bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial DNA haplogroup H association with endometriosis and possible role in inflammation and pain
Authors: Asally Razan , Markham Robert , Manconi Frank 
Published: July 2020

Introduction: Endometriosis is an inflammatory disease characterised by the presence of endometrial-like tissue outside the uterus and affects approximately 10%–15% of women in their reproductive years. Pain is one of the predominant symptoms of the disease. Oxidative stress is involved in the pathophysiology of endometriosis and develops when there is an imbalance between the reactive oxygen species and reactive nitrogen species production, and the elimination capacity of antioxidants in the reproductive tract. High levels of reactive oxygen species can induce pain indirectly through oxidative stress-associated inflammation or directly through sensitising the nociceptive neurons that transmit the signals to the cerebral sensory cortex which are perceived as a feeling of pain. Mitochondria are the main source of reactive oxygen species, which generate through oxidative phosphorylation. Given that the mitochondria are involved in reactive oxygen species formation and energy production, which are required for the activation and proliferation of peripheral lymphocytes, it has been suggested that mitochondrial DNA variants are involved in the pathogenesis of endometriosis. This study has provided a better understanding of maternally inherited risk factors which contribute to the pain mechanisms associated with endometriosis. Results: Mitochondrial DNA haplogroup H was found to be significantly higher in women with endometriosis. This study was the first to report the association between the European mitochondrial haplogroup H and the risk of pain associated with endometriosis. Discussion: The results suggest that there are maternally inherited risk factors in women with endometriosis causing high reactive oxygen species production and oxidative stress, which facilitate pain generation in women with endometriosis.
Trends in Digital Replantation: 10 Years of Experience at a Large Canadian Tertiary Care Center: Les tendances de la replantation digitale : dix ans d’expérience d’un grand centre canadien de soins tertiaires
Authors: Solaja Ogi , Retrouvey Helene , Baltzer Heather 
Published: July 2020

Background: Since 1965, the practice of digital replantation has seen great technical strides and become commonplace worldwide. However, some American authors have recently reported declining rates of replantation. We set out to characterize the patient population and describe treatment patterns from 2005 to 2016 at a large Canadian regional replantation center. Methods: A retrospective cohort of all patients undergoing digital replantation and revascularization from 2005 to 2016 was identified. Data were collected on demographics, injuries, procedures, and outcomes. Descriptive statistics were performed, followed by a comparison of two 5-year periods to evaluate temporal trends. Results: A total of 234 patients were treated with 146 replantation and 204 revascularization procedures. Patients were largely male, healthy, and worked as manual labourers. Overall, the failure rate of individual repairs was 28.7%. Over time, there was a trend toward more crush or avulsion and multidigit injuries, and surgeries performed after 2011 were significantly longer. There was a significant downward trend in the number of patients treated at our center each year. Additionally, there was a statistically significant decrease in the proportion of replanted to revised digits in multidigit cases. Discussion: Our observation of declining replantation rates is in line with recent American observations. The reason for this is not obvious but may represent a change in injury characteristics or surgeon attitudes. Conclusion: We suspect that these changes represent a change in workplace safety and injury characteristics, but further studies are needed to assess patient and surgeon treatment decisions.
Outcomes of COVID-19 in patients with CLL: a multicenter international experience
Authors: Mato Anthony R. , Roeker Lindsey E. , Lamanna Nicole , Allan John N. , Leslie Lori , Pagel John M. , Patel Krish , Osterborg Anders , Wojenski Daniel , Kamdar Manali , Huntington Scott F. , Davids Matthew S. , Brown Jennifer R. , Antic Darko , Jacobs Ryan , Ahn Inhye E. , Pu Jeffrey , Isaac Krista M. , Barr Paul M. , Ujjani Chaitra S. , Geyer Mark B. , Berman Ellin , Zelenetz Andrew D. , Malakhov Nikita , Furman Richard R. , Koropsak Michael , Bailey Neil , Hanson Lotta , Perini Guilherme F. , Ma Shuo , Ryan Christine E. , Wiestner Adrian , Portell Craig A. , Shadman Mazyar , Chong Elise A. , Brander Danielle M. , Sundaram Suchitra , Seddon Amanda N. , Seymour Erlene , Patel Meera , Martinez-Calle Nicolas , Munir Talha , Walewska Renata , Broom Angus , Walter Harriet , El-Sharkawi Dima , Parry Helen , Wilson Matthew R. , Patten Piers E. M. , Hernández-Rivas José-Ángel , Miras Fatima , Fernández Escalada Noemi , Ghione Paola , Nabhan Chadi , Lebowitz Sonia , Bhavsar Erica , López-Jiménez Javier , Naya Daniel , Garcia-Marco Jose Antonio , Skånland Sigrid S. , Cordoba Raul , Eyre Toby A. 
Published: July 2020

Abstract
Given advanced age, comorbidities, and immune dysfunction, chronic lymphocytic leukemia (CLL) patients may be at particularly high risk of infection and poor outcomes related to coronavirus disease 2019 (COVID-19). Robust analysis of outcomes for CLL patients, particularly examining effects of baseline characteristics and CLL-directed therapy, is critical to optimally manage CLL patients through this evolving pandemic. CLL patients diagnosed with symptomatic COVID-19 across 43 international centers (n = 198) were included. Hospital admission occurred in 90%. Median age at COVID-19 diagnosis was 70.5 years. Median Cumulative Illness Rating Scale score was 8 (range, 4-32). Thirty-nine percent were treatment naive (“watch and wait”), while 61% had received ≥1 CLL-directed therapy (median, 2; range, 1-8). Ninety patients (45%) were receiving active CLL therapy at COVID-19 diagnosis, most commonly Bruton tyrosine kinase inhibitors (BTKi’s; n = 68/90 [76%]). At a median follow-up of 16 days, the overall case fatality rate was 33%, though 25% remain admitted. Watch-and-wait and treated cohorts had similar rates of admission (89% vs 90%), intensive care unit admission (35% vs 36%), intubation (33% vs 25%), and mortality (37% vs 32%). CLL-directed treatment with BTKi’s at COVID-19 diagnosis did not impact survival (case fatality rate, 34% vs 35%), though the BTKi was held during the COVID-19 course for most patients. These data suggest that the subgroup of CLL patients admitted with COVID-19, regardless of disease phase or treatment status, are at high risk of death. Future epidemiologic studies are needed to assess severe acute respiratory syndrome coronavirus 2 infection risk, these data should be validated independently, and randomized studies of BTKi’s in COVID-19 are needed to provide definitive evidence of benefit.
Smoking status and second-hand smoke biomarkers in COPD, asthma and healthy controls
Authors: Bradicich Matteo , Schuurmans Macé M. 
Published: July 2020

IntroductionTobacco smoke worsens COPD and asthma. For healthy individuals, quantifying active and second-hand smoke (SHS) exposure clarifies the epidemiology of tobacco consumption and the efficacy of nonsmoking measures. Identifying tobacco exposure biomarkers and cut-offs might allow the creation of sensitive and specific tests.AimWe describe the state-of-the-art serum, urinary cotinine and exhaled carbon monoxide (CO) cut-offs for assessing smoking status and SHS exposure in adult patients with COPD or asthma, and healthy controls.MethodologyAfter a keyword research in the PubMed database, we included papers reporting on the cut-offs of the investigated biomarkers in one of the populations of interest. Papers published before 2000, not in English, or reporting only data on nonadult subjects or on pregnant women were excluded from the analysis. 14 papers were included in the final analysis. We summarised diagnostic cut-offs for smoking status or SHS exposure in COPD, asthmatic and healthy control cohorts, reporting sensitivity and specificity when available.ConclusionSerum and urinary cotinine and exhaled CO are easy-to-standardise, affordable and objective tests for assessing smoking status and SHS exposure. Evidence on cut-offs with good sensitivity and specificity values is available mainly for healthy controls. For COPD and asthmatic patients, most of the currently available evidence focuses on exhaled CO, while studies on the use of cotinine with definite sensitivity and specificity values are still missing. Solid evidence on SHS exposure is available only for healthy controls. An integrated approach with a combination of these markers still needs evaluation.
Regulatory review of the environmental risk assessment of veterinary medicinal products in the European Union, with particular focus on the centralised authorisation procedure
Authors: Fabrega Julia , Carapeto Ricardo 
Published: July 2020

AbstractIn the EU, the requirement for a two-tier-based environmental risk assessment for a veterinary medicinal product applies for marketing authorisations submitted since 1993. This article outlines the framework for conducting environmental risk assessments and provides information about the outcomes and type of substances that often require a higher tier assessment due to environmental concerns, and the tools available within the relevant regulation to reassess potential risks from products already authorised (i.e., referral procedures (under Article 33(4), Article 35 of Directive 2001/82/EC and Article 30(3) of Regulation (EC) No 726/2004)). The majority of pharmaceutical veterinary medicinal products (> 95%) are considered to have a limited environmental release, and their risk assessment ends in the lowest tier (Phase I). To date, 19 referrals have been triggered as a result of environmental concerns, with the outcome from two out of the 19 concluding with an overall benefit/risk balance being negative, and resulting in the withdrawal of products from the market. The way environmental risk assessment for veterinary products will be addressed when the new veterinary regulation (Regulation (EU) 2019/6) comes into force on 28 January 2022 is also presented, and ongoing initiatives and published reports are discussed. The latter recommending policy actions to address water pollution by pharmaceutical residues and advocating a robust international cooperation and the establishment of a ‘One Health’ approach.
SpectralTAD: an R package for defining a hierarchy of topologically associated domains using spectral clustering
Authors: Cresswell Kellen G. , Stansfield John C. , Dozmorov Mikhail G. 
Published: July 2020

Abstract
Background
The three-dimensional (3D) structure of the genome plays a crucial role in gene expression regulation. Chromatin conformation capture technologies (Hi-C) have revealed that the genome is organized in a hierarchy of topologically associated domains (TADs), sub-TADs, and chromatin loops. Identifying such hierarchical structures is a critical step in understanding genome regulation. Existing tools for TAD calling are frequently sensitive to biases in Hi-C data, depend on tunable parameters, and are computationally inefficient.

Methods
To address these challenges, we developed a novel sliding window-based spectral clustering framework that uses gaps between consecutive eigenvectors for TAD boundary identification.

Results
Our method, implemented in an R package, SpectralTAD, detects hierarchical, biologically relevant TADs, has automatic parameter selection, is robust to sequencing depth, resolution, and sparsity of Hi-C data. SpectralTAD outperforms four state-of-the-art TAD callers in simulated and experimental settings. We demonstrate that TAD boundaries shared among multiple levels of the TAD hierarchy were more enriched in classical boundary marks and more conserved across cell lines and tissues. In contrast, boundaries of TADs that cannot be split into sub-TADs showed less enrichment and conservation, suggesting their more dynamic role in genome regulation.

Conclusion
SpectralTAD is available on Bioconductor, http://bioconductor.org/packages/SpectralTAD/.
GenAPI: a tool for gene absence-presence identification in fragmented bacterial genome sequences
Authors: Gabrielaite Migle , Marvig Rasmus L. 
Published: July 2020

Abstract
Background
Bacterial gene loss and acquisition is a well-known phenomenon which contributes to bacterial adaptation through changes in important phenotypes such as virulence, antibiotic resistance and metabolic capability. While advances in DNA sequencing have accelerated our ability to generate short genome sequence reads to disentangle phenotypic changes caused by gene loss and acquisition, the short-read genome sequencing often results in fragmented genome assemblies as a basis for identification of gene loss and acquisition events. However, sensitive and precise determination of gene content change for fragmented genome assemblies remains challenging as analysis needs to account for cases when only a fragment of the gene is assembled or when the gene assembly is split in more than one contig.

Results
We developed GenAPI, a command-line tool that is designed to compare the gene content of bacterial genomes for which only fragmented genome assemblies are available. GenAPI, unlike other available tools of similar purpose, accounts for imperfections in sequencing and assembly, and aims to compensate for them. We tested the performance of GenAPI on three different datasets to show that GenAPI has a high sensitivity while it maintains precision when dealing with partly assembled genes in both simulated and real datasets. Furthermore, we benchmarked the performance of GenAPI with six popular tools for gene presence-absence identification.

Conclusions
Our developed bioinformatics tool, called GenAPI, has the same precision and recall rates when analyzing complete genome sequences as the other tools of the same purpose; however, GenAPI’s performance is markedly better on fragmented genome assemblies.
Determinants of translation efficiency in the evolutionarily-divergent protist Trichomonas vaginalis
Authors: Wang Shuqi E. , Brooks Anna E. S. , Poole Anthony M. , Simoes-Barbosa Augusto 
Published: July 2020

Abstract
Background
Trichomonas vaginalis, the causative agent of a prevalent urogenital infection in humans, is an evolutionarily divergent protozoan. Protein-coding genes in T. vaginalis are largely controlled by two core promoter elements, producing mRNAs with short 5′ UTRs. The specific mechanisms adopted by T. vaginalis to fine-tune the translation efficiency (TE) of mRNAs remain largely unknown.

Results
Using both computational and experimental approaches, this study investigated two key factors influencing TE in T. vaginalis: codon usage and mRNA secondary structure. Statistical dependence between TE and codon adaptation index (CAI) highlighted the impact of codon usage on mRNA translation in T. vaginalis. A genome-wide interrogation revealed that low structural complexity at the 5′ end of mRNA followed closely by a highly structured downstream region correlates with TE variation in this organism. To validate these findings, a synthetic library of 15 synonymous iLOV genes was created, representing five mRNA folding profiles and three codon usage profiles. Fluorescence signals produced by the expression of these synonymous iLOV genes in T. vaginalis were consistent with and validated our in silico predictions.

Conclusions
This study demonstrates the role of codon usage bias and mRNA secondary structure in TE of T. vaginalis mRNAs, contributing to a better understanding of the factors that influence, and possibly regulate, gene expression in this human pathogen.
Comparative population genomic analysis uncovers novel genomic footprints and genes associated with small body size in Chinese pony
Authors: Asadollahpour Nanaei Hojjat , Esmailizadeh Ali , Ayatollahi Mehrgardi Ahmad , Han Jianlin , Wu Dong-Dong , Li Yan , Zhang Ya-Ping 
Published: July 2020

Abstract
Background
Body size is considered as one of the most fundamental properties of an organism. Due to intensive breeding and artificial selection throughout the domestication history, horses exhibit striking variations for heights at withers and body sizes. Debao pony (DBP), a famous Chinese horse, is known for its small body size and lives in Guangxi mountains of southern China. In this study, we employed comparative population genomics to study the genetic basis underlying the small body size of DBP breed based on the whole genome sequencing data. To detect genomic signatures of positive selection, we applied three methods based on population comparison, fixation index (FST), cross population composite likelihood ratio (XP-CLR) and nucleotide diversity (θπ), and further analyzed the results to find genomic regions under selection for body size-related traits.

Results
A number of protein-coding genes in windows with the top 1% values of FST (367 genes), XP-CLR (681 genes), and log2 (θπ ratio) (332 genes) were identified. The most significant signal of positive selection was mapped to the NELL1 gene, probably underlies the body size and development traits, and may also have been selected for short stature in the DBP population. In addition, some other loci on different chromosomes were identified to be potentially involved in the development of body size.

Conclusions
Results of our study identified some positively selected genes across the horse genome, which are possibly involved in body size traits. These novel candidate genes may be useful targets for clarifying our understanding of the molecular basis of body size and as such they should be of great interest for future research into the genetic architecture of relevant traits in horse breeding program.
EDTA-modified carbapenem inactivation method (eCIM) for detecting IMP Metallo-β-lactamase–producing Pseudomonas aeruginosa: an assessment of increasing EDTA concentrations
Authors: Lasko Maxwell J. , Gill Christian M. , Asempa Tomefa E. , Nicolau David P. 
Published: July 2020

Abstract
Background
Prompt identification of carbapenemase-harboring organisms is valuable in informing therapeutic and infection-control measures. The modified carbapenem inactivation method (mCIM) and EDTA-modified carbapenem inactivation method (eCIM) are inexpensive and easy to interpret phenotypic tests endorsed by the Clinical and Laboratory Standards Institute (CLSI) for the detection of carbapenemase-harboring Enterobacterales. Only mCIM is endorsed by CLSI for detecting carbapenemase-harboring Pseudomonas aeruginosa. eCIM’s ability to delineate serine and metallo-β-lactamases (MBL) could be advantageous in areas prevalent with carbapenemase-harboring P. aeruginosa. A recent assessment of mCIM/eCIM on MBL-harboring P. aeruginosa demonstrated high eCIM sensitivity for NDMs and VIMs but not for IMP-producers. Therefore, this study aimed to determine whether increasing EDTA concentrations would enhance eCIM sensitivity for a collection of IMP-harboring P. aeruginosa isolates.
Twenty-six IMP-harboring P. aeruginosa isolates were utilized. For test validation, additional P. aeruginosa isolates harboring NDM (n = 3), VIM (n = 3), KPC (n = 8), wild-type (n = 1), and Enterobacterales isolates harboring IMP (n = 6) and NDM (n = 1) were assessed. The mCIM test was conducted as outlined by CLSI. Simultaneously, the eCIM test was performed with the standard 5 mM EDTA concentration and doubling EDTA concentrations: 10 mM, 20 mM, and 40 mM.

Results
Concentration-dependent improvement was observed among the IMP-harboring P. aeruginosa with eCIM sensitivities at 0, 31, 85, and 100% respectively. Remaining Enterobacterales and P. aeruginosa responded concordantly with their genotype at the standard 5 mM eCIM concentration, with doubling EDTA concentrations providing no greater sensitivity.

Conclusion
Combination of mCIM and an eCIM with a 40 mM EDTA concentration appropriately capture IMP-harboring P. aeruginosa without sacrificing test utility for other carbapenemase-harboring isolates.
Validation of noninvasive continuous arterial pressure measurement by ClearSight System™ during induction of anesthesia for cardiovascular surgery
Authors: Tanioku Tadashi , Yoshida Akari , Aratani Yuichi , Fujii Keisuke , Kawamata Tomoyuki 
Published: July 2020

Abstract
Background
Since blood pressure tends to be unstable during induction of anesthesia in patients undergoing cardiovascular surgery, an artery catheter is often inserted before induction to continuously monitor arterial pressure during induction of anesthesia. ClearSight System™ enables noninvasive continuous measurement of beat-to-beat arterial pressure via a single finger cuff without pain using photoplethysmographic technology. If ClearSight System™ can replace intra-arterial pressure measurement, blood pressure could be easily and noninvasively assessed. However, the validity of ClearSight System™ during induction of anesthesia in patients undergoing cardiovascular surgery has not been evaluated. The aim of this study was to compare blood pressure measured by ClearSight System™ with intra-arterial pressure during induction of anesthesia for cardiovascular surgery.

Methods
This study was registered retrospectively. Data during induction of anesthesia for elective cardiovascular surgery were obtained for patients in whom noninvasive arterial pressure was measured by ClearSight System™ (APcs) and invasive radial arterial pressure (APrad) was measured simultaneously. According to the widely used criteria formulated by international standards from the Association for the Advancement of Medical Instrumentation, the acceptable bias and precision for arterial pressure measurements were fixed at < 5 mmHg and 8 mmHg, respectively.

Results
Data for 18 patients were analyzed. For 3068 analyzed paired measurements, values of APcs vs APrad bias (precision) were 13.2 (17.5), − 9.1 (7.3) and − 3.9 (7.8) mmHg for systolic, diastolic, and mean arterial pressures, respectively.

Conclusions
Mean arterial pressure measured by ClearSight System™ could be considered as an alternative for mean radial arterial pressure during induction of anesthesia for elective cardiovascular surgery.
Management of Respiratory Distress Syndrome due to COVID-19 infection
Authors: Navas-Blanco Jose R. , Dudaryk Roman 
Published: July 2020

AbstractThe management of Acute Respiratory Distress Syndrome (ARDS) secondary to the novel Coronavirus Disease 2019 (COVID-19) proves to be challenging and controversial. Multiple studies have suggested the likelihood of an atypical pathophysiology to explain the spectrum of pulmonary and systemic manifestations caused by the virus. The principal paradox of COVID-19 pneumonia is the presence of severe hypoxemia with preserved pulmonary mechanics. Data derived from the experience of multiple centers around the world have demonstrated that initial clinical efforts should be focused into avoid intubation and mechanical ventilation in hypoxemic COVID-19 patients. On the other hand, COVID-19 patients progressing or presenting into frank ARDS with typical decreased pulmonary compliance, represents another clinical enigma to many clinicians, since routine therapeutic interventions for ARDS are still a subject of debate.