bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of Association Between the CCR5-delta32 Polymorphism and Neurodegenerative Disorders
Authors: Wojta Kevin J. , Ayer Ariane H. , Ramos Eliana M. , Nguyen Peter D. , Karydas Anna M. , Yokoyama Jennifer S. , Kramer Joel , Lee Suzee E. , Boxer Adam , Miller Bruce L. , Coppola Giovanni 
Published: January 2020

Objective:
Recent studies have suggested that diminished Ccr5 functioning has an effect on synaptic plasticity and hippocampal memory in mouse models. CCR5-delta32, a 32-bp frameshift deletion in human CCR5 encoding a nonfunctional receptor, has been reported to have a protective effect against human immunodeficiency virus infection but its role as a modifier of neurodegenerative disease has been minimally explored. We investigated whether the CCR5-delta32 polymorphism could have an effect in the context of human neurodegenerative diseases.

Methods:
We examined the frequency of the CCR5-delta32 polymorphism in a large and well-characterized cohort including 1425 patients with neurodegenerative dementias and 2032 controls.

Results:
We did not observe a significant association between the CCR5-delta32 polymorphism and any of the neurodegenerative diseases screened in this study. However, we observed an earlier age of onset among neurodegenerative disease patients carrying the CCR5-delta32 allele.

Conclusions:
Although our findings were inconclusive, the earlier age of onset observed among neurodegenerative disease patients carrying the CCR5-delta32 allele suggests that the deletion may have a detrimental effect in the context of neurodegeneration.
Correlation Between Optic Disc Peripapillary Capillary Network and Papilledema Grading in Patients With Idiopathic Intracranial Hypertension: A Study of Optical Coherence Tomography Angiography
Authors: Rodriguez Torres Yasaira , Lee Patrick , Mihlstin Melanie , Tomsak Robert L. 
Published: January 2020

Background:
The continued increase in idiopathic intracranial hypertension (IIH) prevalence has many implications for societal health care. Its potential vision-threatening consequences make ophthalmologists key players in its diagnosis and management. Newer technology such as optical coherence tomography angiography (OCT-A) enables evaluation of the branching complexity of the peripapillary capillary plexus, a region where accurate imaging via fluorescein angiography was previously limited.

Methods:
A cross-sectional, observational study of 23 (46 eyes) consecutive patients with IIH. Peripapillary total vasculature was recorded using commercial OCT-A en face vessel density mapping. In addition, OCT-A blood flow slab was compared with papilledema grading. OCT-A images were analyzed using a customized image analysis protocol using ImageJ software (v1.51w) and Photoshop software (Adobe Systems, CA). SPSS software version 25 was used for statistical analysis (SPSS Inc, IBM, Chicago, IL).

Results:
Skeletonized vessel density peripapillary capillary plexus was significantly associated with Frisen papilledema grades, OCT retinal nerve fiber layer (RNFL), and macular ganglion cell layer (GCL) thickness with a P < 0.001, P = 0.022, and P = 0.006, respectively. Every point increase in grade was correlated with a decrease of 9.1 pixels/mm2 in vessel density (R = 0.512, β = −0.115 ± 0.029; P < 0.001). Increased papilledema was correlated with an increased retinal blood flow percentage (R = 0.300, β = 2.114 ± 1.013; P < 0.05) and decreased choroidal blood flow (CBF) percentage (R = 0.300, β = 2.114 ± 1.013; P < 0.05). Every point increase in grade was correlated with a decrease in CBF by 47.4%, as calculated using a linear best-fit line inclusive for all of the data points.

Conclusions:
OCT-A allows for effective visualization and quantification of the peripapillary retinal vasculature. Our results demonstrate a correlation between skeletonized peripapillary density and papilledema grading, OCT RNFL thickness, and GCL thickness. In addition, we show a significant negative correlation between CBF and papilledema grading. These changes provide key findings regarding the pathophysiology of optic neuropathy in papilledema and highlight the potential of OCT-A as a diagnostic tool for papilledema and a clinical marker for detecting early optic nerve damage.
Optic Disc Drusen Associated Anterior Ischemic Optic Neuropathy: Prevalence of Comorbidities and Vascular Risk Factors
Authors: Rueløkke Lea L. , Malmqvist Lasse , Wegener Marianne , Hamann Steffen 
Published: January 2020

Background:
Nonarteritic anterior ischemic optic neuropathy (NA-AION) associated with optic disc drusen (ODD) is termed ODD-AION, where NA-AION with no evidence of ODD is simply termed NA-AION. Patients with ODD-AION have been found to be younger than those with NA-AION but with similar vascular risk factors. This study compares the known risk factors for NA-AION between a group with ODD-AION and a similarly aged group with NA-AION.

Methods:
A case–control study of 13 patients with ODD-AION and 14 patients with NA-AION diagnosed in the period 2008–2017. All patients underwent an interview designed to evaluate history of vascular risk factors and comorbidities and re-examination including enhanced depth imaging optical coherence tomography to confirm the presence or absence of ODD.

Results:
No significant differences were found in demographic or clinical characteristics between the ODD-AION and the NA-AION group. Significantly more ODD-AION patients than NA-AION patients had no vascular risk factors (smoking, arterial hypertension, diabetes mellitus, and dyslipidemia) present (P = 0.047). Significantly fewer patients in the ODD-AION group were diagnosed with arterial hypertension or dyslipidemia than in the NA-AION group.

Conclusions:
In this cross-sectional study, the ODD-AION patients more often had no vascular risk factors as compared to NA-AION patients, which supports the hypothesis that ODD are an independent risk factor for AION.
Remote Pontine Hemorrhage After Left Frontal Lobe Meningioma Resection Presenting as Bilateral Internuclear Ophthalmoplegia
Authors: Lee Maxwell , Al Othman Bayan A. , Kini Tonse A. , Lee Andrew G. 
Published: January 2020

Abstract:
Postoperative hemorrhages are relatively common complications of surgical procedures including craniotomies, and these typically occur at or near the operative site. Bleeding in remote areas (e.g., posterior fossa) after supratentorial craniotomy can occur and may be associated with a high morbidity and mortality. Although remote cerebellar hemorrhage after craniotomy is well described, remote pontine hemorrhage is less common. We describe a bilateral internuclear ophthalmoplegia due to an RPH after otherwise uncomplicated resection of a frontal meningioma. Clinicians should be aware that neuro-ophthalmic findings can occur from hemorrhages remote from the operative site.
Using clinical registries, administrative data and electronic medical records to improve medication safety and effectiveness in dementia
Authors: Ilomäki Jenni , Lai Edward Chia-Cheng , Bell J. Simon 
Published: January 2020

Purpose of review
Clinical registries, routinely collected administrative data and electronic medical records (EMRs) provide new opportunities to investigate medication safety and effectiveness. This review outlines the strengths and limitations of these data, and highlights recent research related to safe and effective medication use in dementia.

Recent findings
Clinical registries, administrative data and EMRs facilitate observational research among people often excluded from randomized controlled trials (RCTs). Larger sample sizes and longer follow-up times permit research into less common adverse events not apparent in RCTs. The validity of diagnoses recorded in administrative data and EMRs remains variable, although positive predictive values are typically high and sensitivity is low. Dispensing records are a rich source of data for estimating medication exposure. Recent research has investigated medications and prescribing patterns as risk factors for incident dementia, strategies to alleviate behavioural symptoms and the management of comorbidity. Common study protocols and common data models are examples of distributed network approaches increasingly used to conduct large and generalizable multi-database studies across different countries.

Summary
Greater availability of electronic health data provides important opportunities to address evidence-practice gaps in relation to medication use and safety in people with dementia.
Evolution, geographic spreading, and demographic distribution of Enterovirus D68
Authors: Hodcroft Emma B. , Dyrdak Robert , Andrés Cristina , Egli Adrian , Reist Josiane , García Martínez de Artola Diego , Alcoba Flórez Julia , Niesters Hubert G. M. , Antón Andrés , Poelman Randy , Reynders Marijke , Wollants Elke , Neher Richard A. , Albert Jan 
Published: January 2020

BackgroundWorldwide outbreaks of enterovirus D68 (EV-D68) in 2014 and 2016 have caused serious respiratory and neurological disease.MethodsWe collected samples from several European countries during the 2018 out-break and determined 53 near full-length genome (‘whole genome’) sequences. These sequences were combined with 718 whole genome and 1,987 VP1-gene publicly available sequences.FindingsIn 2018, circulating strains clustered into multiple subgroups in the B3 and A2 subclades, with different phylogenetic origins. Clusters in subclade B3 emerged from strains circulating primarily in the US and Europe in 2016, though some had deeper roots linking to Asian strains, while clusters in A2 traced back to strains detected in East Asia in 2015-2016. In 2018, all sequences from the USA formed a distinct subgroup, containing only three non-US samples. Alongside the varied origins of seasonal strains, we found that diversification of these variants begins up to 18 months prior to the first diagnostic detection during a EV-D68 season. EV-D68 displays strong signs of continuous antigenic evolution and all 2018 A2 strains had novel patterns in the putative neutralizing epitopes in the BC- and DE-loops. The pattern in the BC-loop of the USA B3 subgroup had not been detected on that continent before. Patients with EV-D68 in subclade A2 were significantly older than patients with a B3 subclade virus. In contrast to other subclades, the age distribution of A2 is distinctly bimodal and was found primarily among children and in the elderly.InterpretationWe hypothesize that EV-D68’s rapid evolution of surface proteins, extensive diversity, and high rate of geographic mixing could be explained by substantial reinfection of adults.FundingUniversity of Basel and Swedish Foundation for Research and Development in Medical Microbiology
Rigor and Transparency Index, a new metric of quality for assessing biological and medical science methods
Authors: Menke Joe , Roelandse Martijn , Ozyurt Burak , Martone Maryann , Bandrowski Anita 
Published: January 2020

AbstractThe reproducibility crisis in science is a multifaceted problem involving practices and incentives, both in the laboratory and in publication. Fortunately, some of the root causes are known and can be addressed by scientists and authors alike. After careful consideration of the available literature, the National Institutes of Health identified several key problems with the way that scientists conduct and report their research and introduced guidelines to improve the rigor and reproducibility of pre-clinical studies. Many journals have implemented policies addressing these same criteria. We currently have, however, no comprehensive data on how these guidelines are impacting the reporting of research. Using SciScore, an automated tool developed to review the methods sections of manuscripts for the presence of criteria associated with the NIH and other reporting guidelines, e.g., ARRIVE, RRIDs, we have analyzed ~1.6 million PubMed Central papers to determine the degree to which articles were addressing these criteria. The tool scores each paper on a ten point scale identifying sentences that are associated with compliance with criteria associated with increased rigor (5 pts) and those associated with key resource identification and authentication (5 pts). From these data, we have built the Rigor and Transparency Index, which is the average score for analyzed papers in a particular journal. Our analyses show that the average score over all journals has increased since 1997, but remains below five, indicating that less than half of the rigor and reproducibility criteria are routinely addressed by authors. To analyze the data further, we examined the prevalence of individual criteria across the literature, e.g., the reporting of a subject’s sex (21-37% of studies between 1997 and 2019), the inclusion of sample size calculations (2-10%), whether the study addressed blinding (3-9%), or the identifiability of key biological resources such as antibodies (11-43%), transgenic organisms (14-22%), and cell lines (33-39%). The greatest increase in prevalence for rigor criteria was seen in the use of randomization of subjects (10-30%), while software tool identifiability improved the most among key resource types (42-87%). We further analyzed individual journals over time that had implemented specific author guidelines covering rigor criteria, and found that in some journals, they had a big impact, whereas in others they did not. We speculate that unless they are enforced, author guidelines alone do little to improve the number of criteria addressed by authors. Our Rigor and Transparency Index did not correlate with the impact factors of journals.
Microbial DNA on the move: sequencing based detection and analysis of transduced DNA in pure cultures and microbial communities
Authors: Kleiner Manuel , Bushnell Brian , Sanderson Kenneth E. , Hooper Lora V. , Duerkop Breck A. 
Published: January 2020

AbstractHorizontal gene transfer (HGT) plays a central role in microbial evolution. Our understanding of the mechanisms, frequency and taxonomic range of HGT in polymicrobial environments is limited, as we currently rely on historical HGT events inferred from genome sequencing and studies involving cultured microorganisms. We lack approaches to observe ongoing HGT in microbial communities. To address this knowledge gap, we developed a DNA sequencing based “transductomics” approach that detects and characterizes microbial DNA transferred via transduction. We validated our approach using model systems representing a range of transduction modes and show that we can detect numerous classes of transducing DNA. Additionally, we show that we can use this methodology to obtain insights into DNA transduction among all major taxonomic groups of the intestinal microbiome. This work extends the genomic toolkit for the broader study of mobile DNA within microbial communities and could be used to understand how phenotypes spread within microbiomes.Significance StatementMicrobes can rapidly evolve new capabilities by acquiring genes from other organisms through a process called horizontal gene transfer (HGT). HGT occurs via different routes, one of which is by the transfer of DNA carried by microbe infecting viruses (phages) or virus-like agents. This process is called transduction and has primarily been studied in the lab using pure cultures or indirectly in environmental communities by analyzing signatures in microbial genomes revealing past transduction events. The transductomics approach that we present here, allows for the detection and characterization of genes that are potentially transferred between microbes in complex microbial communities at the time of measurement and thus provides insights into real-time ongoing horizontal gene transfer.
Functional interaction between Fanconi anemia and mTOR pathways during stalled replication fork recovery
Authors: Nolan Matthew , Knudson Kenneth , Holz Marina K. , Chaudhury Indrajit 
Published: January 2020

ABSTRACTWe have previously demonstrated that Fanconi Anemia (FA) proteins work in concert with other FA and non-FA proteins to mediate stalled replication fork restart. Previous studies suggest a connection between FA protein FANCD2 and a non-FA protein mechanistic target of rapamycin (mTOR). A recent study showed that mTOR is involved in actin-dependent DNA replication fork restart, suggesting possible roles in FA DNA repair pathway. In this study, we demonstrate that during replication stress mTOR interacts and cooperates with FANCD2 to provide cellular stability, mediates stalled replication fork restart and prevents nucleolytic degradation of the nascent DNA strands. Taken together, this study unravels a novel functional cross-talk between two important mechanisms: mTOR and FA DNA repair pathways that ensure genomic stability.
Asymmetrical myofiber architecture along the murine tibialis anterior suggests distinct functional regions
Authors: Bindellini Davide , Voortman Lenard M. , Olie Cyriel S. , van Putten Maaike , van den Akker Erik , Raz Vered 
Published: January 2020

AbstractSkeletal muscle function is inferred from the spatial arrangement of myofiber architecture and the molecular and metabolic features of myofibers. Features of myofiber types can be distinguished by the expression of myosin heavy chain (MyHC) isoforms, indicating contraction properties. In most studies, a local sampling, typically obtained from the median part of the muscle, is used to represent the whole muscle. It remains largely unknown to what extent this local sampling represents the entire muscle. Here we studied myofiber architecture over the entire wild type mouse tibialis anterior muscle, using a high-throughput procedure combining automatic imaging and image processing analyses. We reconstructed myofiber architecture from consecutive cross-sections stained for laminin and MyHC isoforms. The data showed a marked variation in myofiber geometric features, as well as MyHC expression and the distribution of neuromuscular junctions, and suggest that muscle regions with distinct properties can be defined along the entire muscle. We show that in these muscle regions myofiber geometric properties align with biological function and propose that future studies on muscle alterations in pathological or physiological conditions should consider the entire muscle.
Trans-ethnic and ancestry-specific blood-cell genetics in 746,667 individuals from 5 global populations
Authors: Chen Ming-Huei , Raffield Laura M. , Mousas Abdou , Sakaue Saori , Huffman Jennifer E. , Jiang Tao , Akbari Parsa , Vuckovic Dragana , Bao Erik L. , Moscati Arden , Zhong Xue , Manansala Regina , Laplante Véronique , Chen Minhui , Lo Ken Sin , Qian Huijun , Lareau Caleb A. , Beaudoin Mélissa , Akiyama Masato , Bartz Traci M. , Ben-Shlomo Yoav , Beswick Andrew , Bork-Jensen Jette , Bottinger Erwin P. , Brody Jennifer A. , van Rooij Frank J.A. , Chitrala Kumaraswamynaidu , Cho Kelly , Choquet Hélène , Correa Adolfo , Danesh John , Di Angelantonio Emanuele , Dimou Niki , Ding Jingzhong , Elliott Paul , Esko Tõnu , Evans Michele K. , Floyd James S. , Broer Linda , Grarup Niels , Guo Michael H. , Greinacher Andreas , Haessler Jeff , Hansen Torben , Howson Joanna M. M. , Huang Wei , Jorgenson Eric , Kacprowski Tim , Kähönen Mika , Kamatani Yoichiro , Kanai Masahiro , Karthikeyan Savita , Koskeridis Fotis , Lange Leslie A. , Lehtimäki Terho , Lerch Markus M. , Linneberg Allan , Liu Yongmei , Lyytikäinen Leo-Pekka , Manichaikul Ani , Matsuda Koichi , Mohlke Karen L. , Mononen Nina , Murakami Yoshinori , Nadkarni Girish N. , Nauck Matthias , Nikus Kjell , Ouwehand Willem H. , Pankratz Nathan , Pedersen Oluf , Preuss Michael , Psaty Bruce M. , Raitakari Olli T. , Roberts David J. , Rich Stephen S. , Rodriguez Benjamin A.T. , Rosen Jonathan D. , Rotter Jerome I. , Schubert Petra , Spracklen Cassandra N. , Surendran Praveen , Tang Hua , Tardif Jean-Claude , Ghanbari Mohsen , Völker Uwe , Völzke Henry , Watkins Nicholas A. , Zonderman Alan B. , Million Veteran Program VA , Wilson Peter W.F. , Li Yun , Butterworth Adam S. , Gauchat Jean-François , Chiang Charleston W.K. , Li Bingshan , Loos Ruth J.F. , Astle William J. , Evangelou Evangelos , Sankaran Vijay G. , Okada Yukinori , Soranzo Nicole , Johnson Andrew D. , Reiner Alexander P. , Auer Paul L. , Lettre Guillaume 
Published: January 2020

SUMMARYMost loci identified by GWAS have been found in populations of European ancestry (EA). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EA individuals, we identified 5,552 trait-variant associations atP<5×10−9, including 71 novel loci not found in EA populations. We also identified novel ancestry-specific variants not found in EA, including anIL7missense variant in South Asians associated with lymphocyte countin vivoand IL7 secretion levelsin vitro. Fine-mapping prioritized variants annotated as functional, and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EA-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations, and compared genetic architecture and the impact of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.
A randomized parallel algorithm for efficiently finding near-optimal universal hitting sets
Authors: Ekim Barış , Berger Bonnie , Orenstein Yaron 
Published: January 2020

AbstractAs the volume of next generation sequencing data increases, an urgent need for algorithms to efficiently process the data arises.Universal hitting sets(UHS) were recently introduced as an alternative to the central idea of minimizers in sequence analysis with the hopes that they could more efficiently address common tasks such as computing hash functions for read overlap, sparse suffix arrays, and Bloom filters. A UHS is a set ofk-mers that hit every sequence of lengthL, and can thus serve as indices toL-long sequences. Unfortunately, methods for computing small UHSs are not yet practical for real-world sequencing instances due to their serial and deterministic nature, which leads to long runtimes and high memory demands when handling typical values ofk(e.g.k> 13). To address this bottleneck, we present two algorithmic innovations to significantly decrease runtime while keeping memory usage low: (i) we leverage advanced theoretical and architectural techniques to parallelize and decrease memory usage in calculatingk-mer hitting numbers; and (ii) we build upon techniques from randomized Set Cover to select universalk-mers much faster. We implemented these innovations in PASHA, the first randomized parallel algorithm for generating near-optimal UHSs, which newly handlesk> 13. We demonstrate empirically that PASHA produces sets only slightly larger than those of serial deterministic algorithms; moreover, the set size is provably guaranteed to be within a small factor of the optimal size. PASHA’s runtime and memory-usage improvements are orders of magnitude faster than the current best algorithms. We expect our newly-practical construction of UHSs to be adopted in many high-throughput sequence analysis pipelines.