bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why Public Comments Matter: The Case of the National Institutes of Health Policy on Single Institutional Review Board Review of Multicenter Studies
Authors: Ervin Ann-Margret , Taylor Holly A. , Ehrhardt Stephan , Meinert Curtis L. 
Published: March 2018

Purpose
In 2014, the National Institutes of Health (NIH) requested public comments on a draft policy requiring NIH-funded, U.S.-based investigators to use a single institutional review board (sIRB) for ethical review of multicenter studies. The authors conducted a directed content analysis and qualitative summary of the comments and discuss how they shaped the final policy.

Method
Two reviewers independently assessed support for the policy from a review of comments on the draft policy in 2016. A reviewer conducted an open text review to identify prespecified and additional comment themes. A second researcher reviewed 20% of comments; discrepancies were resolved through discussion.

Results
The NIH received 167 comments: 65% (108/167) supportive of the policy, 23% (38/167) not supportive, and 12% (21/167) not indicating support. Clarifications or changes to the policy were suggested in 102/167 comments (61%). Criteria for selecting sIRBs were addressed in 32/102 comments (31%). Also addressed were institutional review board (IRB) responsibilities (39/102; 38%), cost (27/102; 26%), the role of local IRBs (14/102; 14%), and allowable policy exceptions (19/102; 19%). The NIH further clarified or provided guidance for selection criteria, IRB responsibilities, and cost in the final policy (June 2016). Local IRB reviews and exemptions guidance were unchanged.

Conclusions
In this case study, public comments were effective in shaping policy as the NIH modified provisions or planned supplemental guidance in response to comments. Yet critical knowledge gaps remain, and empirical data are necessary. The NIH is considering mechanisms to support the establishment of best practices for sIRB implementation.
Vaginal pH: a simple assessment highly correlated with vaginal morphology and symptoms in postmenopausal women
Authors: Tucker Kelly M. , Godha Keshav , Mirkin Sebastian , Archer David F. 
Published: March 2018

Abstract

Objective:
The aim of the study was to determine the utility of vaginal pH as a marker of menopause and vulvar and vaginal atrophy (VVA) before and after local estrogen treatment.

Methods:
Vaginal pH was determined using standard pH paper strips in two clinical trials involving postmenopausal women with signs and symptoms of VVA evaluated before and after intervention with vaginal estradiol in softgel capsules. The utility of vaginal pH was evaluated as a screening method for VVA due to menopause and correlations were analyzed between vaginal pH and VVA symptoms, physical changes, and maturation of the vaginal epithelium.

Results:
Changes in vaginal pH were significantly correlated with changes in superficial and parabasal cell counts; vaginal epithelial changes of color, integrity, thickness, and secretion; and the VVA symptoms of vaginal dryness and dyspareunia (vaginal pain with intercourse).

Conclusions:
Vaginal pH consistently correlated with parabasal and superficial cells and the visual vaginal epithelial changes and symptoms of dryness and dyspareunia, and is thus a simple outpatient procedure that reflects the hormonal milieu and its effects on the vaginal epithelium.
Association between waist-to-height ratio and anxiety in middle-aged women: a secondary analysis of a cross-sectional multicenter Latin American study
Authors: Arroyo Karen J. , Ramos-Torres Gabriela , Mezones-Holguin Edward , Blümel Juan E. , Barón Germán , Bencosme Ascanio , Benítez Zully , Bravo Luz M. , Calle Andrés , Flores Daniel , Espinoza María T. , Gómez Gustavo , Hernández-Bueno José A. , Martino Mabel , Lima Selva , Monterrosa Alvaro , Mostajo Desiree , Ojeda Eliana , Onatra William , Sánchez Hugo , Tserotas Konstantinos , Vallejo María S. , Witis Silvina , Zúñiga María C. , Chedraui Peter 
Published: March 2018

Abstract

Objective:
The aim of the study was to evaluate the association between waist-to-height ratio (WHtR) and anxiety in middle-aged women.

Methods:
We carried out a secondary analysis of data from a multicenter study of women between 40 and 59 years old from 11 Latin America countries. Anxiety was assessed using the Goldberg Anxiety and Depression Scale. WHtR was calculated according to World Health Organization standards and categorized in tertiles: upper, middle, and lower using 0.45 and 0.6 as cutoff values. Prevalence ratios (PRs) and 95% CIs were calculated by generalized linear models of Poisson family with robust standard errors, both crude and adjusted models based on statistical and epidemiological criteria.

Results:
Data of a total of 5,580 women were analyzed. Mean age was 49.7 ± 5.5 years, and 57.9% were postmenopausal. The 61.3% of women had anxiety and mean WHtR was 0.54 ± 0.1. In the crude model, compared with women in lower tertile, those in the middle (PR: 1.07; 95% CI, 1.01-1.13) and upper (PR: 1.23 95% CI, 1.07-1.29) WHtR tertile were significantly more likely to have anxiety. In the adjusted models, only women in upper tertile were, however, more likely of displaying anxiety than those in lower tertile (PR: 1.13; 95% CI, 1.08-1.18).

Conclusions:
In this series, WHtR was associated with anxiety in middle-aged women. It is advisable to further study this anthropometric measure in order for it to be incorporated in the routine clinical practice and evaluation of middle-aged women.
Climacteric-related symptoms in menopause transition and beyond: a prospective 19-year follow-up study on previously hysterectomized women
Authors: Katainen Riina , Engblom Janne R. , Polo-Kantola Päivi 
Published: March 2018

AbstractObjective:Only a few extended follow-up studies have investigated the natural progress of climacteric-related symptoms. The results have been conflicting. Thus, our aim was to evaluate, through a 19-year longitudinal study, whether these symptoms decrease or disappear as time elapses after menopause.Methods:Our study was a prospective follow-up survey of 65 hysterectomized peri or postmenopausal women. The women were interviewed at the baseline, and at 6 and 19 years thereafter. Changes in various climacteric-related symptoms were evaluated by repeated-measures analysis of variance with time as the independent variable. The analyses were adjusted for baseline age, body mass index, employment, and use of hormone therapy. Climacteric-related symptoms were evaluated with the Women's Health Questionnaire, of which we included seven symptom domains (vasomotor, sleep, depressive, anxiety/fears, cognitive, sexual, and somatic).Results:Vasomotor symptoms decreased remarkably during the follow-up period. In addition, a statistically significant decrease was found in sleep problems and cognitive difficulties. However, the decrease was minor, and thus probably clinically insignificant.Conclusions:The only symptom with notable decrease was vasomotor symptoms. The etiology of other symptoms, commonly connected to menopause transition, is probably multifactorial and not substantially dependent on the climacteric.
Characteristics and Health Outcomes of Post-9/11 Caregivers of US Service Members and Veterans Following Traumatic Brain Injury
Authors: Brickell Tracey A. , French Louis M. , Lippa Sara M. , Lange Rael T. 
Published: March 2018

Objectives:
To (a) characterize a sample of post-9/11 caregivers providing help to service members and veterans (SMV) following traumatic brain injury (TBI), (b) examine the level of support provided, and (c) determine caregiver health and well-being outcomes.

Setting:
Military treatment facility.

Participants:
Caregivers (N = 278) of SMVs who sustained a mild, moderate, severe, or penetrating TBI (96.0% female; 86.0% spouse/partner; age: M = 38.7 years, SD = 10.4). Participants were divided into 3 groups on the basis of the level of support provided (low, medium, high).

Design:
Prospective observational.

Main Measures:
Caregiver Appraisal Scale, SF-36v2 Health Survey, Mayo-Portland Adaptability Inventory-4, Caregiver Questionnaire.

Results:
The majority of caregivers were helping an SMV with mild TBI and comorbid posttraumatic stress disorder/depression, who was injured in a blast-related incident during combat. Caregivers helped predominantly with activities of daily living and/or instrumental activities of daily living and spent more than 40 hours per week providing care. High-support caregivers were more likely to be caring for an SMV with comorbid posttraumatic stress disorder, report poor physical and mental health outcomes, and have a negative impact on employment and finances.

Conclusions:
A better understanding of protective factors is required to ensure that burden of care does not exceed the caregiver's health and financial capacity, or undermine the care, well-being, and recovery of the SMV.
Persistent Increased Enteric Glial Expression of S100β is Associated With Low-grade Inflammation in Patients With Diverticular Disease
Authors: Cossais François , Leuschner Sebastian , Barrenschee Martina , Lange Christina , Ebsen Michael , Vogel Ilka , Böttner Martina , Wedel Thilo 
Published: March 2018

Background:
Diverticular disease (DD) is a common gastrointestinal inflammatory disorder associated with an enteric neuropathy. Although enteric glial cells (EGCs) are essential regulators of intestinal inflammation and motility functions, their contribution to the pathophysiology of DD remains unclear. Therefore, we analyzed the expression of specific EGC markers in patients with DD.

Materials and Methods:
Expression of the glial markers S100β, GFAP, Sox10, and Connexin 43 was analyzed by real-time quantitative PCR in colonic specimens of patients with DD and in that of controls. Protein expression levels of S100β, GFAP, and Connexin 43 were further analyzed using immunohistochemistry in the submucosal and myenteric plexus of patients with DD and in that of controls. Expression of the inflammatory cytokines tumor necrosis factor-α and interleukin-6 was quantified using qPCR, and infiltration of CD3+ lymphocytes was determined using immunohistochemistry.

Results:
Expression of S100β was increased in the submucosal and myenteric plexus of patients with DD compared with that in controls, whereas expression of other glial factors remained unchanged. This increased expression of S100β was correlated to CD3+ lymphocytic infiltrates in patients with DD, whereas no correlation was observed in controls.

Conclusions:
DD is associated with limited but significant alterations of the enteric glial network. The increased expression of S100β is associated with a persistent low-grade inflammation reported in patients with DD, further emphasizing the role of EGCs in intestinal inflammation.
Prospective Follow-up Study of the Recurrence of Pancreatic Cancer Diagnosed at an Early Stage
Authors: Ikemoto Juri , Hanada Keiji , Minami Tomoyuki , Okazaki Akihito , Abe Tomoyuki , Amano Hironobu , Yonehara Shuji 
Published: March 2018

Objectives
Most patients with pancreatic cancer (PC) demonstrate recurrences in the form of metastatic disease. We prospectively evaluated recurrence in PC cases diagnosed at an early stage.

Methods
Thirty cases of PC stage 0 or IA were prospectively followed for at least 1 year after initial surgery. We performed blood tests and contrast-enhanced computed tomography (CT) every 3 to 6 months. Endoscopic ultrasonography (EUS) was performed if CT revealed abnormal findings in the remnant pancreas (RP).

Results
The median follow-up period was 53.9 months. Pancreatic cancer recurred in the RP (n = 8) and liver (n = 1). Computed tomography revealed mass lesions in 5 cases, a cystic lesion in 2 cases, and pancreatic duct dilatation in 1 case. Endoscopic ultrasonography detected mass lesions in 3 cases without a detectable mass on CT. The sensitivity of EUS-guided fine-needle aspiration and pancreatic juice cytology was 75%. Five of 8 cases underwent total resection of the RP, with pathologic findings revealing stage IA in 1 case, stage II in 1 case, and stage III in 3 cases.

Conclusions
Careful long-term follow-up including EUS should be performed in resected PC cases diagnosed at an early stage to check recurrence in the RP.
Barriers and Facilitators to a Good Bowel Preparation for Colonoscopy in Children
Authors: Hart Lara , Nael Humaira , Longmire Natasha M. , Zachos Mary 
Published: March 2018

ABSTRACTBackground:A well‐visualized colon during colonoscopy has a direct impact on interpretation of findings and need for repeat procedure. Studies have been conducted in the adult population to assess factors contributing to improved bowel preparation. The primary aim of this study was to determine barriers and facilitators to good preparation in children.Methods:A qualitative descriptive approach was utilized. Children age 2 to 18 years old, and their parents were recruited from the McMaster University Gastroenterology clinic from May 2015 to January 2016. Semistructured interviews were conducted assessing the understanding of the preparation protocol, and the compliance and tolerability of the preparation. A thematic analysis was conducted.Results:Eleven families participated (7 children and 14 parents). Fifty percent of the children were under 11 years of age, and 73% were undergoing bowel preparation for the first time. Participants identified 26 subthemes, which were categorized into 4 broad themes. Barriers included confusion regarding mixing of the preparation and allowable diet during the preparation day, as well as lack of clarity on expected stool end goals. Facilitators included ease of access of the gastroenterology team, small volume of liquid mixed with the preparation, few adverse effects, and the provision of an understandable handout. Parental motivation to achieve a good outcome was also a facilitator.Conclusions:This is the first qualitative study focusing on children undergoing a home bowel preparation for a colonoscopy. Being able to identify barriers and facilitators will allow gastroenterologists to improve the quality of bowel preparation and overall experience for the pediatric population.
Comparison of Transjugular Liver Biopsy and Percutaneous Liver Biopsy With Tract Embolization in Pediatric Patients
Authors: Tulin‐Silver Sheryl , Obi Chrystal , Kothary Nishita , Lungren Matthew P. 
Published: March 2018

ABSTRACTPurpose:The aim of the study was to compare safety and efficacy of transjugular liver biopsy (TJLB) and percutaneous liver biopsy (PLB) with tract embolization in pediatric patients with liver disease.Materials and Methods:TJLB and PLB between December 2009 and October 2015 were retrospectively reviewed. Primary endpoints were adequate sampling and complication rate. Patient age, weight, coagulation factors, ascites, blood transfusions, adequacy of biopsy sample, number of biopsy samples, and complications were compared.Results:There were 39 TJLB (average age 10.6 years) and 120 PLB (average age 7.1 years) (P value <0.05). Average weight was 40.2 kg for TJLB and 26.8 kg for PLB (P value <0.05). Average platelets were 155 for TJLB and 252 for PLB (P value <0.05). Average international normalized ratio was 1.7 for TJLB and 1.3 for PLB (P value <0.05). Mean postbiopsy hematocrit decrease was 0.8 and 0.9, for TJLB and PLB, respectively. Mean postbiopsy hemoglobin decrease was 0.3 in both groups. Number of core biopsy samples was 4.5 and 4.3, for TJLB and PLB, respectively. There was 1 biopsy yielding insufficient sample in each group. TJLB had 1 (2.6%) complication of supraventricular tachycardia. PLB had 4 (3.3%) complications, with 1 hemoperitoneum, 1 hypotension, 1 patient with decreased hemoglobin, and 1 patient with bilious drainage from the biopsy site.Conclusions:TJLB and PLB with gelatin sponge pledget tract embolization are both safe and effective for the diagnosis of hepatic disease in pediatric patients. To avoid radiation, PLB may be considered as first‐line approach in the pediatric population, even in the setting of coagulopathy.
Presentation and Investigation of Pediatric Bone and Joint Infections in the Pediatric Emergency Department
Authors: Akinkugbe Olugbenga , Stewart Charles , McKenna Caoimhe 
Published: March 2018

Objective
The objective of this study was to evaluate the presenting features of bone and joint infections with a view to identify distinguishing trends that will be useful for pediatric emergency departments.

Methods
We performed a retrospective review of patient records over a 12-year period in the pediatric emergency department of a large regional pediatric teaching center serving a diverse population.

Results
There were 88 cases of osteoarticular infections during the study period. Pain, fever, and impaired function were commonly reported, but overall, there was inconsistency in the presenting features. Inflammatory makers were sensitive tools, particularly in combination. When C-reactive protein, total white cell count, and erythrocyte sedimentation rate were all abnormal, 98% of bone and joint infections were identified.
Causative organisms were identified in only 38% of cases, mostly from cultures of synovial fluid and bone. Streptococcal organisms were significantly more likely to be isolated in children under 5 years than in children over 5 years (P = <0.014). Staphylococcal organisms were significantly more likely to be isolated in children over 5 years than in children under 5 years (P = <0.001). Identification of virulent organisms such as Panton-Valentine leukocidin Staphylococcus aureus and methicillin-resistant S. aureus in our study should prompt review of diagnostic techniques and antibiotic choices.

Conclusions
Overall, children under 5 years were significantly more likely to be diagnosed with septic arthritis than osteomyelitis (P = 0. 006). Children over 12 years were significantly more likely to be diagnosed with osteomyelitis than septic arthritis (P = 0. 019). These trends are useful to consider at presentation and in cases of diagnostic uncertainty.
Poststroke Depression
Authors: Arwert Henk J. , Meesters Jorit J.L. , Boiten Jelis , Balk Ferdi , Wolterbeek Ron , Vliet Vlieland Thea P.M. 
Published: March 2018

Objective
The aim of the study was to ascertain the prevalence of depressive mood and its determinants in the chronic phase after stroke.

Design
Five hundred seventy-six consecutive patients were invited to participate 2 to 5 yrs after hospitalization for a first-ever stroke. Stroke characteristics at hospitalization were collected retrospectively from medical records. Patients and their caregivers completed questionnaires on depression (Hospital Anxiety and Depression Scale [HADS]), sociodemographic characteristics, healthcare usage, daily activities, quality of life, and caregiver strain. Patients with HADS depression scores of less than 8 were compared with patients with HADS depression scores of 8 or higher by means of univariate logistic regression analyses, adjusted for age, sex, and Barthel Index at discharge.

Results
Two hundred seven patients (36%) returned the questionnaires. After a mean follow-up of 36.3 mos, 67 patients (34%) had a HADS depression score of 8 or higher. Male sex and being born abroad were statistically significantly associated with a high HADS depression score, adjusted for age, sex, and stroke severity. Depressed patients had higher anxiety levels, a more avoidant coping style, less daily activities, and a lower quality of life; their caregivers experienced a higher burden.

Conclusions
In the chronic phase after stroke, a considerable proportion of patients has depressive symptoms. This seems to be related to sex, country of origin, anxiety, coping style, daily activities, quality of life, and caregivers' strain. Future research should focus on causal relationships and opportunities for treatment.
Arterial Lactate Concentration at the End of Liver Transplantation Is an Early Predictor of Primary Graft Dysfunction
Authors: Golse Nicolas , Guglielmo Nicola , El Metni Albert , Frosio Fabio , Cosse Cyril , Naili Salima , Ichaï Philippe , Ciacio Oriana , Pittau Gabriella , Allard Marc-Antoine , Castaing Denis , S. A. Cunha Antonio , Cherqui Daniel , Adam René , Vibert Eric 
Published: March 2018

Background:
Although many prognostic factors of primary graft dysfunction after liver transplantation (LT) are available, it remains difficult to predict failure in a given recipient.

Objective:
We aimed to determine whether the intraoperative assay of arterial lactate concentration at the end of LT (LCEOT) might constitute a reliable biological test to predict early outcomes [primary nonfunction (PNF), early graft dysfunction (EAD)].

Methods:
We reviewed data from a prospective database in a single center concerning patients transplanted between January 2015 and December 2016 (n = 296).

Results:
There was no statistical imbalance between the training (year 2015) and validation groups (year 2016) for epidemiological and perioperative feature. Ten patients (3.4%) presented with PNF, and EAD occurred in 62 patients (20.9%); 9 patients died before postoperative day (POD) 90. LCEOT ≥5 mmol/L was the best cut-off point to predict PNF (Se=83.3%, SP=74.3%, positive likelihood ratio (LR+)=3.65, negative likelihood ratio (LR−)=0.25, diagnostic odds ratio (DOR)=14.44) and was predictive of PNF (P = 0.02), EAD (P = 0.05), and death ≤ POD90 (P = 0.06). Added to the validated BAR-score, LCEOT improved its predictive value regarding POD 90 survival with a better AUC (0.87) than BAR score (0.74). The predictive value of LCEOT was confirmed in the validation cohort.

Conclusion:
As a reflection of both hypoperfusion and tissue damage, the assay of arterial LCEOT ≥5 mmol/L appears to be a strong predictor of early graft outcomes and may be used as an endpoint in studies assessing the impact of perioperative management. Its accessibility and low cost could impose it as a reliable parameter to anticipate postoperative management and help clinicians for decision-making in the first PODs.
Kinetic modelling of quantitative proteome data predicts metabolic reprogramming of liver cancer
Authors: Berndt Nikolaus , Egners Antje , Mastrobuoni Guido , Vvedenskaya Olga , Fragoulis Athanassios , Dugourd Aurélien , Bulik Sascha , Pietzke Matthias , Bielow Chris , Gassel Rob van , Damink Steven Olde , Erdem Merve , Saez-Rodriguez Julio , Holzhütter Hermann-Georg , Kempa Stefan , Cramer Thorsten 
Published: March 2018

SummaryMetabolic alterations can serve as targets for diagnosis and therapy of cancer. Due to the highly complex regulation of cellular metabolism, definite identification of metabolic pathway alterations remains challenging and requires sophisticated experimentation. Here, we applied a comprehensive kinetic model of the central carbon metabolism (CCM) to characterize metabolic reprogramming in murine liver cancer. We show that relative differences of protein abundances of metabolic enzymes obtained by mass spectrometry can be used to scale maximal enzyme capacities. Model simulations predicted tumor - specific alterations of various components of the CCM, a selected number of which were subsequently verified byin vitroandin vivoexperiments. Furthermore, we demonstrate the ability of the kinetic model to identify metabolic pathways whose inhibition results in selective tumor cell killing. Our systems biology approach establishes that combining cellular experimentation with computer simulations of physiology-based metabolic models enables a comprehensive understanding of deregulated energetics in cancer.