bluuebunny/crossref_metadata_2025_split huggingface dataset:
DOLAMA study
Authors: Hidalgo-Tenorio Carmen , Cortés Luis López , Gutiérrez Alicia , Santos Jesús , Omar Mohamed , Gálvez Carmen , Sequera Sergio , Jesús Samantha Eisabeth De , Téllez Franciso , Fernández Elisa , García Coral , Pasquau Juan 
Published: August 2019

Abstract
Dolutegravir (DTG) has shown effectiveness in combination with rilpivirine in with experience of antiretroviral therapy (ART) and with 3TC in naïve patients (GEMINI trial). The main objectives of this real-life study were to analyze the effectiveness and safety of 3TC plus DTG in virologically suppressed HIV-1 patients and to conduct a pharmacoeconomic analysis.
We conducted an observational, retrospective and multicenter study of HIV+ patients pretreated for at least 6 months with ART that was then simplified to 3TC + DTG for any reason. We gathered data on viral loads (VLs) during exposure to the DT, calculating the rate with VL < 50 copies/mL at week 48, and on associated adverse effects.
The 177 HIV+ patients were collected, 77.4% male, with average age of 48.5 years and mean count of 252.2cell/μL CD4+ nadir lymphocytes; 96.6% had VL < 50 copies/mL and 674 cells/μL CD4+ lymphocytes. Median time since HIV diagnosis was 15 years, and median ART duration was 13 years, and 34.5% of patients were on mono- or dual-therapy before the switch. At week 48, 82.4% of patients had VL < 50 cop/μL using an intention-to-treat (ITT) analysis, 89.6% according to mITT, and 96.7% according to Per-Protocol analysis. 3.3% patients had virological failure (VF). These effectiveness data and costs were compared with those for 2 reference triple therapies (DTG/ABC/3TC and EVG/cobi/FTC/TAF) in a cost minimization analysis, showing cost savings with administration of DTG+3TC (2741 €/year vs DTG/ABC/3TC and 4164 €/year vs EVG/cobi/FTC/TAF) and in a cost-effectiveness analysis, finding the DT to be the most cost-effective approach (ICER = −548 vs DTG/ABC/3TC and ICER = −4,627€ vs EVG/cobi/FTC/TAF)
The combination of 3TC with DTG appears to be a safe and effective option for the simplification of ART in pretreated and virologically stable HIV-positive patients, being cost-effective and offering the same effectiveness as the triple therapy it replaces.
Stress and Health in Nursing Students
Authors: Olvera Alvarez Hector A. , Provencio-Vasquez Elias , Slavich George M. , Laurent Jose Guillermo Cedeño , Browning Matthew , McKee-Lopez Gloria , Robbins Leslie , Spengler John D. 
Published: August 2019

Background
Evidence suggests that behavioral, social, and environmental factors may modify the effects of life stress on health and performance of new nurses as they transition to hospitals.

Objectives
The aim of this study was to describe the methods of a project designed to investigate the role of social, behavioral, and environmental factors in modifying the adverse effects of stress on new nurses and to discuss demographic, health, and life stress characteristics of the cohort at baseline.

Methods
A prospective cohort design was used to conduct a comprehensive assessment of health endpoints, life stress, behaviors, personal traits, social factors, indicators of engagement and performance, and environmental exposures in nursing students. Adjusted odds ratios and analyses of covariance were used to examine associations between these factors at baseline.

Results
Health indicators in the cohort were comparable or better than in the broader United States population, and lifetime stress exposure was lower than among students from other majors. Exposure to more lifetime stressors was associated with greater risk for various health conditions, including hypertension, diabetes, and depression. Conversely, better social, environmental, behavioral, and personal profiles were associated with protective effects for the same health conditions.

Discussion
These data comprehensively summarize the lives of predominately Hispanic nursing students and highlight risk and resilience factors associated with their health and well-being. The findings are timely, as the nursing field diversifies in preparation to care for a diverse and aging population. Comprehensively assessing stress–health relationships among student nurses ought to inform the policies, practices, and curricula of nursing schools to better prepare nurses to thrive in the often-strenuous healthcare environment.
Review of Recent Physical Activity Guidelines During Pregnancy to Facilitate Advice by Health Care Providers
Authors: Evenson Kelly R. , Mottola Michelle F. , Artal Raul 
Published: August 2019

Importance
Physical activity during pregnancy can offer many maternal and fetal health benefits.

Objective
The aim was to summarize American, Canadian, and international recommendations published recently on physical activity during pregnancy to aid health care providers in their delivery of advice on the topic.

Evidence Acquisition
A descriptive review of 3 national guidelines and 1 international guideline on physical activity during pregnancy was conducted. The guidelines included the 2019 Canadian recommendations, the 2018 United States' Physical Activity Guidelines for Americans (second edition), the 2015 (reaffirmed in 2017) American College of Obstetrics and Gynecology guideline, and the 2016–2018 International Olympic Committee recommendations for recreational and elite athletes.

Results
For apparently healthy women, under the guidance of their health care provider, moderate-intensity physical activity using both aerobic and muscle conditioning activities is recommended. The guidelines recommended at least 150 min/wk spread throughout the week (Canada, United States) or at least 20 to 30 min/d (American College of Obstetrics and Gynecology).

Conclusions and Relevance
This summary of 4 recent guidelines can facilitate use of updated recommendations by health care providers regarding physical activity during pregnancy. More detailed evidence-based guidelines on physical activity during postpartum are needed.

Target Audience
Obstetricians and gynecologists, family physicians

Learning Objectives
After completing this activity, the learner should be better able to describe the most recent recommendations for physical activity during pregnancy; explain the relative and absolute contraindications to physical activity during pregnancy; and identify the warning signs for pregnant women to stop physical activity.
Nocebo Effects in Concussion
Authors: Polich Ginger , Iaccarino Mary A. , Kaptchuk Ted J. , Morales-Quezada Leon , Zafonte Ross 
Published: August 2019

Abstract
Nocebo effects refer to new or worsening symptoms that develop in response to negative health-related information, beliefs, and/or experiences. In recent years, research on concussion pathophysiology has significantly advanced. Through health campaigns and media coverage, emerging knowledge on the risks of this injury has been quickly disseminated to the public, and nowadays, the public perceives concussions as more hazardous to health than ever before. Although advancements in concussion-related research and care are of great importance and value, we ask in this article whether the increasing negative publicity regarding concussion also carries any latent costs. Are additional nocebo effects being fostered? To do so, we will review the literature on the psychological and neurobiological processes underlying nocebo effects, present a series of clinical studies demonstrating the ways in which nocebos may impact concussion outcomes both clinically and societally, then speculate on further potential mechanisms for nocebo effects in concussion. We conclude with an outline of the specific efforts one may take to minimize nocebo effects in concussion-related care.
Personal Phone Calls Lead to Decreased Rates of Missed Appointments in an Adolescent/Young Adult Practice
Authors: Penzias Rebecca , Sanabia Virginia , Shreeve Kyra M. , Bhaumik Urmi , Lenz Caitlin , Woods Elizabeth R. , Forman Sara F. 
Published: August 2019

Introduction:
Nationally, hospital practice missed appointment rates are high. Our goal was to reduce the rate of missed appointments in an Adolescent/Young Adult Practice through quality improvement methods.

Methods:
During the 12-month intervention period, administrative staff called patients the day before their primary or specialty care appointments to remind them of the date, time, and location, as well as patients who did not attend their appointments to ask about the reason for their missed appointment. We implemented Plan-Do-Study-Act interventions and analyzed data to compare missed appointment rates between the 12 months before and after February 1, 2017, the project intervention date.

Results:
Results showed significant reductions in the missed appointment rate for the Adolescent/Young Adult Practice. A control chart showed a shift in the mean overall percent of completed appointments from 76.7% to 79.2%. The most common reasons for missed appointments included forgetting (39.2%), conflicts with work/school (11.0%), or emailing the provider without contacting administrative staff (7.8%). There were significant reductions in missed appointment rates for both males and females as well as patients who were ≥20 years old, identified English or Spanish as their primary language, had public or private insurance, identified as Black or Hispanic, or did or did not require an interpreter.

Conclusion:
These data show that targeted interventions such as personalized reminder calls can be effective in reducing patient missed appointment rates in Adolescent/Young Adult Practices.
Trigeminal nerve and white matter brain abnormalities in chronic orofacial pain disorders
Authors: Moayedi Massieh , Hodaie Mojgan 
Published: August 2019

Abstract
The orofacial region is psychologically important, given that it serves fundamental and important biological purposes. Chronic orofacial pain disorders affect the head and neck region. Although some have clear peripheral etiologies, eg, classic trigeminal neuralgia, others do not have a clear etiology (eg, muscular temporomandibular disorders). However, these disorders provide a unique opportunity in terms of elucidating the neural mechanisms of these chronic pain conditions: both the peripheral and central nervous systems can be simultaneously imaged. Diffusion-weighted imaging and diffusion tensor imaging have provided a method to essentially perform in vivo white matter dissections in humans, and to elucidate abnormal structure related to clinical correlates in disorders, such as chronic orofacial pains. Notably, the trigeminal nerve anatomy and architecture can be captured using diffusion imaging. Here, we review the trigeminal somatosensory pathways, diffusion-weighted imaging methods, and how these have contributed to our understanding of the neural mechanisms of chronic pain disorders affecting the trigeminal system. We also discuss novel findings indicating the potential for trigeminal nerve diffusion imaging to develop diagnostic and precision medicine biomarkers for trigeminal neuralgia. In sum, diffusion imaging serves both an important basic science purpose in identifying pain mechanisms, but is also a clinically powerful tool that can be used to improve treatment outcomes.
Disentangling Associations Between Serum Muscle Biomarkers and Sarcopenia in the Presence of Pain and Inflammation Among Patients With Osteoarthritis
Authors: Kurita Noriaki , Kamitani Tsukasa , Wada Osamu , Shintani Ayumi , Mizuno Kiyonori 
Published: August 2019

Background/Objective
Reduction of muscle markers, such as creatine phosphokinase (CK), in rheumatic diseases and its association with reduced muscle mass may be of clinical importance in osteoarthritis (OA). Considering the complexity of secondary sarcopenia, clarifying the association between muscle markers and sarcopenia and disentangling the involvement of OA-related conditions are of clinical importance. We investigated the association between serum muscle biomarkers and sarcopenia among patients with OA, considering the presence of pain and inflammation.

Methods
Overall, 1425 patients with knee and hip OA scheduled for joint replacement surgery were included in a single-center cross-sectional study from Screening for People Suffering Sarcopenia in Orthopedic cohort of Kobe study. Primary outcome was sarcopenia defined by 2 criteria (the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People). Pain and inflammation were measured using the numeric rating scale and serum C-reactive protein (CRP) levels, respectively. Associations between the biomarkers (serum CK, aspartate aminotransferase, alanine aminotransferase) and sarcopenia were examined using logistic regression models.

Results
Sarcopenia by the Asian Working Group for Sarcopenia criteria was present in 4.0% of patients. In adjusted analyses, sarcopenia was negatively associated with higher serum CK levels, but not with serum aspartate aminotransferase or alanine aminotransferase levels independent of pain score and serum CRP. Neither pain score nor serum CRP level was associated with sarcopenia. Similar results were found when the European Working Group on Sarcopenia in Older People criteria were used.

Conclusions
Serum CK was associated with sarcopenia, suggesting the potential usefulness for sarcopenia detection regardless of pain or inflammation in OA.
Unexpected Race and Ethnicity Differences in the US National Veterans Affairs Kidney Transplant Program
Authors: Myaskovsky Larissa , Kendall Kellee , Li Xingyuan , Chang Chung-Chou H. , Pleis John R. , Croswell Emilee , Ford C. Graham , Switzer Galen E. , Langone Anthony , Mittal-Henkle Anuja , Saha Somnath , Thomas Christie P. , Adams Flohr Jareen , Ramkumar Mohan , Dew Mary Amanda 
Published: August 2019

Background.
Racial/ethnic minorities have lower rates of deceased kidney transplantation (DDKT) and living donor kidney transplantation (LDKT) in the United States. We examined whether social determinants of health (eg, demographics, cultural, psychosocial, knowledge factors) could account for differences in the Veterans Affairs (VA) Kidney Transplantation (KT) Program.

Methods.
We conducted a multicenter longitudinal cohort study of 611 Veterans undergoing evaluation for KT at all National VA KT Centers (2010–2012) using an interview after KT evaluation and tracking participants via medical records through 2017.

Results.
Hispanics were more likely to get any KT (subdistribution hazard ratios [SHR] [95% confidence interval (CI)]: 1.8 [1.2-2.8]) or DDKT (SHR [95% CI]: 2.0 [1.3-3.2]) than non-Hispanic white in univariable analysis. Social determinants of health, including marital status (SHR [95% CI]: 0.6 [0.4-0.9]), religious objection to LDKT (SHR [95% CI]: 0.6 [0.4-1.0]), and donor preference (SHR [95% CI]: 2.5 [1.2-5.1]), accounted for some racial differences, and changes to Kidney Allocation System policy (SHR [95% CI]: 0.3 [0.2-0.5]) mitigated race differences in DDKT in multivariable analysis. For LDKT, non-Hispanic African American Veterans were less likely to receive an LDKT than non-Hispanic white (SHR [95% CI]: 0.2 [0.0-0.7]), but accounting for age (SHR [95% CI]: 1.0 [0.9-1.0]), insurance (SHR [95% CI]: 5.9 [1.1-33.7]), presenting with a living donor (SHR [95% CI]: 4.1 [1.4-12.3]), dialysis duration (SHR [95% CI]: 0.3 [0.2-0.6]), network of potential donors (SHR [95% CI]: 1.0 [1.0-1.1]), self-esteem (SHR [95% CI]: 0.4 [0.2-0.8]), transplant knowledge (SHR [95% CI]: 1.3 [1.0-1.7]), and changes to Kidney Allocation System policy (SHR [95% CI]: 10.3 [2.5-42.1]) in multivariable analysis eliminated those disparities.

Conclusions.
The VA KT Program does not exhibit the same pattern of disparities in KT receipt as non-VA centers. Transplant centers can use identified risk factors to target patients who may need more support to ensure they receive a transplant.
Altered theta / beta frequency synchrony links abnormal anxiety-related behavior to synaptic inhibition in Neuroligin-2 knockout mice
Authors: Cruces-Solis Hugo , Babaev Olga , Ali Heba , Chatain Carolina Piletti , Mykytiuk Vasyl , Balekoglu Nursen , Wenger Sally , Krueger-Burg Dilja 
Published: August 2019

AbstractInhibitory synaptic transmission plays a key role in the circuits underlying anxiety behaviors, but the network mechanisms by which disruptions in synaptic inhibition contribute to pathological anxiety processing remain largely unknown. Here we addressed this question in mice lacking the inhibitory synapse-specific adhesion protein Neuroligin-2 (Nlgn2), which display widespread reduction in inhibitory synaptic transmission as well as a pronounced anxiety phenotype. To investigate how the lack of synaptic inhibition alters the communication between key brain regions in anxiety processing, we recorded local field potentials (LFPs) simultaneously from a network of brain regions involved in anxiety processing, including the basolateral amygdala (BLA), centromedial amygdala, bed nucleus of the stria terminalis, prefrontal cortex and ventral hippocampus (vHPC). We found that LFP power in the vHPC was profoundly increased while vHPC-directed theta frequency synchrony was disrupted in Nlgn2 KO mice under anxiogenic conditions. Instead, deletion of Nlgn2 increased beta frequency synchrony across the anxiety network, and the theta / beta synchrony ratio strongly predicted anxiety behaviors in an open field paradigm. Local deletion of Nlgn2 in the vHPC and BLA revealed that they encode distinct aspects of the anxiety phenotype of the Nlgn2 KO mice, with vHPC linked to anxiety induced freezing and BLA linked to reduction in exploratory activity. Together, our data demonstrate that alterations in long-range functional connectivity link synaptic inhibition to abnormal anxiety behaviors, and that Nlgn2 KO mice represent an interesting model to study the role of inhibitory synaptic transmission in the circuits underlying anxiety disorders.
Structural models of full-length JAK2 kinase
Authors: Ayaz Pelin , Hammarén Henrik M. , Raivola Juuli , Sharon Dina , Hubbard Stevan R. , Silvennoinen Olli , Shan Yibing , Shaw David E. 
Published: August 2019

AbstractThe protein JAK2 is a prototypical member of the Janus kinase family, and mediates signals from numerous cytokine receptors. The constitutively active V617F mutant of JAK2 is prevalent in many bone marrow disorders, blood cancers, and autoimmune diseases, and is an important drug target. Structures have been determined for each of the four individual domains making up JAK2, and for certain pairs of these domains, but no structure of full-length JAK2 is available, and thus the mechanisms underlying JAK2 regulation and the aberrant activity of the V617F mutant have been incompletely understood. Here we propose structural models of full-length JAK2 in both its active and inactive forms. Construction of these models was informed by long-timescale molecular dynamics simulations. Subsequent mutagenesis experiments showed that mutations at the putative interdomain interfaces modulated JAK2 activity. The models provide a structural basis for understanding JAK2 autoinhibition and activation, and suggest that the constitutive activity of the V617F mutant may arise from a dual effect of destabilizing the inactive conformation and stabilizing the active conformation.
Comparing the microbial communities of natural and supplemental nests of an endangered ecosystem engineer
Authors: Thoemmes Megan S. , Cove Michael V. 
Published: August 2019

AbstractSupplemental nests are often used to restore habitats for a variety of rare and endangered taxa. However, though supplemental nests mimic the function of natural nests, they vary in design and building material. We know from previous research on human homes and other buildings that these differences in architecture can alter the types of microbes to which inhabitants are exposed, and these shifts in microbial interactions can be detrimental for health and well-being. Yet, no one has tested whether microbial communities in supplemental structures are distinct from those found in natural nests. Here we sampled the bacteria from inside supplemental nests of the endangered Key Largo woodrat (Neotoma floridana smalli). We then compared the diversity and composition of those bacteria to those collected from natural stick-nests and the forest floor in Key Largo, Florida. In addition, we sampled woodrat bodies to assess the microbiota of nest inhabitants. We observed distinct bacterial communities in Key Largo woodrat nests, relative to the forest environment; however, we could not differentiate between the microbial communities collected from supplemental and natural nests. Furthermore, when we considered genera known to contain bacterial pathogens of wild rodents, supplemental and natural nests exhibited similarly low relative abundances of these taxa. Where we expected to see an accumulation of pathogens, we instead observed high relative abundances of bacteria from antimicrobial-producing groups (i.e., Pseudonocardiaceae and Streptomycetaceae). The microbial biota of Key Largo woodrat individuals resembled those of their nests, with low relative abundances of potentially pathogenic bacteria and high abundances of antimicrobial-producing groups. Our results suggest that, although there is some microbial interaction between nests and nest inhabitants, there are no detectable differences in the types of bacteria to which Key Largo woodrats are exposed in supplemental and natural nest structures.
Conserved CxnC motifs in Kaposi’s sarcoma-associated herpesvirus ORF66 are required for viral late gene expression and mediate its interaction with ORF34
Authors: Didychuk Allison L. , Castañeda Angelica F. , Kushnir Lola O. , Huang Carolyn J. , Glaunsinger Britt A. 
Published: August 2019

ABSTRACTLate gene transcription in the beta- and gammaherpesviruses depends on a set of virally-encoded transcriptional activators (vTAs) that hijack the host transcriptional machinery and direct it to a subset of viral genes that are required for completion of the viral replication cycle and capsid assembly. In Kaposi’s sarcoma-associated herpesvirus (KSHV), these vTAs are encoded by ORF18, ORF24, ORF30, ORF31, ORF34, ORF66. Assembly of the vTAs into a complex is critical for late gene transcription, and thus deciphering the architecture of the complex is central to understanding its transcriptional regulatory activity. Here, we generated an ORF66-null virus and confirmed that it fails to produce late genes and infectious virions. We show that ORF66 is incorporated into the vTA complex primarily through its interaction with ORF34, which is mediated by a set of four conserved cysteine-rich motifs in the C-terminal domain of ORF66. While both ORF24 and ORF66 occupy the canonical K8.1 late gene promoter, their promoter occupancy requires the presence of the other vTAs, suggesting that sequence-specific, stable binding requires assembly of the entire complex on the promoter. Additionally, we find that ORF24 expression is impaired in the absence of a stable vTA complex. This work extends our knowledge about the architecture of the KSHV vPIC and suggests that it functions as a complex to recognize late gene promoters.IMPORTANCEKaposi’s sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) is an oncogenic gammaherpesvirus that is the causative agent of multiple human cancers. Release of infectious virions requires production of capsid proteins and other late genes, whose production are transcriptionally controlled by a complex of six virally-encoded proteins that hijack the host transcription machinery. It is poorly understood how this complex assembles or what function five of its six components play in transcription. Here, we demonstrate that ORF66 is an essential component of this complex in KSHV and that its inclusion in the complex is mediated through its C-terminal domain, which contains highly conserved cysteine-rich motifs reminiscent of zinc finger motifs. Additionally, we examine assembly of the viral pre-initiation complex at late gene promoters and find that while sequence-specific binding of late gene promoters requires ORF24, it additionally requires a fully assembled viral pre-initation complex.