bluuebunny/crossref_metadata_2025_split huggingface dataset:
Practice Patterns of Physicians and Nurse Practitioners in Primary Care
Authors: Neprash Hannah T. , Smith Laura Barrie , Sheridan Bethany , Hempstead Katherine , Kozhimannil Katy B. 
Published: September 2020

Background:
Primary care practices increasingly include nurse practitioners (NPs), in addition to physicians. Little is known about how the patient mix and clinical activities of colocated physicians and NPs compare.

Objectives:
To describe the clinical activities of NPs, compared with physicians.

Research Design:
We used claims and electronic health record data from athenahealth Inc., on primary care practices in 2017 and a cross-sectional analysis with practice fixed effects.

Subjects:
Patients receiving treatment from physicians and NPs within primary care practices.

Measures:
First, we measured patient characteristics (payer, age, sex, race, chronic condition count) and visit characteristics (new patient, scheduled duration, same-day visit, after-hours visit). Second, we measured procedures performed and diagnoses recorded during each visit. Finally, we measured daily quantity (visit volume, minutes scheduled for patient care, total work relative value units billed) of care.

Results:
Relative to physicians, NPs treated younger and healthier patients. NPs also had a larger share of patients who were female, non-White, and covered by Medicaid, commercial insurance, or no insurance. NPs scheduled longer appointments and treated more patients on a same-day or after-hours basis. On average, “overlapping” services—those performed by NPs and physicians within the same practice—represented 92% of all service volume. The small share of services performed exclusively by physicians reflected greater clinical intensity. On a daily basis, NPs provided fewer and less intense visits than physicians within the same practice.

Conclusions:
Our findings suggest considerable overlap between the clinical activities of colocated NPs and physicians, with some differentiation based on intensity of services provided.
Prevalence and Factors Associated With HIV and Sexually Transmitted Infections Among Female Sex Workers in Bamako, Mali
Authors: Tounkara Fatoumata Korika , Téguété Ibrahima , Guédou Fernand A. , Keita Bintou , Alary Michel 
Published: September 2020

Background
We aimed to (1) estimate the prevalence of HIV and other sexually transmitted infections (STIs) among female sex workers (FSWs) in Bamako, Mali, and (2) identify factors associated with STIs including HIV infection in this population.

Methods
We analyzed baseline data from a prospective observational cohort study on cervical cancer screening, human papillomavirus, and HIV infections among FSWs 18 years or older recruited in Bamako. Multivariable log-binomial regression was used to estimate the adjusted prevalence ratios (APRs) with 95% confidence interval (95% CI) for HIV infection and STIs versus associated factors.

Results
Among 353 women participating in the study, mean age was 26.8 (±7.6) years. HIV prevalence was 20.4%, whereas 35.1% of the FSWs had at least one STI. Factors significantly associated with HIV were older age (P < 0.0001, test for trend), duration of sex work ≥6 years (APR, 1.92; 95% CI, 1.22–3.02), uneducated status (APR, 2.24; 95% CI, 1.16–4.34), less than 10 clients in the last 7 days (APR, 1.55; 95% CI, 1.02–2.34), and gonococcal (APR, 1.85; 95% CI, 1.21–2.82) and chlamydial (APR, 2.58; 95% CI, 1.44–4.62) infections. Younger age (P = 0.018, test for trend), having ≥10 clients in the last week (APR, 1.47; 95% CI, 1.11–1.94), and HIV infection (APR, 2.00; 95% CI, 1.49–2.69) were significantly associated with STIs.

Conclusions
HIV and curable STI prevalence are high among FSWs in Bamako. There is thus a need to enhance the efficiency of interventions toward FSWs in Mali to reduce the burden of HIV and STIs among them and prevent HIV spread to the general population.
Regionalization of trauma care by operative experience: Does the volume of emergent laparotomy matter?
Authors: Tang Andrew , Chehab Mohamad , Ditillo Michael , Asmar Samer , Khurrum Muhammad , Douglas Molly , Bible Letitia , Kulvatunyou Narong , Joseph Bellal 
Published: September 2020

INTRODUCTION
The volume-outcome relationship led to the regionalization of trauma care. The relationship between trauma centers’ injury-specific laparotomy volume and outcomes has not been explored. The aim of our study was to examine the relationship between a trauma center’s injury-specific laparotomy volume and outcomes in blunt and penetrating trauma patients.

METHODS
We performed a (2017) analysis of the Trauma Quality Improvement Program database. We included adult (age, ≥18 years) blunt and penetrating trauma patients who required emergent laparotomies for hemorrhage control. Trauma centers were stratified based on their blunt and penetrating laparotomy volumes: high volume (HV), ≥25 cases per year; medium volume (MV), 13 to 24 cases per year; and low volume (LV), ≤12 cases per year. Multivariate regression analysis was performed to explore predictors of in-hospital mortality.

RESULTS
A total of 8,588 patients underwent emergent laparotomy for either blunt (4,936; 57.5%) or penetrating injuries (3,652; 42.5%). Overall, mean ± SD age was 40 ± 17 years, abdomen Abbreviated Injury Scale was 3 (2–4), and Injury Severity Score was 26 (17–35). For American College of Surgeons (ACS) level I centers, 50% were HV; 29%, MV; and 21%, LV. For ACS level II centers, 7% were HV; 23%, MV; and 70%, LV. For ACS level III centers, 100% were LV. On multivariate regression analysis, admission of blunt and penetrating trauma patients to HV blunt and HV penetrating centers, respectively, was independently associated with improved in-hospital mortality. High-volume blunt centers had a significantly lower time to laparotomy (72 [41–144] minutes) versus MV (81 [49–145] minutes) and LV (94 [56–158] minutes) centers (p < 0.001). The same trend was observed for HV penetrating trauma centers (35 [24–52] minutes) versus MV (46 [33–63] minutes) and LV (51 [38–69] minutes) centers (p < 0.001).

CONCLUSION
Blunt and penetrating injury patients requiring emergent laparotomy had higher survival when admitted to trauma centers with HV operative experience for their particular mechanism of injury. The regionalization of trauma care should be based on a thorough evaluation of trauma centers’ injury-specific operative experience.

LEVEL OF EVIDENCE
Prognostic, Level III; Therapeutic/Care management, Level IV.
The critical threshold value of systolic blood pressure for aortic occlusion in trauma patients in profound hemorrhagic shock
Authors: Ordoñez Carlos A. , Rodríguez Fernando , Orlas Claudia P. , Parra Michael W. , Caicedo Yaset , Guzmán Mónica , Serna José J. , Salcedo Alexander , Zogg Cheryl K. , Herrera-Escobar Juan P. , Meléndez Juan J. , Angamarca Edison , Serna Carlos A. , Martínez Diana , García Alberto F. , Brenner Megan 
Published: September 2020

BACKGROUND
This study aimed to determine the critical threshold of systolic blood pressure (SBP) for aortic occlusion (AO) in severely injured patients with profound hemorrhagic shock.

METHODS
All adult patients (>15 years) undergoing AO via resuscitative endovascular balloon occlusion of the aorta (REBOA) or thoracotomy with aortic cross clamping (TACC) between 2014 and 2018 at level I trauma center were included. Patients who required cardiopulmonary resuscitation in the prehospital setting were excluded. A logistic regression analysis based on mechanism of injury, age, Injury Severity Score, REBOA/TACC, and SBP on admission was done.

RESULTS
A total of 107 patients underwent AO. In 57, TACC was performed, and in 50, REBOA was performed. Sixty patients who underwent AO developed traumatic cardiac arrest (TCA), and 47 did not (no TCA). Penetrating trauma was more prevalent in the TCA group (TCA, 90% vs. no TCA, 74%; p < 0.05) but did not modify 24-hour mortality (odds ratio, 0.51; 95% confidence interval, 0.13–2.00; p = 0.337). Overall, 24-hour mortality was 47% (50) and 52% (56) for 28-day mortality. When the SBP reached 60 mm Hg, the predicted mortality at 24 hours was more than 50% and a SBP lower than 70 mm Hg was also associated with an increased of probability of cardiac arrest.

CONCLUSION
Systolic blood pressure of 60 mm Hg appears to be the optimal value upon which AO must be performed immediately to prevent the probability of death (>50%). However, values of SBP less than 70 mm Hg also increase the probability of cardiac arrest.

LEVEL OF EVIDENCE
Therapeutic study, level IV.
Inhibitor binding influences the protonation states of histidines in SARS-CoV-2 main protease
Authors: Pavlova Anna , Lynch Diane L. , Daidone Isabella , Zanetti-Polzi Laura , Smith Micholas Dean , Chipot Chris , Kneller Daniel W. , Kovalevsky Andrey , Coates Leighton , Golosov Andrei A. , Dickson Callum J. , Velez-Vega Camilo , Duca José S. , Vermaas Josh V. , Pang Yui Tik , Acharya Atanu , Parks Jerry M. , Smith Jeremy C. , Gumbart James C. 
Published: September 2020

AbstractThe main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an attractive target for antiviral therapeutics. Recently, many high-resolution apo and inhibitor-bound structures of Mpro, a cysteine protease, have been determined, facilitating structure-based drug design. Mproplays a central role in the viral life cycle by catalyzing the cleavage of SARS-CoV-2 polyproteins. In addition to the catalytic dyad His41-Cys145, Mprocontains multiple histidines including His163, His164, and His172. The protonation states of these histidines and the catalytic nu-cleophile Cys145 have been debated in previous studies of SARS-CoV Mpro, but have yet to be investigated for SARS-CoV-2. In this work we have used molecular dynamics simulations to determine the structural stability of SARS-CoV-2 Mproas a function of the protonation assignments for these residues. We simulated both the apo and inhibitor-bound enzyme and found that the conformational stability of the binding site, bound inhibitors, and the hydrogen bond networks of Mproare highly sensitive to these assignments. Additionally, the two inhibitors studied, the peptidomimetic N3 and anα-ketoamide, display distinct His41/His164 protonation-state-dependent stabilities. While the apo and the N3-bound systems favored Nδ(HD) and Nϵ(HE) protonation of His41 and His164, respectively, theα-ketoamide was not stably bound in this state. Our results illustrate the importance of using appropriate histidine protonation states to accurately model the structure and dynamics of SARS-CoV-2 Mproin both the apo and inhibitor-bound states, a necessary prerequisite for drug-design efforts.
Epitope - based peptide vaccine against glycoprotein GPC precursor ofLujo virususing immunoinformatics approaches
Authors: Mohammed Arwa A. , Elkhalifa Mayada E. , Elamin Khadija E. , Mohammed Rawan A. , Ibrahim Musab E. , Dirar Amina I. , Migdar Sara H. , Hamid Maha A. , Elawad Emeirii H. , Abdelsalam Salam O. , Hassan Mohamed A. 
Published: September 2020

AbstractBackgroundLujo virus(LUJV) is a highly fatal human pathogen belonging to theArenaviridaefamily.Lujo viruscauses viral hemorrhagic fever (VHF). AnIn silicomolecular docking was performed on the GPC domain ofLujo virusin complex with the first CUB domain of neuropilin-2.The aimof this study is to predict effective epitope-based vaccine against glycoprotein GPC precursor ofLujo virususing immunoinformatics approaches.Methods and Materialsglycoprotein GPC precursor ofLujo virusSequence was retrieved from NCBI. Different prediction tools were used to analyze the nominee’s epitopes in BepiPred-2.0: Sequential B-Cell Epitope Predictor for B-cell, T-cell MHC class II & I. Then the proposed peptides were docked using Autodock 4.0 software program.Results and ConclusionsThe proposed and promising peptides FWYLNHTKL and YMFSVTLCI shows a very strong binding affinity to MHC class I & II alleles with high population coverage for the world, South Africa and Sudan. This indicates a strong potential to formulate a new vaccine, especially with the peptide YMFSVTLCI which is likely to be the first proposed epitope-based vaccine against glycoprotein GPC ofLujo virus. This study recommends an in-vivo assessment for the most promising peptides especially FWYLNHTKL, YMFSVTLCI and LPCPKPHRLR.
Foraging strategies under extreme events: Contrasting adaptations by benthic macrofauna to drastic biogeochemical disturbance
Authors: Wang Yiming V. , Lebrato Mario , Tseng Li-Chun , Larsen Thomas , Smith-Sánchez Nicolás , Lee Pei-Wen , Molinero Juan-Carlos , Hwang Jiang-Shiou , Chan Tin-Yam , Garbe-Schönberg Dieter 
Published: September 2020

ABSTRACTExtreme events caused by global change are increasingly affecting the ocean’s biogeochemical cycling and ecosystem functioning, but it is challenging to observe how food webs respond to rapid habitat disturbances. Benthic communities are particularly vulnerable because their habitats are easily affected by extreme events. Here, we examined how benthic macrofauna responded to a “near shutdown” of shallow marine hydrothermal vents, triggered by M5.8 earthquake and C5 typhoon events. Despite reduced vent fluxes, we shows that the endemic vent crab Xenograpsus testudinatus continued to rely on chemosynthetic sulfur bacteria rather than photosynthetic sources. We posit this obligate nutritional dependence caused a population decline of vent crabs. In contrast, the non-endemic mollusks exhibited much greater dietary plasticity with no detectable impact on the population. Our study based on naturally occurring extreme events exemplifies how specialist species in marine system are particularly vulnerable to the unprecedented evolutionary and environmental pressures exerted by human activities worldwide.
Deletion of Stim1 in hypothalamic arcuate nucleus Kiss1 neurons potentiates synchronous GCaMP activity and protects against diet-induced obesity
Authors: Qiu Jian , Stincic Todd L. , Bosch Martha A. , Connors Ashley M. , Petrie Stefanie Kaech , Rønnekleiv Oline K. , Kelly Martin J. 
Published: September 2020

AbstractKisspeptin (Kiss1) neurons are essential for reproduction, but their role in the control of energy balance and other homeostatic functions remains unclear. High frequency firing of hypothalamic arcuate Kiss1 (Kiss1ARH) neurons releases kisspeptin into the median eminence, and neurokinin B (NKB) and dynorphin onto neighboring Kiss1ARHneurons to generate a slow excitatory postsynaptic potential (EPSP) mediated by TRPC5 channels that entrains intermittent, synchronous firing of Kiss1ARHneurons. High frequency optogenetic stimulation of Kiss1ARHneurons releases glutamate to excite the anorexigenic proopiomelanocortin (POMC) neurons and inhibit the orexigenic neuropeptide Y/agouti-related peptide (AgRP) neurons via metabotropic glutamate receptors. At the molecular level, the endoplasmic reticulum calcium-sensing protein stromal interaction molecule 1 (STIM1) is critically involved in the regulation of neuronal Ca2+signaling and neuronal excitability through its interaction with plasma membrane calcium (e.g., TRPC) channels. 17β-estradiol (E2) downregulatesStim1mRNA expression in female arcuate neurons. Therefore, we hypothesized that deletion ofStim1in Kiss1ARHneurons would increase neuronal excitability and their synchronous firing, which ultimately would affect energy homeostasis. Using optogenetics in combination with whole-cell recording and GCaMP6 imaging in slices, we discovered that the deletion ofStim1in Kiss1 neurons significantly increased the amplitude of the slow EPSP and augmented synchronous [Ca2+]i oscillations in Kiss1ARHneurons. Deletion ofStim1in Kiss1ARHneurons amplified the actions of NKB and protected ovariectomized female mice from developing obesity and glucose intolerance with high-fat dieting. Therefore, STIM1 appears to play a critical role in regulating synchronous firing of Kiss1ARHneurons, which ultimately affects energy homeostasis.Significance StatementHypothalamic arcuate kisspeptin (Kiss1ARH) neurons are essential for stimulating the pulsatile release of gonadotropin releasing hormone (GnRH) and maintaining fertility. However, Kiss1ARHneurons appear to be a key player in coordinating energy balance with reproduction. The regulation of calcium channels and hence calcium signaling is critically dependent on the endoplasmic reticulum calcium-sensing protein stromal interaction molecule 1 (STIM1), which interacts with the plasma membrane calcium channels. We have conditionally deletedStim1in Kiss1ARHneurons and found that it significantly increased the excitability of Kiss1ARHneurons and protected ovariectomized female mice from developing obesity and glucose intolerance with high-fat dieting.
ImmunoCluster: A computational framework for the non-specialist to profile cellular heterogeneity in cytometry datasets
Authors: Opzoomer James W. , Timms Jessica , Blighe Kevin , Mourikis Thanos P. , Chapuis Nicolas , Bekoe Richard , Kareemaghay Sedigeh , Nocerino Paola , Apollonio Benedetta , Ramsay Alan G. , Tavassoli Mahvash , Harrison Claire , Ciccarelli Francesca , Parker Peter , Fontenay Michaela , Barber Paul R. , Arnold James N. , Kordasti Shahram 
Published: September 2020

AbstractHigh dimensional cytometry is an innovative tool for immune monitoring in health and disease, it has provided novel insight into the underlying biology as well as biomarkers for a variety of diseases. However, the analysis of multiparametric “big data” usually requires specialist computational knowledge. Here we describeImmunoCluster (https://github.com/kordastilab/ImmunoCluster)an R package for immune profiling cellular heterogeneity in high dimensional liquid and imaging mass cytometry, and flow cytometry data, designed to facilitate computational analysis by a non-specialist. The analysis framework implemented withinImmunoClusteris readily scalable to millions of cells and provides a variety of visualization and analytical approaches, as well as a rich array of plotting tools that can be tailored to users’ needs. The protocol consists of three core computational stages: 1, data import and quality control, 2, dimensionality reduction and unsupervised clustering; and 3, annotation and differential testing, all contained within an R-based open-source framework.
Physiological System Dysregulation in Gene Expression Correlates Negatively with Age
Authors: Dufour Frédérik , Jacques Pierre-Étienne , Cohen Alan A. 
Published: September 2020

AbstractWe attempted to identify gene expression systems that dysregulate with age in human peripheral blood samples across five public datasets. Dysregulation of gene ontology (GO)-defined systems was measured using the Mahalanobis distance (DM), a measure of multivariant aberrance. We expected many weak positive DM-age correlations, indicating loss of homeostatic control. Out of the 5180 GO terms tested, we found 230 systems that replicated in at least three datasets. Surprisingly, all 230 systems showed negative DM-age correlations, in contrast to findings with clinical biomarkers. These systems were mostly metabolic functions related to small molecules and nitrogen compounds, transport functions, biosynthetic processes and response to stress functions. These results suggest a loss of responsiveness in these gene expression systems during the aging process, and contrast to some previous literature showing increased gene expression heterogeneity with age.
Improving laser standards for three-photon microscopy
Authors: Farinella Deano M. , Roy Arani , Liu Chao J. , Kara Prakash 
Published: September 2020

AbstractSignificanceThree-photon excitation microscopy has double-to-triple the penetration depth in biological tissue over two-photon imaging and thus has the potential to revolutionize the visualization of biological processesin vivo. However, unlike the ‘plug-and-play’ operation and performance of lasers used in two-photon imaging, three-photon microscopy presents new technological challenges that require a closer look at the fidelity of laser pulses.AimWe implemented state-of-the-art pulse measurements and developed new techniques for examining the performance of lasers used in three-photon microscopy. We then demonstrated how these techniques can be used to provide precise measurements of pulse shape, pulse energy and pulse-to-pulse intensity variability, all of which ultimately impact imaging.ApproachWe built inexpensive tools, e.g., a second harmonic generation frequency resolved optical gating (SHG-FROG) device, and a deep-memory diode imaging (DMDI) apparatus, to examine laser pulse fidelity.ResultsFirst, SHG-FROG revealed very large third order dispersion (TOD). This extent of phase distortion prevents the efficient temporal compression of laser pulses to their theoretical limit. Furthermore, TOD cannot be quantified when using a conventional method of obtaining the laser pulse duration, e.g., when using an autocorrelator. Finally, DMDI showed the effectiveness of detecting pulse-to-pulse intensity fluctuations on timescales relevant to three-photon imaging, which were otherwise not captured using conventional instruments and statistics.ConclusionsThe distortion of individual laser pulses caused by TOD poses significant challenges to three-photon imaging by preventing effective compression of laser pulses and decreasing the efficiency of nonlinear excitation. Moreover, an acceptably low pulse-to-pulse amplitude variability should not be assumed. Particularly for low repetition rate laser sources used in three-photon microscopy, pulse-to-pulse variability also degrades image quality. If three-photon imaging is to become mainstream, our diagnostics may be used by laser manufacturers to improve system design and by end-users to validate the performance of their current and future imaging systems.
GiantGALgene clusters for the melibiose-galactose pathway inTorulaspora
Authors: Venkatesh Anjan , Murray Anthony L. , Coughlan Aisling Y. , Wolfe Kenneth H. 
Published: September 2020

AbstractIn many yeast species the three genes at the center of the galactose catabolism pathway,GAL1,GAL10andGAL7, are neighbors in the genome and form a metabolic gene cluster. We report here that some yeast strains in the genusTorulasporahave much largerGALclusters that include genes for melibiase (MEL1), galactose permease (GAL2), glucose transporter (HGT1), phosphoglucomutase (PGM1), and the transcription factorGAL4, in addition toGAL1,GAL10, andGAL7. Together, these 8 genes encode almost all the steps in the pathway for catabolism of extracellular melibiose (a disaccharide of galactose and glucose). We show that a progenitor 5-gene cluster containingGAL 7-1-10-4-2was likely present in the common ancestor ofTorulasporaandZygotorulaspora. It addedPGM1andMEL1in the ancestor of mostTorulasporaspecies. It underwent further expansion in theT. pretoriensisclade, involving the fusion of three progenitor clusters in tandem and the gain ofHGT1. These giantGALclusters are highly polymorphic in structure, and subject to horizontal transfers, pseudogenization and gene losses. We identify recent horizontal transfers of completeGALclusters fromT. franciscaeinto one strain ofT. delbrueckii, and from a relative ofT. maleeaeinto one strain ofT. globosa. The variability and dynamic evolution ofGALclusters inTorulasporaindicates that there is strong natural selection on theGALpathway in this genus.