bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenging Case: The Role of Genetic Testing in Complex Autism
Authors: Solgi Mohadeseh , Fernandez Jasmine , Zuckerman Katharine E. , Shapiro Desiree , Augustyn Marilyn 
Published: November 2021

CASE:
S is a 12-year-old boy with autism spectrum disorder (ASD), seizure disorder, cerebral palsy, and intellectual disability who presented to the primary care clinician for a preventative care visit.
S was born at full term after an unremarkable pregnancy. His developmental delays were first noted at around 8 months, when he could not sit independently and had intermittently poor eye contact. He was referred to Part C Early Intervention and subsequently evaluated by a neurodevelopmental pediatrician, where he was noted to be hypotonic, with delayed motor and cognitive skills. Initial genetics evaluation included karyotype, fragile X testing, Angelman and Prader-Willi DNA fluorescence in situ hybridization probes, POLG sequencing, MECP2 testing, a microarray, creatinine kinase, very long-chain fatty acids, lymphocyte arylsulfatase, urine organic acids, and plasma amino acids, all of which were normal.
As time progressed, S continued to have motor and communication delays and developed choreic movements. He also developed episodes concerning for seizure, including periods of staring while awake and episodes of extremity shaking lasting a few seconds with associated eye deviation, which eventually progressed to generalized seizures. He also developed periods of lethargy. Outpatient workup included several EEGs, which were notable for foci in the right frontal and left temporal regions. He has had several brain MRIs showing generalized volume loss and had critical laboratory tests during a period of lethargy, which were unconcerning. He was treated with multiple antiseizure medications. He was diagnosed with ASD at age 5 years because of delayed language, poor social communication, and repetitive behaviors.
Over time, S continued to experience global developmental delays and autistic-like behaviors and remained minimally verbal. However, clinicians noted a number of developmental strengths, including a generally positive mood, a willingness to participate in therapy, improved receptive language skills, attachment to his mother, and a love of nature and the outdoors. He participated in a number of therapy modalities including speech/language therapy, occupational therapy, physical therapy, applied behavioral analysis, aqua therapy, partner-assisted scanning, and therapeutic horseback riding.
In 2019, whole-exome sequencing was newly covered by the state Medicaid program, and testing was obtained in 2020. Whole-exome sequencing revealed a de novo STXBP1 pathogenic variant c.874C>T (p.Arg292Cys), which is associated with developmental and epileptic encephalopathy. His presentation is consistent with STXBP1 encephalopathy including refractory epilepsy, ASD, intellectual disability, and movement disorders.
What are important considerations in genetic testing for children with autism? How does a genetic testing result alter management for clinicians and families?
Vasoprotective Actions of Nitroxyl (HNO): A Story of Sibling Rivalry
Authors: Kemp-Harper Barbara 
Published: November 2021

Abstract:
Nitroxyl (HNO), the 1 electron-reduced and protonated form of nitric oxide (NO•), has emerged as a nitrogen oxide with a suite of vasoprotective properties and therapeutic advantages over its redox sibling. Although HNO has garnered much attention due to its cardioprotective actions in heart failure, its ability to modulate vascular function, without the limitations of tolerance development and NO• resistance, is desirable in the treatment of vascular disease. HNO serves as a potent vasodilator and antiaggregatory agent and has an ability to limit vascular inflammation and reactive oxygen species generation. In addition, its resistance to scavenging by reactive oxygen species and ability to target distinct vascular signaling pathways (Kv, KATP, and calcitonin gene-related peptide) contribute to its preserved efficacy in hypertension, diabetes, and hypercholesterolemia. In this review, the vasoprotective actions of HNO will be compared with those of NO•, and the therapeutic utility of HNO donors in the treatment of angina, acute cardiovascular emergencies, and chronic vascular disease are discussed.
Attitudes May Be Hard to Change: Canadian Organ Donors Consider Face and Hand Donation
Authors: Lafreniere Ann-Sophie , Al-Halabi Becher , Thibaudeau Stephanie , Temple-Oberle Claire 
Published: November 2021

Objective:
Despite the success of composite tissue allograft (CTA) such as face and hand transplant at improving recipients’ quality of life, organ donors’ hesitation needs to be better understood. The aim of the study was to assess Canadian organ donors’ willingness to donate their face and hands, and the efficacy of an educational intervention.

Methods:
Canadians registered for organ donation were invited to complete an online survey about CTA. An interactive vignette was introduced part way through to clarify transplant-related concepts, with repeat of questions post-vignette exposure to assess attitudes pliability.

Results:
A total of 942 participants completed the survey. Fifty-two percent of donors were willing to donate their face after passing, whereas 80% were willing to donate their hands. Reasons to refuse CTA donation included the risk of upsetting their family, having someone look like them, and wanting their body to remain intact. Donors’ willingness to donate their face (38%, P < 0.001) and hands (79%, P = 0.67) decreased following vignette exposure. Comparative analysis of our interventional vignette with a similar study where donors’ donation readiness increased after an educational intervention revealed that our vignette lacked a strong enough emotional component to positively impact donors’ attitude to CTA, and may have exposed participants to alternatives to transplant they were not previously aware of.

Conclusions:
Canadian organ donors surveyed were willing to donate their face and hands following death, a willingness reduced after watching our informative vignette. Further qualitative work is required to better understand the educational needs and areas to address to increase donors’ acceptance of CTA.
The Association of Patient Educational Attainment With Cardiac Rehabilitation Adherence and Health Outcomes
Authors: Gaalema Diann E. , Savage Patrick D. , O'Neill Steven , Bolívar Hypatia A. , Denkmann Deborah , Priest Jeffrey S. , Khadanga Sherrie , Ades Philip A. 
Published: November 2021

Purpose:
Participating in cardiac rehabilitation (CR) after a cardiac event provides many clinical benefits. Patients of lower socioeconomic status (SES) are less likely to attend CR. It is unclear whether they attain similar clinical benefits as patients with higher SES. This study examines how educational attainment (one measure of SES) predicts both adherence to and improvements during CR.

Methods:
This was a prospective observational study of 1407 patients enrolled between January 2016 and December 2019 in a CR program located in Burlington, VT. Years of education, smoking status (self-reported and objectively measured), depression symptom level (Patient Health Questionnaire), self-reported physical function (Medical Outcomes Survey), level of fitness (peak metabolic equivalent, peak oxygen uptake, and handgrip strength), and body composition (body mass index and waist circumference) were obtained at entry to, and for a subset (n = 917), at exit from CR. Associations of educational attainment with baseline characteristics were examined using Kruskal-Wallis or Pearson's χ2 tests as appropriate. Associations of educational attainment with improvements during CR were examined using analysis of covariance or logistic regression as appropriate.

Results:
Educational attainment was significantly associated with most patient characteristics examined at intake and was a significant predictor of the number of CR sessions completed. Lower educational attainment was associated with less improvement in cardiorespiratory fitness, even when controlling for other variables.

Conclusions:
Patients with lower SES attend fewer sessions of CR than their higher SES counterparts and may not attain the same level of benefit from attending. Programs need to increase attendance within this population and consider program modifications that further support behavioral changes during CR.
Building Capacity Through ICCPR Cardiovascular Rehabilitation Foundations Certification (CRFC)
Authors: Babu Abraham Samuel , Heald Fiorella A. , Contractor Aashish , Ghisi Gabriela L. M. , Buckley John , Mola Ana , Atrey Alison , Lopez-Jimenez Francisco , Grace Sherry L. 
Published: November 2021

Purpose:
The International Council of Cardiovascular Prevention and Rehabilitation (ICCPR) developed an online Cardiovascular Rehabilitation Foundations Certification (CRFC; https://globalcardiacrehab.com/Certification) in October 2017, to build cardiac rehabilitation (CR) delivery capacity in low-resource settings based on their guidelines. Herein we evaluate its reach globally, barriers to its completion, as well as satisfaction and impact of the course among those completing it.

Methods:
The country of origin of all applicants was tallied. An online survey was developed for learners who completed the CRFC (completers), and for those who applied but did not yet complete the program (noncompleters), administered using Google Forms.

Results:
With regard to reach, 236 applications were received from 23/203 (11%) countries in the world; 51 (22%) were from low- or middle-income countries. A total of 130 (55%) have completed the CRFC; mean scores on the final examination were 88.3 ± 7.1%, with no difference by country income classification (P= .052). Sixteen (22%) noncompleters and 37 (34%) completers responded to the survey. Barriers reported by noncompleters were time constraints, cost, and technical issues. Overall satisfaction (scale 1-5) with the CRFC was high (4.49 ± 0.51); most completers would highly recommend the CRFC to others (4.30 ± 0.66), and perceived that the information provided will contribute to their work and/or the care of their patients (4.38 ± 0.89); 29 (78%) had used the information from the CRFC in their practice.

Conclusions:
The reach of the CRFC still needs to be broadened, in particular in low-resource settings. Learners are highly satisfied with the certification, and its impacts on CR practice are encouraging. Input has been implemented to improve the CRFC.
Benchmarking Depressive Symptoms in Cardiac Rehabilitation
Authors: Middleton William A. , Savage Patrick D. , Khadanga Sherrie , Rengo Jason L. , Ades Philip A. , Gaalema Diann E. 
Published: November 2021

Purpose:
Depression affects cardiac health and is important to track within cardiac rehabilitation (CR). Using two depression screeners within one sample, we calculated prevalence of baseline depressive symptomology, improvements during CR, and predictors of both.

Methods:
Data were drawn from the University of Vermont Medical Center CR program prospectively collected database. A total of 1781 patients who attended between January 2011 and July 2019 were included. Two depression screeners (Geriatric Depression Scale-Short Form [GDS-SF] and Patient Health Questionnaire-9 [PHQ-9]) were compared on proportion of the sample categorized with ≥ mild or moderate levels of depressive symptoms (PHQ-9 ≥5, ≥10; GDS-SF ≥6, ≥10). Changes in depressive symptoms by screener were examined within patients who had completed ≥9 sessions of CR. Patient characteristics associated with depressive symptoms at entry, and changes in symptoms were identified.

Results:
Within those who completed ≥9 sessions of CR with exit scores on both screeners (n = 1201), entrance prevalence of ≥ mild and ≥ moderate depressive symptoms differed by screener (32% and 9% PHQ-9; 12% and 3% GDS-SF; both P< .001). Patients who were younger, female, with lower cardiorespiratory fitness (CRF) scores were more likely to have ≥ mild depressive symptoms at entry. Most patients with ≥ mild symptoms decreased severity by ≥1 category by exit (PHQ-9 = 73%; GDS-SF = 77%). Nonsurgical diagnosis and lower CRF were associated with less improvement in symptoms on the PHQ-9 (both P< .05).

Conclusion:
Our results provide initial benchmarks of depressive symptoms in CR. They identify younger patients, women, patients with lower CRF, and those with nonsurgical diagnosis as higher risk groups for having depressive symptoms or lack of improvement in symptoms.
Implementation and Effectiveness of a Veterans Affairs–Based Comprehensive Lung Cancer Survivorship Program
Authors: Rabe Brian J. , Stafford Jordan W. , Hassinger Alisa D. , Swartzwelder Harry S. , Shofer Scott L. 
Published: November 2021

Purpose:
Few programs exist to address persistent impairment in functional status, quality of life, and mental health in lung cancer survivors. We aimed to determine whether a 12-wk multimodal survivorship program imparts clinical benefit.

Methods:
Any patient at the Durham Veterans Affairs Medical Center with lung cancer and a Karnofsky score of ≥60 could participate. Chronic obstructive pulmonary disease medications were optimized at the enrollment visit. Participants with a Hospital Anxiety and Depression Scale (HADS) score of >8 were offered pharmacotherapy and mental health referral. Participants did home-based exercise with a goal of 1 hr/d, 5 d/wk. They were called weekly to assess exercise progress and review depression/anxiety symptoms. Participants were offered pharmacotherapy for smoking cessation.

Results:
Twenty-three (50%) of the first 46 enrollees completed the full 12-wk program. Paired changes from enrollment to completion (mean ± SD) were observed in 6-min walk test (73.6 ± 96.9 m, P = .002), BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise) index (−1.45 ± 1.64 points, P < .001), Duke Activity Status Index (3.84 ± 7.12 points, P = .02), Fried Frailty Index (−0.588 ± 0.939 points, P = .02), modified Medical Research Council dyspnea scale (−0.619 ± 1.284 points, P = .04), Functional Assessment of Cancer Therapy-Lung Emotional subscale score (1.52 ± 2.96 points, P = .03), HADS total score (−2.63 ± 4.34 points, P = .02), and HADS Anxiety subscale score (−1.47 ± 2.29 points, P = .01).

Conclusions:
A comprehensive Lung Cancer Survivorship Program provides clinically meaningful improvements in functional status, quality of life, and mental health.
Cross-sectional comparison of office and ambulatory pulse wave velocity by two methods, and their changes after lifestyle or medical interventions in hypertension
Authors: Batta Dóra , Körösi Beáta , Gyöngyösi Helga , Nemcsik-Bencze Zsófia , László Andrea , Tislér András , Cseprekál Orsolya , Nemcsik János 
Published: November 2021

Objective:
Pulse wave velocity (PWV), the most accepted biomarker of arterial stiffening can be measured by different methods and in the past decade, its 24 h monitoring has also become available. The aim of our study was to compare office and ambulatory PWVs and in a proportion of patients to compare the changes of PWVs after the initiation of lifestyle modifications or antihypertensive medication.

Methods:
Office carotid–femoral PWV was measured with the tonometric PulsePen device (PP PWV), first hour and 24 h ambulatory oscillometric PWVs were evaluated with Mobil-O-Graph (MOB first hour PWV and MOB 24 h PWV, respectively). In new hypertensive patients, the measurements were repeated 3 months after the initiation of antihypertensive medication. In white-coat hypertensive patients after lifestyle modifications the measurements were repeated at 12 months.

Results:
One hundred and five participants were involved with 22 new hypertensive and 22 white-coat hypertensive (WhHT) patients. PP PWV [8.7 (7.3–9.9) m/s] differed from MOB first hour PWV [7.3 (6.5–8.8) m/s] and MOB 24 h PWV [7.4 (6.4–8.8) m/s] as well (P < 0.05). PP PWV significantly decreased both in hypertensive [by 0.9 (0.4–1.5) m/s, P < 0.05] and WhHT patients [by 0.3 (−0.1 to 1) m/s, P < 0.05]. MOB first hour PWV did not change neither in hypertensive patients, nor in WhHT patients. MOB 24 h PWV decreased only in hypertensive patients [by 0.2 (0–0.6) m/s], which was less pronounced compared with PP PWV (P < 0.05).

Conclusion:
The significant differences observed both in the cross-sectional and in the prospective parts of our study suggests that the two methods are not interchangeable.
The Switch From Paliperidone Long-Acting Injectable 1- to 3-Monthly
Authors: Mauri Massimo Carlo , Franco Gemma , Minutillo Alessandro , Paletta Silvia , Di Pace Chiara , Reggiori Alessandra , Baldelli Sara , Cattaneo Dario 
Published: November 2021

Abstract

Purpose/Background
The aim of the study was a preliminary evaluation of the maintenance of clinical efficacy and tolerability of paliperidone palmitate in patients with schizophrenia during the transition phase from 1-monthly paliperidone palmitate formulation (PP1M) to PP3M, with the evaluation of plasma levels of the drug.

Methods/Procedures
A prospective observational study was conducted for 13 months involving 22 outpatients, aged 18 to 66 years and clinically stabilized. Patients were affected by schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. For each patient, clinical assessment, safety and tolerability, and drug plasma level determination were performed. Clinical efficacy was assessed by Brief Psychiatric Rating Scale, Positive and Negative Symptom Scale, and Hamilton Rating Scale for Depression. During the first 4 months of the study, once-monthly paliperidone palmitate was administered, and then during the following 9 months, the 3-monthly formulation was administered.

Findings/Results
The time course of the Brief Psychiatric Rating Scale total scores showed a statistically significant (P = 0.006) improvement from T0 to T8; Positive and Negative Symptom Scale scores showed a similar time course, with a statistically significant (P = 0.0016) reduction of the mean total score; Hamilton Rating Scale for Depression mean scores showed a statistically significant (P = 0.003) reduction with substantial maintenance of clinical stabilization of the patients. Only 1 patient dropped out after the first PP3M injection.

Implications/Conclusions
Our preliminary data currently confirm the maintenance of clinical stability shifting from PP1M to PP3M.
Liquid biopsies in pediatric oncology: opportunities and obstacles
Authors: Sundby R. Taylor , Pan Alex , Shern Jack F. 
Published: November 2021

Purpose of review
Liquid biopsies have emerged as a noninvasive alternative to tissue biopsy with potential applications during all stages of pediatric oncology care. The purpose of this review is to provide a survey of pediatric cell-free DNA (cfDNA) studies, illustrate their potential applications in pediatric oncology, and to discuss technological challenges and approaches to overcome these hurdles.

Recent findings
Recent literature has demonstrated liquid biopsies’ ability to inform treatment selection at diagnosis, monitor clonal evolution during treatment, sensitively detect minimum residual disease following local control, and provide sensitive posttherapy surveillance. Advantages include reduced procedural anesthesia, molecular profiling unbiased by tissue heterogeneity, and ability to track clonal evolution. Challenges to wider implementation in pediatric oncology, however, include blood volume restrictions and relatively low mutational burden in childhood cancers. Multiomic approaches address challenges presented by low-mutational burden, and novel bioinformatic analyses allow a single assay to yield increasing amounts of information, reducing blood volume requirements.

Summary
Liquid biopsies hold tremendous promise in pediatric oncology, enabling noninvasive serial surveillance with adaptive care. Already integrated into adult care, recent advances in technologies and bioinformatics have improved applicability to the pediatric cancer landscape.
Simulation-Based Training Improves Fellows’ Competence in Brain Death Discussion and Declaration
Authors: Chen Patrick M. , Trando Aaron , LaBuzetta Jamie Nicole 
Published: November 2021

Background:
Despite well-defined American Academy of Neurology guidelines for death by whole brain criteria (brain death), there is marked variability in national practice, which some have attributed to lack of formal education. Further, communication with surrogates and families about brain death is integral to brain death declaration. As such, we developed a targeted brain death curriculum combining didactics and simulation-based education to improve examination and subsequent communication skills with families.

Methods:
Multidisciplinary critical care fellows participated in (1) didactic and case-based curriculum, (2) brain death simulated examination (SimMan3G mannequin), and (3) a standardized family scenario with delivery of a brain death diagnosis to a surrogate “family member”. Fellows completed a precurriculum and postcurriculum multiple choice knowledge test and survey (Likert 1 to 10 scale) evaluating measures regarding diagnosis and communication of brain death. t Test and 2-tailed Wilcoxon signed rank test were used for statistical analysis (P<0.05).

Results:
Thirteen critical care fellows participated in the curriculum. Most fellows [80% (N=12)] had only participated in 0 to 5 brain death declarations before this intervention. There was significant improvement across all measures: self-rated knowledge (P=0.004), perceived knowledge relative to peers (P=0.002), confidence (P=0.001), and comfort (P=0.001) with performing a brain death exam, and comfort with family discussion (P=0.01). Objective test scores improved from 56 to 73% after simulation (P=0.004). All fellows found the curriculum beneficial.

Conclusion:
Trainees may lack sufficient exposure to brain death education. Didactics with simulation-based education can improve objective knowledge and subjective measures of comfort with brain death declaration and surrogate communication.
Marfan Syndrome Presenting as Spontaneous Coronary Artery Dissection and Arteriopathy
Authors: Blech Benzion , Dhamija Radhika , Ingall Timothy 
Published: November 2021

Introduction:
Spontaneous coronary artery dissection (SCAD) is a term used to define a spontaneous separation of the coronary artery wall not related to underlying risk factors, such as trauma or underlying atherosclerotic disease. While SCAD has a range of different etiologies, with fibromuscular dysplasia being the most common, most cases of SCAD have no concomitant arteriopathy.

Case Report:
Here we describe a case of a patient who presented to our institution with SCAD and evidence of an asymptomatic arteriopathy involving extracranial segments of the carotid and vertebral arteries, later found to have a pathogenic variant in the FBN1 gene and ultimately diagnosed with Marfan syndrome. This has only been rarely described in the literature as an etiology for SCAD.

Conclusion:
Although rare, it is important to consider underlying connective tissue disorders in patients presenting with spontaneous coronary artery dissection and arteriopathy without underlying cardiovascular risk factors.