ethics Committee of West China Hospital of Stomatology of Sichuan University with the approval number: WCHSIRB-D-2021-300. Consent to participate was not applicable.
Non-invasive imaging of tau-targeted probe uptake by whole brain multi-spectral optoacoustic tomography
Authors: Vagenknecht Patrick , Luzgin Artur , Ono Maiko , JI BIN , Higuchi Makoto , Noain Daniela , Maschio Cinzia A , Sobek Jens , Chen Zhenyue , Konietzko Uwe , Gerez Juan , Riek Roland , Razansky Daniel , Klohs Jan , Nitsch Roger , Dean-Ben Xose Luis , Ni Ruiqing 
Published: August 2021

Abstract
Background
Abnormal tau accumulation within the brain plays an important role in tauopathies such as Alzheimer’s disease and Frontotemporal dementia. High-resolution imaging of tau deposits at the whole-brain scale in animal disease models are highly desired. Herein, we approach this challenge by non-invasively imaging the brain of P301L mice of 4-repeat tau with concurrent volumetric multi-spectral optoacoustic tomography (vMSOT) at ~ 115 µm spatial resolution using tau-targeted pyridinyl-butadienyl-benzothiazole derivative PBB5 (i.v.).
Results
PBB5 showed specific binding to recombinant K18 tau fibrils by fluorescence assay, to post-mortem Alzheimer’s disease brain tissue homogenate by competitive binding against [11C]PBB3, and to tau deposits (AT-8 positive) in post-mortem corticobasal degeneration and progressive supranuclear palsy brains. Concurrent vMSOT and epi-fluorescence imaging of in vivo PBB5 targeting (i.v.) was performed in P301L and non-transgenic littermate mice. A dose dependent optoacoustic and fluorescence signal intensity was observed in the mouse brains with i.v. administration of different concentrations of PBB5. i.v. administration of PBB5 in P301L mice showed higher retention in tau-laden cortex and hippocampus compared to wild-type, confirmed by ex vivo vMSOT, epi-fluorescence, multiphoton microscopy, immunofluorescence staining using AT-8 antibody for phosphorylated tau.
Conclusions
We demonstrated non-invasive 3D whole-brain imaging of tau in P301L mice with a vMSOT system using PBB5 at a previously unachieved ~ 115 µm spatial resolution. This platform provides new tool to study tau spreading and clearance in tauopathy mouse model, foreseeable in monitoring of tau targeting putative therapeutics.