bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors for Contralateral Slipped Capital Femoral Epiphysis: A Meta-analysis of Cohort and Case-control Studies
Authors: Swarup Ishaan , Goodbody Christine , Goto Rie , Sankar Wudbhav N. , Fabricant Peter D. 
Published: December 2019

Background:
Slipped capital femoral epiphysis (SCFE) is an important cause of hip pain and disability in pediatric patients. SCFE occurs bilaterally in 12% to 80% of cases, and the risk of contralateral SCFE is noted to be 2335 times higher than the index SCFE. Several studies have reported risk factors for contralateral SCFE; however, these studies have not been systematically analyzed. The purpose of this systematic review and meta-analysis was to review and analyze risk factors for subsequent contralateral SCFE and identify the strongest risk factors for a subsequent slip.

Methods:
A systematic review was performed of all observational studies focusing on risk factors for subsequent contralateral SCFE indexed in Medline, Embase, and Cochrane databases. Data extraction was performed and summarized using descriptive statistics. Meta-analysis was performed for risk factors with sufficient constituent study data. Quality assessment was performed using the Newcastle-Ottawa Scale, and funnel plots were generated to assess publication bias.

Results:
The initial search strategy identified 226 references, and after exclusions, 20 studies were included in this analysis. Demographic risk factors included age, sex, weight, body mass index, ethnicity, and urban/rural residence; clinical risk factors included endocrine abnormality, duration of symptoms, slip stability, and slip chronicity; and radiographic risk factors included slip angle, triradiate cartilage, alpha angle, posterior sloping angle (PSA), physeal sloping angle, modified Oxford score, and bone age. Younger patient age, body mass index≥95th percentile, presence of an endocrine abnormality, higher PSA of the unaffected hip, and lower modified Oxford score have been noted to be significant risk factors for contralateral SCFE. Meta-analysis showed that younger age (−0.9; confidence interval, −1.1, −0.6), and higher PSA (4.7 degrees; 95% confidence interval, 3.3-6.2 degrees) of the unaffected hip were predictive of subsequent contralateral SCFE. The majority of studies were of good quality.

Conclusion:
There are several risk factors for subsequent contralateral SCFE. On the basis of the available data, younger patients with a high PSA of the unaffected hip would most likely benefit from prophylactic fixation of the unaffected hip.

Level of Evidence:
Level II.
Prospective Evaluation of a Treatment Protocol Based on Fracture Displacement for Pediatric Lateral Condyle Humerus Fractures: A Preliminary Study
Authors: Nazareth Alexander , VandenBerg Curtis D. , Sarkisova Natalya , Goldstein Rachel Y. , Andras Lindsay M. , Lightdale-Miric Nina R. , Pace James Lee , Skaggs David L. 
Published: December 2019

Background:
To prospectively evaluate a displacement-based classification system and an outcome-derived algorithm in the treatment of children with lateral condyle fractures.

Methods:
All children with a lateral condyle fracture were prospectively enrolled at our institution between 2013 and 2016. Fractures were classified and treated on the basis of the following classification system: type 1: <2 mm; treated with long arm casting, type II: 2 to 4 mm; treated with closed reduction and percutaneous pinning (CRPP), and type III: >4 mm; open reduction and percutaneous pinning (ORPP). Functional outcomes were assessed at 6 to 12 weeks and at 1-year follow-ups using the Pediatric Outcomes Data Collection Instrument (PODCI).

Results:
A total of 55 patients (mean age, 6 y; range 2 to 12 y) were prospectively enrolled. There were 17 (31%) type I fractures treated with a long arm cast, 8 (15%) type II treated with CRPP, and 30 (54%) type III treated with ORPP. Postoperative complications included delayed union (N=5) and pin site infection (N=3). Delayed unions on the basis of fracture type was type I (1/17, 6%), type II (1/8, 13%), and type III (3/30, 10%) (P=0.85). The rate of delayed unions in type II and III fractures fixed with k-wires was 11% (4/38). Four patients required a second operation with screw fixation. No significant differences were found across PODCI domains at 1-year follow-up when comparing our study population with normative data.

Conclusions:
This is the first prospective study of a treatment protocol for pediatric lateral condyle fractures and validates the use of displacement as a guide for best evidence-based treatment. Children with a lateral condyle fracture can achieve excellent functional outcomes in all classification types with comparable complication rates when radiographic fracture displacement is used to guide surgical and clinical decision making.

Level of Evidence:
Level II.
Senotherapeutics for HIV and aging
Authors: Szaniawski Matthew A. , Spivak Adam M. 
Published: December 2019

Purpose of review
To summarize the state of chronic, treated HIV infection and its contribution to accelerated aging, and to evaluate recent research relevant to the study and treatment of aging and senescence.

Recent findings
Chronic treated HIV-1 infection is associated with significant risk of end-organ impairment, non-AIDS-associated malignancies, and accelerated physiologic aging. Coupled with the chronologic aging of the HIV-1-positive population, the development of therapies that target these processes is of great clinical importance. Age-related diseases are partly the result of cellular senescence. Both immune and nonimmune cell subsets are thought to mediate this senescent phenotype, a state of stable cell cycle arrest characterized by sustained release of pro-inflammatory mediators. Recent research in the field of aging has identified a number of ‘senotherapeutics’ to combat aging-related diseases, pharmacologic agents that act either by selectively promoting the death of senescent cells (‘senolytics’) or modifying senescent phenotype (‘senomorphics’).

Summary
Senescence is a hallmark of aging-related diseases that is characterized by stable cell cycle arrest and chronic inflammation. Chronic HIV-1 infection predisposes patients to aging-related illnesses and is similarly marked by a senescence-like phenotype. A better understanding of the role of HIV-1 in aging will inform the development of therapeutics aimed at eliminating senescent cells that drive accelerated physiologic aging.
A Review of Imaging Biomarkers of the Ocular Surface
Authors: Binotti William W. , Bayraktutar Betul , Ozmen M. Cuneyt , Cox Stephanie M. , Hamrah Pedram 
Published: December 2019

Abstract:
A biomarker is a “characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions.” Recently, calls for biomarkers for ocular surface diseases have increased, and advancements in imaging technologies have aided in allowing imaging biomarkers to serve as a potential solution for this need. This review focuses on the state of imaging biomarkers for ocular surface diseases, specifically non-invasive tear break-up time (NIBUT), tear meniscus measurement and corneal epithelial thickness with anterior segment optical coherence tomography (OCT), meibomian gland morphology with infrared meibography and in vivo confocal microscopy (IVCM), ocular redness with grading scales, and cellular corneal immune cells and nerve assessment by IVCM. Extensive literature review was performed for analytical and clinical validation that currently exists for potential imaging biomarkers. Our summary suggests that the reported analytical and clinical validation state for potential imaging biomarkers is broad, with some having good to excellent intra- and intergrader agreement to date. Examples of these include NIBUT for dry eye disease, ocular redness grading scales, and detection of corneal immune cells by IVCM for grading and monitoring inflammation. Further examples are nerve assessment by IVCM for monitoring severity of diabetes mellitus and neurotrophic keratitis, and corneal epithelial thickness assessment with anterior segment OCT for the diagnosis of early keratoconus. However, additional analytical validation for these biomarkers is required before clinical application as a biomarker.
Biophysical Agent Curriculum in Entry-Level Physical Therapist Education Programs Across the United States: A Survey
Authors: Greco Jamie L. , Lamberg Eric M. 
Published: December 2019

Introduction:
The literature supporting the use of biophysical agents (BPAs) for patient care in Physical Therapy is conflicting. Although some guidelines exist, the academic institution makes decisions as to which individual BPAs are included in the Doctor of Physical Therapy curriculum. This study investigated current BPA curricular content in physical therapist education programs.

Subjects/Methods:
Two hundred thirty-eight emails were sent to program directors and/or individuals with an identified role of teaching BPAs at accredited physical therapist education programs across the United States. Eighty-six people completed the survey (response rate 35%). The survey consisted of 4 sections: instructor demographics (teaching responsibilities and role), institutional demographics (geographical location, and cohort size), curricular content (timing of course, contact hours, curricular changes, student assessment, and importance of BPA inclusion), and one open-ended response question.

Results:
For most programs, BPA is a stand-alone course (72.3%) taught in the first year of curriculum (72.0%). The most common instructional method included a combination of lecture and laboratory (89.2%). A combined percentage of 77% of respondents reported changes to the BPA curriculum in the past 5 years (ie, decrease in contact hours, change in content, or change in delivery method).

Discussion and Conclusion:
Evidence and clinical practice patterns were referenced by respondents as factors contributing to changes. Certain BPAs are taught using multiple methods, assessed in a variety of ways, and perceived by instructors to be more important to include in the curriculum than others. In addition, there is variation among BPAs regarding the expected levels of competency for students. Overall, the extent to which each BPA is taught in physical therapist education program curriculum aligns with current need for instruction in safe, appropriate operation and clinical usage. However, educators need to be cognizant of both clinical practice patterns and changing evidence and to be willing to alter curriculum as needed to graduate competent physical therapists.
Relevance of Microvascular Flow Assessments in Critically Ill Neonates and Children: A Systematic Review
Authors: Maitoza Laura A. , Neeman Eitan , Funaro Melissa , Pierce Richard W. 
Published: December 2019

Objectives:
Resolution of impaired microvascular flow may lag the normalization of macrocirculatory variables. The significance of microcirculatory dysfunction in critically ill children and neonates is unknown, but microcirculatory variables can be measured using Doppler or videomicroscopy imaging techniques. We outline the current understanding of the role of the microcirculation in critical illness, review methods for its assessment, and perform a systematic review of how it has been monitored in critically ill neonates and children.

Design:
Systematic review (PROSPERO CRD42019117993).

Setting:
Not applicable.

Subjects:
Not applicable.

Interventions:
None.

Measurements and Results:
We systematically searched MEDLINE, EMBASE, PubMed, and Web of Science. We included studies of critically ill patients 0 to 18 years old investigating microcirculatory blood flow. Two reviewers analyzed abstracts and articles. Results were qualitatively analyzed due to study heterogeneity. A total of 2,559 abstracts met search criteria, of which 94 underwent full-text review. Of those, 36 met inclusion criteria. Seven studies investigated microcirculatory changes in critically ill children. Twenty studies investigated the microcirculatory changes in neonates with variable diagnoses compared with a diverse set of clinical endpoints. Nine studies assessed the effects of age, sex, and birth weight on microvascular flow in neonates. Across all studies, microcirculatory dysfunction was associated with poor outcomes and may not correlate with observed macrovascular function.

Conclusions:
Assessment of microvascular flow in critically ill children and neonates is possible, although significant challenges remain. In many such patients, microvascular blood flow is disrupted despite medical management targeting normalized macrovascular variables. Future studies are needed to define normal pediatric microvascular flow variables and to assess the impact of patient and treatment factors on its function.
Using the North Dakota IIS to Assess the Response of Health Care Providers to the ACIP Recommendation for Tdap Vaccination During Pregnancy
Authors: Woinarowicz Mary , Howell Molly 
Published: December 2019

Objectives:
To evaluate the response of North Dakota health care providers to follow the recommendation set forth by the Advisory Committee on Immunization Practices (ACIP) to administer a dose of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine to women during each pregnancy using the North Dakota Immunization Information System (NDIIS).

Methods:
Data from the NDIIS for North Dakota infants born during calendar years 2013-2018 were extracted. Mother's name was taken from the newborn records and matched to NDIIS female client records to identify the population of mothers of newborns who would have been recommended to receive Tdap during their pregnancy. Doses of Tdap vaccine administered after October 1, 2012, were extracted from the NDIIS, and the dose records were matched back to the mother's record. The time from baby's birthdate back to the doses of Tdap vaccine administered to the mother was measured to find any doses that would have been administered during pregnancy.

Results:
The percentage of women receiving Tdap vaccine during pregnancy increased from 31.5% in 2013 to 60.6% in 2018. Of those women who received Tdap during pregnancy, 94% received the vaccine during the ACIP-recommended interval of 27 to 36 weeks' gestation, using the assumption that all babies were born at 40 weeks' gestation.

Conclusions:
North Dakota health care providers have responded positively to the recommendation of the ACIP to administer a dose of Tdap vaccine to women during each pregnancy and have increased their administration of the vaccine to their patients.
Semantic Enrichment of Streaming Healthcare Data
Authors: Cotter Daniel , Bumgardner V. K. Cody 
Published: December 2019

AbstractIn the past decade, the healthcare industry has made significant advances in the digitization of patient information. However, a lack of interoperability among healthcare systems still imposes a high cost to patients, hospitals, and insurers. Currently, most systems pass messages using idiosyncratic messaging standards that require specialized knowledge to interpret. This increases the cost of systems integration and often puts more advanced uses of data out of reach. In this project, we demonstrate how two open standards, FHIR and RDF, can be combined both to integrate data from disparate sources in real time and make that data queryable and susceptible to automated inference. To validate the effectiveness of the semantic engine, we perform simulations of real-time data feeds and demonstrate how they can be combined and used by client-side applications with no knowledge of the underlying sources.
The influence of common polygenic risk and gene sets on social skills group training response in autism spectrum disorder
Authors: Li Danyang , Choque-Olsson Nora , Jiao Hong , Norgren Nina , Jonsson Ulf , Bölte Sven , Tammimies Kristiina 
Published: December 2019

AbstractSocial skills group training (SSGT) is one of the most frequently used behavior interventions in children and adolescents with autism spectrum disorder (ASD). Current evidence suggests that the effects are moderate and heterogeneous. Genetic predisposition could be one of the factors contributing to this heterogeneity. Therefore, we used polygenic risk score (PRS) and gene-set analysis to investigate the association between SSGT response and common variants in autistic individuals. Participants from the largest randomized clinical trial of SSGT in ASD to date were selected for genotyping. Polygenic risk scores (PRSs) for ASD, attention deficit hyperactivity disorder (ADHD), and educational attainment (EA) were calculated, and their associations with the intervention outcome at post-intervention and follow-up were tested using mixed linear model. In addition, thirty-two gene sets within five categories (synaptic, glial, FMRP, glutamate, and mitochondrial) were selected to evaluate their role in the intervention outcome. Individuals with higher PRSs for ASD and ADHD had inferior response after SSGT. After multiple test correction, significant results were kept for higher ADHD PRS at follow-up (β = 6.67, p = 0.016). Five gene sets within synaptic category showed modest association with reduced response to SSGT in ASD. Taken together, we provided preliminary evidence that genetic liability calculated using PRS and common variants in synapse gene sets could influence the outcome of SSGT. Our results hold promise for future research into the genetic contribution to individual response to ASD interventions, and should be validated in larger cohorts.
Ratiometric quorum sensing inEnterococcus faecalisconjugation
Authors: Banderas Alvaro , Carcano Arthur , Sina Elisa , Li Shuang , Lindner Ariel B. 
Published: December 2019

AbstractPlasmid-mediated horizontal gene transfer of antibiotic-resistance and virulence in pathogenic bacteria underlies a major public health issue. Understanding how, in the absence of antibiotic-mediated selection, plasmid-bearing cells avoid being outnumbered by plasmid-free cells, is key to developing counter strategies. Here we quantified the induction ofEnterococcus faecalis’ plasmidial sex-pheromone pathway to show that the integration of the stimulatory (mate-sensing) and inhibitory (self-sensing) signaling modules from the pCF10 conjugative plasmid, provides a precise measure of the recipient-to-donor ratio, agnostic to variations in population size. Such ratiometric control of conjugation favors vertical plasmid-transfer under low mating likelihood and allows activation of conjugation functions only under high mating likelihood. We further show that this strategy constitutes a cost-effective investment into mating effort, as overstimulation produces unproductive self-aggregation and reductions in the growth rate. A mathematical model suggests that ratiometric control of conjugation limits the spread of antibiotic resistance in absence of antibiotics, predicting a long-term stable co-existence of donors and recipients. Our results demonstrate how population-level parameters can control transfer of antibiotic-resistance in bacteria, opening the door for biotic control strategies. Ratiometric sensing in bacteria mirrors sexual behaviors observed in eukaryotes.
Systems genetics analysis identify calcium signalling defects as novel cause of congenital heart disease
Authors: Izarzugaza Jose M.G. , Ellesøe Sabrina G. , Doganli Canan , Ehlers Natasja Spring , Dalgaard Marlene D. , Audain Enrique , Dombrowsky Gregor , Sifrim Alejandro , Wilsdon Anna , Thienpont Bernard , Breckpot Jeroen , Gewillig Marc ,   Competence Network for Congenital Heart Defects, Germany, Brook J. David , Hitz Marc-Phillip , Larsen Lars A. , Brunak Søren 
Published: December 2019

AbstractBackgroundCongenital heart disease (CHD) occurs in almost 1% of newborn children and is considered a multifactorial disorder. CHD may segregate in families due to significant contribution of genetic factors in the disease aetiology. The aim of the study was to identify pathophysiological mechanisms in families segregating CHD.MethodsWe used whole exome sequencing to identify rare genetic variants in ninety consenting participants from 32 Danish families with recurrent CHD. We applied a systems biology approach to identify developmental mechanisms influenced by accumulation of rare variants. We used an independent cohort of 714 CHD cases and 4922 controls for replication and performed functional investigations using zebrafish asin vivomodel.ResultsWe identified 1,785 genes, in which rare alleles were shared between affected individuals within a family. These genes were enriched for known cardiac developmental genes and 218 of the genes were mutated in more than one family. Our analysis revealed a functional cluster, enriched for proteins with a known participation in calcium signalling. Replication confirmed increased mutation burden of calcium-signalling genes in CHD patients. Functional investigation of zebrafish orthologues ofITPR1,PLCB2andADCY2verified a role in cardiac development and suggests a combinatorial effect of inactivation of these genes.ConclusionsThe study identifies abnormal calcium signalling as a novel pathophysiological mechanism in human CHD and confirms the complex genetic architecture underlying CHD.
Combining genotype, phenotype, and environmental data to delineate site-adjusted provenance strategies for ecological restoration
Authors: Carvalho Carolina S. , Forester Brenna R. , Mitre Simone K. , Alves Ronnie , Imperatriz-Fonseca Vera L. , Ramos Silvio J. , Resende-Moreira Luciana C. , Siqueira José O. , Trevelin Leonardo C. , Caldeira Cecilio F. , Gastauer Markus , Jaffé Rodolfo 
Published: December 2019

AbstractDespite the importance of climate-adjusted provenancing to mitigate the effects of environmental change, climatic considerations alone are insufficient when restoring highly degraded sites. Here we propose a comprehensive landscape genomic approach to assist the restoration of moderately disturbed and highly degraded sites. To illustrate it we employ genomic datasets comprising thousands of single nucleotide polymorphisms from two plant species suitable for the restoration of iron-rich Amazonian Savannas. We first use a subset of neutral loci to assess genetic structure and determine the genetic neighborhood size. We then identify genotype-phenotype-environment associations, map adaptive genetic variation, and predict adaptive genotypes for restoration sites. Whereas local provenances were found optimal to restore a moderately disturbed site, a mixture of genotypes seemed the most promising strategy to recover a highly degraded mining site. We discuss how our results can help define site-adjusted provenancing strategies, and argue that our methods can be more broadly applied to assist other restoration initiatives.