bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient logging and querying for blockchain-based cross-site genomic dataset access audit
Authors: Ma Shuaicheng , Cao Yang , Xiong Li 
Published: July 2020

Abstract
Background
Genomic data have been collected by different institutions and companies and need to be shared for broader use. In a cross-site genomic data sharing system, a secure and transparent access control audit module plays an essential role in ensuring the accountability. A centralized access log audit system is vulnerable to the single point of attack and also lack transparency since the log could be tampered by a malicious system administrator or internal adversaries. Several studies have proposed blockchain-based access audit to solve this problem but without considering the efficiency of the audit queries. The 2018 iDASH competition first track provides us with an opportunity to design efficient logging and querying system for cross-site genomic dataset access audit. We designed a blockchain-based log system which can provide a light-weight and widely compatible module for existing blockchain platforms. The submitted solution won the third place of the competition. In this paper, we report the technical details in our system.

Methods
We present two methods: baseline method and enhanced method. We started with the baseline method and then adjusted our implementation based on the competition evaluation criteria and characteristics of the log system. To overcome obstacles of indexing on the immutable Blockchain system, we designed a hierarchical timestamp structure which supports efficient range queries on the timestamp field.

Results
We implemented our methods in Python3, tested the scalability, and compared the performance using the test data supplied by competition organizer. We successfully boosted the log retrieval speed for complex AND queries that contain multiple predicates. For the range query, we boosted the speed for at least one order of magnitude. The storage usage is reduced by 25%.

Conclusion
We demonstrate that Blockchain can be used to build a time and space efficient log and query genomic dataset audit trail. Therefore, it provides a promising solution for sharing genomic data with accountability requirement across multiple sites.
A high fat diet with a high C18:0/C16:0 ratio induced worse metabolic and transcriptomic profiles in C57BL/6 mice
Authors: Wang Liqiang , Xu Fei , Song Zhenfeng , Han Dan , Zhang Jingyi , Chen Linjun , Na Lixin 
Published: July 2020

Abstract
Background
Differential effects of individual saturated fatty acids (SFAs), particularly stearic acid (C18:0), relative to the shorter-chain SFAs have drawn interest for more accurate nutritional guidelines. However, specific biologic and pathologic functions that can be assigned to particular SFAs are very limited. The present study was designed to compare changes in metabolic and transcriptomic profiles in mice caused by a high C18:0 diet and high palmitic acid (C16:0) diet.

Methods
Male C57BL/6 mice were assigned to a normal fat diet (NFD), a high fat diet with high C18:0/C16:0 ratio (HSF) or an isocaloric high fat diet with a low C18:0/C16:0 ratio (LSF) for 10 weeks. An oral glucose tolerance test, 72-h energy expenditure measurement and CT scan of body fat were done before sacrifice. Fasting glucose and lipids were determined by an autobiochemical analyzer. Blood insulin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were measured by enzyme-linked immunosorbent assay methods. Free fatty acids (FFAs) profiles in blood and liver were determined by using gas chromatography-mass spectrometry. Microarray analysis was applied to investigate changes in transcriptomic profiles in the liver. Pathway analysis and gene ontology analysis were applied to describe the roles of differentially expressed mRNAs.

Results
Compared with the NFD group, body weight, body fat ratio, fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride, IL-6, serum and liver FFAs including total FFAs, C16:0 and C18:0 were increased in both high fat diet groups and were much higher in the HSF group than those in the LSF group. Both HSF and LSF mice exhibited distinguishable long non-coding RNA (lncRNA), microRNA and mRNA expression profiles when compared with those of NFD mice. Additionally, more differentially expressed lncRNAs and mRNAs were observed in the HSF group than in the LSF group. Some biological functions and pathways, other than energy metabolism regulation, were identified as differentially expressed mRNAs between the HSF group and the LSF group.

Conclusion
The high fat diet with a high C18:0/C16:0 ratio induced more severe glucose and lipid metabolic disorders and inflammation and affected expression of more lncRNAs and mRNAs than an isocaloric low C18:0/C16:0 ratio diet in mice. These results provide new insights into the differences in biological functions and related mechanisms, other than glucose and lipid metabolism, between C16:0 and C18:0.
Salpingectomy may decrease antral follicle count but not live birth rate for IVF-ET patients aged 35–39 years: a retrospective study
Authors: Chen Tong , Zhao Feiyan , Wang Qin , Liu Chang , Lan Yonglian , Wang Shuyu , Xin Zhimin , Yang Xiaokui 
Published: July 2020

Abstract
Purpose
Problems with fallopian tubes are one of the main reasons for women to undergo in vitro fertilization-embryo transfer (IVF-ET). A large proportion of women with ectopic pregnancy, fallopian tube obstruction and hydrosalpinx have had one or both fallopian tubes removed by salpingectomy. With increasing age, ovarian reserve deteriorates, the numbers of retrieved oocytes, available embryos and high-quality embryos are reduced, and the live birth rate for women treated with IVF treatment is affected. Thus, it is important to understand how salpingectomy affects live birth rates for IVF patients of different ages. This study analyzed how patients’ age and salpingectomy influenced ovarian reserve, ovarian response and pregnancy outcomes for infertile women undergoing IVF-ET.

Methods
A total of 1922 patients that underwent IVF-ET treatment from January 1, 2012, to December 31, 2018, were included in this retrospective study. The patients were divided into two groups according to whether or not they had a previous history of salpingectomy. The salpingectomy (group A, 534 patients) and control groups (group B, 1388 patients) were then further divided into two subgroups according to patient age (age<35 years, and age 35–39 years). Ovarian reserve, ovarian response, and IVF outcomes were investigated for each subgroup. Logistic regression model was used to estimate the relationship between clinical pregnancy and live births and patients’ baseline characteristics.

Results
In the salpingectomy group, antral follicle counts (AFC) were significantly lower for the subgroup aged 35 to 39 years compared with the control group. But this difference did not appear in women younger than 35 years. In addition, there were no significant differences in levels of basal follicle stimulation hormone (FSH), basal luteinizing hormone (LH), basal estradiol (E2), total gonadotropins (Gn) dose, duration of Gn, numbers of retrieved oocytes, fertilization rates, numbers of available embryos, live birth rates, clinical pregnancy rates, miscarriage rates, ectopic pregnancy rates, or multiple pregnancy rates between the salpingectomy group and the control group (P > 0.05). Age is a risk factor for the clinical pregnancy and live birth.

Conclusion
Salpingectomy may decrease antral follicle count but not live birth rate for IVF-ET patients aged 35–39 years. The increased female age was negative related with clinical pregnancy and live birth.
Bioinformatics analysis of gene expression profile of serous ovarian carcinomas to screen key genes and pathways
Authors: Fei Hongjun , Chen Songchang , Xu Chenming 
Published: July 2020

Abstract
Background
Serous ovarian carcinomas (SCA) are the most common and most aggressive ovarian carcinoma subtype which etiology remains unclear. To investigate the prospective role of mRNAs in the tumorigenesis and progression of SCA, the aberrantly expressed mRNAs were calculated based on the NCBI-GEO RNA-seq data.

Results
Of 21,755 genes with 89 SCA and SBOT cases from 3 independent laboratories, 59 mRNAs were identified as differentially expressed genes (DEGs) (|log2Fold Change| > 1.585, also |FoldChange| > 3 and adjusted P < 0.05) by DESeq R. There were 26 up-regulated DEGs and 33 down-regulated DEGs screened. The hierarchical clustering analysis, functional analysis and pathway enrichment analysis were performed on all DEGs and found that Polo-like kinase (PLK) signaling events are important. PPI network constructed with different filtration conditions screened out 4 common hub genes (KIF11, CDC20, PBK and TOP2A). Mutual exclusivity or co-occurrence analysis of 4 hub genes identified a tendency towards co-occurrence between KIF11 and CDC20 or TOP2A in SCA (p < 0.05). To analyze further the potential role of KIF11 in SCA, the co-expression profiles of KIF11 in SCA were identified and we found that CDC20 co-expressed with KIF11 also is DEG that we screened out before. To verify our previous results in this paper, we assessed the expression levels of 4 hub DEGs (all up-regulated) and 4 down-regulated DEGs in Oncomine database. And the results were consistent with previous conclusions obtained from GEO series. The survival curves showed that KIF11, CDC20 and TOP2A expression are significantly related to prognosis of SCA patients.

Conclusions
From all the above results, we speculate that KIF11, CDC20 and TOP2A played an important role in SCA.
Withaferin A: a potential therapeutic agent against COVID-19 infection
Authors: Straughn Alex R. , Kakar Sham S. 
Published: July 2020

AbstractThe outbreak and continued spread of the novel coronavirus disease 2019 (COVID-19) is a preeminent global health threat that has resulted in the infection of over 11.5 million people worldwide. In addition, the pandemic has claimed the lives of over 530,000 people worldwide. Age and the presence of underlying comorbid conditions have been found to be key determinants of patient mortality. One such comorbidity is the presence of an oncological malignancy, with cancer patients exhibiting an approximate two-fold increase in mortality rate. Due to a lack of data, no consensus has been reached about the best practices for the diagnosis and treatment of cancer patients. Interestingly, two independent research groups have discovered that Withaferin A (WFA), a steroidal lactone with anti-inflammatory and anti-tumorigenic properties, may bind to the viral spike (S-) protein of SARS-CoV-2. Further, preliminary data from our research group has demonstrated that WFA does not alter expression of ACE2 in the lungs of tumor-bearing female mice. Downregulation of ACE2 has recently been demonstrated to increase the severity of COVID-19. Therefore, WFA demonstrates real potential as a therapeutic agent to treat or prevent the spread of COVID-19 due to the reported interference in viral S-protein to host receptor binding and its lack of effect on ACE2 expression in the lungs.
Nutrition of the COVID-19 patient in the intensive care unit (ICU): a practical guidance
Authors: Thibault Ronan , Seguin Philippe , Tamion Fabienne , Pichard Claude , Singer Pierre 
Published: July 2020

AbstractFive to 10% of the coronavirus SARS-CoV-2-infected patients, i.e., with new coronavirus disease 2019 (COVID-19), are presenting with an acute respiratory distress syndrome (ARDS) requiring urgent respiratory and hemodynamic support in the intensive care unit (ICU). However, nutrition is an important element of care. The nutritional assessment and the early nutritional care management of COVID-19 patients must be integrated into the overall therapeutic strategy. The international recommendations on nutrition in the ICU should be followed. Some specific issues about the nutrition of the COVID-19 patients in the ICU should be emphasized. We propose a flow chart and ten key issues for optimizing the nutrition management of COVID-19 patients in the ICU.
Assembly of the threespine stickleback Y chromosome reveals convergent signatures of sex chromosome evolution
Authors: Peichel Catherine L. , McCann Shaugnessy R. , Ross Joseph A. , Naftaly Alice F. S. , Urton James R. , Cech Jennifer N. , Grimwood Jane , Schmutz Jeremy , Myers Richard M. , Kingsley David M. , White Michael A. 
Published: July 2020

Abstract
Background
Heteromorphic sex chromosomes have evolved repeatedly across diverse species. Suppression of recombination between X and Y chromosomes leads to degeneration of the Y chromosome. The progression of degeneration is not well understood, as complete sequence assemblies of heteromorphic Y chromosomes have only been generated across a handful of taxa with highly degenerate sex chromosomes. Here, we describe the assembly of the threespine stickleback (Gasterosteus aculeatus) Y chromosome, which is less than 26 million years old and at an intermediate stage of degeneration. Our previous work identified that the non-recombining region between the X and the Y spans approximately 17.5 Mb on the X chromosome.

Results
We combine long-read sequencing with a Hi-C-based proximity guided assembly to generate a 15.87 Mb assembly of the Y chromosome. Our assembly is concordant with cytogenetic maps and Sanger sequences of over 90 Y chromosome BAC clones. We find three evolutionary strata on the Y chromosome, consistent with the three inversions identified by our previous cytogenetic analyses. The threespine stickleback Y shows convergence with more degenerate sex chromosomes in the retention of haploinsufficient genes and the accumulation of genes with testis-biased expression, many of which are recent duplicates. However, we find no evidence for large amplicons identified in other sex chromosome systems. We also report an excellent candidate for the master sex-determination gene: a translocated copy of Amh (Amhy).

Conclusions
Together, our work shows that the evolutionary forces shaping sex chromosomes can cause relatively rapid changes in the overall genetic architecture of Y chromosomes.
Unusual fetal ascites and spontaneous bladder rupture in a female fetus: a case report
Authors: Cadoret Florence , Brazet Edith , Sartor Agnès , Lacroix Isabelle , Casper Charlotte , Decramer Stéphane , Parant Olivier 
Published: July 2020

Abstract
Background
Fetal bladder rupture causing urinary ascites is uncommon. It is generally related to invasive fetal medicine procedures or obstructive disorders such as in posterior urethral valves in male fetuses. An exceptional case of spontaneous bladder rupture in a female fetus occurred in a pregnant woman treated with high doses of opiates in an intensive care unit. This unusual obstetric situation leads to discussion of the possible causes of fetal bladder rupture, its management, and the pediatric prognosis.

Case presentation
We report the case of a 30-year-old nulliparous black woman with a history of mesenteric cystic lymphangioma and multiple bowel resections leading to chronic malabsorption. During her pregnancy, our patient presented with an occlusive syndrome and major bilateral renal dilation. Urinary derivation resulted in iatrogenic bilateral ureteral perforation. Our patient thus presented with major uroperitoneum, bilateral pleural effusion and acute renal failure, treated by thoracic drainage and bilateral nephrostomy. Postoperative pain required treatment with level III analgesics. In this context, 5 days after morphine treatment introduction an enlarged fetal bladder was observed, followed 3 days later by voluminous fetal ascites. The diagnosis of spontaneous bladder rupture was suspected. After multidisciplinary discussion, expectant management was decided. At 31 weeks and 4 days gestation, our patient went into spontaneous labor with a subsequent vaginal delivery. The infant required resuscitation and paracentesis of ascites at birth. Her neonatal course was favorable with a simple urethral bladder drainage. Cystography at day 9 was normal. At 2 years of follow-up, the mother and the child have a normal course.

Conclusions
An iatrogenic origin of megacystis in a female fetus must be evoked in the event of maternal administration of high doses of opiates in the second part of her pregnancy. In our case, the megacystis was followed by spontaneous bladder rupture at 30 weeks of gestation, with a favorable maternal fetal issue.
Late-onset ovarian hyperstimulation syndrome developing during ovarian stimulation in an ectopic pregnancy: a case report
Authors: Huang Haipeng , Takai Yasushi , Samejima Kouki , Narita Tatsuya , Ichinose Shunichiro , Itaya Yukiko , Ono Yoshihisa , Matsunaga Shigetaka , Saitoh Masahiro , Baba Kazunori , Hayashi Naoki , Seki Hiroyuki 
Published: July 2020

Abstract
Background
Ovarian hyperstimulation syndrome is normally induced by ovarian stimulation drugs. Severe cases of ovarian hyperstimulation syndrome involve complications such as renal failure and thrombosis. Evidence has recently been developed for a method to prevent ovarian hyperstimulation syndrome. Most cases of ovarian hyperstimulation syndrome are of an early-onset type, which occurs shortly after injection of human chorionic gonadotropin. However, late-onset ovarian hyperstimulation syndrome, which occurs in a pregnancy cycle, also requires caution. We report our experience in treating a woman who was transported to our hospital with a severe case of ovarian hyperstimulation syndrome occurring during ovarian stimulation and who was determined to have an ectopic pregnancy.

Case presentation
Assisted reproductive technology was planned for a 29-year-old nulligravida Japanese woman diagnosed with bilateral fallopian tube obstruction and right-sided hydrosalpinx. On day 1 of controlled ovarian stimulation, the result of her human chorionic gonadotropin urine test was negative, and her serum levels of luteinizing hormone, estradiol, and progesterone were normal. On day 11 of controlled ovarian stimulation, the levels of estradiol and progesterone had risen to 9679 pg/ml and 16 ng/ml, respectively, prompting suspension of controlled ovarian stimulation. Eleven days after controlled ovarian stimulation was suspended, the patient demonstrated ascites that did not improve despite administration of cabergoline, and she was transported to our hospital 2 days after. Late-onset ovarian hyperstimulation syndrome suggested that she was pregnant, and her serum human chorionic gonadotropin level was 27,778 IU/ml. She underwent laparoscopic bilateral salpingectomy and was diagnosed with right tubal pregnancy.

Conclusion
In an ectopic pregnancy, human chorionic gonadotropin sometimes increases later than in an intrauterine pregnancy. In our patient’s case, endogenous human chorionic gonadotropin following the start of controlled ovarian stimulation may have caused late-onset ovarian hyperstimulation syndrome. The key to early detection of similar cases may be to suspect pregnancy in the event of unexpectedly high progesterone levels during ovarian stimulation.
Ex vivo cultivated oral mucosal epithelial cell transplantation for limbal stem cell deficiency: a review
Authors: Cabral Joao Victor , Jackson Catherine Joan , Utheim Tor Paaske , Jirsova Katerina 
Published: July 2020

AbstractDestruction or dysfunction of limbal epithelial stem cells (LESCs) leads to unilateral or bilateral limbal stem cell deficiency (LSCD). Fifteen years have passed since the first transplantation of ex vivo cultivated oral mucosal epithelial cells (COMET) in humans in 2004, which represents the first use of a cultured non-limbal autologous cell type to treat bilateral LSCD. This review summarizes clinical outcomes from COMET studies published from 2004 to 2019 and reviews results with emphasis on the culture methods by which grafted cell sheets were prepared.
Probucol enhances the therapeutic efficiency of mesenchymal stem cells in the treatment of erectile dysfunction in diabetic rats by prolonging their survival time via Nrf2 pathway
Authors: Wang Haoran , Zhang Keqin , Ruan Zheng , Sun Dingqi , Zhang Hui , Lin Guiting , Hu Liangliang , Zhao Shengtian , Fu Qiang 
Published: July 2020

Abstract
Background
Intracavernous injection of mesenchymal stem cells (MSCs) is a promising method for diabetic mellitus-induced erectile dysfunction (DMED), but short survival time of MSCs in cavernous is a fatal defect for therapy. This study investigated therapeutic efficiency and potential mechanism of probucol combined with MSCs.

Methods
In vivo study, a total of forty-eight 10-week-old male Sprague-Dawley (SD) rats were used. Twelve rats received intraperitoneal injection of PBS as the sham group; the rest received intraperitoneal injection of 60 mg/kg streptozotocin to establish DM models. DM rats were randomly divided into three groups: received intracavernosal (IC) injection of either PBS (DM group), MSCs (M group), or administrated probucol after intracavernosal injection of MSCs (P + M group). Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement. After euthanasia, penile tissue was investigated for histologic examination and Western blotting. In in vitro experiment, H2O2 was used to create oxidative stress environment to detect changes in cell viability. CCK8 was used to measure cell viability of MSCs treated with or without probucol. Intracellular ROS changes were detected by flow cytometry. Autophagy and apoptosis were detected by Western blotting and confocal microscopy.

Results
Recovery of erectile function was observed in the P + M group. The combination therapy decreased fibrosis and increased endothelial function compared with MSC therapy alone. Western blotting results confirmed the increased expression of Nrf2 and HO-1 in cavernous body. H2O2 induced high oxidative stress and reduced cell viability in vitro, which was gradually reversed with increased concentration of probucol. H2O2 reduced Nrf2 expression, which was reversed by probucol’s intervention. Furthermore, the expression of Bax, Caspase3, and Cleaved-Caspase3 decreased, and the expression of Bcl-2 increased in a dose-dependent manner because of probucol’s intervention. In addition, Beclin1 and LC3II both increased in a dose-dependent manner. Meanwhile, the expression of P62 decreased. In the study of autophagy flux, we found probucol did not block it.

Conclusion
Probucol enhanced therapeutic efficiency of MSCs in DMED by prolonging their survival time, which mediated through improving the transplanted microenvironment of MSCs, increasing self-antioxidant ability of MSCs, strengthening protective autophagy, and inhibiting apoptosis of MSCs via Nrf2 pathway.

Graphical abstract
Schematic model showing combined probucol and MSCs to improve DMED. Probucol increases self-antioxidant ability of MSCs, strengthening protective autophagy and inhibiting apoptosis via Nrf2/HO-1 and Nrf2/autophagy pathways.