bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer-specific CTCF binding facilitates oncogenic transcriptional dysregulation
Authors: Fang Celestia , Wang Zhenjia , Han Cuijuan , Safgren Stephanie L. , Helmin Kathryn A. , Adelman Emmalee R. , Serafin Valentina , Basso Giuseppe , Eagen Kyle P. , Gaspar-Maia Alexandre , Figueroa Maria E. , Singer Benjamin D. , Ratan Aakrosh , Ntziachristos Panagiotis , Zang Chongzhi 
Published: September 2020

AbstractBackgroundThe three-dimensional genome organization is critical for gene regulation and can malfunction in diseases like cancer. As a key regulator of genome organization, CCCTC-binding factor (CTCF) has been characterized as a DNA-binding protein with important functions in maintaining the topological structure of chromatin and inducing DNA looping. Among the prolific binding sites in the genome, several events with altered CTCF occupancy have been reported as associated with effects in physiology or disease. However, hitherto there is no comprehensive survey of genome-wide CTCF binding patterns across different human cancers.ResultsTo dissect functions of CTCF binding, we systematically analyze over 700 CTCF ChIP-seq profiles across human tissues and cancers and identify cancer-specific CTCF binding patterns in six cancer types. We show that cancer-specific lost and gained CTCF binding events are associated with altered chromatin interactions, partially with DNA methylation changes, and rarely with sequence mutations. While lost bindings primarily occur near gene promoters, most gained CTCF binding events exhibit enhancer activities and are induced by oncogenic transcription factors. We validate these findings in T cell acute lymphoblastic leukemia cell lines and patient samples and show that oncogenic NOTCH1 induces specific CTCF binding and they cooperatively activate expression of target genes, indicating transcriptional condensation phenomena.ConclusionsSpecific CTCF binding events occur in human cancers. Cancer-specific CTCF binding can be induced by other transcription factors to regulate oncogenic gene expression. Our results substantiate CTCF binding alteration as a functional epigenomic signature of cancer.
Systematic genetic and proteomic screens during gametogenesis identify H2BK34 methylation as an evolutionary conserved meiotic mark
Authors: Crespo Marion , Luense Lacey J. , Arlotto Marie , Hu Jialei , Dorsey Jean , García-Oliver Encar , Shah Parisha P. , Pflieger Delphine , Berger Shelley L. , Govin Jérôme 
Published: September 2020

Abstract
Background
Gametes are highly differentiated cells specialized to carry and protect the parental genetic information. During male germ cell maturation, histone proteins undergo distinct changes that result in a highly compacted chromatin organization. Technical difficulties exclude comprehensive analysis of precise histone mutations during mammalian spermatogenesis. The model organism Saccharomyces cerevisiae possesses a differentiation pathway termed sporulation which exhibits striking similarities to mammalian spermatogenesis. This study took advantage of this yeast pathway to first perform systematic mutational and proteomics screens on histones, revealing amino acid residues which are essential for the formation of spores.

Methods
A systematic mutational screen has been performed on the histones H2A and H2B, generating ~ 250 mutants using two genetic backgrounds and assessing their ability to form spores. In addition, histones were purified at key stages of sporulation and post-translational modifications analyzed by mass spectrometry.

Results
The mutation of 75 H2A H2B residues affected sporulation, many of which were localized to the nucleosome lateral surface. The use of different genetic backgrounds confirmed the importance of many of the residues, as 48% of yeast histone mutants exhibited impaired formation of spores in both genetic backgrounds. Extensive proteomic analysis identified 67 unique post-translational modifications during sporulation, 27 of which were previously unreported in yeast. Furthermore, 33 modifications are located on residues that were found to be essential for efficient sporulation in our genetic mutation screens. The quantitative analysis of these modifications revealed a massive deacetylation of all core histones during the pre-meiotic phase and a close interplay between H4 acetylation and methylation during yeast sporulation. Methylation of H2BK37 was also identified as a new histone marker of meiosis and the mouse paralog, H2BK34, was also enriched for methylation during meiosis in the testes, establishing conservation during mammalian spermatogenesis.

Conclusion
Our results demonstrate that a combination of genetic and proteomic approaches applied to yeast sporulation can reveal new aspects of chromatin signaling pathways during mammalian spermatogenesis.
Pancreaticoduodenectomy in a patient with intestinal malrotation and distal cholangiocarcinoma: a case report and review of the literature
Authors: Arabi Nassir Alhaboob , Abdoun Areej Abdalla , Ali Mohamed Osama , Elhaj Saria Kabashi , Mohd. Sawsan Abuelgassim 
Published: September 2020

Abstract
Background
A combination of intestinal malrotation and distal cholangiocarcinoma is considered a rare condition and poses some difficulties in surgical management. We present a case of a patient with asymptomatic nonrotation of the midgut with a concomitant distal cholangiocarcinoma who underwent successful pancreaticoduodenectomy.

Case presentation
A 52-year-old Sudanese man presented to our hospital with progressive painless jaundice associated with dark urine, pale stool, and itching for the last 2 months. He had no other complaint or significant previous medical history apart from being an ex-smoker. His clinical examination revealed a palpable gallbladder and scratch mark. His other systems were unremarkable. His blood test results showed a normal complete blood count, elevated total bilirubin (mainly direct bilirubin), elevated alkaline phosphatase, and normal cancer antigen 19-9 and carcinoembryonic antigen. Ultrasound, computed tomography of the abdomen, and magnetic resonance cholangiopancreatography showed a dilated intrahepatic and extrahepatic biliary system down to the distal part, where the lumen was obstructed by a periampullary mass measuring 2.4 by 2.1 cm. The patient’s gallbladder was distended. He had no liver metastases or ascites and few lymph nodes. Inversion of the superior mesenteric artery and superior mesenteric vein but no invasion was seen, and malrotation of the bowel was observed with the large bowel on the left side and the small bowel to the right of the abdomen. Endoscopic retrograde cholangiopancreatography showed a fleshy ampulla that was stented. Laparotomy showed malrotation, with the duodenum straight on the right side of the midline, and Ladd’s band crossed the second portion of the duodenum. The vessels were approached from the lateral side meticulously after kocherization of the duodenum and pancreas, dissection along an extended portion of the superior mesenteric artery to assure preservation of the superior mesenteric artery and branches going to the jejunum, Ladd’s procedure, division of the jejunum 10 cm below the uncinate process of pancreas, and modified pancreaticoduodenectomy were performed, and anastomoses were performed in the standard fashion. The patient had an uneventful postoperative course, started oral feeding after 5 days, and discharged to home on day 10 for regular follow-up. Histopathology confirmed distal cholangiocarcinoma, and the patient was referred for further oncological management.

Conclusions
Pancreaticoduodenectomy can be safely performed in patients with intestinal malrotation with some modifications of the standard approach. Meticulous dissection after preoperative identification of vascular anomaly and a lateral approach are of great help to reduce morbidity.
Exercise enhances mitochondrial fission and mitophagy to improve myopathy following critical limb ischemia in elderly mice via the PGC1a/FNDC5/irisin pathway
Authors: He Wuyang , Wang Peng , Chen Qingwei , Li Chunqiu 
Published: September 2020

Abstract
Background
Elderly populations are susceptible to critical limb ischemia (CLI), but conventional treatments cannot significantly decrease amputation and mortality. Although exercise is an effective “non-pharmacological medicine” targeting mitochondria to improve skeletal muscle function, few studies have focused on the application of exercise in CLI.

Methods
Elderly male C57BL/6 mice (14 months old) were used to establish a CLI model to assess the effect of exercise on perfusion, performance recovery, apoptosis, mitochondrial function, and mitochondrial turnover in gastrocnemius muscle. The potential underlying mechanism mediated by PGC1a/FNDC5/irisin was confirmed in hypoxic and nutrient-deprived myotubes undergoing electrical pulse stimuli (EPS).

Results
Exercise significantly accelerated the perfusion recovery and exercise performance in ischemic limbs following CLI. Exercise improved the mitochondrial membrane potential and total ATP production and decreased apoptosis in the ischemic limbs. Exercise increased the formation of mitochondrial derived vesicle-like structures and decreased the mitochondrial length in the ischemic limbs, accompanied by upregulated PGC1a/FNDC5/irisin expression. In vitro, PGC1a/FNDC5/irisin downregulation decreased EPS-elevated PINK1, Parkin, DRP1, and LC3B mRNA levels. The irisin levels in the culture medium were correlated with the expression of mitochondrial fission and mitophagy markers in myotubes.

Conclusion
Exercise enhanced mitochondrial fission and selective autophagy to promote the recovery of myopathy after CLI in elderly mice through the PGC1a/FNDC5/irisin pathway, supporting the efficacy of exercise therapy in elderly individuals with CLI and demonstrating the potential of targeting PGC1a/FNDC5/irisin as a new strategy for the treatment of CLI.
Is greater generic competition also linked to lower drug prices in South Korea?
Authors: Son Kyung-Bok 
Published: September 2020

AbstractBackgroundAlthough the association between the price of generic drugs and market competitiveness has been explored in various high-income countries, this association has not been empirically evaluated in South Korea. We aim to determine the association between the prices of generic drugs and market competitiveness in South Korea.MethodsA list of originator drugs approved by the national authority from 2000 to 2019 and their corresponding generic drugs were grouped along with the baseline information. The market was categorized into four groups based on the number of manufacturers: duopoly (2 manufacturers); low- (3–25 manufacturers); medium- (26–75 manufacturers); and high-competition (more than 76 manufacturers) markets. Price variance, calculated as the difference between the maximum price and minimum price divided by the maximum price, was obtained. A multivariate regression model was applied to regress price variance on the characteristics of market competitiveness, controlling for the characteristics of the originator drugs and their price level in the market.ResultsA total of 986 originator drugs were identified and then divided into duopoly (31%), low- (56%), medium- (9%), and high-competition (4%) markets; the median of the price variance for these markets was 0.013, 0.077, 0.200, and 0.228, respectively. In a multivariate regression model, price variance was associated with the characteristics of the originator drug, including the Anatomical Therapeutic Chemical classification, the route of administration, and the approval year. Controlling for the characteristics of the originator drugs, market competitiveness was positively associated with price variance.ConclusionsThe positive association between price variance and market competitiveness is still consistent in South Korea, where rare price competition among a large number of generic manufacturers has been reported. However, no significant price variance was observed between medium- and high-competition markets. These findings support policies for managing a large number of generic manufacturers in South Korea.
PRV UL13 inhibits cGAS–STING-mediated IFN-β production by phosphorylating IRF3
Authors: Bo Zongyi , Miao Yurun , Xi Rui , Zhong Qiuping , Bao Chenyi , Chen Huan , Sun Liumei , Qian Yingjuan , Jung Yong-Sam , Dai Jianjun 
Published: September 2020

AbstractCyclic GMP-AMP (cGAMP) synthase (cGAS) is an intracellular sensor of cytoplasmic viral DNA created during virus infection, which subsequently activates the stimulator of interferon gene (STING)-dependent type I interferon response to eliminate pathogens. In contrast, viruses have developed different strategies to modulate this signalling pathway. Pseudorabies virus (PRV), an alphaherpesvirus, is the causative agent of Aujeszky’s disease (AD), a notable disease that causes substantial economic loss to the swine industry globally. Previous reports have shown that PRV infection induces cGAS-dependent IFN-β production, conversely hydrolysing cGAMP, a second messenger synthesized by cGAS, and attenuates PRV-induced IRF3 activation and IFN-β secretion. However, it is not clear whether PRV open reading frames (ORFs) modulate the cGAS–STING-IRF3 pathway. Here, 50 PRV ORFs were screened, showing that PRV UL13 serine/threonine kinase blocks the cGAS–STING-IRF3-, poly(I:C)- or VSV-mediated transcriptional activation of the IFN-β gene. Importantly, it was discovered that UL13 phosphorylates IRF3, and its kinase activity is indispensable for such an inhibitory effect. Moreover, UL13 does not affect IRF3 dimerization, nuclear translocation or association with CREB-binding protein (CBP) but attenuates the binding of IRF3 to the IRF3-responsive promoter. Consistent with this, it was discovered that UL13 inhibits the expression of multiple interferon-stimulated genes (ISGs) induced by cGAS–STING or poly(I:C). Finally, it was determined that PRV infection can activate IRF3 by recruiting it to the nucleus, and PRVΔUL13 mutants enhance the transactivation level of the IFN-β gene. Taken together, the data from the present study demonstrated that PRV UL13 inhibits cGAS–STING-mediated IFN-β production by phosphorylating IRF3.
Dietary Bacillus spp. enhanced growth and disease resistance of weaned pigs by modulating intestinal microbiota and systemic immunity
Authors: He Yijie , Jinno Cynthia , Kim Kwangwook , Wu Zhaohai , Tan Bie , Li Xunde , Whelan Rose , Liu Yanhong 
Published: September 2020

Abstract
Background
Previous research has shown that dietary supplementation of Bacillus spp. probiotics exerts beneficial effects on animals’ growth. However, limited studies have evaluated the efficacy of Bacillus spp. on weaned pigs and their effects on host gut health and microbiome, and systemic immunity using a disease challenge model. The objective of this experiment was to investigate the effects of two Bacillus spp. strains (Bacillus subtilis DSM 32540 and Bacillus pumilus DSM 32539) on growth performance, diarrhea, intestinal health, microbiome, and systemic immunity of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli (ETEC).

Results
Pigs in PRO1 (Bacillus subtilis DSM 32540) had greater (P < 0.05) body weight on d 7 and 14 PI, greater (P < 0.05) ADG from d 0 to 7 and d 7 to 14 PI, compared with pigs in CON (Control). Pigs in PRO1 had milder (P < 0.05) diarrhea on d 2 and 3 PI compared with pigs in CON. However, no differences were observed in growth performance and diarrhea score between PRO2 (Bacillus pumilus DSM 32539) and CON groups. Supplementation of PRO1 decreased (P < 0.05) lymphocyte counts on d 7 and 14 PI, compared with CON. Supplementation of PRO1 and PRO2 both reduced (P < 0.05) total coliforms in mesenteric lymph nodes on d 21 PI. Pigs in PRO2 had greater (P < 0.05) goblet cell number and sulfomucin percentage in duodenal villi and greater (P < 0.05) sialomucin percentage in jejunal villi than pigs in CON. Supplementation of PRO1 up-regulated (P < 0.05) MUC2 gene expression in jejunal mucosa and reduced (P < 0.05) PTGS-2 and IL1B gene expression in ileal mucosa on d 21 PI, compared with CON. Pigs in PRO1 had reduced (P < 0.05) relative abundance of families Lachnospiraceae, Peptostreptococcaceae and Pasteurellaceae in the ileum.

Conclusions
Supplementation of Bacillus subtilis DSM 32540 improved growth performance, alleviated diarrhea severity, enhanced gut health, and reduced systemic inflammation of weaned pigs infected with ETEC F18. Although Bacillus pumilus DSM 32539 was able to alleviate systemic inflammation, it had limited impacts on growth performance and severity of diarrhea of ETEC F18 challenged weaned pigs.
Learning in the presence of concept recurrence in data stream clustering
Authors: Namitha K. , Santhosh Kumar G. 
Published: September 2020

AbstractIn the case of real-world data streams, the underlying data distribution will not be static; it is subject to variation over time, which is known as the primary reason for concept drift. Concept drift poses severe problems to the accuracy of a model in online learning scenarios. The recurring concept is a particular case of concept drift where the concepts already seen in the past reappear as the stream evolves. This problem is not yet studied in the context of stream clustering. This paper proposes a novel algorithm for identifying the recurring concepts in data stream clustering. During concept recurrence, the most matching model is retrieved from the repository and reused. The algorithm has minimum memory requirements and works online with the stream. Some of the concepts and definitions, already familiar in concept recurrence studies of stream classification have been redefined for clustering. The experiments conducted on real and synthetic data streams reveal that the proposed algorithm has the potential to identify recurring concepts.
Emergency contraceptive knowledge, utilization and associated factors among secondary school students in Wolkite town, southern Ethiopia, cross sectional study
Authors: Mesfin Dereje 
Published: September 2020

Abstract
Background
Ethiopia is one of the sub-Saharan African countries with high maternal mortality and morbidity, unsafe abortion and adolescent births. Despite different policy measures taken by the government to improve sexual and reproductive health among adolescents their success is not well studied in Ethiopia. The objective of this study is to explore emergency contraceptive related knowledge, practice and its determinants among secondary school students in southern Ethiopia.

Methods
An institution-based cross-sectional study was conducted in selected high schools of Wolkite town, Southern Ethiopia from December to November 2019. Single population proportion formula was used to calculate sample size. A total of 327 female students participated in the study with a total response rate of 97%. Data were collected using a self-administered, structured questionnaire and cleaned, entered and analyzed using Statistical package for social science software version 21.

Result
153 (54.8%) of the study participants had good knowledge about emergency contraceptives and only (40.5%) of sexually active participates used emergency contraceptives after unprotected sex. Type of admission and grade level of participants and discussion of reproductive health related issues with parents were significantly associated with good knowledge of Emergency contraceptive. Having partner and grade level of students were among the significant determinants of emergency contraceptive utilization.

Conclusion
The study showed an acceptable level of emergency contraceptive knowledge but only less than half of sexually active respondents used emergency contraceptives. To prevent unintended pregnancy among secondary school students sexual and reproductive health education should be given to students starting from their enrollment. Furthermore, parents should be encouraged to freely discuss sexual and reproductive health matters with their children.
Indication of lethal interactions between a solitary bottlenose dolphin (Tursiops truncatus) and harbor porpoises (Phocoena phocoena) in the German Baltic Sea
Authors: Gross Stephanie , Claus Philip , Wohlsein Peter , Kesselring Tina , Lakemeyer Jan , Reckendorf Anja , Roller Marco , Tiedemann Ralph , Siebert Ursula 
Published: September 2020

AbstractBackgroundAggressive interactions between bottlenose dolphins (Tursiops truncatus) and harbor porpoises (Phocoena phocoena) have been reported in different parts of the world since the late 1990s. In the Baltic Sea, harbor porpoises are the only native cetacean species, while bottlenose dolphins may appear there temporarily. In the fall of 2016, a solitary male photo-identified bottlenose dolphin stayed in the German Baltic Sea of Schleswig-Holstein for 3 months. During that time, the necropsies of the stranded harbor porpoises revealed types of trauma of varying degrees in six animals, which is unusual in this area. The purpose of this study was to determine if the appearance of the bottlenose dolphin could be linked to the trauma of the harbor porpoise carcasses.ResultsPathological findings in these animals included subcutaneous, thoracic and abdominal hemorrhages, multiple, mainly bilateral, rib fractures, and one instance of lung laceration. These findings correspond with the previously reported dolphin-caused injuries in other regions. Moreover, public sighting reports showed a spatial and temporal correlation between the appearance of the dolphin and the stranding of fatally injured harbor porpoises.ConclusionDespite the fact that no attack has been witnessed in German waters to date, our findings indicate the first record of lethal interactions between a bottlenose dolphin and harbor porpoises in the German Baltic Sea. Furthermore, to our knowledge, this is the first report of porpoise aggression by a socially isolated bottlenose dolphin.
Effects of abamectin on lesser grain borer, Rhyzopertha dominica F. (Coleoptera: Bostrichidae), infestation on some stored grains
Authors: Perišić Vesna , Perišić Vladimir , Vukajlović Filip , Predojević Dragana , Rajičić Vera , Andrić Goran , Kljajić Petar 
Published: September 2020

Abstract
Background
Modern methods of stored wheat grain protection from insect pests strive towards optimizing the use of different techniques and methods within integrated pest management (IPM) programs. One of the methods of integral grain protection is the application of natural originating insecticides.

Main body
The potential of the natural origin synthetic insecticide abamectin (a product of soil bacteria, Streptomyces avermitilis fermentation) on the grain borer, Rhyzopertha dominica F. (Coleoptera: Bostrichidae), in stored wheat, barley, ray, oats, and triticale was evaluated. The evaluation was conducted in 3 rates. The effects of its application on the infestation of R. dominica on certain physical and chemical traits of cereal grains were examined. The efficacy of abamectin after 7 days of exposure, in all applied dosages, was low (< 56.5% in wheat and < 30.5% in other grains). Abamectin efficacy was significantly increased after 14 days of exposure. R. dominica mortality was 99.0 and 100% after 21-day exposure at the abamectin rates of 0.5 and 1.0 mg kg−1, respectively. Ten weeks after grain treatment, the 3 examined rates prevented the emergence of progeny. The amount of the damaged grains and dockage, as a nus-product of feeding of R. dominica larvae and imago, compared to the untreated, infested sample was significantly smaller, which represents a positive aspect of abamectin application. The application did not change significantly the moisture, protein, and ash contents, in comparison to the control.

Conclusion
Positive aspects of the abamectin application on different grain species (wheat, barley, rye, oats, and triticale) caused the highest rates of R. dominica mortality after 21 days of exposure where a total prevention of progeny emergence and absence of changes on technological grain properties occurred.