bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opioid Prescriptions for Female Pelvic Reconstructive Surgery Patients Before and After Implementation of Tennessee State Legislation
Authors: Samimi Parisa , Panza Joseph , Heft Jessica , Wang Li , Adam Rony 
Published: September 2019

Objectives
Limited data exist regarding the impact of state legislation on opioid-prescribing patterns, particularly in states with the highest opioid-prescribing rates in the nation. Our primary objective was to examine the change in the amount of opioid morphine equivalents (OMEs) prescribed at discharge to patients undergoing female pelvic reconstructive surgery after the implementation of state legislation created in response to the opioid crisis.

Methods
At our institution, state legislation went into effect on July 1, 2018, implementing limitations on OMEs prescribed to patients. This retrospective cohort study examines all adult women undergoing female pelvic reconstructive surgery from January 1, 2018, to December 31, 2018. The study compares prescribing practices 6 months before and 6 months after the state law was enacted.

Results
In total, 346 patients met inclusion criteria. The 2 groups had similar demographics. Surgical procedures were well distributed, with 52% of cases occurring in the first 6 months of the calendar year. At the time of discharge, 324 (96.7%) patients received an opioid prescription, with an overall average of 197 OMEs. After the implementation of state legislation on July 1, 2018, the amount of OMEs prescribed at discharge significantly decreased, from a median of 210 mg (interquartile range, 150–225) to 150 mg (interquartile range 135–225; P = 0.02).

Conclusions
State legislation was associated with a significant decrease in prescribed OMEs at the time of discharge in patients undergoing female pelvic reconstructive surgery. These results support ongoing legislative efforts to address the current opioid crisis.
Behaviors Characteristic of Autism Spectrum Disorder in a Geriatric Cohort With Mild Cognitive Impairment or Early Dementia
Authors: Rhodus Elizabeth K. , Barber Justin , Abner Erin L. , Duff Danielle M.C. , Bardach Shoshana H. , Caban-Holt Allison , Lightner Donita , Rowles Graham D. , Schmitt Frederick A. , Jicha Gregory A. 
Published: September 2019

Introduction:
Autism spectrum disorder (ASD) represents a heterogenous cluster of clinical phenotypes that are classically diagnosed by the time of adolescence. The possibility of late-life emergence of ASD has been poorly explored.

Methods:
To more fully characterize the possibility of late-life emergence of behaviors characteristic of ASD in mild cognitive impairment and AD, we surveyed caregivers of 142 older persons with cognitive impairment from the University of Kentucky Alzheimer’s Disease Center Longitudinal Cohort using the Gilliam Autism Rating Scale-2.

Results:
Participants with high autism index ratings (autism “possible/very likely,” n=23) reported significantly (statistically and clinically) younger age at the onset of cognitive impairment than those who scored in the autism “unlikely” range (n=119): 71.14±10.9 vs. 76.65±8.25 (P=0.034). In addition, those in the autism “possible/very likely” group demonstrated advanced severity of cognitive impairment, indicated by the Clinical Dementia Rating Scale Sum of Boxes scores.

Discussion:
Data demonstrate that ASD behaviors may seem de novo of degenerative dementia and such behaviors are more prevalent in those with early onset dementia. Further work elucidating a connection between ASD and dementia could shed light on subclinical forms of ASD, identify areas of shared neuroanatomic involvement between ASD and dementias, and provide valuable insights that might hasten the development of therapeutic strategies.
Insomnia-related Memory Impairment in Individuals With Very Complex Chronic Pain
Authors: Bothelius Kristoffer , Hysing Eva-Britt , Filén Tove , Lundeborg Linnea , Gordh Torsten 
Published: September 2019

Objective:
To investigate the specific effect of insomnia on neuropsychological functioning in patients with very complex chronic pain.

Background:
Individuals with insomnia disorder or chronic pain often experience cognitive deficits, with both conditions appearing to correlate with impairments in neuropsychological functions. As insomnia often occurs comorbid with chronic pain, distinguishing the differential effects of these two syndromes on an individual’s neuropsychological functioning can be challenging. Comorbid depressive symptoms in these individuals, which may also affect cognitive function, may further obscure the associations between chronic pain, insomnia, and the neuropsychological profile.

Methods:
The neuropsychological function of 22 individuals with very complex chronic pain was assessed using specialized tests examining aspects of memory and executive functioning. The severity of insomnia, depression, and anxiety was measured using questionnaires, and pain levels were assessed using a visual analog scale. Pain medications were transformed to the morphine-equivalent daily dose.

Results:
Insomnia severity was found to predict memory function, accounting for 32.4% of the variance: A 1 SD increase in insomnia severity decreased memory function by 0.57 SD. The negative correlation between insomnia and memory was significant even after controlling for pain level, morphine-equivalent daily dose, and comorbid levels of anxiety and depression.

Conclusions:
Insomnia severity independently predicted memory function in patients with very complex chronic pain, even after controlling for other factors known to impair cognitive function. Insomnia may possibly explain some of the cognitive impairments related to chronic pain; thus, screening for, and treating, sleep disturbances may be a central aspect of chronic pain rehabilitation.
The Dynamic Strength of the Hair-Cell Tip Link Reveals Mechanisms of Hearing and Deafness
Authors: Mulhall Eric M. , Ward Andrew , Yang Darren , Koussa Mounir A. , Corey David P. , Wong Wesley P. 
Published: September 2019

AbstractOur senses of hearing and balance rely on the extraordinarily sensitive molecular machinery of the inner ear to convert deflections as small as the width of a single carbon atom1,2 into electrical signals that the brain can process3. In humans and other vertebrates, transduction is mediated by hair cells4, where tension on tip links conveys force to mechanosensitive ion channels5. Each tip link comprises two helical filaments of atypical cadherins bound at their N-termini through two unique adhesion bonds6–8. Tip links must be strong enough to maintain a connection to the mechanotransduction channel under the dynamic forces exerted by sound or head movement—yet might also act as mechanical circuit breakers, releasing under extreme conditions to preserve the delicate structures within the hair cell. Previous studies have argued that this connection is exceptionally static, disrupted only by harsh chemical conditions or loud sound9–12. However, no direct mechanical measurements of the full tip-link connection have been performed. Here we describe the dynamics of the tip-link connection at single-molecule resolution and show how avidity conferred by its double stranded architecture enhances mechanical strength and lifetime, yet still enables it to act as a dynamic mechanical circuit breaker. We also show how the dynamic strength of the connection is facilitated by strong cis-dimerization and tuned by extracellular Ca2+, and we describe the unexpected etiology of a hereditary human deafness mutation. Remarkably, the connection is several thousand times more dynamic than previously thought, challenging current assumptions about tip-link stability and turnover rate, and providing insight into how the mechanotransduction apparatus conveys mechanical information. Our results reveal fundamental mechanisms that underlie mechanoelectric transduction in the inner ear, and provide a foundation for studying multi-component linkages in other biological systems.
A new strategy for selection of crop cultivated varieties based on yield factors driving and meteorological prediction
Authors: Zhu Rongsheng , Sun Kai , Yan Xuehui , Xin Dawei , Jiang Hongwei , Zhang Zhanguo , Li Yang , Hu Zhenbang , Qi Zhaoming , Yang Chunming , Chen Qingshan 
Published: September 2019

AbstractMeteorological conditions, as an uncontrollable factor, have a direct impact on the growth and yield of crops in the field. It’s particularly important to choose the cultivated varieties suitable for environmental change. As for this problem, a new strategy for selection of crop cultivated varieties is proposed in this paper. The experiment selected Harbin pilot (Heilongjiang, China) and Changchun pilot (Jilin, China). In the experiment, the cultivated varieties suitable for forecasting meteorological conditions in 2015 could be provided according to the meteorological data of 2005-2014 years and the yield data of different soybean varieties in Harbin pilot. The same method was also taken in Changchun pilot. The results showed that the recommended varieties of Harbin pilot and Changchun pilot had 70% and 50% probability respectively for selection of soybean cultivated varieties when the yield evaluation trait was 100-seed-weight. As for seed weight per plant, the possibility of more than 60% of the recommended varieties in two pilots is to provide prejudgment. Therefore, this method can help to improve the current situation of the impact of uncontrollable meteorological conditions on crop yield and also can be applied to the selection of any other crops cultivated varieties under a certain environment.
Osteoporosis- and obesity-risk interrelationships: An epigenetic analysis of GWAS-derived SNPs at the developmental geneTBX15
Authors: Zhang Xiao , Ehrlich Kenneth C. , Yu Fangtang , Hu Xiaojun , Deng Hong-Wen , Shen Hui , Ehrlich Melanie 
Published: September 2019

AbstractA major challenge in translating findings from genome-wide association studies (GWAS) to biological mechanisms is pinpointing functional variants because only a very small percentage of variants associated with a given trait actually impact the trait. We used an extensive epigenetics, transcriptomics, and genetics analysis of theTBX15/WARS2neighborhood to prioritize this region’s best-candidate causal variants for the genetic risk of osteoporosis (estimated bone density, eBMD) and obesity (waist-hip ratio or waist circumference adjusted for body mass index).TBX15encodes a transcription factor that is important in bone development and adipose biology. Manual curation of 692 GWAS-derived variants gave eight strong candidates for causal SNPs that modulateTBX15transcription in subcutaneous adipose tissue (SAT) or osteoblasts, which highly and specifically express this gene. None of these SNPs were prioritized by Bayesian fine-mapping. The eight regulatory causal SNPs were in enhancer or promoter chromatin seen preferentially in SAT or osteoblasts atTBX15intron-1 or upstream. They overlap strongly predicted, allele-specific transcription factor binding sites. Our analysis suggests that these SNPs act independently of two missense SNPs inTBX15. Remarkably, five of the regulatory SNPs were associated with eBMD and obesity and had the same trait-increasing allele for both. We found thatWARS2obesity-related SNPs can be ascribed to high linkage disequilibrium withTBX15intron-1 SNPs. Our findings from GWAS index, proxy, and imputed SNPs suggest that a few SNPs, including three in a 0.7-kb cluster, act as causal regulatory variants to fine-tuneTBX15expression and, thereby, affect both obesity and osteoporosis risk.
Basal forebrain parvalbumin neurons mediate arousals from sleep induced by hypercarbia or auditory stimuli
Authors: McKenna James T. , Thankachan Stephen , Uygun David S , Shukla Charu , Cordeira Joshua , McNally James M. , Katsuki Fumi , Zant Janneke , Gamble Mackenzie C. , Deisseroth Karl , McCarley Robert W. , Brown Ritchie E. , Strecker Robert E. , Basheer Radhika 
Published: September 2019

SUMMARYBrief arousals from sleep in patients with sleep apnea and other disorders prevent restful sleep, and contribute to cognitive, metabolic and physiologic dysfunction. Little is currently known about which neural systems mediate these brief arousals, hindering the development of treatments. The basal forebrain (BF) receives inputs from many nuclei of the ascending arousal system. These inputs include the brainstem parabrachial neurons which promote arousal in response to elevated blood carbon dioxide levels, as seen in sleep apnea. Optical inhibition of the terminals of parabrachial neurons in the BF impairs cortical arousals to hypercarbia, but which cell types within the BF mediate cortical arousals in response to hypercarbia or other sensory stimuli is unknown. Here using optogenetic techniques in mice, we show that BF parvalbumin (PV) neurons fulfill several criteria for a system mediating brief arousals from sleep. Optical stimulation of BF PV neurons during the light period, when mice normally sleep, caused rapid transitions to wakefulness and increased wake bout durations. Unlike many other ascending arousal systems, arousals induced by stimulation of BF PV neurons were brief, resulting in only a small (13.6%) increase in the total amount of wakefulness. Bilateral optical inhibition of BF PV neurons increased the latency to arousal produced by hypercarbia or auditory stimuli. Thus, BF PV neurons are an important component of the brain circuitry which generates brief arousals from sleep in response to internal and external sensory stimuli.
Optimal design of single-cell RNA sequencing experiments for cell-type-specific eQTL analysis
Authors: Mandric Igor , Schwarz Tommer , Majumdar Arunabha , Perez Richard , Subramaniam Meena , Ye Chun Jimmie , Pasaniuc Bogdan , Halperin Eran 
Published: September 2019

AbstractSingle-cell RNA-sequencing (scRNA-Seq) is a compelling approach to simultaneously measure cellular composition and state which is impossible with bulk profiling approaches. However, it has not yet become a widely used tool in population-scale analyses, due to its prohibitively high cost. Here we show that given the same budget, the statistical power of cell-type-specific expression quantitative trait loci (eQTL) mapping can be increased through low-coverage per-cell sequencing of more samples rather than high-coverage sequencing of fewer samples. We also show that multiple experimental designs with different numbers of samples, cells per sample and reads per cell could have similar statistical power, and choosing an appropriate design can yield large cost savings especially when multiplexed workflows are considered. Finally, we provide a practical approach on selecting cost-effective designs for maximizing cell-type-specific eQTL power.
2D-HELS-AA MS Seq: Direct sequencing of tRNA reveals its different isoforms and multiple dynamic base modifications
Authors: Zhang Ning , Shi Shundi , Wang Xuanting , Ni Wenhao , Yuan Xiaohong , Duan Jiachen , Jia Tony Z. , Yoo Barney , Ziegler Ashley , Russo James J. , Li Wenjia , Zhang Shenglong 
Published: September 2019

AbstractWe report a direct method for sequencing tRNAPhewithout cDNA by combining 2-dimensional hydrophobic RNA end-labeling with an anchor-based algorithm in mass spectrometry-based sequencing (2D-HELS-AA MS Seq). The entire tRNAPhewas sequenced and the identity, location and abundance of all 11 base modifications were determined. Changes in ratios of wybutosine and its depurinated form under different conditions were quantified, pointing to the ability of our technology to determine dynamic changes of nucleotide modifications. Two truncated isoforms at 3’CCA tail of the tRNAPhe(75 nt CC, 80% and 74 nt C, 3%) were identified in addition to the 76 nt tRNAPhewith a full-length 3’CCA tail (17%). We also discovered a new isoform with A-G transitions at both the 44 and 45 positions in the tRNAPhevariable loop.One Sentence SummaryDirect 2D-HELS-AA MS Seq of tRNA reveals different isoforms and base modifications
Orb-weaving spiders show a correlated syndrome of morphology and web structure in the wild
Authors: Fisher David N. , Yeager Justin , Pruitt Jonathan N. 
Published: September 2019

AbstractExtended phenotypes are traits that exist outside the physical body of the organism. Despite their potential role in the lives of both the organisms that express them and other organisms that can be influenced by extended phenotypes, the consistency and covariance with morphological and behaviour traits of extended phenotypes is rarely evaluated, especially in wild organisms. We repeatedly measured an extended phenotype that directly influences an organism’s prey acquisition, the web structure, of wild orb-weaving spiders (Micrathena vigorsii), which re-build their webs each day. We related web structure traits to behavioural traits and body size (length). Both web diameter and web density were repeatably different among individuals, while reaction to a predation threat was slightly so, but response to a prey stimulus and web symmetry were not. There was a syndrome between morphology and web structure traits, where larger spiders spun webs that were wider, had webs with increased thread spacing, and the spider tended to react more slowly to a predation threat. When a spider built a relatively larger web it was also relatively a less dense and less symmetrical web. The repeatability of web construction and relationship with spider body size we found may be common features of intra-population variation in web structure in spiders. Individual variation along the morphology and web structure syndrome could represent variation in individual foraging strategies, or age-based correlated changes. By estimating the consistency and covariances of extended phenotypes we can begin to evaluate what maintains their variation and how they might evolve.
IdentifyingClostridioides difficile-inhibiting gut commensals using culturomics, phenotyping, and combinatorial community assembly
Authors: Ghimire Sudeep , Roy Chayan , Wongkuna Supapit , Antony Linto , Fenske Gavin , Maji Abhijit , Keena Mitchel Chan , Foley Andrew , Scaria Joy 
Published: September 2019

ABSTRACTA major function of the gut microbiota is to provide colonization resistance, wherein pathogens are inhibited or suppressed below infectious level. However, the fraction of gut microbiota required for colonization resistance remains unclear. We used culturomics to isolate a gut microbiota culture collection comprising 1590 isolates belonging to 102 species. Estimated by metagenomic sequencing of fecal samples used for culture, this culture collection represents 50.73% of taxonomic diversity and 70% functional capacity. Using whole genome sequencing we characterized species representatives from this collection, and predicted their phenotypic traits, further characterizing isolates by defining nutrient utilization profile and short chain fatty acid (SCFA) production. When screened using a co-culture assay, 66 species in our culture collection inhibitedC. difficile. Several phenotypes, particularly, growth rate, production of SCFAs, and the utilization of mannitol, sorbitol or succinate correlated withC. difficileinhibition. We used a combinatorial community assembly approach to formulate defined bacterial mixes inhibitory toC. difficile. When 256 combinations were tested, we found both species composition and blend size to be important in inhibition. Our results show that the interaction of bacteria with each other in a mix and with other members of gut commensals must be investigated for designing defined bacterial mixes for inhibitingC. difficile in vivo.IMPORTANCEAntibiotic treatment causes instability of gut microbiota and the loss of colonization resistance, allowing pathogens such asC. difficileto colonize, causing recurrent infection and mortality. Although fecal microbiome transplantation has shown to be an effective treatment forC. difficileinfection (CDI), a more desirable approach would be the use of a defined mix of inhibitory gut bacteria.C. difficile-inhibiting species and bacterial combinations we identify herein improve our understanding of the ecological interactions controlling colonization resistance againstC. difficile, and could aid the design of defined bacteriotherapy as a non-antibiotic alternative against CDI.
A high-quality reference genome assembly of the saltwater crocodile,Crocodylus porosus, reveals patterns of selection in Crocodylidae
Authors: Ghosh Arnab , Johnson Matthew G. , Osmanski Austin B. , Louha Swarnali , Bayona-Vásquez Natalia J. , Glenn Travis C. , Gongora Jaime , Green Richard E. , Isberg Sally , Stevens Richard D. , Ray David A. 
Published: September 2019

AbstractCrocodilians are an economically, culturally, and biologically important group. To improve researchers’ ability to study genome structure, evolution, and gene regulation in the clade, we generated a high-qualityde novogenome assembly of the saltwater crocodile,Crocodylus porosus, from Illumina short read data from genomic libraries andin vitroproximity-ligation libraries. The assembled genome is 2,123.5 Mb, with N50 scaffold size of 17.7 Mb and N90 scaffold size of 3.8 Mb. We then annotated this new assembly, increasing the number of annotated genes by 74%. In total, 96% of 23,242 annotated genes were associated with a functional protein domain. Furthermore, multiple non-coding functional regions and mappable genetic markers were identified. Upon analysis and overlapping the results of branch length estimation and site selection tests for detecting potential selection, we found 16 putative genes under positive selection in crocodilians, ten inC. porosusand six inA. mississippiensis. The annotatedC. porosusgenome will serve as an important platform for osmoregulatory, physiological and sex determination studies, as well as an important reference in investigating the phylogenetic relationships of crocodilians, birds, and other tetrapods.
A Pairwise Distance Distribution Correction (DDC) algorithm to eliminate blinking-caused artifacts in super-resolution microscopy
Authors: Bohrer Christopher H. , Yang Xinxing , Weng Xiaoli , Tenner Brian , Thakur Shreyasi , McQuillen Ryan , Ross Brian , Wooten Matthew , Chen Xin , Lakadamyali Melike , Zhang Jin , Roberts Elijah , Xiao Jie 
Published: September 2019

AbstractIn single-molecule localization based super-resolution microscopy (SMLM), a fluorophore stochastically switches between fluorescent- and dark-states, leading to intermittent emission of fluorescence, a phenomenon known as blinking. Intermittent emissions create multiple localizations belonging to the same molecule, resulting in blinking-artifacts within SMLM images. These artifacts are often interpreted as true biological assemblies, confounding quantitative analyses and interpretations. Multiple methods have been developed to eliminate these artifacts, but they either require additional experiments, arbitrary thresholds, or specific photo-kinetic models. Here we present a method, termed Distance Distribution Correction (DDC), to eliminate blinking-caused repeat localizations without any additional calibrations. The approach relies on the finding that the true pairwise distance distribution of different fluorophores in an SMLM image can be naturally obtained from the imaging sequence by using distances between localizations separated by a time much longer than the average fluorescence survival time. We show that using the true pairwise distribution we can define and then maximize the likelihood of obtaining a particular set of localizations void of blinking-artifacts, generating an accurate reconstruction of the underlying cellular structure. Using both simulated and experimental data, we show that DDC surpasses all previous existing blinking-artifact correction methodologies, resulting in drastic improvements in obtaining the closest estimate of the true spatial organization and number of fluorescent emitters in a wide range of applications. The simplicity and robustness of DDC will allow it to become the field standard in SMLM imaging, enabling the most accurate reconstruction and quantification of SMLM images to date.