bluuebunny/crossref_metadata_2025_split huggingface dataset:
Misclassification of Aggressive Basal Cell Carcinoma Subtypes and Implications for Management
Authors: Moon Deborah , Randall Grant , Higgins Shauna , Sutton Adam V. , Wysong Ashley 
Published: April 2021

BACKGROUND
Management of basal cell carcinoma (BCC) varies by histopathologic subtype; however, biopsies may inadequately characterize them as nonaggressive, risking potential suboptimal treatment.

OBJECTIVE
To characterize the rate of undetected aggressive BCC subtypes by size, location, and histopathology type.

MATERIALS AND METHODS
Retrospective cohort study of 928 BCCs treated with Mohs Micrographic Surgery (MMS) at a tertiary academic institution from 2015 to 2017, comparing patient and tumor characteristics and histopathologic subtype on biopsy versus Mohs.

RESULTS
Among the 825 BCCs with known subtypes on biopsy, 68% (561/825) were classified as nonaggressive, 28% (159/561) of which were subsequently found to have aggressive subtypes on MMS. Aggressive features were more often underrepresented in biopsy samples taken from Area H compared with Area M/L (odd ratio [OR] 2.65, 95% confidence interval [CI] 1.73–4.08, p < .001) or those with nodular subtypes (OR 2.19, CI 1.08–4.45, p = .03). Of concern, these unsuspected aggressive BCCs required more Mohs stages for clearance (mean 2.37, SD 0.72, p < .001) compared with BCCs that remained nonaggressive on both biopsy and Mohs (mean 1.50, SD 0.75).

CONCLUSION
Given the high percentage of BCCs with unsuspected aggressive subtypes, higher clinical suspicion for undiagnosed high-risk BCCs should be given to nodular BCCs and to BCCs on Area H.
Effect of an educational intervention on women's healthcare provider knowledge gaps about breast density, breast cancer risk, and screening
Authors: Seitzman Robin L. , Pushkin JoAnn , Berg Wendie A. 
Published: April 2021

Abstract

Objectives:
We sought to assess the effect of an educational intervention, based on DenseBreast-info.org website content, on women's healthcare provider knowledge of breast density, its risk and screening implications, and comfort level discussing these topics with patients.

Methods:
US-based women's healthcare providers participated in a web-based pretest/posttest study from May 14, 2019 to September 30, 2019. Pretest included demographics; comfort/knowledge discussing breast density impact on risk and screening; and educational material. Posttest contained the same knowledge and comfort questions. We assessed mean pretest/posttest score and comfort level differences (paired t tests) and pretest/posttest knowledge gap differences (McNemar test). We evaluated associations of baseline characteristics with pretest score and score improvement using multiple linear regression, and associations with knowledge gaps using logistic regression.

Results:
Of 177 providers analyzed, 74.0% (131/177) were physicians and 71.8% (127/177) practiced obstetrics/gynecology. Average test score increased from 40.9% (5.7/14) responses correct pretest to 72.1% (10.1/14) posttest (P < 0.001). Pretest, 56.5% (100/177) knew women with extremely dense breasts have four-to-six-fold greater breast cancer risk than those with fatty breasts; 29.4% (52/177) knew risk increases with increasing glandular tissue; only 5.6% (10/177) knew 3D/tomosynthesis does not improve cancer detection in extremely dense breasts over 2D mammography; and 70.6% (125/177) would consider supplemental ultrasound after mammography in an average-risk 50-year old with dense breasts. Postintervention, these knowledge gaps resolved or reduced (all P < 0.005) and comfort in discussing breast density implications increased (all P < 0.001).

Conclusions:
Important knowledge gaps about implications of breast density exist among women's healthcare providers, which can be effectively addressed with web-based education.

Video Summary:
http://links.lww.com/MENO/A753.
A core outcome set for vasomotor symptoms associated with menopause: the COMMA (Core Outcomes in Menopause) global initiative
Authors: Lensen Sarah , Archer David , Bell Robin J. , Carpenter Janet S. , Christmas Monica , Davis Susan R. , Giblin Karen , Goldstein Steven R. , Hillard Tim , Hunter Myra S. , Iliodromiti Stamatina , Jaisamrarn Unnop , Joffe Hadine , Khandelwal Sunila , Kiesel Ludwig , Kim Bobae V. , Lambalk Cornelis B. , Lumsden Mary Ann , Maki Pauline M. , Nappi Rossella E. , Panay Nick , Roberts Helen , Shifren Jan , Simon James A. , Vincent Amanda , Wolfman Wendy , Hickey Martha 
Published: April 2021

Abstract

Objective:
Vasomotor symptoms (VMS) (hot flashes and night sweats) affect most women over the menopause transition. Comparing the safety and effectiveness of treatments for vasomotor symptoms is limited by the use of inconsistent outcome measures, and uncertainty as to which outcomes are most important to symptomatic women. To address this, we have developed a Core Outcome Set (COS) for use in clinical trials of treatments for VMS.

Methods:
We systematically reviewed the primary outcomes measured in randomized controlled trials of treatments for VMS. These were refined and entered into a two-round modified Delphi survey completed by clinicians, researchers, and postmenopausal women between November 2019 and March 2020. Outcomes were scored on a nine-point scale from “not important” to “critically important.” Two international consensus meetings were held to finalize the COS.

Results:
Based on the systematic review, 13 separate outcomes were included in the Delphi process. This was completed by 227 participants of whom 58% were postmenopausal women, 34% clinicians, and 8% researchers. Predefined thresholds were applied to categorize importance scores obtained during Round 2 of the Delphi survey. These informed discussions at the consensus meetings which were attended by 56 participants from 28 countries. The final COS includes six outcomes: 1) frequency of VMS, 2) severity of VMS, 3) distress, bother or interference caused by VMS, 4) impact on sleep, 5) satisfaction with treatment, and 6) side-effects of treatment.

Conclusion:
Implementation of this COS will: better enable research studies to accurately reflect the joint priorities of postmenopausal women, clinicians and researchers, standardize outcome reporting, and facilitate combining and comparing results from different studies, and ultimately improve outcomes for women with bothersome VMS.

Video Summary:

http://links.lww.com/MENO/A763.
Antibiotic Safety and Effectiveness in Premature Infants With Complicated Intraabdominal Infections
Authors: Smith Michael J. , Boutzoukas Angelique , Autmizguine Julie , Hudak Mark L. , Zinkhan Erin , Bloom Barry T. , Heresi Gloria , Lavery Adrian P. , Courtney Sherry E. , Sokol Gregory M. , Cotten C. Michael , Bliss Joseph M. , Mendley Susan , Bendel Catherine , Dammann Christiane E. L. , Weitkamp Jörn-Hendrik , Saxonhouse Matthew A. , Mundakel Gratias T. , Debski Julie , Sharma Gaurav , Erinjeri Jinson , Gao Jamie , Benjamin Daniel K. , Hornik Christoph P. , Smith P. Brian , Cohen-Wolkowiez Michael ,   on behalf of the Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee
Published: April 2021

Background:
In premature infants, complicated intraabdominal infections (cIAIs) are a leading cause of morbidity and mortality. Although universally prescribed, the safety and effectiveness of commonly used antibiotic regimens have not been established in this population.

Methods:
Infants ≤33 weeks gestational age and <121 days postnatal age with cIAI were randomized to ≤10 days of ampicillin, gentamicin, and metronidazole (group 1); ampicillin, gentamicin, and clindamycin (group 2); or piperacillin-tazobactam and gentamicin (group 3) at doses stratified by postmenstrual age. Due to slow enrollment, a protocol amendment allowed eligible infants already receiving study regimens to enroll without randomization. The primary outcome was mortality within 30 days of study drug completion. Secondary outcomes included adverse events, outcomes of special interest, and therapeutic success (absence of death, negative cultures, and clinical cure score >4) 30 days after study drug completion.

Results:
One hundred eighty infants [128 randomized (R), 52 nonrandomized (NR)] were enrolled: 63 in group 1 (45 R, 18 NR), 47 in group 2 (41 R, 6 NR), and 70 in group 3 (42 R, 28 NR). Thirty-day mortality was 8%, 7%, and 9% in groups 1, 2, and 3, respectively. There were no differences in safety outcomes between antibiotic regimens. After adjusting for treatment group and gestational age, mortality rates through end of follow-up were 4.22 [95% confidence interval (CI): 1.39–12.13], 4.53 (95% CI: 1.21–15.50), and 4.07 (95% CI: 1.22–12.70) for groups 1, 2, and 3, respectively.

Conclusions:
Each of the antibiotic regimens are safe in premature infants with cIAI.

Clinical Trial Registration:
NCT0199499
Clinical Characteristics of Patients With Kawasaki Disease Whose Siblings Had the Same Disease
Authors: Hayashida Kanako , Ae Ryusuke , Masuda Hiroya , Kosami Koki , Matsumura Masami , Makino Nobuko , Matsubara Yuri , Sasahara Teppei , Nakamura Yosikazu 
Published: April 2021

Background:
Some patients with Kawasaki disease (KD) have siblings who developed the same disease. Using a large-scale epidemiologic dataset, the present study aimed to determine the clinical characteristics of this population.

Methods:
We analyzed 89,725 patients diagnosed with KD during 2011–2018 who were registered in the nationwide Japanese KD survey database. Multivariable logistic regression analyses were performed to determine factors associated with sibling history of KD.

Results:
Of the 89,725 patients, 1777 (2%) had sibling history of KD. Annual prevalence ranged from 1.5% to 2.3% during the study period and showed a tendency toward an increasing trend. Patients with recurrent KD and parental history of KD were significantly associated with sibling history of KD (adjusted odds ratio [95% confidence interval] = 2.15 [1.82–2.54] and 2.64 [2.02–3.47], respectively). Although patients with a sibling history of KD were significantly associated with initial intravenous immunoglobulin treatment resistance (1.14 [1.02–1.28]), no significant association was found between sibling history and coronary artery abnormality development. Among patients with a sibling history of KD, male patients were less likely to have recurrent KD than female patients (0.68 [0.49–0.96]).

Conclusions:
The significant association between sibling history and parental history may indicate genetic susceptibility to KD onset. Among those with a sibling history, recurrent KD was more likely to occur in female patients. Further studies focusing on this population may contribute toward identification of the cause of KD onset.
Infective Endocarditis in Children in Queensland, Australia
Authors: Mahony Michelle , Lean David , Pham Lily , Horvath Robert , Suna Jessica , Ward Cameron , Veerappan Sundar , Versluis Kathryn , Nourse Clare 
Published: April 2021

Background:
Infective endocarditis (IE) is a rare entity in children associated with significant morbidity and mortality. To optimize management, it is important to understand local epidemiology, risk factors, clinical features and outcome. These are investigated in this retrospective 10-year study of endocarditis in children in Queensland.

Methods:
Children <18 years with IE were identified from the state-wide pediatric cardiology center (Mater Children’s Hospital, 2009–2014; Queensland Children’s Hospital, 2014–2018) through International Classification of Diseases codes and local cardiology database. Clinical records were assessed by a clinician and echocardiograms by a cardiologist. Incidence was calculated using Australian Bureau of Statistics Queensland Estimated Resident Population data, 2019.

Results:
Fifty-one children were identified, with an overall estimated incidence of 0.84 per 100,000 per year; 0.69 per 100,000 in 2009–2013 and 0.99 per 100,000 in 2014–2018, respectively. Twenty-four (47.1%) children were male and 10 (19.6%) were identified as Aboriginal or Torres Strait Islander peoples. Underlying cardiac conditions were present in 29 (56.9%): 25 congenital heart disease, 3 rheumatic heart disease and 1 cardiomyopathy. A causative pathogen was identified in 46 (90.2%) children with Staphylococcus aureus most common. Thirty-six (70.6%) met criteria for “Definite IE” as per modified Duke criteria, with the remainder “Possible IE.” Surgery was required in 26 (51%). Median duration of antibiotics was 42 (interquartile range = 32–51) days and hospitalization 49 (interquartile range = 34–75) days. One child died due to IE.

Conclusions:
IE in children in Queensland is increasing in incidence and is higher than the reported incidence in New Zealand and the United States. Congenital heart disease is the most common risk factor and S. aureus is the commonest responsible organism. Aboriginal or Torres Strait Islander children are over-represented. Mortality remains low.
Strengthening the Acute Care Curriculum
Authors: Sabatke Megan J. , Young Ashley M. , Johnson Audrey M. , Darbee Joan , Mayer Kirby P. 
Published: April 2021

Objective:
The purpose of this study was to describe the effect of acute care curriculum changes on a university's doctor of physical therapy (DPT) graduates by aggregating quantitative data from 2 academic surveys.

Methods:
This was a retrospective study describing physical therapist students' perspective, confidence, and employment in acute care physical therapy using data from 2 academic surveys administered to graduates from a DPT program.

Results:
From 2010 to 2018, 569 students graduated from the DPT program with a median of 100% (interquartile range 97%-100.5%) response rate for the self-assessment survey and a median of 38% (interquartile range 33%-48%) completion of the graduate outcome survey. The majority of DPT graduates self-reported being at or above expected level of competence with cardiopulmonary and complex patients, which appeared to increase from 77.4% and 88.7% in 2012 to 97% and 100% in 2018, respectively. Similar increasing trends were noted with the number of first jobs in the acute care setting (+5.4%) and interest (+9.1%) in the acute care setting, but not as consistently. DPT graduates' level of comfort in the acute care setting did not change over time.

Conclusions:
Curricular changes devised to enhance acute care physical therapy training in a program's DPT curriculum may have led to graduates reporting increased competency in the unique skill set needed to work in this setting. DPT programs require the continued assessment of educational requirements and competencies to fulfill the growing need for physical therapists in the acute care setting.
The Effect of Blue-enriched White Light on Cognitive Performances and Sleepiness of Simulated Shift Workers
Authors: Song Yanping , Lv Xinrui , Qin Wei , Dang Weimin , Chen Zhizhong , Nie Jingxin , Liu Baohua , Dong Wentian 
Published: April 2021

Background:
Shift work is associated with reduced performance and efficiency, the current study aimed at investigating whether blue-enriched white light could improve workers’ performance.

Methods:
The study, which adopted a randomized controlled trial, was conducted among 48 simulated shift workers. The participants performed sustained attention task, working memory task, and sleepiness task during night shift work. The data was analyzed using two-way repeated measure ANOVA.

Results:
The results indicated that, compared to conventional light, participants’ correct responses of the sustained attention significantly increased when they were exposed to blue-enriched white light, correspondingly, the commission errors and omission errors declined. Furthermore, the blue-enriched white light had a significant effect on the decrease of sleepiness. However, the working memory was not significantly affected.

Conclusion:
Exposing to blue-enriched white light can improve sustained attention and reduce sleepiness.
National Institutes of Health Advancing Multimorbidity Research
Authors: Salive Marcel E. , Suls Jerry , Farhat Tilda , Klabunde Carrie N. 
Published: April 2021

Background:
Multimorbidity, the co-occurrence of 2 or more chronic diseases, is more common than having a single chronic disease, especially among persons age 65 years and older. The routine measurement of multimorbidity can facilitate a better understanding of potential causes and interactions and promote more effective treatment and improved outcomes.

Objectives:
To present a multimorbidity research framework and identify gaps in the research literature related to multimorbidity.

Design:
In preparation for an expert panel workshop convened in September 2018, planning committee members reviewed the literature and developed a guiding framework that informed the selection of topics and speakers.

Results:
The framework, grounded in a patient-centered approach, incorporates the concept of concordant and discordant comorbidity, and includes potential causes, interactions, and outcomes. This work informed workshop presentations and discussion related to identifying and selecting the best available multimorbidity instruments and determining future research needs.

Conclusions:
Multimorbidity research can be advanced by addressing gaps in study design and target populations, and by increasing attention to universal outcome measurement.
Glycerol-3-phosphate and fibroblast growth factor 23 regulation
Authors: Simic Petra , Babitt Jodie L. , Rhee Eugene P. 
Published: April 2021

Purpose of review
Both classical and nonclassical factors regulate fibroblast growth factor 23 (FGF23), with impacts on gene expression and proteolytic cleavage. Here, we review recent publications that extend current knowledge on these factors.

Recent findings
Emerging nonclassical FGF23 regulators such as erythropoietin cause a balanced increase in FGF23 expression and cleavage, with minimal or no increase in biologically active intact FGF23 (iFGF23) in blood. However, circulating FGF23 profiles may not reflect the bone marrow microenvironment. For example, granulocyte colony-stimulating factor increases local marrow iFGF23 levels without impacting circulating iFGF23 levels. The view that phosphate does not increase bone FGF23 production also warrants reconsideration, as phosphate can reduce iFGF23 cleavage and phosphate-containing calciprotein particles increase FGF23 expression. Finally, a screen of renal venous plasma identifies glycerol-3-phosphate as a kidney-derived molecule that circulates to bone and bone marrow, where it is converted to lysophosphatidic acid and signals through a G-protein coupled receptor to increase FGF23 synthesis.

Summary
FGF23 regulation is complex, requiring consideration of known and emerging stimuli, expression and cleavage, and circulating and local levels. Recent work identifies glycerol-3-phosphate as an FGF23 regulator derived from the injured kidney; whether it participates in FGF23 production downstream of classical or nonclassical factors requires further study.
The Nlrp3 inflammasome – the evolving story of its positive and negative effects on hematopoiesis
Authors: Ratajczak Mariusz Z. , Kucia Magdalena 
Published: April 2021

Purpose of review
Hematopoiesis is co-regulated by innate immunity, which is an ancient evolutionary defense mechanism also involved in the development and regeneration of damaged tissues. This review seeks to shed more light on the workings of the Nlrp3 inflammasome, which is an intracellular innate immunity pattern recognition receptor and sensor of changes in the hematopoietic microenvironment, and focus on its role in hematopoieisis.

Recent findings
Hematopoietic stem progenitor cells (HSPCs) are exposed to several external mediators of innate immunity. Moreover, since hemato/lymphopoietic cells develop from a common stem cell, their behavior and fate are coregulated by intracellular innate immunity pathways. Therefore, the Nlrp3 inflammasome is functional both in immune cells and in HSPCs and affects hematopoiesis in either a positive or negative way, depending on its activity level. Specifically, while a physiological level of activation regulates the trafficking of HSPCs and most likely maintains their pool in the bone marrow, hyperactivation may lead to irreversible cell damage by pyroptosis and HSPC senescence and contribute to the origination of myelodysplasia and hematopoietic malignancies.

Summary
Modulation of the level of Nrp3 inflammasome activation will enable improvements in HSPC mobilization, homing, and engraftment strategies. It may also control pathological activation of this protein complex during HSPC senescence, graft-versus-host disease, the induction of cytokine storms, and the development of hematopoietic malignancies.
Validity and Diagnosis in Physical and Rehabilitation Medicine
Authors: Hassan Samah , Kumbhare Dinesh 
Published: April 2021

AbstractObtaining a diagnosis is an essential and integral part of physical and rehabilitation medicine in practice and research. Standardized psychometric properties are required of any classifications, diagnostic criteria, and diagnostic rules used. Physicians and researchers, in physical and rehabilitation medicine, need to understand these properties to determine the accuracy and consistency of their diagnosis. Although chronic musculoskeletal pain disorders are among the highly prevalent disorders seen in physical and rehabilitation medicine, limitations regarding existing diagnostic criteria for chronic musculoskeletal pain disorders still exist. Hence, the quest for developing diagnostic tools for chronic musculoskeletal pain that align with the standard properties remains open. These are discussed with an example for existing diagnostic criteria for fibromyalgia. This article primarily aimed to provide an overview of standard psychometric properties. A secondary aim was to critically appraise the tools currently used to diagnose chronic musculoskeletal pain disorders. The challenges and limitations of existing diagnostic tools are discussed. Potential approaches on how to improve the conceptualization of the construct of musculoskeletal pain disorders are also discussed. Adopting a network perspective, for example, can better constitute the disease instead of a single known underlying etiology for persistent or recurrent pain symptoms.