bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coolpup.py: versatile pile-up analysis of Hi-C data
Authors: Flyamer Ilya M , Illingworth Robert S , Bickmore Wendy A 
Published: January 2020

Abstract

Motivation
Hi-C is currently the method of choice to investigate the global 3D organization of the genome. A major limitation of Hi-C is the sequencing depth required to robustly detect loops in the data. A popular approach used to mitigate this issue, even in single-cell Hi-C data, is genome-wide averaging (piling-up) of peaks, or other features, annotated in high-resolution datasets, to measure their prominence in less deeply sequenced data. However, current tools do not provide a computationally efficient and versatile implementation of this approach.

Results
Here, we describe coolpup.py—a versatile tool to perform pile-up analysis on Hi-C data. We demonstrate its utility by replicating previously published findings regarding the role of cohesin and CTCF in 3D genome organization, as well as discovering novel details of Polycomb-driven interactions. We also present a novel variation of the pile-up approach that can aid the statistical analysis of looping interactions. We anticipate that coolpup.py will aid in Hi-C data analysis by allowing easy to use, versatile and efficient generation of pile-ups.

Availability and implementation
Coolpup.py is cross-platform, open-source and free (MIT licensed) software. Source code is available from https://github.com/Phlya/coolpuppy and it can be installed from the Python Packaging Index.
Ultraviolet screening increases with elevation in translucent bracts of Rheum nobile (Polygonaceae), an alpine ‘glasshouse’ plant from the high Himalayas
Authors: Song Bo , Gao Yongqian , Stöcklin Jürg , Song Minshu , Sun Lu , Sun Hang 
Published: January 2020

Abstract
Specialized bracts of Himalayan ‘glasshouse’ plants are well known for adapting to diverse stresses in alpine environments, thus ensuring normal sexual reproduction. However, little information is available on how such specialized plants cope with the elevational increase in stress. In this study, we determine the elevational pattern of ultraviolet (UV) protection provided by the translucent bracts of Rheum nobile, a giant ‘glasshouse’ plant species, endemic to the high Himalayas, and examine its effect on pollen germination and pollen tube growth. Both UV-A and UV-B radiation in the open air increased with elevation, but their intensity beneath bracts remained constant with elevation, suggesting that the bracts of R. nobile growing at higher elevations have an increased ability to screen UV radiation. Enhanced UV-B radiation, equivalent to that experienced at higher elevations (4800 m a.s.l.) compared to that at lower elevations (4200 m a.s.l.), significantly reduced pollen germination and pollen tube growth. Pollen grains from plants at higher elevations were not more tolerant to UV-B radiation. UV absorbance and the content of flavonoids in bracts increased with elevation, but a similar trend was not found in either UV reflectance or adaxial trichome density, suggesting that bract UV absorbance may play a more active role than bract UV reflectance in helping plants cope with the increasing UV radiation. Our results indicate that the bracts of R. nobile have the ability to cope with enhanced UV radiation with increasing elevation through increased UV absorbance, thus protecting pollen grains from injury caused by higher levels of UV radiation, and consequently ensuring normal sexual reproduction in stressful high-alpine conditions.
Strategies to prevent hypertrophic scar formation: a review of therapeutic interventions based on molecular evidence
Authors: Shirakami Eri , Yamakawa Sho , Hayashida Kenji 
Published: January 2020

AbstractOnce scar tissues mature, it is impossible for the surrounding tissue to regenerate normal dermal tissue. Therefore, it is essential to understand the fundamental mechanisms and establish effective strategies to inhibit aberrant scar formation. Hypertrophic scar formation is considered a result of the imbalance between extracellular matrix synthesis and degradation during wound healing. However, the underlying mechanisms of hypertrophic scar development are poorly understood. The purpose of this review was to outline the management in the early stage after wound healing to prevent hypertrophic scar formation, focusing on strategies excluding therapeutic agents of internal use. Treatment aimed at molecular targets, including cytokines, will be future options to prevent and treat hypertrophic scars. More basic studies and clinical trials, including combination therapy, are required to investigate the mechanisms and prevent hypertrophic scar formation.
Dopamine Differentially Regulates Response Dynamics of Prefrontal Cortical Principal Neurons and Interneurons to Optogenetic Stimulation of Inputs from Ventral Tegmental Area
Authors: Zhong Ping , Qin Luye , Yan Zhen 
Published: January 2020

Abstract
Prefrontal cortex (PFC) is highly influenced by the inputs from ventral tegmental area (VTA); however, how the projection from VTA impacts PFC neurons and how the synaptically released dopamine affects PFC activity are largely unclear. Using optogenetics and electrophysiological approaches, we examined the impact of VTA stimulation on PFC principal neurons and parvalbumin-positive (PV+) interneurons and the modulatory role of dopamine. We found that the brief activation of the VTA–PFC circuit immediately induced action potential firing, which was mediated by glutamatergic transmission. However, strong stimulation of VTA gradually induced a marked and prolonged enhancement of the excitability of PFC PV+ interneurons and a modest and short-lived enhancement of the excitability of PFC principal neurons. Blocking dopamine receptors (DARs) shortened the VTA excitation of PFC PV+ interneurons and prolonged the VTA excitation of PFC principal neurons. Blocking GABAA receptors induced a similar effect as DAR antagonists in PFC principal neurons, suggesting that the dopaminergic effect is through influencing the inhibitory transmission system. These results have revealed a role of dopamine in regulating the temporal dynamics of excitation/inhibition balance in VTA–PFC circuit, which provides insights into the functional consequence of activating dopamine system in the mesocortical system.
Diphtheria in Metro Manila, the Philippines 2006–2017: A Clinical, Molecular, and Spatial Characterization
Authors: Saito Nobuo , Dimapilis Virginia O , Fujii Hiroshi , Suzuki Motoi , Telan Elizabeth Freda O , Umipig Dorcas Valencia , Solante Rontgene M , Dimapilis Alexis Q , De Guzman Ferdinand , Salva Eumelia P , Nakayama Fumihito , Toda Kohei , Smith Chris , Ariyoshi Koya , Parry Christopher M 
Published: January 2020

Abstract

Background
Diphtheria is a vaccine-preventable disease that persists as a global health problem. An understanding of the pattern of disease is lacking in low- and middle-income countries such as the Philippines.

Methods
We conducted a retrospective review of the clinical, microbiological, and epidemiological features of patients admitted with a clinical diagnosis of diphtheria to an infectious disease referral hospital in Metro Manila, the Philippines, between 2006 and 2017. Cases were mapped and the distribution was compared with population density. Corynebacterium diphtheriae isolates from between 2015 and 2017 were examined by multilocus sequence typing (MLST).

Results
We studied 267 patients (range:12−54 cases/year) admitted between 2006 and 2017. The case fatality rate (CFR) was 43.8% (95% confidence interval, 37.8−50.0%). A higher number of cases and CFR was observed among children &lt;10 years. Mortality was associated with a delayed admission to hospital and a lack of diphtheria antitoxin. Between 2015 and 2017 there were 42 laboratory-confirmed cases. We identified 6 multilocus sequence types (STs). ST-302 was the most common (17/34, 48.6%), followed by ST67 (7/34, 20%) and ST458 (5/34, 14%). Case mapping showed a wide distribution of diphtheria patients in Metro Manila. Higher case numbers were found in densely populated areas but with no apparent clustering of ST types.

Conclusions
Our analysis indicates that diphtheria remains endemic in Metro Manila and that the infection is frequently fatal in young children. Improved vaccine coverage and a sustainable supply of diphtheria antitoxin should be prioritized.
Impact of Difficult-to-Treat Resistance in Gram-negative Bacteremia on Mortality: Retrospective Analysis of Nationwide Surveillance Data
Authors: Huh Kyungmin , Chung Doo Ryeon , Ha Young Eun , Ko Jae-Hoon , Kim Si-Ho , Kim Min-Ji , Huh Hee Jae , Lee Nam Yong , Cho Sun Young , Kang Cheol-In , Peck Kyong Ran , Song Jae-Hoon ,   Korean Antimicrobial Resistance Surveillance Network (KARS-Net) Investigators
Published: January 2020

Abstract

Background
Clinically relevant categorization of antimicrobial resistance is critical to mitigating the threat it poses. Difficult-to-treat resistance (DTR) is a recently proposed category defined as nonsusceptibility to all first-line antibiotic agents.

Methods
A retrospective study was conducted with nonduplicate cases of gram-negative bloodstream infection (GNBSI) caused by 4 major taxa (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter species) identified from a nationwide surveillance database. DTR was defined as nonsusceptibility to all the β-lactams and fluoroquinolones tested. Patient characteristics and mortality were compared between DTR GNBSI and GNBSI caused by carbapenem-resistant but not DTR and extended-spectrum cephalosporin–resistant but not DTR isolates using Centers for Disease Control and Prevention definitions. Adjusted odds ratios (aORs) for 30-day in-hospital mortality were examined for DTR in overall and in propensity score–matched cohorts.

Results
A total of 1167 episodes of monomicrobial GNBSI were identified, and 147 (12.6%) of the isolates were DTR. The majority of DTR isolates were Acinetobacter species (79.6%) and P. aeruginosa (17.7%). DTR infections were associated with previous antibiotic use, healthcare contact, ventilator use, and lower respiratory tract infection. Crude mortality for GNBSI caused by DTR was 50.3%. A multivariable model showed that only DTR, but not other categories, was significantly associated with mortality (adjusted odds ratio [aOR], 3.58 [95% confidence interval {CI}, 1.27–10.19]). DTR was also a significant predictor for mortality in the analysis of propensity score–matched cohorts (aOR, 3.48 [95% CI, 1.82–6.79]).

Conclusions
In patients with GNBSI, DTR was associated with higher mortality than those in other resistance categories. Our findings suggest that DTR could be useful for surveillance and prognostication.
Human-dominated land cover corresponds to spatial variation in Mourning Dove (Zenaida macroura) reproductive output across the United States
Authors: Muñoz David , Miller David 
Published: January 2020

Abstract
Studies examining impacts of land cover typically focus on abundance, distribution, and/or community richness, overlooking underlying demographic processes such as survival or reproduction. Here, we present findings from a unique dataset that allowed us to measure the relationship between land cover and reproductive output across the distribution of the Mourning Dove (Zenaida macroura). We used hunter-derived, Mourning Dove wing data across 1,271 counties in the United States from 2008 to 2014 to estimate spatially explicit age ratios (juveniles: adults), an index of local reproductive output. We also used raster imagery data to estimate relationships between reproductive output and land cover and crop cover. We found that low reproductive output occurs in regions where Mourning Dove declines have been steepest. Our findings reveal that impacts of land cover vary geographically, but even at a coarse resolution, small changes in the relative proportion of human-dominated landscapes can have a significant impact on the reproductive output of this generalist species. Maize and soybean systems correlate with up to a 57% reduction in Mourning Dove reproductive output in the eastern United States. In the western United States, developed areas correlate with a 41% increase in reproductive output. Across the United States, native habitats had neutral or negative relationships with age ratios. Our study contributes continental-scale evidence that Mourning Dove reproductive output is largely driven by human-dominated land cover including agricultural and residential areas. With Mourning Doves declining across the range, discerning more fine-scale land cover factors is critical for ensuring Mourning Dove populations persist into the future.
Non-incisional pleurectomy/decortication
Authors: Hasegawa Seiki , Hashimoto Masaki , Kondo Nobuyuki , Miyamoto Yoshihiro 
Published: January 2020

Abstract
One of the potential disadvantages of conventional pleurectomy/decortication for malignant pleural mesothelioma is the need for opening the pleural sac, which might worsen survival. In this study, we have introduced non-incisional pleurectomy/decortication as an alternative technique that does not require the opening of the pleural sac.
Prognostic factors following complete resection of non-superior sulcus lung cancer invading the chest wall
Authors: Jones Gregory D , Caso Raul , No Jae Seong , Tan Kay See , Dycoco Joseph , Bains Manjit S , Rusch Valerie W , Huang James , Isbell James M , Molena Daniela , Park Bernard J , Jones David R , Rocco Gaetano 
Published: January 2020

Abstract

OBJECTIVES
Locally advanced non-small-cell lung cancer (NSCLC) with chest wall invasion carries a high risk of recurrence and portends poor survival (30–40% and 20–50%, respectively). No studies have identified prognostic factors in patients who underwent R0 resection for non-superior sulcus NSCLC.

METHODS
A retrospective review was conducted for all chest wall resections for NSCLC from 2004 to 2018. Patients with superior sulcus tumours, partial (&lt;1 rib) or incomplete (R1/R2) resection or distant metastasis were excluded. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Cox proportional hazards modelling was used to determine factors associated with DFS and OS.

RESULTS
A total of 100 patients met inclusion criteria. Seventy-three (73%) patients underwent induction therapy, and all but 12 (16%) patients experienced a partial radiological response. A median of 3 ribs was resected (range 1–7), and 67 (67%) patients underwent chest wall reconstruction. The 5-year DFS and OS were 36% and 45%, respectively. Pathological N2 status [hazard ratio (HR) 3.12, confidence interval (CI) 1.56–6.25; P = 0.001], intraoperative blood transfusion (HR 2.24, CI 1.28–3.92; P = 0.005) and preoperative forced vital capacity (per % forced vital capacity, HR 0.97, CI 0.96–0.99; P = 0.013) were associated with DFS. Increasing pathological stage, lack of radiological response to induction therapy (HR 7.35, CI 2.35–22.99; P = 0.001) and cardiovascular comorbidity (HR 2.43, CI 1.36–4.36; P = 0.003) were associated with OS.

CONCLUSIONS
We demonstrate that blood transfusion and forced vital capacity are associated with DFS after R0 resection for non-superior sulcus NSCLC, while radiological response to induction therapy greatly influences OS. We confirm that pathological nodal status and pathological stage are reproducible determinants of DFS and OS, respectively.
Discovery of a New TLR Gene and Gene Expansion Event through Improved Desert Tortoise Genome Assembly with Chromosome-Scale Scaffolds
Authors: Dolby Greer A , Morales Matheo , Webster Timothy H , DeNardo Dale F , Wilson Melissa A , Kusumi Kenro 
Published: January 2020

AbstractToll-like receptors (TLRs) are a complex family of innate immune genes that are well characterized in mammals and birds but less well understood in nonavian sauropsids (reptiles). The advent of highly contiguous draft genomes of nonmodel organisms enables study of such gene families through analysis of synteny and sequence identity. Here, we analyze TLR genes from the genomes of 22 tetrapod species. Findings reveal a TLR8 gene expansion in crocodilians and turtles (TLR8B), and a second duplication (TLR8C) specifically within turtles, followed by pseudogenization of that gene in the nonfreshwater species (desert tortoise and green sea turtle). Additionally, the Mojave desert tortoise (Gopherus agassizii) has a stop codon in TLR8B (TLR8-1) that is polymorphic among conspecifics. Revised orthology further reveals a new TLR homolog, TLR21-like, which is exclusive to lizards, snakes, turtles, and crocodilians. These analyses were made possible by a new draft genome assembly of the desert tortoise (gopAga2.0), which used chromatin-based assembly to yield draft chromosomal scaffolds (L50 = 26 scaffolds, N50 = 28.36 Mb, longest scaffold = 107 Mb) and an enhanced de novo genome annotation with 25,469 genes. Our three-step approach to orthology curation and comparative analysis of TLR genes shows what new insights are possible using genome assemblies with chromosome-scale scaffolds that permit integration of synteny conservation data.
Neonatal BCG Vaccination Reduces Interferon-γ Responsiveness to Heterologous Pathogens in Infants From a Randomized Controlled Trial
Authors: Freyne Bridget , Messina Nicole L , Donath Susan , Germano Susie , Bonnici Rhian , Gardiner Kaya , Casalaz Dan , Robins-Browne Roy M , Netea Mihai G , Flanagan Katie L , Kollmann Toby , Curtis Nigel ,   Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR) Group, Abruzzo Veronica , Allen Katie , Morrison Clare , Ponsonby Anne-Louise , Vuillermin Peter 
Published: January 2020

AbstractBackgroundBCG vaccination has beneficial nonspecific (heterologous) effects that protect against nonmycobacterial infections. We have previously reported that BCG vaccination at birth alters in vitro cytokine responses to heterologous stimulants in the neonatal period. This study investigated heterologous responses in 167 infants in the same trial 7 months after randomization.MethodsA whole-blood assay was used to interrogate in vitro cytokine responses to heterologous stimulants (killed pathogens) and Toll-like receptor (TLR) ligands.ResultsCompared to BCG-naive infants, BCG-vaccinated infants had increased production of interferon gamma (IFN-γ) and monokine induced by gamma interferon (MIG) (CXCL9) in response to mycobacterial stimulation and decreased production of IFN-γ in response to heterologous stimulation and TLR ligands. Reduced IFN-γ responses were attributable to a decrease in the proportion of infants who mounted a detectable IFN-γ response. BCG-vaccinated infants also had increased production of MIG (CXCL9) and interleukin-8 (IL-8), and decreased production of IL-10, macrophage inflammatory protein-1α (MIP-1α), and MIP-1β, the pattern of which varied by stimulant. IL-1Ra responses following TLR1/2 (Pam3CYSK4) stimulation were increased in BCG-vaccinated infants. Both sex and maternal BCG vaccination status influenced the effect of neonatal BCG vaccination.ConclusionsBCG vaccination leads to changes in IFN-γ responsiveness to heterologous stimulation. BCG-induced changes in other cytokine responses to heterologous stimulation vary by pathogen.
Invasive Pulmonary Aspergillosis in Adults With Avian Influenza A (H7N9) Pneumonia in China: A Retrospective Study
Authors: Zou Pengfei , Wang Chen , Zheng Shufa , Guo Feifei , Yang Li , Zhang Yan , Liu Peng , Shen Yinzhong , Wang Yiming , Zhang Xuan , Tang Lingling , Gao Hainv , Li Lanjuan 
Published: January 2020

Abstract
Cases of severe influenza with Aspergillus infection are commonly reported in patients with severe influenza. However, the epidemiology, risk factors, and outcomes of invasive pulmonary aspergillosis (IPA) in patients with avian influenza A (H7N9) infection remain unclear. We performed a retrospective multicenter cohort study. Data were collected from patients with avian influenza A (H7N9) infection admitted to 17 hospitals across China from February 2013 through February 2018. We found that IPA was diagnosed in 18 (5.4%) of 335 patients; 61.1% of patients with IPA (11 of 18) were identified before or within 2 days after an H7N9 virus–negative result. The median hospital stays in patients with or without IPA were 23.5 and 18 days, respectively (P &lt; .01), and the median intensive care unit stays, respectively, were 22 and 12 days (P &lt; .01). Smoking in the past year and antibiotic use for &gt;7 days before admission were independently associated with IPA (adjusted odds ratio [95% confidence interval], 6.2 [1.7–26] for smoking and 4.89 [1.0–89] for antibiotic use). These findings provided important insights into the epidemiology and outcomes of IPA in patients with H7N9 infection in China.
Mechanisms of new blood-vessel formation and proliferative heterogeneity of endothelial cells
Authors: Naito Hisamichi , Iba Tomohiro , Takakura Nobuyuki 
Published: January 2020

Abstract
The vast blood-vessel network of the circulatory system is crucial for maintaining bodily homeostasis, delivering essential molecules and blood cells, and removing waste products. Blood-vessel dysfunction and dysregulation of new blood-vessel formation are related to the onset and progression of many diseases including cancer, ischemic disease, inflammation and immune disorders. Endothelial cells (ECs) are fundamental components of blood vessels and their proliferation is essential for new vessel formation, making them good therapeutic targets for regulating the latter. New blood-vessel formation occurs by vasculogenesis and angiogenesis during development. Induction of ECs termed tip, stalk and phalanx cells by interactions between vascular endothelial growth factor A (VEGF-A) and its receptors (VEGFR1–3) and between Notch and Delta-like Notch ligands (DLLs) is crucial for regulation of angiogenesis. Although the importance of angiogenesis is unequivocal in the adult, vasculogenesis effected by endothelial progenitor cells (EPCs) may also contribute to post-natal vessel formation. However, the definition of these cells is ambiguous and they include several distinct cell types under the simple classification of ‘EPC’. Furthermore, recent evidence indicates that ECs within the intima show clonal expansion in some situations and that they may harbor vascular-resident endothelial stem cells. In this article, we summarize recent knowledge on vascular development and new blood-vessel formation in the adult. We also introduce concepts of EC heterogeneity and EC clonal expansion, referring to our own recent findings.