bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in Incidence and Outcomes of Clostridium difficile Colitis in Hospitalized Patients of Febrile Neutropenia
Authors: Siddiqui Nauman S. , Khan Zubair , Khan Mohammad S. , Khan Zarmina , Haq Khwaja F. , Solanki Shantanu D. , Munigala Satish , Khan Muhammad A. , Saif Muhammad W. , Nawras Ali 
Published: January 2019

Introduction:
Clostridium difficile infection (CDI) has been attracting attention lately as the most common hospital acquired infection. Patients with neutropenia because of malignancy seem to be at an increased risk for developing CDI. There is currently limited data that assesses the national burden and outcomes of CDI in Febrile Neutropenia (FN).

Methods:
We analyzed the National Inpatient Sample (NIS) database for all subjects with discharge diagnosis of FN with or without CDI (ICD-9 codes 288.00, 288.03,780.60, and 008.45) as primary or secondary diagnosis during the period from 2008 to 2014. All analyses were performed with SAS, version 9.4 (SAS Institute).

Results:
From 2008 to 2014 there were total 19422 discharges of FN patients with CDI. There was a rising incidence of CDI in patients with FN from 4.11% (in 2008) to 5.83% (in 2014). The In-hospital mortality showed a decreasing trend from 7.79% (in 2008) to 5.32% (in 2014), likely because of improvements in diagnostics and treatment. The overall mortality (6.37% vs. 4.61%), length of stay >5 days (76.45% vs. 50.98%), hospital charges >50,000 dollars (64.43% vs. 40.29%), colectomy and colostomy (0.35% vs. 0.15%), and discharge to skilled nursing facility (10.47% vs. 6.43%) was significantly more in FN patients with CDI versus without CDI over 7 years (2008 to 2014). Age above 65 years, Hispanic race, hematological malignancies, urban hospital settings, and sepsis were significant predictors of mortality in febrile neutropenia patients with CDI.

Discussion:
Despite the significant decrease in mortality, the incidence of CDI is rising in hospitalized FN patients with underlying hematological malignancies. Risk factor modification, with the best possible empiric antibiotic regimen is imperative for reducing mortality and health care costs in this cohort.
Efficacy and Safety of Recombinant Activated Factor VII Off-label Use in a Pediatric Hematology/Oncology Cohort
Authors: Mesleh Shayeb Akram , Su Yin , Kang Guolian , Elbahlawan Lama , Reiss Ulrike M. 
Published: January 2019

Background:
Recombinant activated factor VII (rFVIIa) has been used off-label to treat or prevent severe bleeding in patients for whom conventional treatments are unsuccessful. However, studies in children remain limited.

Procedure:
To examine the efficacy and safety of rFVIIa, we performed a retrospective analysis of rFVIIa off-label use in a pediatric hematology/oncology cohort at a single center from 2006 to 2014.

Results:
Of 58 patients identified, 46 (79.3%) received rFVIIa to treat bleeding and 12 (20.7%) to prevent bleeding. Thirty-three (71.7%) patients had life-threatening bleeding. In the treatment group, 63.0% patients were responders (ie, bleeding decreased or stopped) and 37.0% were nonresponders (ie, bleeding did not change). Blood products usage was similar between responders and nonresponders. After rFVIIa administration, prothrombin time, partial thromboplastin time and lactate were significantly lower, but fibrinogen was significantly higher in responders than nonresponders. Venous thromboembolism developed in 5.2% (3/58) patients, but its relation to rFVIIa remains unclear. Responders had significantly lower mortality than nonresponders (17.2% vs. 82.4%, P<0.0001).

Conclusions:
rFVIIa controlled most bleeding events in this cohort, despite predominance of life-threatening bleeding, suggesting good efficacy. Venous thromboembolism rate was low. Further studies are warranted to identify predictors of favorable response to rFVIIa in similar patients.
Hydronephrosis Associated With Pelvic Organ Prolapse: A Systematic Review
Authors: Siddique Moiuri , Ingraham Caitlin , Kudish Bela , Iglesia Cheryl B. , Polland Allison 
Published: January 2019

Objectives
The aim of this study was to report the prevalence of hydronephrosis associated with pelvic organ prolapse (POP).

Methods
We conducted a MEDLINE and PubMed search from 1996 to October 2016 using PRISMA guidelines. Eight studies met criteria for inclusion, including 3 prospective and 5 retrospective studies.

Results
The prevalence of hydronephrosis ranged from 3.5% to 30.6% in studies that included multiple stages of prolapse. Hydronephrosis correlated with prolapse severity in multiple studies, but serum creatinine did not consistently predict hydronephrosis. Two studies reported a significantly higher prevalence of hydronephrosis in patients with uterovaginal prolapse compared with vaginal vault prolapse. Complete resolution of hydronephrosis was described in 56% to 83% of patients after undergoing surgical treatment for advanced prolapse.

Conclusions
Hydronephrosis among patients with POP is not rare, and we suggest consideration of upper tract evaluation in patients presenting with POP, particularly in those with advanced uterovaginal prolapse electing to proceed with expectant or conservative management.
High-throughput enrichment and isolation of megakaryocyte progenitor cells from the mouse bone marrow
Authors: Bush Lucas M. , Healy Connor P. , Marvin James E. , Deans Tara L. 
Published: January 2019

AbstractMegakaryocytes are a rare population of cells that develop in the bone marrow and function to produce platelets that circulate throughout the body and form clots to stop or prevent bleeding. A major challenge in studying megakaryocyte development, and the diseases that arise from their dysfunction, is the identification, classification, and enrichment of megakaryocyte progenitor cells that are produced during hematopoiesis. Here, we present a high throughput strategy for identifying and isolating megakaryocytes and their progenitor cells from a heterogeneous population of bone marrow samples. Specifically, we couple thrombopoietin (TPO) induction, image flow cytometry, and principle components analysis (PCA) to identify and enrich for megakaryocyte progenitor cells that are capable of self-renewal and directly differentiating into mature megakaryocytes. This enrichment strategy distinguishes megakaryocyte progenitors from other lineage-committed cells in a high throughput manner. Furthermore, by using image flow cytometry with PCA, we have identified a combination of markers and characteristics that can be used to isolate megakaryocyte progenitor cells using standard flow cytometry methods. Altogether, these techniques enable the high throughput enrichment and isolation of cells in the megakaryocyte lineage and have the potential to enable rapid disease identification and diagnoses ahead of severe disease progression.
RNAIndel: discovering somatic coding indels from tumor RNA-Seq data
Authors: Hagiwara Kohei , Ding Liang , Edmonson Michael N. , Rice Stephen V. , Newman Scott , Meshinchi Soheil , Ries Rhonda E. , Rusch Michael , Zhang Jinghui 
Published: January 2019

AbstractReliable identification of expressed somatic insertion/deletion (indels) is an unmet demand due to artifacts generated in PCR-based RNA-Seq library preparation and the lack of normal RNA-Seq data, presenting analytical challenges for discovery of somatic indels in tumor trasncriptome.By implementing features characterized by PCR-free whole-genome and whole-exome sequencing into a machine-learning framework, we present RNAIndel, a tool for predicting somatic, germline and artifact indels from tumor RNA-Seq data alone. RNAIndel robustly predicts 87□93% of somatic indels from 235 samples with heterogeneous conditions, even recovering subclonal (VAF range 0.01–0.15) driver indels missed by targeted deep-sequencing, outperforming the current best-practice for RNA-Seq variant calling which had 57% sensitivity but with 12 times more false positives.RNAIndel is freely available at https://github.com/stjude/RNAIndelContactjinghui.zhang@stjude.org
Dissociating orexin-dependent and -independent functions of orexin neurons using novel orexin-Flp knock-in mice
Authors: Chowdhury Srikanta , Jung Hung Chi , Izawa Shuntaro , Inutsuka Ayumu , Kawamura Meiko , Kawashima Takashi , Bito Haruhiko , Imayoshi Itaru , Abe Manabu , Sakimura Kenji , Yamanaka Akihiro 
Published: January 2019

AbstractUninterrupted arousal is important for survival during threatening situations. Activation of orexin/hypocretin neurons is implicated in sustained arousal. However, orexin neurons produce and release orexin as well as several co-transmitters including dynorphin and glutamate. Thus, it is important to disambiguate orexin peptide-dependent and -independent physiological functions of orexin neurons. To attain this, we generated a novel orexin-flippase (Flp) knock-in (KI) mouse line. Crossing with Flp-reporter or Cre-expressing mice showed gene expression exclusively in orexin neurons. Histological studies confirmed that orexin was completely knock-out (KO) in KI/KI homozygous mice. Orexin neurons without orexin showed altered electrophysiological properties, as well as received decreased glutamatergic inputs. Selective chemogenetic activation revealed that both orexin and co-transmitters functioned to increase wakefulness, however, orexin was indispensable to promote sustained arousal. Surprisingly, activation of orexin neurons without orexin caused a significant increase in the total time spent in cataplexy. Taken together, orexin is essential to maintain basic membrane properties and input-output computation of orexin neurons, as well as to exert awake-sustaining aptitude of orexin neurons.
GABA neurons in the ventral tegmental area regulate non-rapid eye movement sleep in mice
Authors: Chowdhury Srikanta , Matsubara Takanori , Miyazaki Toh , Ono Daisuke , Abe Manabu , Sakimura Kenji , Yamanaka Akihiro 
Published: January 2019

AbstractThe daily sleep/wakefulness cycle is regulated by coordinated interactions between sleep- and wakefulness-regulating neural circuitry. However, the detailed neural circuitry mediating sleep is far from understood. Here, we found that glutamic acid decarboxylase 67 (Gad67)-positive GABAergic neurons in the ventral tegmental area (VTAGad67+) are a key regulator of non-rapid eye movement (NREM) sleep in mice. VTAGad67+ neurons project to multiple brain areas implicated in sleep/wakefulness regulation such as the lateral hypothalamus (LH) and dorsal raphe nucleus. Chemogenetic activation of VTAGad67+ neurons promoted NREM sleep with higher delta power whereas optogenetic inhibition of these neurons induced prompt arousal from NREM sleep under highly somnolescent conditions, but not during REM sleep. In vivo fiber photometry recordings revealed that VTAGad67+ neurons showed the highest population activity in NREM sleep and the lowest activity in REM sleep. Acute brain slice electrophysiology combined with optogenetics revealed that VTAGad67+ neurons directly innervate and inhibit wake-promoting orexin/hypocretin neurons in the LH by releasing GABA. Taken together, we reveal that VTAGad67+ neurons play a crucial role in the regulation of NREM sleep.
Indolergic receptors of the elephant mosquitoToxorhynchites amboinensis
Authors: Amir Dekel , Yakir Esther , Bohbot Jonathan D. 
Published: January 2019

AbstractThe conservation of the mosquito indolergic receptors across the Culicinae and Anophelinae mosquito lineages, which spans 200 million years of evolution, is a testament to the central role of indolic compounds in the biology of these insects. Indole and skatole have been associated with the detection of oviposition sites and animal hosts. To evaluate the potential ecological role of these two compounds, we have used a pharmacological approach to characterize homologs of the indolergic receptorsOr2and Or10in the non-hematophagous elephant mosquitoToxorhynchites amboinensis. We provide evidence that both receptors are narrowly tuned to indole and skatole like their counterparts from hematophagous mosquitoes. These findings indicate that indole and skatole are operating in a non-animal-host seeking context inToxorhynchitesand underscore the importance of understanding their roles in hematophagous mosquitoes.
Reference genome for the WHO reference strain for Mycobacterium bovis BCG Danish, the present tuberculosis vaccine
Authors: Borgers Katlyn , Ou Jheng-Yang , Zheng Po-Xing , Tiels Petra , Van Hecke Annelies , Plets Evelyn , Michielsen Gitte , Festjens Nele , Callewaert Nico , Lin Yao-Cheng 
Published: January 2019

ABSTRACTMycobacterium bovis bacillus Calmette-Guérin (M. bovis BCG) is the only vaccine available against tuberculosis (TB). This study reports on an integrated genome analysis workflow for BCG, resulting in the completely assembled genome sequence of BCG Danish 1331 (07/270), one of the WHO reference strains for BCG vaccines. We demonstrate how this analysis workflow enables the resolution of genome duplications and of the genome of engineered derivatives of this vaccine strain.
Myosin Orientation in a Muscle Fiber Determined with High Angular Resolution Using Bifunctional Spin Labels
Authors: Savich Yahor , Binder Benjamin P. , Thompson Andrew R. , Thomas David D. 
Published: January 2019

ABSTRACTWe have measured the orientation of the myosin light chain domain (lever arm) elements in demembranated muscle fibers by electron paramagnetic resonance (EPR), using a bifunctional spin label (BSL), with angular resolution of 4 degrees. Despite advances in X-ray crystallography and cryo-electron microscopy (cryo-EM), and fluorescence polarization, none of these techniques provide high-resolution structural information about the myosin light chain domain under ambient conditions in a muscle fiber. Two cysteines, 4 residues apart, were engineered on two α-helices in the myosin regulatory light chain (RLC), permitting stereoselective site-directed labeling with BSL. One labeled helix (helix E) is adjacent to the myosin lever arm, the other helix (helix B) is located farther apart from the motor domain beyond the “hinge” of the myosin. By exchanging BSL-labeled RLC onto oriented muscle fibers, we obtained EPR spectra that determined angular distributions of BSL with high resolution, which enabled the accurate determination of helix orientation of individual structural elements with respect to the muscle fiber axis. In the absence of ATP (rigor), each of the two labeled helices exhibited both ordered (σ ~ 9-11 degrees) and disordered (σ > 38 degrees) populations. We used these angles to determine the orientation of the myosin lever arm, concluding that the oriented population has lever arms that are perpendicular to the muscle fiber axis. This orientation is ~33 degrees different than predicted from a standard “lever arm down” model based on cryo-EM of actin decorated with isolated myosin heads, but it is compatible with fluorescence polarization and EM data obtained from muscle fibers. The addition of ATP, in the absence of Ca2+, shifted the orientation to a much more disordered distribution.SummaryWe used electron paramagnetic resonance to determine the orientation of elements within the myosin regulatory light chain in skinned skeletal muscle fibers. A bifunctional spin label provided sufficient resolution to detect an ordered population of lever arms perpendicular to actin.
The Effects of Alcohol and Cannabinoid Exposure during the Brain Growth Spurt on Behavioral Development in Rats
Authors: Breit Kristen R. , Zamudio Brandonn , Thomas Jennifer D. 
Published: January 2019

AbstractCannabis is the most commonly used illicit drug among pregnant women. Moreover, over half of pregnant women who are consuming cannabis are also consuming alcohol; however, the consequences of combined prenatal alcohol and cannabis exposure on fetal development are not well understood. The current study examined behavioral development following exposure to ethanol (EtOH) and/or CP-55,940 (CP), a cannabinoid receptor agonist. From postnatal days (PD) 4-9, a period of brain development equivalent to the third trimester, Sprague-Dawley rats received EtOH (5.25g/kg/day) or sham intubation, as well as CP (0.4 mg/kg/day) or vehicle. All subjects were tested on open field activity (PD 18-21), spatial learning (PD 40-46), and elevated plus maze (PD 30) tasks. Both EtOH and CP increased locomotor activity in the open field, and the combination produced more severe overactivity than either exposure alone. Similarly, increases in thigmotaxis in the Morris water maze were caused by either EtOH or CP alone, and were more severe with combined exposure, although only EtOH impaired spatial learning. Finally, developmental CP, but not EtOH, increased time spent in the open arms on the elevated plus maze. Overall, these data indicate that EtOH and CP produce some independent domain-specific effects, but many effects of EtOH and CP on behavior were additive. Importantly, these data suggest that combined prenatal exposure to alcohol and cannabis may be more damaging to the developing fetus, which has implications for the lives of affected individuals and families and also for establishing public health policy.
Cortical and Cardiovascular Regulation Support Adaptation to Ambient Sound Environment
Authors: Hao Yu , Gupta Disha , Sun Qiuyan , Yao Lin 
Published: January 2019

AbstractAdaptation in complex biological systems is a consequence of sensitivity to environmental changes. We investigate how responses to unattended background sound changes are influenced by the interaction of external (pitch sequence context) and internal factors (biological regulation). Cortical responses (electroencephalograph Mismatch Negativity) demonstrated increased intensity and prolonged latency in unattended pitch changes in the context of the ascending pitch sequence compared with the descending pitch sequence. Moreover, ascending pitch context is associated with more activation of anterior cingula cortex and insula, suggesting arousal effect and internal regulation. However, the intensified and prolonged responses were supported by cortical and cardiovascular biomarkers for regulation respectively. These findings suggest that biological regulation may be associated with environmental context and play different roles in response sensitivity in terms of intensity and speed.
Genetic predisposition to mosaic Y chromosome loss in blood is associated with genomic instability in other tissues and susceptibility to non-haematological cancers
Authors: Thompson Deborah J. , Genovese Giulio , Halvardson Jonatan , Ulirsch Jacob C. , Wright Daniel J. , Terao Chikashi , Davidsson Olafur B. , Day Felix R. , Sulem Patrick , Jiang Yunxuan , Danielsson Marcus , Davies Hanna , Dennis Joe , Dunlop Malcolm G. , Easton Douglas F. , Fisher Victoria A. , Zink Florian , Houlston Richard S. , Ingelsson Martin , Kar Siddhartha , Kerrison Nicola D. , Kristjansson Ragnar P. , Li Rong , Loveday Chey , Mattisson Jonas , McCarroll Steven A. , Murakami Yoshinori , Murray Anna , Olszewski Pawel , Rychlicka-Buniowska Edyta , Scott Robert A. , Thorsteinsdottir Unnur , Tomlinson Ian , Moghadam Behrooz Torabi , Turnbull Clare , Wareham Nicholas J. , Gudbjartsson Daniel F. ,   INTEGRAL-ILCCO,   The Breast Cancer Association Consortium,   CIMBA,   The Endometrial Cancer Association Consortium,   The Ovarian Cancer Association Consortium,   The PRACTICAL Consortium,   The Kidney Cancer GWAS Meta-Analysis Project,   eQTLGen Consortium,   BIOS Consortium,   23andMe Research Team, Kamatani Yoichiro , Finucane Hilary K. , Hoffmann Eva R. , Jackson Steve P. , Stefansson Kari , Auton Adam , Ong Ken K. , Machiela Mitchell J. , Loh Po-Ru , Dumanski Jan P. , Chanock Stephen J. , Forsberg Lars A. , Perry John R. B. 
Published: January 2019

AbstractMosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism, yet our knowledge of the causes and consequences of this is limited. Using a newly developed approach, we estimate that 20% of the UK Biobank male population (N=205,011) has detectable LOY. We identify 156 autosomal genetic determinants of LOY, which we replicate in 757,114 men of European and Japanese ancestry. These loci highlight genes involved in cell-cycle regulation, cancer susceptibility, somatic drivers of tumour growth and cancer therapy targets. Genetic susceptibility to LOY is associated with non-haematological health outcomes in both men and women, supporting the hypothesis that clonal haematopoiesis is a biomarker of genome instability in other tissues. Single-cell RNA sequencing identifies dysregulated autosomal gene expression in leukocytes with LOY, providing insights into how LOY may confer cellular growth advantage. Collectively, these data highlight the utility of studying clonal mosaicism to uncover fundamental mechanisms underlying cancer and other ageing-related diseases.
Contribution of Lateral Gene Transfer to the evolution of the eukaryotic fungus Piromyces sp. E2: Massive bacterial transfer of genes involved in carbohydrate metabolism
Authors: Duarte Isabel , Huynen Martijn A. 
Published: January 2019

ABSTRACTLateral gene transfer (also known as Horizontal Gene Transfer) is the transmission of genetic material between phylogenetically unrelated organisms. Previous studies have been showing the importance of this process for the evolution of unicellular eukaryotes, particularly those living in highly competitive niches such as the herbivore gut.Pyromices sp. is an obligate anaerobic chytrid fungus that grows as a commensal organism in the gut of mammalian herbivores, possessing hydrogenosomes instead of mitochondria, producing hydrogen, and playing a key role in the digestion of plant cell wall material. These particular features make its genome particularly valuable for the study of the evolution and adaptation of unicellular eukaryotes to the cellulose-rich and anaerobic environment of the herbivore gut.Here we performed a detailed large-scale lateral gene transfer (LGT) analysis of the genome from the chytrid fungus Piromyces sp. strain E2. For this we set out to elucidate (i) which proteins were likely transferred to its genome, (ii) from which bacterial donor species, and (iii) which functions were laterally acquired. Using sequence comparison and phylogenetic analyses, we have found 704 LGT candidates, representing nearly 5% of the Piromyces sp. orfeome (i.e. the complete set of open reading frames), mostly transferred from Firmicutes, Fibrobacteres, Bacteroidetes and Proteobacteria, closely following the microbial abundance reported for the herbivore gut. With respect to the functional analysis, the LGT candidate set includes proteins from 250 different orthologous groups, with a clear over-representation of genes belonging to the Carbohydrate Transport and Metabolism functional class. Finally, we performed a graph density analysis on the metabolic pathways formed by the LGT candidate proteins, showing that the acquired functions fit cohesively within Piromyces metabolic network, and are not randomly distributed within the global KEGG metabolic map. Overall, our study suggests that Piromyces’ adaptation to living anaerobically and in the a cellulose-rich environment has been undoubtedly fostered by the acquisition of foreign genes from bacterial neighbors, showing the global importance of such evolutionary mechanisms for successful eukaryotic thriving in such competitive environments.