bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Religious Intolerance Good for Your Health?
Authors: Burke Ciarán 
Published: October 2020

Abstract
Legal responses to the covid-19 pandemic have varied widely. Korea represents an interesting case study, as it seemed particularly well prepared, having enacted legislation in the wake of the mers outbreak, in 2015, to tackle future pandemics. This obviated recourse to emergency powers legislation, and couched Korea’s response in normal legislation, which tends to raise fewer human rights concerns than may arise under emergency measures. Despite this, however, Korea’s response to covid-19 raises significant questions about its compliance with core human rights norms under the International Convention on Civil and Political Rights, including freedom of religion and non-discrimination. These arose with regard to the state’s treatmennt of members of the Shincheonji Church of Jesus (scj), a relatively small, occasionally controversial, religious group. The treatment of the scj by the Korean state raises questions about whether its legal approach to tackling covid-19 was fit for purpose.
Acute myeloid leukemia–induced remodeling of the human bone marrow niche predicts clinical outcome
Authors: Chen Yiyang , Hoffmeister Lina Marie , Zaun Yasmin , Arnold Lucas , Schmid Kurt Werner , Giebel Bernd , Klein-Hitpass Ludger , Hanenberg Helmut , Squire Anthony , Reinhardt H. Christian , Dührsen Ulrich , Bertram Stefanie , Hanoun Maher 
Published: October 2020

Abstract
Murine models of myeloid neoplasia show how leukemia infiltration alters the hematopoietic stem cell (HSC) niche to reinforce malignancy at the expense of healthy hematopoiesis. However, little is known about the bone marrow architecture in humans and its impact on clinical outcome. Here, we dissect the bone marrow niche in patients with acute myeloid leukemia (AML) at first diagnosis. We combined immunohistochemical stainings with global gene expression analyses from these AML patients and correlated them with clinical features. Mesenchymal stem and progenitor cells (MSPCs) lost quiescence and significantly expanded in the bone marrow of AML patients. Strikingly, their HSC- and niche-regulating capacities were impaired with significant inhibition of osteogenesis and bone formation in a cell contact–dependent manner through inhibition of cytoplasmic β-catenin. Assessment of bone metabolism by quantifying peripheral blood osteocalcin levels revealed 30% lower expression in AML patients at first diagnosis than in non-leukemic donors. Furthermore, patients with osteocalcin levels ≤11 ng/mL showed inferior overall survival with a 1-year survival rate of 38.7% whereas patients with higher osteocalcin levels reached a survival rate of 66.8%. These novel insights into the human AML bone marrow microenvironment help translate findings from preclinical models and detect new targets which might pave the way for niche-targeted therapies in AML patients.
Heterozygous germ line CSF3R variants as risk alleles for development of hematologic malignancies
Authors: Trottier Amy M. , Druhan Lawrence J. , Kraft Ira L. , Lance Amanda , Feurstein Simone , Helgeson Maria , Segal Jeremy P. , Das Soma , Avalos Belinda R. , Godley Lucy A. 
Published: October 2020

AbstractColony-stimulating factor 3 receptor (CSF3R) encodes the receptor for granulocyte colony-stimulating factor (G-CSF), a cytokine vital for granulocyte proliferation and differentiation. Acquired activating heterozygous variants in CSF3R are the main cause of chronic neutrophilic leukemia, a hyperproliferative disorder. In contrast, biallelic germ line hypomorphic variants in CSF3R are a rare cause of severe congenital neutropenia, a hypoproliferative condition. The impact of heterozygous germ line CSF3R variants, however, is unknown. We identified CSF3R as a new germ line hematologic malignancy predisposition gene through analysis of 832 next-generation sequencing tests conducted in 632 patients with hematologic malignancies. Among germ line CSF3R variants, 3 were abnormal in functional testing, indicating their deleterious nature. p.Trp547* was identified in 2 unrelated men with myelodysplastic syndromes diagnosed at 76 and 33 years of age, respectively. p.Trp547* is a loss-of-function nonsense variant in the extracellular domain that results in decreased CSF3R messenger RNA expression and abrogation of CSF3R surface expression and proliferative responses to G-CSF. p.Ala119Thr is a missense variant found in 2 patients with multiple myeloma and acute lymphoblastic leukemia, respectively. This variant is located between the extracellular immunoglobulin-like and cytokine receptor homology domains and results in decreased G-CSF sensitivity. p.Pro784Thr was identified in a 67-year-old man with multiple myeloma. p.Pro784Thr is a missense variant in the cytoplasmic domain that inhibits CSF3R internalization, producing a gain-of-function phenotype and G-CSF hypersensitivity. Our findings identify germ line heterozygous CSF3R variants as risk factors for development of myeloid and lymphoid malignancies.
Horizontal meta-analysis identifies common deregulated genes across AML subgroups providing a robust prognostic signature
Authors: Nehme Ali , Dakik Hassan , Picou Frédéric , Cheok Meyling , Preudhomme Claude , Dombret Hervé , Lambert Juliette , Gyan Emmanuel , Pigneux Arnaud , Récher Christian , Béné Marie C. , Gouilleux Fabrice , Zibara Kazem , Herault Olivier , Mazurier Frédéric 
Published: October 2020

Abstract
Advances in transcriptomics have improved our understanding of leukemic development and helped to enhance the stratification of patients. The tendency of transcriptomic studies to combine AML samples, regardless of cytogenetic abnormalities, could lead to bias in differential gene expression analysis because of the differential representation of AML subgroups. Hence, we performed a horizontal meta-analysis that integrated transcriptomic data on AML from multiple studies, to enrich the less frequent cytogenetic subgroups and to uncover common genes involved in the development of AML and response to therapy. A total of 28 Affymetrix microarray data sets containing 3940 AML samples were downloaded from the Gene Expression Omnibus database. After stringent quality control, transcriptomic data on 1534 samples from 11 data sets, covering 10 AML cytogenetically defined subgroups, were retained and merged with the data on 198 healthy bone marrow samples. Differentially expressed genes between each cytogenetic subgroup and normal samples were extracted, enabling the unbiased identification of 330 commonly deregulated genes (CODEGs), which showed enriched profiles of myeloid differentiation, leukemic stem cell status, and relapse. Most of these genes were downregulated, in accordance with DNA hypermethylation. CODEGs were then used to create a prognostic score based on the weighted sum of expression of 22 core genes (CODEG22). The score was validated with microarray data of 5 independent cohorts and by quantitative real time-polymerase chain reaction in a cohort of 142 samples. CODEG22-based stratification of patients, globally and into subpopulations of cytologically healthy and elderly individuals, may complement the European LeukemiaNet classification, for a more accurate prediction of AML outcomes.
MazEF-rifampicin interaction suggests a mechanism for rifampicin induced inhibition of persisters
Authors: Alexander Cyrus , Guru Ankeeta , Pradhan Pinkilata , Mallick Sunanda , Mahanandia Nimai Charan , Subudhi Bharat Bhusan , Beuria Tushar Kant 
Published: October 2020

AbstractBackgroundPersistence is a natural phenomenon whereby a subset of a population of isogenic bacteria either grow slow or become dormant conferring them with the ability to withstand various stresses including antibiotics. In a clinical setting bacterial persistence often leads to the recalcitrance of various infections increasing the treatment time and cost. Additionally, some studies also indicate that persistence can also pave way for the emergence of resistant strains. In a laboratory setting this persistent phenotype is enriched in nutritionally deprived environments. Consequently, in a batch culture the late stationary phase is enriched with persistent bacteria. The mechanism of persister cell formation and its regulation is not well understood. Toxin-antitoxin (TA) systems have been implicated to be responsible for bacterial persistence and rifampicin is used to treat highly persistent bacterial strains. The current study tries to explore a possible interaction between rifampicin and the MazEF TA system that furthers the former’s success rate in treating persistent bacteria.ResultsIn the current study we found that the population of bacteria in the death phase of a batch culture consists of metabolically inactive live cells resembling persisters, which showed higher membrane depolarization as compared to the log phase bacteria. We also observed an increase in the expression of the MazEF TA modules in this phase. Since rifampicin is used to kill the persisters, we assessed the interaction of rifampicin with MazEF complex. We showed that rifampicin moderately interacts with MazEF complex with 1:1 stoichiometry.ConclusionOur study suggests that the interaction of rifampicin with MazEF complex might play an important role in inhibition of persisters.
Ontogeny of hepatic metabolism in mule ducks highlights different gene expression profiles between carbohydrate and lipid metabolic pathways
Authors: Massimino William , Davail Stéphane , Secula Aurélie , Andrieux Charlotte , Bernadet Marie-Dominique , Pioche Tracy , Ricaud Karine , Gontier Karine , Morisson Mireille , Collin Anne , Panserat Stéphane , Houssier Marianne 
Published: October 2020

Abstract
Background
The production of foie gras involves different metabolic pathways in the liver of overfed ducks such as lipid synthesis and carbohydrates catabolism, but the establishment of these pathways has not yet been described with precision during embryogenesis. The early environment can have short- and long-term impacts on the physiology of many animal species and can be used to influence physiological responses that is called programming. This study proposes to describe the basal hepatic metabolism at the level of mRNA in mule duck embryos in order to reveal potential interesting programming windows in the context of foie gras production. To this end, a kinetic study was designed to determine the level of expression of selected genes involved in steatosis-related liver functions throughout embryogenesis.
The livers of 20 mule duck embryos were collected every 4 days from the 12th day of embryogenesis (E12) until 4 days after hatching (D4), and gene expression analysis was performed. The expression levels of 50 mRNAs were quantified for these 7 sampling points and classified into 4 major cellular pathways.

Results
Interestingly, most mRNAs involved in lipid metabolism are overexpressed after hatching (FASN, SCD1, ACOX1), whereas genes implicated in carbohydrate metabolism (HK1, GAPDH, GLUT1) and development (HGF, IGF, FGFR2) are predominantly overexpressed from E12 to E20. Finally, regarding cellular stress, gene expression appears quite stable throughout development, contrasting with strong expression after hatching (CYP2E1, HSBP1, HSP90AA1).

Conclusion
For the first time we described the kinetics of hepatic ontogenesis at mRNA level in mule ducks and highlighted different expression patterns depending on the cellular pathway. These results could be particularly useful in the design of embryonic programming for the production of foie gras.
The role of the msaABCR operon in implant-associated chronic osteomyelitis in Staphylococcus aureus USA300 LAC
Authors: Sahukhal Gyan S. , Tucci Michelle , Benghuzzi Hamed , Wilson Gerri , Elasri Mohamed O. 
Published: October 2020

Abstract
Background
The msaABCR operon regulates several staphylococcal phenotypes such as biofilm formation, capsule production, protease production, pigmentation, antibiotic resistance, and persister cells formation. The msaABCR operon is required for maintaining the cell wall integrity via affecting peptidoglycan cross-linking. The msaABCR operon also plays a role in oxidative stress defense mechanism, which is required to facilitate persistent and recurrent staphylococcal infections. Staphylococcus aureus is the most frequent cause of chronic implant-associated osteomyelitis (OM). The CA-MRSA USA300 strains are predominant in the United States and cause severe infections, including bone and joint infections.

Results
The USA300 LAC strain caused significant bone damage, as evidenced by the presence of severe bone necrosis with multiple foci of sequestra and large numbers of multinucleated osteoclasts. Intraosseous survival and biofilm formation on the K-wires by USA300 LAC strains was pronounced. However, the msaABCR deletion mutant was attenuated. We observed minimal bone necrosis, with no evidence of intramedullary abscess and/or fibrosis, along reduced intraosseous bacterial population and significantly less biofilm formation on the K-wires by the msaABCR mutant. microCT analysis of infected bone showed significant bone loss and damage in the USA300 LAC and complemented strain, whereas the msaABCR mutant’s effect was reduced. In addition, we observed increased osteoblasts response and new bone formation around the K-wires in the bone infected by the msaABCR mutant. Whole-cell proteomics analysis of msaABCR mutant cells showed significant downregulation of proteins, cell adhesion factors, and virulence factors that interact with osteoblasts and are associated with chronic OM caused by S. aureus.

Conclusion
This study showed that deletion of msaABCR operon in USA300 LAC strain lead to defective biofilm in K-wire implants, decreased intraosseous survival, and reduced cortical bone destruction. Thus, msaABCR plays a role in implant-associated chronic osteomyelitis by regulating extracellular proteases, cell adhesions factors and virulence factors. However additional studies are required to further define the contribution of msaABCR-regulated molecules in osteomyelitis pathogenesis.
Diversity of mucoid to non-mucoid switch among carbapenemase-producing Klebsiella pneumoniae
Authors: Chiarelli Adriana , Cabanel Nicolas , Rosinski-Chupin Isabelle , Zongo Pengdbamba Dieudonné , Naas Thierry , Bonnin Rémy A. , Glaser Philippe 
Published: October 2020

Abstract
Background
Klebsiella pneumoniae is a leading cause of intractable hospital-acquired multidrug-resistant infections and carbapenemase-producing K. pneumoniae (CPKp) are particularly feared. Most of the clinical isolates produce capsule as a major virulence factor. Recombination events at the capsule locus are frequent and responsible for capsule diversity within Klebsiella spp. Capsule diversity may also occur within clonal bacterial populations generating differences in colony aspect. However, little is known about this phenomenon of phenotypic variation in CPKp and its consequences.

Results
Here, we explored the genetic causes of in vitro switching from capsulated, mucoid to non-mucoid, non-capsulated phenotype in eight clinical CPKp isolates. We compared capsulated, mucoid colony variants with one of their non-capsulated, non-mucoid isogenic variant. The two colony variants were distinguished by their appearance on solid medium. Whole genome comparison was used to infer mutations causing phenotypic differences. The frequency of phenotypic switch was strain-dependent and increased along with colony development on plate. We observed, for 72 non-capsulated variants that the loss of the mucoid phenotype correlates with capsule deficiency and diverse genetic events, including transposition of insertion sequences or point mutations, affecting genes belonging to the capsule operon. Reduced or loss of capsular production was associated with various in vitro phenotypic changes, affecting susceptibility to carbapenem but not to colistin, in vitro biofilm formation and autoaggregation.

Conclusions
The different impact of the phenotypic variation among the eight isolates in terms of capsule content, biofilm production and carbapenem susceptibility suggested heterogeneous selective advantage for capsular loss according to the strain and the mutation. Based on our results, we believe that attention should be paid in the phenotypic characterization of CPKp clinical isolates, particularly of traits related to virulence and carbapenem resistance.
Integration analysis of PacBio SMRT- and Illumina RNA-seq reveals candidate genes and pathway involved in selenium metabolism in hyperaccumulator Cardamine violifolia
Authors: Rao Shen , Yu Tian , Cong Xin , Xu Feng , Lai Xiaozhuo , Zhang Weiwei , Liao Yongling , Cheng Shuiyuan 
Published: October 2020

Abstract
Background
Cardamine violifolia, native to China, is one of the selenium (Se) hyperaccumulators. The mechanism of Se metabolism and tolerance remains unclear, and only limited genetic information is currently available. Therefore, we combined a PacBio single-molecule real-time (SMRT) transcriptome library and the Illumina RNA-seq data of sodium selenate (Na2SeO4)-treated C. violifolia to further reveal the molecular mechanism of Se metabolism.

Results
The concentrations of the total, inorganic, and organic Se in C. violifolia seedlings significantly increased as the Na2SeO4 treatment concentration increased. From SMRT full-length transcriptome of C. violifolia, we obtained 26,745 annotated nonredundant transcripts, 14,269 simple sequence repeats, 283 alternative splices, and 3407 transcription factors. Fifty-one genes from 134 transcripts were identified to be involved in Se metabolism, including transporter, assimilatory enzyme, and several specific genes. Analysis of Illumina RNA-Seq data showed that a total of 948 differentially expressed genes (DEGs) were filtered from the four groups with Na2SeO4 treatment, among which 11 DEGs were related to Se metabolism. The enrichment analysis of KEGG pathways of all the DEGs showed that they were significantly enriched in five pathways, such as hormone signal transduction and plant-pathogen interaction pathways. Four genes related to Se metabolism, adenosine triphosphate sulfurase 1, adenosine 5′-phosphosulfate reductase 3, cysteine (Cys) desulfurase 1, and serine acetyltransferase 2, were regulated by lncRNAs. Twenty potential hub genes (e.g., sulfate transporter 1;1, Cys synthase, methionine gamma-lyase, and Se-binding protein 1) were screened and identified to play important roles in Se accumulation and tolerance in C. violifolia as concluded by weighted gene correlation network analysis. Based on combinative analysis of expression profiling and annotation of genes as well as Se speciation and concentration in C. violifolia under the treatments with different Na2SeO4 concentrations, a putative Se metabolism and assimilation pathway in C. violifolia was proposed.

Conclusion
Our data provide abundant information on putative gene transcriptions and pathway involved in Se metabolism of C. violifolia. The findings present a genetic resource and provide novel insights into the mechanism of Se hyperaccumulation in C. violifolia.
Myocardial ischemia 10 years after a modified Cabrol procedure in a 42-year-old patient with Marfan syndrome
Authors: Hsiao Ya Wei , Huang Jiann Woei 
Published: October 2020

Abstract
Background
Marfan syndrome, a genetic disorder of the connective tissue, may cause aortic root dilation with aortic insufficiency, aortic dissection and mitral prolapse with mitral insufficiency. We present a case of a late complication of the modified Cabrol procedure that included replacing the ascending aorta with a composite graft.

Case presentation
In February 2019, a 42-year-old female patient with Marfan syndrome who presented with chest pain was sent to the Emergency Department. She had undergone the modified Cabrol procedure 10 years prior. Upon presenting, laboratory analysis revealed elevated troponin-I levels. Electrocardiogram showed new inverted T waves over lead I, aVL and V4 to V6. Contrast computed tomography (CT) revealed thrombosis in the Dacron graft. Percutaneous coronary angiography was conducted, and a large thrombus in the graft was noted. Thrombolytic therapy and percutaneous coronary intervention were performed, after which the patient had no more symptoms and was discharged without complications.

Conclusions
Aortic root surgery, including the Cabrol or modified Cabrol procedure, is necessary for complicated cases of aortic dilations, such as in patients with Marfan syndrome, even though the Cabrol or modified Cabrol procedure has a high complication rate. Regarding this case, we were surprised by the timing of the myocardial ischemia and the position of the thrombus, which differed from other cases. To better manage such a patient’s condition and to detect the formation of thrombus early, completeness of the graft and possible stenosis of the anastomosis site to avoid preventable myocardial ischemia, we suggest that patients should have regular image follow-up, even years after the Cabrol or modified Cabrol procedure.
Eosinophilic peritonitis with colon cancer: a case report
Authors: Ataka Ryo , Tanaka Hirokazu , Yagi Shintaro , Yamane Kei , Yoshino Kenji , Miyauchi Tomoyuki , Yoh Tomoaki , Arafuka Keiichi , Fujita Shinichi , Hamada Akihiko , Endo Bunji , Uemoto Shinji 
Published: October 2020

Abstract
Background
Eosinophilic gastrointestinal disorders (EGIDs) are a rare group of inflammatory disorders that can occur anywhere along the gastrointestinal tract, from the esophagus to the rectum. In particular, those with malignant or benign tumors are extremely rare.

Case presentation
A 62-year-old man was referred to our hospital with a chief complaint of abdominal fullness. The peripheral white blood cell count was 19,400/µL, and the eosinophil count was 13,300/µL. Abdominal computed tomography showed massive ascites. Cytology of the ascitic fluid showed a large amount of eosinophils and no malignancy. Upper and lower gastrointestinal endoscopies were performed on the suspicion of EGIDs, and colon cancer with no other abnormalities was found. The biopsies of the cancer lesions and non-cancer lesions also showed significant differences in eosinophil counts per high-power field (HPF) between the cancer and non-cancer lesions (median 77.5 [IQR 52–115] vs. 40.5 [35–56]/HPF, P < 0.05). Exploratory laparoscopy showed cloudy massive ascites and thickening of the mesentery. Pathological examination of the mesentery showed a large amount of eosinophils (median 177.5 [IQR 91–227]/HPF) and no malignancy. Based on these findings, it was suspected that the massive ascites due to eosinophilic peritonitis could be associated with colon cancer. Steroid administration resulted in immediate disappearance of the ascites, and laparoscopic left hemicolectomy was safely performed 6 weeks after steroid administration.

Conclusion
This report presented a case of eosinophilic peritonitis that could be related to colon cancer. Exploratory laparoscopy was useful to detect the cause of ascites. The possibility that eosinophilic peritonitis was associated with colon cancer is discussed based on the histopathological findings.