bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cosmc is required for T cell persistence in the periphery
Authors: Cutler Christopher E , Jones Mark B , Cutler Alicia A , Mener Amanda , Arthur Connie M , Stowell Sean R , Cummings Richard D 
Published: July 2019

AbstractT lymphocytes, a key arm of adaptive immunity, are known to dynamically regulate O-glycosylation during T cell maturation and when responding to stimuli; however, the direct role of O-glycans in T cell maturation remains largely unknown. Using a conditional knockout of the gene (C1GalT1C1 or Cosmc) encoding the specific chaperone Cosmc, we generated mice whose T cells lack extended O-glycans (T cell conditional Cosmc knock out or TCKO mice) and homogeneously express the truncated Tn antigen. Loss of Cosmc is highly deleterious to T cell persistence, with near-complete elimination of Cosmc-null T cells from spleen and lymph nodes. Total T cell counts are 20% of wild type (WT), among which only 5% express the truncated glycans, with the remaining 95% consisting of escapers from Cre-mediated recombination. TCKO thymocytes were able to complete thymic maturation but failed to populate the secondary lymphoid organs both natively and upon adoptive transfer to WT recipients. Our results demonstrate that extended O-glycosylation is required for the establishment and maintenance of the peripheral T cell population.
Trends of Utilization of Tumor Necrosis Factor Antagonists in Children With Inflammatory Bowel Disease: A Canadian Population-Based Study
Authors: El-Matary Wael , Leung Stella , Tennakoon Aruni , Benchimol Eric I , Bernstein Charles N , Targownik Laura E 
Published: July 2019

Abstract

Background
Population-based studies examining the prevalence of anti–tumor necrosis factor (anti-TNF) antagonist utilization in children and young adults with inflammatory bowel disease (IBD) are lacking. We aimed to describe the trend of anti-TNF utilization in pediatric IBD over time.

Methods
Survival analyses were performed for all patients diagnosed with IBD before age 18 years in the province of Manitoba to determine the time from diagnosis to first anti-TNF prescription in different time eras (2005–2008, 2008–2012, 2012–2016).

Results
There were 291 persons diagnosed with IBD (157 with Crohn’s disease [CD] and 134 with ulcerative colitis [UC]) over the study period. The likelihood of being initiated on an anti-TNF by 1, 2, and 5 years postdiagnosis was 18.4%, 30.5%, and 42.6%, respectively. The proportion of persons aged <18 years utilizing anti-TNFs rose over time; in 2010, 13.0% of CD and 4.9% of UC; by 2016, 60.0% of CD and 25.5% of UC. For those diagnosed after 2012, 42.5% of CD and 28.4% of UC patients had been prescribed an anti-TNF antagonist within 12 months of IBD diagnosis. Initiating an anti-TNF without prior exposure to an immunosuppressive agent increased over time (before 2008: 0%; 2008–2012: 18.2%; 2012–2016: 42.8%; P < 0.001). There was a significant reduction in median cumulative dose of corticosteroids (CS) in the year before anti-TNF initiation (2005–2008: 4360 mg; 2008–2012: 2010 mg; 2012–2016: 1395 mg prednisone equivalents; P < 0.001).

Conclusions
Over a period of 11 years, anti-TNFs are being used earlier in the course of pediatric IBD, with a parallel reduction in the cumulative CS dose.
Association Between Reduced Brain Glucose Metabolism and Cortical Thickness in Alcoholics: Evidence of Neurotoxicity
Authors: Tomasi Dardo G , Wiers Corinde E , Shokri-Kojori Ehsan , Zehra Amna , Ramirez Veronica , Freeman Clara , Burns Jamie , Kure Liu Christopher , Manza Peter , Kim Sung W , Wang Gene-Jack , Volkow Nora D 
Published: July 2019

Abstract

Background
Excessive alcohol consumption is associated with reduced cortical thickness (CT) and lower cerebral metabolic rate of glucose (CMRGlu), but the correlation between these 2 measures has not been investigated.

Methods
We tested the association between CT and cerebral CMRGlu in 19 participants with alcohol use disorder (AUD) and 20 healthy controls. Participants underwent 2-Deoxy-2-[18F]fluoroglucose positron emission tomography to map CMRGlu and magnetic resonance imaging to assess CT.

Results
Although performance accuracy on a broad range of cognitive domains did not differ significantly between AUD and HC, AUD had widespread decreases in CT and CMRGlu. CMRGlu, normalized to cerebellum (rCMRGlu), showed significant correlation with CT across participants. Although there were large group differences in CMRGlu (>17%) and CT (>6%) in medial orbitofrontal and BA 47, the superior parietal cortex showed large reductions in CMRGlu (~17%) and minimal CT differences (~2.2%). Though total lifetime alcohol (TLA) was associated with CT and rCMRGlu, the causal mediation analysis revealed significant direct effects of TLA on rCMRGlu but not on CT, and there were no significant mediation effects of TLA, CT, and rCMRGlu.

Conclusions
The significant correlation between decrements in CT and CMRGlu across AUD participants is suggestive of alcohol-induced neurotoxicity, whereas the findings that the most metabolically affected regions in AUD had minimal atrophy and vice versa indicates that changes in CT and CMRGlu reflect distinct responses to alcohol across brain regions.
Predictors and Correlates of Pediatric Postburn Pruritus in Preschool Children of Ages 0 to 4
Authors: Stewart Dylan , Caradec Jill , Ziegfeld Susan , Reynolds Elizabeth , Ostrander Rick , Parrish Carisa 
Published: July 2019

AbstractPruritus is a common problem following burn injuries; however, the literature to date has focused on adult survivors and/or pediatric survivors of large burns. The current study examines acute postburn pruritus in children under the age of 4 years (N = 256) with smaller burns (mean TBSA = 3.99%), which represents the most common type of patient typically treated in pediatric burn centers. Parents rated their child for pruritus, irritability, and sleep disturbances; additionally, parents completed a self-report of distress. Nearly half (47.3%) were rated by parents as displayed some level of pruritus, with the greatest proportion rated as mild. Regression analysis indicated that child minority status, greater burn TBSA, and more days elapsed since burn predicted higher levels of pruritus. In turn, pruritus was positively correlated with child irritability, delayed sleep onset, sleep disturbance, and parent distress. Thus, our results indicate that parent-rated pruritus in young pediatric burn patients is important to evaluate, as itch is significantly associated with other important clinical outcomes as early as the first month of the burn for pediatric patients and their parents.
Oral Mucosal Injury Caused by Targeted Cancer Therapies
Authors: Carrozzo M , Eriksen J Grau , Bensadoun R -J , Boers-Doets C B , Lalla R V , Peterson D E 
Published: July 2019

AbstractTargeted cancer therapies have fundamentally transformed the treatment of many types of cancers over the past decade, including breast, colorectal, lung, and pancreatic cancers, as well as lymphoma, leukemia, and multiple myeloma. The unique mechanisms of action of these agents have resulted in many patients experiencing enhanced tumor response together with a reduced adverse event profile as well. Toxicities do continue to occur, however, and in selected cases can be clinically challenging to manage. Of particular importance in the context of this monograph is that the pathobiology for oral mucosal lesions caused by targeted cancer therapies has only been preliminarily investigated. There is distinct need for novel basic, translational, and clinical research strategies to enhance design of preventive and therapeutic approaches for patients at risk for development of these lesions. The research modeling can be conceptually enhanced by extrapolating “lessons learned” from selected oral mucosal conditions in patients without cancer as well. This approach may permit determination of the extent to which pathobiology and clinical management are either similar to or uniquely distinct from oral mucosal lesions caused by targeted cancer therapies. Modeling associated with oral mucosal disease in non-oncology patients is thus presented in this context as well. This article addresses this emerging paradigm, with emphasis on current mechanistic modeling and clinical treatment. This approach is in turn designed to foster delineation of new research strategies, with the goal of enhancing cancer patient treatment in the future.
Overcoming the structural surface effect with a realistic treatment of turbulent convection in 1D stellar models
Authors: Jørgensen Andreas Christ Sølvsten , Weiss Achim 
Published: July 2019

Abstract
State-of-the-art 1D stellar evolution codes rely on simplifying assumptions, such as mixing length theory, in order to describe superadiabatic convection. As a result, 1D stellar structure models do not correctly recover the surface layers of the Sun and other stars with convective envelopes. We present a method that overcomes this structural drawback by employing 3D hydrodynamic simulations of stellar envelopes: at every time-step of the evolution interpolated 3D envelopes are appended to the 1D structure and are used to supply realistic boundary conditions for the stellar interior. In contrast to previous attempts, our method includes mean 3D turbulent pressure. We apply our method to model the present Sun. The structural shortcomings of standard stellar models lead to systematic errors in the stellar oscillation frequencies inferred from the model. We show that our method fully corrects for this error. Furthermore, we show that our realistic treatment of superadiabatic convection alters the predicted evolution of the Sun. Our results hence have important implications for the characterization of stars. This has ramifications for neighbouring fields, such as exoplanet research and galactic archaeology, for which accurate stellar models play a key role.
A low-complexity region in human XRN1 directly recruits deadenylation and decapping factors in 5′–3′ messenger RNA decay
Authors: Chang Chung-Te , Muthukumar Sowndarya , Weber Ramona , Levdansky Yevgen , Chen Ying , Bhandari Dipankar , Igreja Catia , Wohlbold Lara , Valkov Eugene , Izaurralde Elisa 
Published: July 2019

AbstractXRN1 is the major cytoplasmic exoribonuclease in eukaryotes, which degrades deadenylated and decapped mRNAs in the last step of the 5′–3′ mRNA decay pathway. Metazoan XRN1 interacts with decapping factors coupling the final stages of decay. Here, we reveal a direct interaction between XRN1 and the CCR4–NOT deadenylase complex mediated by a low-complexity region in XRN1, which we term the ‘C-terminal interacting region’ or CIR. The CIR represses reporter mRNA deadenylation in human cells when overexpressed and inhibits CCR4–NOT and isolated CAF1 deadenylase activity in vitro. Through complementation studies in an XRN1-null cell line, we dissect the specific contributions of XRN1 domains and regions toward decay of an mRNA reporter. We observe that XRN1 binding to the decapping activator EDC4 counteracts the dominant negative effect of CIR overexpression on decay. Another decapping activator PatL1 directly interacts with CIR and alleviates the CIR-mediated inhibition of CCR4–NOT activity in vitro. Ribosome profiling revealed that XRN1 loss impacts not only on mRNA levels but also on the translational efficiency of many cellular transcripts likely as a consequence of incomplete decay. Our findings reveal an additional layer of direct interactions in a tightly integrated network of factors mediating deadenylation, decapping and 5′–3′ exonucleolytic decay.
Cytoplasmic DNA can be detected by RNA fluorescence in situ hybridization
Authors: Greenberg Eliraz , Hochberg-Laufer Hodaya , Blanga Shalev , Kinor Noa , Shav-Tal Yaron 
Published: July 2019

Abstract
Fluorescence in situ hybridization (FISH) can be used for the intracellular detection of DNA or RNA molecules. The detection of DNA sequences by DNA FISH requires the denaturation of the DNA double helix to allow the hybridization of the fluorescent probe with DNA in a single stranded form. These hybridization conditions require high temperature and low pH that can damage RNA, and therefore RNA is not typically detectable by DNA FISH. In contrast, RNA FISH does not require a denaturation step since RNA is single stranded, and therefore DNA molecules are not detectable by RNA FISH. Hence, DNA FISH and RNA FISH are mutually exclusive. In this study, we show that plasmid DNA transiently transfected into cells is readily detectable in the cytoplasm by RNA FISH without need for denaturation, shortly after transfection and for several hours. The plasmids, however, are usually not detectable in the nucleus except when the plasmids are efficiently directed into the nucleus, which may imply a more open packaging state for DNA after transfection. This detection of plasmid DNA in the cytoplasm has implications for RNA FISH experiments and opens a window to study conditions when DNA is present in the cytoplasm.
The effect of sex and body weight on lung volumes during sleep
Authors: Avraam Joanne , Dawson Andrew , Rochford Peter D , Brazzale Danny J , O’donoghue Fergal J , Trinder John , Jordan Amy S 
Published: July 2019

Abstract

Study Objectives
Low lung volumes are thought to contribute to obstructive sleep apnea (OSA). OSA is worse in the supine versus lateral body position, men versus women, obese versus normal-weight (NW) individuals and REM versus NREM sleep. All of these conditions may be associated with low lung volumes. The aim was to measure FRC during wake, NREM, and REM in NW and overweight (OW) men and women while in the supine and lateral body positions.

Methods
Eighty-one healthy adults were instrumented for polysomnography, but with nasal pressure replaced with a sealed, non-vented mask connected to an N2 washout system. During wakefulness and sleep, repeated measurements of FRC were made in both supine and right lateral positions.

Results
Two hundred eighty-five FRC measures were obtained during sleep in 29 NW (body mass index [BMI] = 22 ± 0.3 kg/m2) and 29 OW (BMI = 29 ± 0.7 kg/m2) individuals. During wakefulness, FRC differed between BMI groups and positions (supine: OW = 58 ± 3 and NW = 68 ± 3% predicted; lateral OW = 71 ± 3, NW = 81 ± 3% predicted). FRC fell from wake to NREM sleep in all participants and in both positions by a similar amount. As a result, during NREM sleep FRC was lower in OW than NW individuals (supine 46 ± 3 and 56 ± 3% predicted, respectively). FRC during REM was similar to NREM and no sex differences were observed in any position or sleep stage.

Conclusions
Reductions in FRC while supine and with increased body weight may contribute to worsened OSA in these conditions, but low lung volumes appear unlikely to explain the worsening of OSA in REM and in men versus women.
Isolated rapid eye movement sleep behavior disorder and cyclic alternating pattern: is sleep microstructure a predictive parameter of neurodegeneration?
Authors: Melpignano Andrea , Parrino Liborio , Santamaria Joan , Gaig Carles , Trippi Irene , Serradell Monica , Mutti Carlotta , Riccò Matteo , Iranzo Alex 
Published: July 2019

Abstract

Objective
To evaluate the role of sleep cyclic alternating pattern (CAP) in patients with isolated REM sleep behavior disorder (IRBD) and ascertain whether CAP metrics might represent a marker of phenoconversion to a defined neurodegenerative condition.

Methods
Sixty-seven IRBD patients were included and classified into patients who phenoconverted to a neurodegenerative disease (RBD converters: converter REM sleep behavior disorder [cRBD]; n = 34) and remained disease-free (RBD non-converters: non-converter REM sleep behavior disorder [ncRBD]; n = 33) having a similar follow-up duration. Fourteen age- and gender-balanced healthy controls were included for comparisons.

Results
Compared to controls, CAP rate and CAP index were significantly decreased in IRBD mainly due to a decrease of A1 phase subtypes (A1 index) despite an increase in duration of both CAP A and B phases. The cRBD group had significantly lower values of CAP rate and CAP index when compared with the ncRBD group and controls. A1 index was significantly reduced in both ncRBD and cRBD groups compared to controls. When compared to the ncRBD group, A3 index was significantly decreased in the cRBD group. The Kaplan-Meier curve applied to cRBD estimated that a value of CAP rate below 32.9% was related to an average risk of conversion of 9.2 years after baseline polysomnography.

Conclusion
IRBD is not exclusively a rapid eye movement (REM) sleep parasomnia, as non-rapid eye movement (non-REM) sleep microstructure can also be affected by CAP changes. Further studies are necessary to confirm that a reduction of specific CAP metrics is a marker of neurodegeneration in IRBD.
Yes…and! Actor Improvisation Enhances Psychiatric-Mental Health Nursing Education
Authors: Foley David M. , Robinson Jacqueline 
Published: July 2019

Abstract
Based on a comparative dearth of simulation products to support the attainment of key skills in psychiatric-mental health nursing, the authors developed scripted scenarios to provide students with exposure to low-incidence/high-risk simulated clinical scenarios in the classroom setting. Acting students from the university’s theater school were provided with character sketches and information on psychopathology-psychopharmacology to add a sense of authenticity to the performances. In turn, students questioned the actor-patients in character. The actor-patients employed the improvisational technique of “yes…and” to further develop their characters and provide deeper opportunities for faculty-student engagement and psychiatric-mental health nursing skills development.
Skeletal traction pin diameter and deflection under load: a biomechanical evaluation with clinical correlation
Authors: Evans Cody L. , Hadeed Michael M. , Casp Aaron J. , Yarboro Seth R. 
Published: July 2019

Background:
There is scant literature to guide the placement of skeletal traction. The purpose of this study was to test a tensioned traction bow, a nontensioned traction bow, and a traction set up without a bow to measure the amount of pin deflection. By quantifying the deflection of various traction systems under load, guidelines can be provided regarding equipment selection for skeletal traction. The goal was to develop a protocol to minimize the equipment necessary and time to traction placement.

Methods:
A Sawbones® skeletal traction model was designed to measure the amount of deflection of Steinmann pins of various diameters using a Kirschner tensioning bow, a Böhler (nontensioning) device, and a simple design using only weight and nylon cord. Increasing weight was added to each system and deflection recorded. Data were then evaluated to determine the smallest pin diameter that can reasonably withstand a weight of 35 pounds using the cord-only traction design.

Results:
Overall, larger pins deflected less. When comparing the traction systems, the tensioned bow had the least deflection, followed by the nontensioned bow, and the cord-only system. In the cord-only system, the 2.8-mm pin was the smallest diameter that successfully withstood the maximum weight without failing. The cord-only design was left in place for 48 hr without further increase in deflection.

Conclusions:
A simple skeletal traction design consisting of a 2.8-mm smooth Steinmann pin, segment of nylon cord, and weight can be applied with limited tools in a safe and efficient manner.
The Community Orthopaedic Surgeon Taking Trauma Call: Lateral Humeral Condyle Fracture Pearls and Pitfalls
Authors: Ho Christine A. , Mehlman Charles T. 
Published: July 2019

Summary:
Lateral condyle fractures are second only to supracondylar humeral fractures when it comes to pediatric elbow fractures. Whether minimally displaced or substantially displaced, these growth plate fractures may present significant treatment challenges. These include nonunion, malunion, avascular necrosis, and growth disturbance. It must be remembered that lateral condyle fractures often represent significantly displaced intra-articular fractures involving the epiphysis that demand anatomic reduction and stable internal fixation. This article focuses on some of the pertinent pearls and pitfalls regarding these common elbow injuries using ample clinical examples.
The Community Orthopaedic Surgeon Taking Trauma Call: Pediatric Midshaft Clavicle Fracture Pearls and Pitfalls
Authors: Vargas-Vila Mario A. , Mehlman Charles T. , Pennock Andrew T. 
Published: July 2019

Summary:Pediatric diaphyseal clavicle fractures are a common injury, particularly in the adolescent athlete. There are no consensus guidelines for operative versus nonoperative management of these injuries; however, there has been a dramatic increase in operative treatment over the past 15 years, primarily guided by literature pertaining to the adult population. Despite this trend, current literature suggests that the majority of these injuries can be treated nonoperatively with good functional outcomes, high rates of return to sport, and low incidence of complications such as nonunion, symptomatic malunion, and refracture. For the rare patient treated nonoperatively who develops a symptomatic nonunion or malunion, delayed corrective surgery remains a viable treatment option. When surgical fixation is pursued, good outcomes have been universally reported, but the optimal indication for surgery remains elusive in this adolescent population.
Interprofessional Learning to Improve Communication in Challenging Healthcare Conversations: What Clinicians Learn From Each Other
Authors: Bell Sigall K. , Langer Thorsten , Luff Donna , Rider Elizabeth A. , Brandano Jessica , Meyer Elaine C. 
Published: July 2019

Introduction:
Although contemporary health care involves complex interactions among clinicians of varying professions, opportunities to learn together are relatively few. The authors assessed participants' views about the educational value of learning with colleagues of mixed health care professions in communication and relational skills training focused on challenging conversations.

Methods:
Between 2010 and 2013, 783 participants enrolled in 46 workshops hosted by the Institute for Professionalism and Ethical Practice at Boston Children's Hospital, Boston, USA. Participants received pre–, post–, and 3-month follow-up questionnaires with quantitative and qualitative questions about their experiences learning with clinicians of varying professions (“interprofessional learning”). Descriptive statistics and chi-square tests were used to compare participant groups. Responses to open-ended questions were coded according to standard principles of content analysis.

Results:
Seven hundred twenty-two (92%) participants completed surveys. Previous interprofessional learning was reported by 60% of respondents, but generally comprised <30% of their education. Clinicians with <3 years of work experience were least likely to have previous interprofessional learning. Nearly all (96%) participants reported interprofessional colleagues contributed valuably to their learning. Asked specifically what they learned, participants described five themes: Stronger Teamwork, Patient-Centered Focus, Specific Communication Skills, Content-Specific Knowledge, and Shared Global Values. After 3 months, 64% of respondents reported that workshop participation helped make their interactions with interprofessional colleagues more collaborative.

Discussion:
Communication skills training for challenging health care conversations is a valuable opportunity for interprofessional learning and generates sustained positive attitudes about collaboration. Clinicians learn from their colleagues a deeper understanding of each other's professional roles, challenges, and unique contributions; specific communication approaches; and a sense of belonging to a collaborative community reinforcing the patient at the center of care.