bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct features between HLA-DR+ and HLA-DR− PD-1hi CXCR5– T peripheral helper cells in seropositive rheumatoid arthritis
Authors: Yamada Hiroki , Sasaki Takanori , Matsumoto Kotaro , Suzuki Katsuya , Takeshita Masaru , Tanemura Shuhei , Seki Noriyasu , Tsujimoto Hideto , Takeuchi Tsutomu 
Published: June 2020

AbstractObjectivesPD-1hi CXCR5– T peripheral helper (Tph) cells are newly identified pathogenic CD4 helper T cells in RA. We evaluated the usefulness of Tph cell subsets as biomarkers of RA.MethodsRA patients who visited our rheumatology department between May 2015 and September 2017 and met the 2010 ACR/EULAR classification criteria were included. We compared the correlation of DAS28-ESR between Tph cell subsets and 40 immune cell subsets. We also explored which subsets reflected the chronological changes in the disease activity after treatment.ResultsThirty-four seropositive RA patients, 11 seronegative RA patients and 34 healthy controls were included. Tph cell subsets that correlated with the DAS28-ESR were HLA-DR+ Tph cells (rs = 0.50, P = 0.002), HLA-DR– Tph cells (rs = 0.39, P = 0.03) and Tph1 cells (rs = 0.41, P = 0.02). Among the other 40 immune cell subsets, HLA-DR+ Th1-17 cells (rs = 0.38, P = 0.03), activated B cells (rs = –0.35, P = 0.04), plasma cells (rs = 0.43, P = 0.01) and CD14++ CD16+ monocytes (rs = 0.36, P = 0.04) correlated, but not strongly as HLA-DR+ Tph cells. However, MTX treatment reduced the proportion of HLA-DR+ Tph cells independently of the disease activity. In contrast, HLA-DR– Tph cells accurately reflected the change in the DAS28-ESR during MTX treatment.ConclusionHLA-DR+ Tph cells were decreased with MTX treatment, independent of the disease activity, while HLA-DR– Tph cells reflected the disease activity accurately during the treatment.
The Gut Microbiome and Xenobiotics: Identifying Knowledge Gaps
Authors: Sutherland Vicki L , McQueen Charlene A , Mendrick Donna , Gulezian Donna , Cerniglia Carl , Foley Steven , Forry Sam , Khare Sangeeta , Liang Xue , Manautou Jose E , Tweedie Donald , Young Howard , Alekseyenko Alexander V , Burns Frank , Dietert Rod , Wilson Alan , Chen Connie 
Published: June 2020

Abstract
There is an increasing awareness that the gut microbiome plays a critical role in human health and disease, but mechanistic insights are often lacking. In June 2018, the Health and Environmental Sciences Institute (HESI) held a workshop, “The Gut Microbiome: Markers of Human Health, Drug Efficacy and Xenobiotic Toxicity” (https://hesiglobal.org/event/the-gut-microbiome-workshop) to identify data gaps in determining how gut microbiome alterations may affect human health. Speakers and stakeholders from academia, government, and industry addressed multiple topics including the current science on the gut microbiome, endogenous and exogenous metabolites, biomarkers, and model systems. The workshop presentations and breakout group discussions formed the basis for identifying data gaps and research needs. Two critical issues that emerged were defining the microbial composition and function related to health and developing standards for models, methods and analysis in order to increase the ability to compare and replicate studies. A series of key recommendations were formulated to focus efforts to further understand host-microbiome interactions and the consequences of exposure to xenobiotics as well as identifying biomarkers of microbiome-associated disease and toxicity.
Framework and Outcomes of a Critical Care Pharmacy Visiting Clinical Professor Program
Authors: Louzon Patricia R. , Willmon Julie , Coles Laura , Barreto Erin F. 
Published: June 2020

Objectives:
Experiences with utilizing a visiting clinical professor program to mentor institutions and collaborate on best practices in critical care pharmacy are described to provide a framework for these services and a synopsis of key outcomes.

Design:
The Society of Critical Care Medicine Clinical Pharmacy and Pharmacology Section implemented a visiting clinical professor program to address the need for collaboration, idea-sharing, mentorship, and diffusion of innovation to clinicians in critical care practice.

Setting:
Critical care pharmacy departments at 12 medical centers.

Subjects:
Twelve visiting clinical professors and host institutions from 2007-2018.

Intervention:
After an application is submitted to the section steering committee, an experienced clinician is paired with an institution, and a site visit is planned in collaboration with the visiting clinical professor program coordinators. The expert clinician visits the institution to share their insights and best practices based on visit goals and objectives. Reflective debriefing with both the host institution and the visiting clinical professor occurs after the visit.

Measurements and Main Results:
The program has demonstrated numerous benefits including shared best practices related to critical care clinical services, expansion and refinement of care delivery models, development and optimization of research programs, and advancement of new training programs including specialty pharmacy residencies. Both the site and visiting professor find these partnerships beneficial, which has resulted in sustained success of the program over an 11-year period. Key resultant deliverables after visits have included new pharmacist positions, advancement of pharmacy services, and expanded access to academic opportunities.

Conclusions:
A professional organization led visiting clinical professor program is viable, sustainable, and yields clear benefit for critical care pharmacy programs across the country. Application of this framework to other areas of pharmacy practice may be an avenue to share best practices and advance pharmacy services.
Patient and Care Delivery Characteristics Associated With Harm From Neuromuscular Blockade
Authors: Poole Brian R. , Reese Zachary A. , Dechen Tenzin , Tocci Noah , Elsamadisi Pansy , Holland Susan , Hayes Margaret M. , Stevens Jennifer P. 
Published: June 2020

Objectives:
To identify the prevalence of and evaluate factors associated with down-titration of sedation in patients receiving neuromuscular blockade.

Design:
Retrospective cohort study.

Setting:
Tertiary care teaching hospital in Boston, MA.

Patients:
All patients over 18 years old admitted to the medical, surgical, or cardiac ICUs from 2013 to 2016, and who received cisatracurium for at least 24 hours.

Interventions:
We examined patients for whom sedation was decreased despite accompanying ongoing neuromuscular blockade administration.

Measurements and Main Results:
Of the 300 patients who met inclusion criteria (39% female, mean age of 57 yr old), 168 (56%) had sedation down-titrated while receiving neuromuscular blockade with a mean decrease in sedation dose of 18.7%. Factors associated with down-titration of sedation were bispectral index usage (90/168 [53.6%] vs 50/168 [29.8%] patients; p < 0.01; odds ratio, 1.82; 1.12–2.94), and bolus dose of neuromuscular blockade prior to continuous infusion (138/168 [82.1%] vs 79/168 [47.0%] patients; p < 0.0001).

Conclusions:
Down-titration of sedation among mechanically ventilated patients receiving neuromuscular blockade was common and was correlated with bispectral index monitor usage. Clinicians should be aware of the limitations of quantitative electroencephalography monitoring devices and recognize their potential to cause inappropriate down-titration of sedation. Substantial opportunity exists to improve the quality of care of patients receiving neuromuscular blockade through development of guidelines and standardized care pathways.
Optimized culture of retinal ganglion cells and amacrine cells from adult mice
Authors: Park Yong H , Snook Joshua D , Zhuang Iris , Shen Guofu , Frankfort Benjamin J 
Published: June 2020

AbstractCell culture is widely utilized to study the cellular and molecular biology of different neuronal cell populations. Current techniques to study enriched neuronsin vitroare primarily limited to embryonic/neonatal animals and induced pluripotent stem cells (iPSC). Although the use of these cultures is valuable, the accessibility of purified primary adult neuronal cultures would allow for improved assessment of certain neurological diseases and pathways at the cellular level. Using a modified 7-step immunopanning technique to isolate for retinal ganglion cells (RGCs) and amacrine cells (ACs) from adult mouse retinas, we have successfully developed a model of neuronal culture that maintains for at least one week. Isolations of Thy1.2+cells are enriched for RGCs, with the isolation cell yield being congruent to the theoretical yield of RGCs in a mouse retina. ACs of two different populations (CD15+and CD57+) can also be isolated. The populations of these three adult neurons in culture are healthy, with neurite outgrowths in some cases greater than 500µm in length. Optimization of culture conditions for RGCs and CD15+cells revealed that neuronal survival and the likelihood of neurite outgrowth respond inversely to different culture media. Serially diluted concentrations of puromycin decreased cultured adult RGCs in a dose-dependent manner, demonstrating the potential usefulness of these adult neuronal cultures in screening assays. This novel culture system can be used to model adult neuronsin vivo. Studies can now be expanded in conjunction with other methodologies to study the neurobiology of function, aging, and diseases.
The Amsterdam Open MRI Collection, a set of multimodal MRI datasets for individual difference analyses
Authors: Snoek Lukas , van der Miesen Maite M. , Beemsterboer Tinka , van der Leij Andries , Eigenhuis Annemarie , Scholte H. Steven 
Published: June 2020

AbstractWe present the Amsterdam Open MRI Collection (AOMIC): three datasets with multimodal (3T) MRI data including structural (T1-weighted), diffusion-weighted, and (resting-state and task-based) functional BOLD MRI data, as well as detailed demographics and psychometric variables from a large set of healthy participants (N = 928, N = 226, and N = 216). Notably, task-based fMRI was collected during various robust paradigms (targeting naturalistic vision, emotion perception, working memory, face perception, cognitive conflict and control, and response inhibition) for which extensively annotated event-files are available. For each dataset and data modality, we provide the data in both raw and preprocessed form (both compliant with the Brain Imaging Data Structure), which were subjected to extensive (automated and manual) quality control. All data is publicly available from the Openneuro data sharing platform.
Photoperiod-Induced Neurotransmitter Switching in the Circadian Pacemaker Regulates Hypothalamic Dopamine Expression
Authors: Porcu Alessandra , Booreddy Sathwik , Welsh David K. , Dulcis Davide 
Published: June 2020

AbstractLight, circadian clocks, and rhythmic behaviors interact closely to produce a temporal order that is essential for the survival of most living organisms. In mammals, the principal circadian pacemaker in the brain is the suprachiasmatic nucleus (SCN), which receives direct retinal input and synchronizes itself and other brain regions to the external light-dark cycle. Altered day length (photoperiod) and disrupted circadian rhythms are associated with impaired memory and mood in both humans and animal models. Prior work demonstrated that altering photoperiod can change neurotransmitter (NT) expression in the periventricular nucleus (PeVN) of the hypothalamus in adult rat brain. Here we show that neuromedin S-(NMS-) and vasoactive intestinal polypeptide-(VIP-) expressing neurons in the SCN also display photoperiod-induced neurotransmitter switching. Such photoperiod-dependent NT plasticity is retained inBmal1-KO mice, indicating that NT plasticity in the SCN does not require a functional circadian clock. Utilizing a conditional viral DO-DIO vector as an historical marker of NT expression in the SCN, we further reveal that short-day photoperiod induces a cluster ofnon-NMS-expressing neurons to undergo NT switching and acquire the NMS phenotype. Selective chemogenetic activation of NMS neurons, but not VIP neurons, during the dark phase induces a significant delay in the timing of locomotor activity onset and is sufficient to increase the number of dopaminergic neurons in the PeVN. Our findings provide novel insights into molecular adaptations of the SCN neuronal network in response to altered photoperiod that affect neuronal circuit function in the hypothalamus and lead to changes in circadian behavior.
Epidemiological characteristics of patients with residual SARS-Cov-2 in Linyi, China
Authors: Pan Qiang , Gao Feng , Peng Rensheng , Li Mingshan 
Published: June 2020

AbstractPatients with 2019 novel Coronavirus infection are probably show positive testing results again. In order to better treat these patients and provide basis for further control measures, we analyze the epidemiological outcomes and clinical features of patients with residual Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) in Linyi city. From January 23 to March 31 in 2020, epidemiological and clinical information of confirmed patients are collected for analysis. Stool and pharyngeal swab samples are collected for RT-PCR testing. 64 confirmed patients are included and 17 patients present re-positive testing after discharge. For these 17 patients, 70.59% are family aggregated, the interval between first time of negative testing and first time of re-positive testing is 11.82±3.42 days. There is no difference between patients with continued negative testing results and re-positive testing. After discharge, the interval between first time of negative testing and first time of re-positive testing is associated with severity of disease (p=0.013). Besides, the duration from first time to last time of re-positive testing is associated with exposure or contact history (p=0.049) and severity of disease (p=0.001). The analysis reveals epidemiological characteristics of patients with residual SARS-Cov-2 and provide basis for further control measures.
Identification of novel tetracycline resistance genetet(X14) and its co-occurrence withtet(X2) in a tigecycline-resistant and colistin-resistantEmpedobacter stercoris
Authors: Cheng Yingying , Chen Yong , Liu Yang , Guo Yuqi , Zhou Yanzi , Xiao Tingting , Zhang Shuntian , Xu Hao , Chen Yunbo , Shan Tongling , Xiao Yonghong , Zhou Kai 
Published: June 2020

AbstractTigecycline is one of the last-resort antibiotics to treat severe infections. Recently, tigecycline resistance has sporadically emerged with an increasing trend, and Tet(X) family represents a new resistance mechanism of tigecycline. In this study, a novel chromosome-encoded tigecycline resistance gene,tet(X14), was identified in a tigecycline-resistant and colistin-resistantEmpedobacter stercorisstrain ES183 recovered from a pig fecal sample in China. Tet(X14) shows 67.14-96.39% sequence identity to the other variants [Tet(X) to Tet(X13)]. Overexpression of Tet(X14) inEscherichia coliconfers 16-fold increase in tigecycline MIC (from 0.125 to 2 mg/L), which is lower than that of Tet(X3), Tet(X4) and Tet(X6). Structural modelling predicted that Tet(X14) shared a high homology with the other 12 variants with RMSD value from 0.003 to 0.055, and Tet(X14) can interact with tetracyclines by a similar pattern as the other Tet(X)s.tet(X14) and two copies oftet(X2) were identified on a genome island with abnormal GC content carried by the chromosome of ES183, and no mobile genetic elements were found surrounding, suggesting thattet(X14) might be heterologously obtained by ES183 via recombination. Blasting in Genbank revealed that Tet(X14) was exclusively detected on the chromosome ofRiemerella anatipestifer, mainly encoded on antimicrobial resistance islands.E. stercorisandR. anatipestiferbelong to the familyFlavobacteriaceae, suggesting that the members ofFlavobacteriaceaemaybe the major reservoir oftet(X14). Our study reports a novel chromosome-encoded tigecycline resistance genetet(X14). The expanded members of Tet(X) family warrants the potential large-scale dissemination and the necessity of continuous surveillance fortet(X)-mediated tigecycline resistance.
A genome-scale CRISPR screen reveals PRMT1 as a critical regulator of androgen receptor signaling in prostate cancer
Authors: Tang Stephen , Metaferia Nebiyou Y. , Nogueira Marina F. , Gelbard Maya K. , Abou Alaiwi Sarah , Seo Ji-Heui , Hwang Justin H. , Strathdee Craig A. , Baca Sylvan C. , Li Jiao , AbuHammad Shatha , Zhang Xiaoyang , Doench John G. , Hahn William C. , Takeda David Y. , Freedman Matthew L. , Choi Peter S. , Viswanathan Srinivas R. 
Published: June 2020

ABSTRACTAndrogen receptor (AR) signaling is the central driver of prostate cancer across disease states. While androgen deprivation therapy (ADT) is effective in the initial treatment of prostate cancer, resistance to ADT or to next-generation androgen pathway inhibitors invariably arises, most commonly through re-activation of the AR axis. Thus, orthogonal approaches to inhibit AR signaling in advanced prostate cancer are essential. Here, via genome-scale CRISPR/Cas9 screening, we identify protein arginine methyltransferase 1 (PRMT1) as a critical mediator ofARexpression and signaling. PRMT1 regulates recruitment of AR to genomic target sites and inhibition of PRMT1 impairs AR binding at lineage-specific enhancers, leading to decreased expression of key oncogenes, includingARitself. Additionally, AR-driven prostate cancer cells are uniquely susceptible to combined AR and PRMT1 inhibition. Our findings implicate PRMT1 as a key regulator of AR output and provide a preclinical framework for co-targeting of AR and PRMT1 in advanced prostate cancer.
High-throughput simulations indicate feasibility of navigation by familiarity with a local sensor such as scorpion pectines
Authors: Musaelian Albert , Gaffin Douglas D. 
Published: June 2020

AbstractScorpions have arguably the most elaborate “tongues” on the planet: two paired ventral combs, called pectines, that are covered in thousands of chemo-tactile peg sensilla and that sweep the ground as the animal walks. Males use their pectines to detect female pheromones during the mating season, but females have pectines too: What additional purpose must the pectines serve? Why are there so many pegs? We take a computational approach to test the hypothesis that scorpions use their pectines to navigate by chemo-textural familiarity in a manner analogous to the visual navigation-by-scene-familiarity hypothesis for hymenopteran insects. We have developed a general model of navigation by familiarity with a local sensor and have chosen a range of plausible parameters for it based on the existing behavioral, physiological, morphological, and neurological understanding of the pectines. Similarly, we constructed virtual environments based on the scorpion’s native sand habitat. Using a novel methodology of highly parallel high-throughput simulations, we comprehensively tested 2160 combinations of sensory and environmental properties in each of 24 different situations, giving a total of 51,840 trials. Our results show that navigation by familiarity with a local pectine-like sensor is feasible. Further, they suggest a subtle interplay between “complexity” and “continuity” in navigation by familiarity and give the surprising result that more complexity — more detail and more information — is not always better for navigational performance.Author summaryScorpions’ pectines are intricate taste-and-touch sensory appendages that brush the ground as the animal walks. Pectines are involved in detecting pheromones, but their exquisite complexity — a pair of pectines can have around 100,000 sensory neurons — suggests that they do more. One hypothesis is “Navigation by Scene Familiarity,” which explains how bees and ants use their compound eyes to navigate home: the insect visually scans side to side as it moves, compares what it sees to scenes learned along a training path, and moves in the direction that looks most familiar. We propose that the scorpions’ pectines can be used to navigate similarly: instead of looking around, they sweep side to side sensing local chemical and textural information. We crafted simulated scorpions based on current understanding of the pectines and tested their navigational performance in virtual versions of the animals’ sandy habitat. Using a supercomputer, we varied nine environmental, sensory, and situational properties and ran a total of 51,840 trials of simulated navigation. We showed that navigation by familiarity with a local sensor like the pectinesisfeasible. Surprisingly, we also found that having a more detailed landscape and/or a more sensitive sensor is not always optimal.
Seasonal changes in recombination rate, crossover interference, and their response to desiccation stress in a natural population ofDrosophila melanogasterfrom India
Authors: Aggarwal Dau Dayal , Rybnikov Sviatoslav , Sapielkin Shaul , Rashkovetsky Eugenia , Frenkel Zeev , Singh Manvender , Michalak Pawel , Korol Abraham B. 
Published: June 2020

AbstractEnvironmental seasonality is a potent evolutionary force, capable to maintain polymorphism, promote phenotypic plasticity, and cause bet-hedging. InDrosophila, it has been reported to affect life-history traits, tolerance to abiotic stressors, and immunity. Oscillations in frequencies of alleles underlying fitness-related traits were also documented alongside SNP alleles across genome. Here, we test for seasonal changes in recombination in a naturalD. melanogasterpopulation from India using morphological markers of the three major chromosomes. We show that winter flies (collected after the dry season) have significantly higher desiccation tolerance than their autumn counterparts. This difference proved to hold also for hybrids with three independent marker stocks, suggesting its genetic rather than plastic nature. Significant segment-specific changes are documented for recombination rate (in five of 13 intervals) and crossover interference (in five of 16 studied pairs of intervals); both single- and double-crossover rates tended to increase in the winter cohort. The winter flies also display weaker plasticity of recombination characteristics to desiccation. We ascribe the observed differences to indirect selection on recombination caused by directional selection on desiccation tolerance. Our findings suggest that changes in recombination can arise even after a short period of seasonal adaptation (~8–10 generations).
Using plant traits to understand the contribution of biodiversity effects to community productivity in an agricultural system
Authors: Engbersen Nadine , Stefan Laura , Brooker Rob W. , Schöb Christian 
Published: June 2020

SummaryIncreasing biodiversity generally enhances productivity through selection and complementarity effects not only in natural but also in agricultural systems. However, explaining why diversity enhances productivity remains a central goal in agricultural science.In a field experiment, we constructed monocultures, 2- and 4-species mixtures from eight crop species with and without fertilizer and both in temperate Switzerland and semi-arid Spain. We measured environmental factors and plant traits and related these in structural equation models to selection and complementarity effects to explain yield differences between monocultures and mixtures.Increased crop diversity increased yield in Switzerland. This positive biodiversity effect was driven to almost same extents by selection and complementarity effects, which increased with plant height and C:N ratio, respectively. Also, ecological processes driving yield increases from monocultures to mixtures differed from those responsible for yield increases through the diversification of mixtures.While selection effects were mainly driven by one species, complementarity effects were linked to higher productivity per unit N. Yield increases due to mixture diversification were driven only by complementarity and were not mediated through the measured traits, suggesting that ecological processes beyond those measured in this study were responsible for positive diversity effects on yield beyond 2-species mixtures.