bluuebunny/crossref_metadata_2025_split huggingface dataset:
Missed diagnosis of lissencephaly after prenatal diagnosis: A case report
Authors: Liu Mengna , Liu Xiao , Wu Jiebin , Sha Jing , Zhai Jingfang , Zhang Bei 
Published: February 2023

Rationale:
Lissencephaly (LIS) is a rare and serious cortical malformation characterized by a smooth or nearly smooth brain surface. With the progress of molecular genetics, platelet-activating factor acetylhydrolase brain isoform Ib is the most frequent type during the fetal period. Here, we report an infant with LIS who was missed although undergoing prenatal diagnosis. We aim to share our experiences and lessons.

Patient concerns:
A 2-month-old male infant presented recurrent convulsions. Karyotype and copy number variation sequencing were conducted to be normal at the 23-week gestation because of bipedal varus and ventricular septal defect (2.3 mm). After birth, he suffered from epilepsy confirmed by video electroencephalogram exam, meanwhile, computed tomography and magnetic resonance imaging revealed pachygyria. The infant was diagnosed with LIS carrying a de-novo mutation c.817 C > T (p.Arg273 Ter,138) in exon 8 of platelet-activating factor acetylhydrolase brain isoform Ib (NM_000430) detected by whole-exome sequencing.

Diagnoses:
Based on the clinical characteristics, imaging, and genetic test findings, the infant was diagnosed with LIS.

Interventions:
The patient was treated with topiramate and dose was adjusted according to the seizure frequency.

Outcomes:
The infant had recurrent seizures. The muscle tone of his extremities increased, and he could not look up or turn over actively at the age of 6 months.

Lessons:
Comprehensive evaluation of a multi-disciplinary team should be recommended for patients with epilepsy and cerebral hypoplasia. Individuals with LIS during the fetal period might be missed due to atypical features. In fetuses with structural abnormalities, if karyotype and copy number variation sequencing are both normal, whole-exome sequencing may be an effective complementary means to detect pathogenic variants.
Pneumatosis Intestinalis in Children With Intestinal Failure: The Result of Intestinal Stress From Enteral Feeding?
Authors: Reppucci Marina L. , Nolan Margo M. , Cooper Emily , Gallagher Lauren T. , Diaz-Miron Jose , Somme Stig , Soden Jason , Gumer Lindsey , Acker Shannon N. 
Published: February 2023

Objective:
The incidence and significance of pneumatosis intestinalis (PI) in children with a diagnosis of intestinal failure is not well understood. The aim of this study was to identify clinical and anatomical factors associated with the imaging findings of PI in patients with intestinal failure.

Methods:
We performed a retrospective review of all children with a diagnosis of intestinal failure at Children’s Hospital Colorado between January 2019 and April 2022. Patients were stratified and compared based on the incidence of PI on abdominal imaging. Differences were compared using 2-sample Wilcoxon tests, chi-square, or Fisher exact tests.

Results:
There were 111 patients identified with a diagnosis of intestinal failure and 30.6% (34) developed at least 1 instance of PI. There were no differences in etiology of intestinal failure or anatomy between those who developed PI and those who did not. Patients who developed PI, were less likely to be on total parental nutrition (60.6% vs 98.6%, P < 0.001) and more likely to be receiving any form of enteral feeds (87.9% vs 66.2%, P = 0.035) or tube feeds (75.8% vs 44.2%, P = 0.0045). Of the children with PI, 30.3% (10) were undergoing an enteral feed advancement at time of PI development. Three patients with PI underwent laparotomy for PI treatment, 2 of which were negative laparotomies.

Conclusions:
The development of PI in children with intestinal failure is likely a benign finding. It is associated with enteral feeding and may be due to increased intestinal stress.
Demonstrating the Value of the Clinical Nurse Specialist
Authors: Fischer-Cartlidge Erica , Hoffman Megan 
Published: February 2023

Purpose/Objectives
The purpose of this article is to provide a guide to identifying measurements of value and how to calculate different types of return on investment (ROI). Exemplars of clinical nurse specialist (CNS) work efforts with ROI will be presented.

Description of the Project/Problem
The CNS is the oldest advanced practice role; however, the role can be vague, making it difficult to articulate the value of the CNS in the organization. Functioning in 3 spheres of impact, the CNS can easily impact practice; however, demonstrating the value of this work is not always on top of mind and is rarely taught in academic programs.

Outcome
This article describes the difference between revenue generation, cost savings, and cost avoidance, as well as various structural, process, and outcome measures that can be used to calculate ROI. Resources available for performing ROI calculations will be described and shared.

Conclusion
Distributing work across the 3 spheres creates various opportunities for the CNS to demonstrate value; however, the CNS must be able to articulate that value to the organization. Developing the skill set to consistently identify metrics can be challenging; however, it is critical to the ongoing success and future of the CNS role. Utilizing these metrics to demonstrate the value and then disseminating the outcomes of these contributions will continue to promote the value of the CNS in the future.
HIV-PASS (Pain and Sadness Support): Randomized Controlled Trial of a Behavioral Health Intervention for Interference Due to Pain in People Living With HIV, Chronic Pain, and Depression
Authors: Uebelacker Lisa A. , Pinkston Megan M. , Busch Andrew M. , Baker Jason V. , Anderson Bradley , Caviness Celeste M. , Herman Debra S. , Weisberg Risa B. , Abrantes Ana M. , Stein Michael D. 
Published: February 2023

ABSTRACT

Objective
This study aimed to determine whether HIV-Pain and Sadness Support (HIV-PASS), a collaborative behavioral health intervention based on behavioral activation, is associated with decreased pain-related interference with daily activities, depression, and other outcomes in people living with HIV.

Methods
We conducted a three-site clinical trial (n = 187) in which we randomly assigned participants to receive either HIV-PASS or health education control condition. In both conditions, participants received seven intervention sessions, comprising an initial in-person joint meeting with the participant, their HIV primary care provider and a behavioral health specialist, and six, primarily telephone-based, meetings with the behavioral health specialist and participant. The intervention period lasted 3 months, and follow-up assessments were conducted for an additional 9 months.

Results
Compared with health education, HIV-PASS was associated with significantly lower pain-related interference with daily activities at the end of month 3 (our primary outcome; b = −1.31, 95% confidence interval = −2.28 to −0.34). We did not observe other differences between groups at 3 months in secondary outcomes that included worst or average pain in the past week, depression symptoms, anxiety, and perceived overall mental and physical health. There were no differences between groups on any outcomes at 12 months after enrollment.

Conclusions
A targeted intervention can have positive effects on pain interference. At the end of intervention, effects we found were in a clinically significant range. However, effects diminished once the intervention period ended.

Trial Registration

ClinicalTrials.gov NCT02766751.
Resistance-minimizing strategies for introducing a novel antibiotic for gonorrhea treatment: a mathematical modeling study
Authors: Reichert E , Yaesoubi R , Rönn MM , Gift TL , Salomon JA , Grad YH 
Published: February 2023

AbstractBackgroundGonorrhea is a highly prevalent sexually transmitted infection and an urgent public health concern due to increasing antibiotic resistance. Only ceftriaxone remains as the recommended treatment in the U.S. The prospect of approval of new anti-gonococcal antibiotics raises the question of how to deploy a new drug to maximize its clinically useful lifespan.MethodsWe used a compartmental model of gonorrhea transmission in the U.S. population of men who have sex with men to compare strategies for introducing a new antibiotic for gonorrhea treatment. The strategies tested included holding the new antibiotic in reserve until the current therapy reached a threshold prevalence of resistance; using either drug, considering immediate and gradual introduction of the new drug; and combination therapy. The primary outcome of interest was the time until 5% prevalence of resistance to both the novel drug and to the current first-line drug (ceftriaxone).FindingsThe reserve strategy was consistently inferior for mitigating antibiotic resistance under the parameter space explored. The reserve strategy was increasingly outperformed by the other strategies as the probability ofde novoresistance emergence decreased and as the fitness costs associated with resistance increased. Combination therapy tended to prolong the development of antibiotic resistance and minimize the number of annual gonococcal infections.InterpretationOur study argues for rapid introduction of new anti-gonococcal antibiotics, recognizing that the feasibility of each strategy must incorporate cost, safety, and other practical concerns. The analyses should be revisited once robust estimates of key parameters–likelihood of emergence of resistance and fitness costs of resistance for the new antibiotic–are available.FundingU.S. Centers for Disease Control and Prevention (CDC), National Institute of Allergy and Infectious Diseases
Large-scale empirical identification of candidate comparators for pharmacoepidemiological studies
Authors: Bohn Justin , Gilbert James P. , Knoll Christopher , Kern David M. , Ryan Patrick B. 
Published: February 2023

ABSTRACTObjectivesThe new user cohort design has emerged as a best practice for the estimation of drug effects from observational data. However, despite its advantages, this design requires the selection and evaluation of comparators for appropriateness, a process which can be challenging. In this paper, we introduce an empirical approach to rank candidate comparators in terms of their similarity to a target drug in high-dimensional covariate space.MethodsWe generated new user cohorts for each RxNorm ingredient in five administrative claims databases, then extracted aggregated pre-treatment covariate data for each cohort across five clinically oriented domains. We formed all pairs of cohorts with ≥ 1,000 patients and computed a scalar similarity score, defined as the average of cosine similarities computed within each domain, for each pair. Ranked lists of candidate comparators were then generated for each cohort.ResultsAcross up to 1,350 cohorts forming 922,761 comparisons, drugs that were more similar in the ATC hierarchy had higher cohort similarity scores. The most similar candidate comparators for each of six example drugs corresponded to alternative treatments used in the target drug’s indication(s), and choosing the top-ranked comparator for randomly selected drugs tended to produce balance on a majority of covariates. This approach also ranked highly those comparators chosen in high quality published new user cohort design studies.ConclusionEmpirical comparator recommendations may serve as a useful aid to investigators and could ultimately enable the automated generation of new user cohort design-derived evidence, a process that has previously been limited to self-controlled designs.KEY POINTSEmpirical comparator recommendations based on similarity to a target cohort’s covariate profile can aid investigators in study design and align with subject matter knowledge and published literature.
BIOMARKERS OF AIRWAY INFLAMMATION AND ASTHMA SYMPTOM CONTROL IN CHILDREN
Authors: Alieva J.S. , Furman E.G. , Khuzina E.A. , Abdrakhmanova S.T. , Ponomareva M.S. , Sheludko V.S. , Sokolovsky V.L. 
Published: February 2023

AbstractINTRODUCTIONBronchial asthma (BA) is a heterogeneous pulmonary disease with various phenotypes based on detection of multiple biomarkers. However, most of the biomarkers are still experimental and present limitations for clinical practice.OBJECTIVEThe purpose of this study was to investigate the relationship between the level of the available T2-inflammatory biomarkers in childhood with poor asthma control and features of asthma management.MATERIAL AND METHODSThe study comprised 100 patients aged 5–17 years (median age 13 years) with an established bronchial asthma diagnosis. The level of asthma control of each patient was assessed by the Asthma Control Test (ACT and C-ACT) and the Composite Asthma Severity Index (CASI). T2-inflammatory biomarkers of the mucous membranes of the respiratory tract include total immunoglobulin E (IgE total) levels, peripheral blood eosinophil levels, fractional exhaled nitric oxide (FeNO) and a nasal smear eosinophil count. A measure of association was determined by standard statistical methods for data analysis.RESULTSDespite the prescribed basic therapy, the majority of children do not achieve adequate asthma symptom control. This research revealed that 43% of patients had at least one or more elevated markers of T2-inflammation. High levels of IgE total, increased levels of blood eosinophils (≥400 cells/µL), as well as high FeNO values (≥ 20 ppb) prevail in children with partially controlled and uncontrolled asthma. The most significant biomarker of poor asthma control in children is the total serum IgE concentration ≥ 100 IU/ml. In addition, a significant positive correlation was found between peripheral blood eosinophil levels and the ACT/C-ACT scores (r=0.287, p=0.0039).CONCLUSIONAllergic asthma in children is typically associated with Th2-lymphocytes predominance and eosinophilic airway inflammation. T2-inflammatory biomarkers may be useful in assessing airway inflammation activity and asthma-control assessment in children.
Maternal diabetes and overweight as risk factors for congenital heart defects in offspring - A nationwide register study from Finland
Authors: Turunen R , Pulakka A , Metsälä J , Vahlberg T , Ojala T , Gissler M , Kajantie E , Helle E 
Published: February 2023

AbstractImportanceCongenital heart defects (CHDs) affect 1–2% of newborns and are associated with significant mortality and morbidity. Understanding risk factors underlying CHDs is essential for prevention.ObjectiveTo determine the association between maternal diabetes and overweight/obesity and CHDs among offspring.DesignNationwide population-based register study.SettingFinlandParticipantsAll children born between 2006–2016 (N=620 751), and their mothers.ExposuresMaternal pre-pregnancy body mass index (BMI) categorized as underweight (<18.5 kg/m2), normal (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30 kg/m2). Maternal diabetes classified as no diabetes, type 1 (T1DM), type 2/other (T2DM), and gestational diabetes (GDM).Main Outcomes and MeasuresOdds ratio (OR) of isolated CHD in the child. In addition, nine anatomical CHD subgroups were studied.ResultsOf the 620 751 children born in Finland during the study period, 10 254 (1.65%) had an isolated CHD. T1DM was associated with an increased risk of having a child with any CHD (OR 3.71 (95% CI 3.16–4.35)), whereas maternal overweight (OR 0.98 (95% CI 0.98–1.04)) and obesity (OR 1.00 (95% CI 0.93–1.07)) were not. When analyzing anatomical subgroups, T1DM was associated with an increased risk in six subgroups. Maternal overweight was associated with complex defects (OR 2.24 (95% CI 1.01–4.94)), left ventricular outflow tract obstruction (OR 1.26, (95% CI 1.07–1.49), maternal obesity with complex defects (OR 3.22 (95% CI 1.31–7.92)), and right ventricular outflow tract obstruction (OR 1.26, (95% CI 1.01–1.55)). At the population level, maternal diabetes was responsible for 3.0% and maternal overweight and obesity for 0.7% of offspring’s CHD.Conclusions and RelevanceThis study indicated a less profound association between maternal overweight and obesity and CHD in the offspring than previously reported. The different risk profiles of T1DM and overweight/obesity may suggest distinct underlying teratogenic mechanisms.
Clinical, biochemical and molecular analysis in a cohort of individuals with gyrate atrophy
Authors: Palmer Eleanor , Stepien Karolina M. , Campbell Christopher , Barton Stephanie , Ghosh Arunabha , Broomfield Alexander , Woodall Alison , Wilcox Gisela , Sergouniotis Panagiotis I. , Black Graeme C. 
Published: February 2023

ABSTRACTBackgroundGyrate atrophy of the choroid and retina is a rare autosomal recessive metabolic disorder caused by biallelic variants in theOATgene, encoding the enzyme ornithineƍ-aminotransferase. Impaired enzymatic activity leads to systemic hyperornithaemia, which in turn underlies progressive chorioretinal degeneration. In this study, we describe the clinical and molecular findings in a cohort of individuals with gyrate atrophy.MethodsStudy participants were recruited through a tertiary UK clinical ophthalmic genetic service. All cases had a biochemical and molecular diagnosis of gyrate atrophy. Retrospective phenotypic and biochemical data were collected using electronic healthcare records.Results18 affected individuals from 12 families (8 male, 12 female) met the study inclusion criteria. The median age at diagnosis was 8 years (range 10 months – 33 years) and all cases had hyperornithaemia (median: 800 micromoles/L; range: 458-1244 micromoles/L). Common features at presentation included high myopia (10/18) and nyctalopia (5/18). Ophthalmic findings were present in all study participants who were above the age of 6 years. One third of patients had co-existing macular oedema and two thirds developed pre-senile cataracts. Compliance with dietary modifications was suboptimal in most cases. A subset of participants had extraocular features including a trend towards reduced fat-free mass and developmental delay.ConclusionsOur findings highlight the importance of multidisciplinary care in families with gyrate atrophy. Secondary ophthalmic complications such as macular oedema and cataract formation are common. Management of affected individuals remains challenging due to the highly restrictive nature of the recommended diet and the limited evidence-base for current strategies.
“I felt shamed and blamed”: An exploration of the parental lived experience of School Distress
Authors: Mullally Sinéad L. , Connolly Sophie E. 
Published: February 2023

ABSTRACTSchool Distress refers to a child or young person’s (CYP) difficulty attending school due to the extreme emotional distress they experience before/during/after school. Limited research exists on the impact of School Distress on the parents/carers supporting these CYP. Using a case–control, concurrent embedded mixed-method design, we explored this lived experience. 947 parents of CYP with School Distress completed a bespoke online questionnaire, alongside two control parent groups (n=149, n=25) and one professional group (n=19).Findings revealed a devastating impact on the mental health of parents, with parents displaying significantly heightened daily anxiety and significantly lower mood during, but not before, their children’s school attendance difficulties. In addition, parents with children experiencing School Distress reported significantly more negative emotion states and significantly fewer positive emotion states. Parents also reported overwhelmingly negative treatment from professionals, including being disbelieved or blamed for their children’s difficulties, threatened with fines and court action, and disempowered by the actions of professionals surrounding their child. Significant, deleterious impacts were also evident across all aspects of their lives, including their careers, finances, and other children. Perhaps unsurprisingly, half of these parents reported developing a new mental health condition since their child’s difficulties began, with the experience itself rated as the second most threatening potential life event, superseded only by the death of a first-degree relative (including a child or spouse). On the other hand, professionals working with CYP with School Distress did not experience these deleterious mental health or wider life consequences. Despite understanding how threatening the experience is for parents, they were often quick to blame parents for their children’s difficulties. Professionals, like parents, expressed frustration with the lack of help available for these CYP and their families.This study highlights a bleak, adversarial, and lonely picture for parents of CYP struggling to attend school. More specifically, the findings depict a system rife with parental blame; a system that appears to isolate parents through hostile, threatening, and punitive actions. A wider lack of societal understanding of the experience of School Distress further compounds this dearth of support for parents, placing parental mental health in further peril.
Genome-wide Association Study of Traumatic Brain Injury in U.S. Military Veterans Enrolled in the VA Million Veteran Program
Authors: Merritt Victoria C. , Maihofer Adam X. , Gasperi Marianna , Ketema Elizabeth , Chanfreau-Coffinier Catherine , Stein Murray B. , Panizzon Matthew S. , Hauger Richard L. , Logue Mark W. , Delano-Wood Lisa , Nievergelt Caroline M. 
Published: February 2023

AbstractLarge-scale genetic studies of traumatic brain injury (TBI) are lacking; thus, our understanding of the influence of genetic factors on TBI risk and recovery is incomplete. This study aimed to conduct a genome-wide association study (GWAS) of TBI in VA Million Veteran Program enrollees. Participants included a multi-ancestry cohort (European, African, and Hispanic ancestries; N=304,485; 111,494 TBI cases, 192,991 controls). TBI was assessed using MVP survey data and ICD codes from the Veterans Health Administration’s electronic health record. GWAS was performed using logistic regression in PLINK, and meta-analyzed in METAL. FUMA was used for post-GWAS analysis. Genomic structural equation modeling (gSEM) was conducted to investigate underlying genetic associations with TBI, and bivariate MiXeR was used to estimate phenotype specific and shared polygenicity. SNP-based heritability was 0.060 (SE=0.004,p=7.83×10−66). GWAS analysis identified 15 genome-wide significant (GWS) loci atp<5×10−8. Gene-based analyses revealed 14 gene-wide significant genes, includingNCAM1, APOE, FTO, andFOXP2. Gene tissue expression analysis identified the brain as significantly enriched, particularly in the frontal cortex, anterior cingulate cortex, and nucleus accumbens. Genetic correlations with TBI were significant for risk-taking behaviors and psychiatric disorders, but generally not significant for the neurocognitive variables investigated. gSEM analysis revealed stronger associations with risk-taking traits than with psychiatric traits. Finally, the genetic architecture of TBI was similar to polygenic psychiatric disorders. Neurodegenerative disorders including Alzheimer’s and Parkinson’s disease showed much less polygenicity, however, the proportion of shared variance with TBI was high. This first well-powered GWAS of TBI identified 15 loci including genes relevant to TBI biology, and showed that TBI is a heritable trait with comparable genetic architecture and high genetic correlation with psychiatric traits. Our findings set the stage for future TBI GWASs that focus on injury severity and diversity and chronicity of symptom sequelae.