bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital outcome measures in pulmonary clinical trials
Authors: Farrand Erica , Swigris Jeffrey J. 
Published: May 2023

Purpose of review
We highlight recent advances in the development and use of digital outcome measures in clinical trials, focusing on how to select the appropriate technology, use digital data to define trial endpoints, and glean important lessons from current experiences with digital outcome measures in pulmonary medicine.

Recent findings
A review of emerging literature demonstrates that the use of digital health technologies, particularly pulse oximeters, remote spirometers, accelerometers, and Electronic Patient-Reported Outcomes, has surged in both pulmonary practice and clinical trials. Lessons learned from their use can help researchers to design the next generation of clinical trials leveraging digital outcomes to improve health.

Summary
In pulmonary diseases, digital health technologies provide validated, reliable, and usable data on patients in real-world environments. More broadly, digital endpoints have accelerated innovation in clinical trial design, improved clinical trial efficiency, and centered patients. As investigators adopt digital health technologies, it is important to follow a framework informed by both the opportunities and challenges of digitization. Successful use of digital health technologies will transform clinical trials by improving accessibility, efficiency, patient-centricity, and expanding opportunities for personalized medicine.
Heterogeneity of Asthma Care Among Hispanic Subgroups
Authors: Kim Yonsu , Moonie Sheniz , Cochran Chris 
Published: May 2023

Background:
Studies found heterogeneity of asthma prevalence among Hispanic subgroups using survey data but addressed under-diagnosis issues due to limited access to health care and diagnosis bias.

Objectives:
To examine heterogeneity by language in health care utilization for asthma among Hispanic subgroups.

Research Design:
A retrospective, longitudinal cohort study of Medi-Cal claims data (2018–2019) using logistic regression to estimate the odds ratio of health care utilization for asthma.

Subjects:
In all, 12,056 (ages 5–64) Hispanics living in Los Angeles were identified as having persistent asthma.

Measures:
Primary language is the predictor variable and outcome measures include ED visits, hospitalizations, and outpatient visits.

Results:
The odds of ED visits among Spanish-speaking Hispanics were lower than English-speaking Hispanics in the subsequent 6 (95% CI=0.65–0.93) and 12 (95% CI=0.66–0.87) months. Spanish-speaking Hispanics were less likely than their English-speaking counterparts to utilize hospitalization in the 6 months (95% CI=0.48–0.98), while they were more likely to utilize outpatient care (95% CI=1.04–1.24). For Hispanics of Mexican origin, the odds of ED visits among Spanish-speaking Hispanics were also lower in the 6 and 12 months (95% CI=0.63–0.93, 95% CI=0.62–0.83), but their odds of outpatient visits were higher for outpatient visits in the 6 months (95% CI=1.04–1.26).

Conclusions:
Spanish-speaking Hispanics with persistent asthma were less likely than English-speaking Hispanics to utilize ED visits and hospitalizations but were more likely to utilize outpatient visits. The findings suggest the reduced burden of asthma among the Spanish-speaking Hispanic subgroup and contribute to explaining the protection effect, specifically among Spanish-speaking Hispanics living in highly segregated communities.
“Calvarial Vault Remodeling Technique for Lambdoid Craniosynostosis.”
Authors: Chiang Sarah N , Varagur Kaamya , Skolnick Gary B , Naidoo Sybill D , Smyth Matthew D , Patel Kamlesh B 
Published: May 2023

Summary:
Premature fusion of the lambdoid suture is the most uncommon single suture synostosis. It presents with a classic “windswept” appearance, with a trapezoid-shaped head and significant skull asymmetry notable for an ipsilateral mastoid bulge and contralateral frontal bossing. Due to the rarity of lambdoid synostosis, little is known about optimal techniques for its treatment. In particular, the proximity of the lambdoid suture to critical intracranial structures such as the superior sagittal and transverse sinuses represents a potential for significant intraoperative bleeding. Prior work has shown that parietal asymmetry persists after repair in these cases. Here, we present a technique for the treatment of unilateral lambdoid craniosynostosis along with two representative cases.
This calvarial vault remodeling technique requires the removal of both ipsilateral and contralateral parietal bones. These are moved across hemispheres and re-inset on opposite sides to help correct the parietal asymmetry. Obliquely orientated barrel stave osteotomies are performed to provide a safe mechanism for correction of occipital flattening. Our early results show improvement in correction of volume asymmetry one year post-operatively relative to patients treated with prior calvarial vault remodeling techniques. We believe the technique presented here corrects the windswept appearance in patients with lambdoid craniosynostosis while also reducing the potential for complications. Further work will be necessary to confirm this technique’s long-term efficacy in a larger cohort.
Less Is Better: Full-Incision Double-Eyelid Blepharoplasty with Rapid Recovery
Authors: Zhang Yi , Li Mengjuan , Lei Shaorong , Long Jianhong , Qi Min 
Published: May 2023

Summary:
Full-incision double-eyelid blepharoplasty is effective, but postoperative complications, such as local trauma and persistent tissue swelling, are major concerns. Because tissue swelling is caused by the obstruction of blood and lymphatic flow, the authors modified the conventional full-incision method to minimize the trauma as much as possible. Twenty-five patients underwent the modified procedure. There was minor swelling immediately after the surgery, which subsided 1 to 5 days after the surgery. No patient reported loss of the double eyelid crease. Only 2 patients underwent a second operation because of a low crease. Satisfactory results were obtained in 92% of patients (23 of 25). According to our understanding of this technique, less trauma is the key to obtaining better results under certain conditions.
Integrated Approaches for Reconstruction of Facial Paralysis
Authors: Chen Shihheng , Chen Hung-Chi , Tang Yueh-Bih 
Published: May 2023

Background
Facial paralysis can affect periorbital muscles, oral competence, and facial expressions with significant facial deformities, which could occur in either children or adults with variable severity, duration, and degree of recovery.

Objective
The present study was aimed to delineate treatment plans for facial paralysis with different clinical scenarios and to report the results of these patients.

Methods
Patients were grouped according to different presentations as follows: (1) facial paralysis with incomplete recovery; (2) young patients of facial paralysis without recovery; (3) senile patients of facial palsy without recovery; (4) combined facial palsy with mandibular deficiency, vascularized bone reconstruction for mandible with (a) subsequent muscle transfer or (b) simultaneous sling operation or (c) simultaneous facial nerve exploration and cross nerve grafting; (5) palsy of frontal branch of facial nerve; (6) palsy of zygomatic-buccal branch of facial nerve; (7) palsy of marginal mandibular branch of facial nerve; (8) partial recovery with dyskinesia; and (9) facial paralysis with dynamic asymmetry and muscle atrophy. According to clinical scenarios, different treatment plans were provided, and clinical outcomes were evaluated and presented.

Results
All patient groups achieved fair or satisfactory outcomes. Revisions using sling procedures, botulinum toxin injection, and filler or fat graft as supplement further refined the ultimate outcomes.

Conclusions
For reconstruction of facial paralysis, individualized integrated treatment plans are mandatory according to the presentation and condition of the patient. Comprehensive considerations and strategic solutions for the existing disabilities have been appreciated by the patients. The least numbers of operations with considerate correction of asymmetry were the major concerns of the patients.
Systematic review search strategies are poorly described and not reproducible: a cross-sectional meta-research study
Authors: Rethlefsen Melissa L. , Brigham Tara J. , Price Carrie , Moher David , Bouter Lex M. , Kirkham Jamie J. , Schroter Sara , Zeegers Maurice P. 
Published: May 2023

ABSTRACTObjectiveTo determine the reproducibility of biomedical systematic review search strategies.DesignCross-sectional meta-research study.PopulationRandom sample of 100 systematic reviews indexed in MEDLINE in November 2021.Main Outcome MeasuresThe primary outcome measure is the percentage of systematic reviews for which all database searches can be reproduced. This was operationalized as fulfilling six key PRISMA-S reporting guideline items (database name, multi-database searching, full search strategies, limits and restrictions, date(s) of searches, and total records) and having all database searches reproduced within 10% of the number of original results.ResultsThe 100 systematic review articles contained 453 database searches. Of those, 214 (47.2%) provided complete database information (named the database and platform; PRISMA-S item 1). Only 22 (4.9%) database searches reported all six PRISMA-S items. Forty-seven (10.4%) database searches could be reproduced within 10% of the number of results from the original search; 6 searches differed by more than 1000% between the originally reported number of results and the reproduction. Only one systematic review article provided the necessary details for all database searches to be fully reproducible.ConclusionSystematic review search reporting is poor. As systematic reviews and clinical practice guidelines based upon them continue to proliferate, so does research waste. To correct this will require a multi-faceted response from systematic review authors, peer reviewers, journal editors, and database providers.
PREVALENCE OF MYOPIA AMONG PUBLIC SCHOOL CHILDREN IN SOUTHERN BRAZIL
Authors: Gus Patrícia Ioschpe , de Maman Raquel Silveira , Lengler Arthur Dementshuk , Martins Antônia Stumpf , Torres Arteche Maria Antônia , Pieta Marina Puerari , Leivas Gabriel , Carloto Rafael , Marinho Diane , Tartarella Márcia Beatriz , Pakter Helena , Fabris Caroline , Castro Terla , Kronbauer Fernando , Colossi Carina , Jong Monica , Resnikoff Serge 
Published: May 2023

AbstractPurposeMyopia has been considered a public health issue by the World Health Organization since 2015. The growing incidence of myopia worldwide, called the myopia epidemic, and its potential blinding complications in adulthood like cataract, glaucoma, retinal detachment and maculopathy, have been extensively published and discussed in peer review papers. Nonetheless, little information about Latin America is available. This study aims to detect the prevalence of myopia in southern Brazil, the biggest country of South America.MethodsA prospective cross sectional study recruited 330 public school children between 2019 and 2021, aged 5 to 20 years old. All children underwent a comprehensive eye examination and detailed lifestyle questionnaire. The Pearson correlation coefficient, Kruskal Wallys and the Chi-Square Test were used to assess simple correlations and associations between myopia and medical conditions, use of medications, ophthalmic history and family history of ocular conditions, besides demographics and lifestyle focused on screen time/day. Associations between the results of the ophthalmologic evaluation and all factors included in the questionnaire were analyzed using the Generalized Estimating Equation model (GEE). The prevalence of hyperopia and astigmatism were also assessed.ResultsTotal prevalence of myopia was 17.4% (CI 13.8 – 21.7%). Low myopia (-0.50D to -5.75D) comprised 15.2% (CI 11.9 – 19.3%) and high myopia (-6,00D or worse) was 2.1% (CI 1.1 – 4.1%). Relative risk of myopia for females was 1.6 (CI 1.00 – 2.57%) and each additional hour of screen time increased a child’s chance of having myopia by 6.5%. The prevalence of hyperopia was 7,7% (CI 5.4 -10.9%) and of astigmatism, either myopic or hyperopic, was 25.6% (CI 21.4 – 30.2%).ConclusionsBrazil has always been considered a hyperopic country. These are the highest reported prevalences of myopia under cycloplegia and the first paper to present myopia as a more prevalent refractive error than hyperopia among Brazilian school children to date.
Distinct Neurocognitive Profiles and Clinical Phenotypes Associated with Copy Number Variation at the 22q11.2 Locus
Authors: O’Hora Kathleen P. , Kushan-Wells Leila , Hoftman Gil D. , Jalbrzikowski Maria , Gur Raquel C. , Gur Ruben , Bearden Carrie E. 
Published: May 2023

AbstractRare genetic variants that confer large effects on neurodevelopment and behavioral phenotypes can reveal novel gene-brain-behavior relationships relevant to autism. Copy number variation at the 22q11.2 locus offer one compelling example, as both the 22q11.2 deletion (22qDel) and duplication (22qDup) confer increased likelihood of autism spectrum disorders (ASD) and cognitive deficits, but only 22qDel confers increased psychosis risk. Here, we used the Penn Computerized Neurocognitive Battery (Penn-CNB) to characterized neurocognitive profiles of 126 individuals: 55 22qDel carriers (MAge=19.2 years, 49.1% male), 30 22qDup carriers (MAge=17.3 years, 53.3 % male), and 41 typically developing (TD) subjects (MAge=17.3 years, 39.0 % male). We performed linear mixed models to assess group differences in overall neurocognitive profiles, domain scores, and individual test scores. We found all three groups exhibited distinct overall neurocognitive profiles. 22qDel and 22qDup carriers showed significant accuracy deficits across all domains relative to controls (Episodic Memory, Executive Function, Complex Cognition, Social Cognition, and Sensorimotor Speed), with 22qDel carriers exhibiting more severe accuracy deficits, particularly in Episodic Memory. However, 22qDup carriers generally showed greater slowing than 22qDel carriers. Notably, slower social cognition speed was uniquely associated with increased global psychopathology and poorer psychosocial functioning in 22qDup. Compared to TD, 22q11.2 CNV carriers failed to show age-associated improvements in multiple cognitive domains. Exploratory analyses revealed 22q11.2 CNV carriers with ASD exhibited differential neurocognitive profiles, based on 22q11.2 copy number. These results suggest that there are distinct neurocognitive profiles associated with either a loss or gain of genomic material at the 22q11.2 locus.
Associations of rest-activity rhythm disturbances with stroke risk and post-stroke adverse outcomes
Authors: Gao Lei , Zheng Xi , Baker Sarah N. , Li Peng , Scheer Frank A.J.L. , Nogueira Ricardo C , Hu Kun 
Published: May 2023

AbstractBackgroundAlmost all biological and disease processes are influenced by circadian clocks and display ∼24-hour rhythms. Disruption of these rhythms may be an important novel risk factor for stroke. We evaluated the association between 24-h rest-activity rhythm measures, stroke risk, and major post-stroke adverse outcomes.MethodsIn this cohort study, we examined ∼100,000 participants in the UK Biobank (44-79 years old; ∼57% females) who underwent an actigraphy (6-7 days) and 5-year median follow-up. We derived: (1) most active 10 hours activity counts (M10) across the 24-h cycle and the timing of its midpoint (M10 midpoint); (2) the least active 5 hours counts (L5) and its midpoint timing (L5 midpoint); (3) relative amplitude (RA) - (M10-L5)/(M10+L5); (4)interdaily stability(IS): stability and (5)intradaily variability(IV), fragmentation of the rhythm. Cox proportional hazard models were constructed for time to (i) incident stroke (n=1,652); and (ii) post-stroke adverse outcomes (dementia, depression, disability, or death).ResultsSuppressed RA (lower M10 and higher L5) was associated with stroke risk after adjusting for demographics; the risk was highest in the lowest quartile [Q1] for RA (HR=1.62; 95% CI:1.36-1.93,p<0.001) compared to the top quartile [Q4]. Participants withlaterM10 midpoint timing (14:00-15:26, HR=1.26, CI:1.07-1.49,p=0.007) also had a higher risk for stroke thanearlier(12:17-13:10) participants. A fragmented rhythm (IV) was also associated with a higher risk for stroke (Q4 vs. Q1; HR=1.27; CI:1.06-1.50,p=0.008), but differences in the stability of rhythms (IS) were not. Suppressed RA was associated with an increased risk of unfavorable post-stroke outcomes (Q1 vs. Q4; 1.78 [1.29-2.47];p<0.001). All the associations were independent of age, sex, race, obesity, sleep disorders, cardiovascular diseases or risks, and other morbidity burdens.ConclusionSuppressed 24-h rest-activity rhythm may be a risk factor for stroke and an early indicator of major post-stroke adverse outcomes.
Effects of age and sex on patient-reported outcomes following total knee arthroplasty with a rotating bearing tibial platform design: A single-surgeon practice registry study
Authors: Fatima Manaal , Scholes Corey , Ireland John 
Published: May 2023

Withdrawal statementThe authors have withdrawn their manuscript owing to a manufacturer’s recall notice for the implant reported. The results reported here may have been impacted by a higher than expected rate of implant revision, which cannot be verified in the available data. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Identification of neuropathology-based subgroups in multiple sclerosis using a data-driven approach
Authors: de Boer Alyse , van den Bosch Aletta M.R. , Mekkes Nienke J. , Fransen Nina , Hoekstra Eric , Smolders Joost , Hamann Jörg , Huitinga Inge , Holtman Inge R. 
Published: May 2023

AbstractMultiple sclerosis (MS) is a heterogeneous disorder with regards to clinical presentation and pathophysiology. Stratification into biologically distinct subgroups could enhance prognostication and efficacious allocation to disease-modifying therapies. In this study, we identified MS subgroups by performing a clustering analysis on neuropathology data collected for MS donors in the Netherlands Brain Bank (NBB) autopsy cohort. The input dataset contained detailed information on white matter lesion load, the proportion of active, mixed active/inactive, inactive and remyelinating lesions, microglia morphology in these lesions, and the presence of microglial nodules, perivascular cuffs and cortical lesions for 228 donors. A factor analysis was performed to reduce noise and redundancy prior to hierarchical clustering with K-means consolidation. Four subgroups with distinct patterns of white matter lesions were identified. These were subsequently validated with additional clinical, neuropathological and genetic data. The subgroups differed with regards to disease progression and duration, the timing of motor, sensory and other relevant signs and symptoms, patterns of cortical lesions and the presence of B cells. Age at MS onset and sex, previously associated with milder forms of MS, did not differ between the subgroups; the subgroups could also not be distinguished based on the manifestation of clinical signs and symptoms. The available genetic data was used to calculate MS polygenic risk scores (PRSs) for donors included in the NBB cohort. The MS PRS did not differ between the subgroups, but was significantly correlated with the first and second dimension of the factor analysis, the latter lending genetic support to our subdivision. Taken together, these findings suggest a complex relationship between neuropathological subgroups and clinical characteristics, indicating that post-mortem cohort studies are critical to better stratify patients and understand underlying neuropathophysiological mechanisms, in order to ultimately achieve personalised medicine in MS.
CHIR99021 causes inactivation of Tyrosine Hydroxylase and depletion of dopamine in rat brain striatum
Authors: Hamdon Sally , Fernandez-Gonzalez Pol , Omar Muhammad Yusof , González-Sepúlveda Marta , Ortiz Jordi , Gil Carles 
Published: May 2023

ABSTRACTCHIR99021, also known as laduviglusib or CT99021, is a Glycogen-synthase kinase 3β (GSK3β) inhibitor, which has been reported as a promising drug for cardiomyocyte regeneration or treatment of sensorial hearing loss. Since the activation of dopamine (DA) receptors regulates dopamine synthesis and they can signal through the β-arrestin pathway and GSK3β, we decided to check the effect of GSK3β inhibitors (CHIR99021, SB216763 and lithium ion) in the control of DA synthesis. Usingex vivoexperiments with minces from rat brain striatum, we observed that CHIR99021, but not SB216763 nor lithium, causes a complete abrogation of DA synthesis and accumulation at low µM concentrations, pointing to off-target effects of CHIR99021. This decrease can be attributed to tyrosine hydroxylase (TH) inhibition since the accumulation of L-DOPA in the presence of a DOPA decarboxylase inhibitor was similarly decreased. On the other hand, CHIR99021 caused a dramatic increase in the DOPAC / DA ratio, an indicator of DA metabolization, and hindered DA incorporation into striatum tissue to the same extent as tetrabenazine, thus pointing to some effect on DA storage that triggers DA feedback inhibition of TH. In addition, CHIR99021 or SB216763, but not lithium, decreased TH phosphorylation in Ser19, but not in Ser31 or Ser40. These results demonstrate that CHIR99021 can lead to TH inactivation and DA depletion in brain striatum, opening the possibility of its use in DA-related disorders, and shows effects to be considered in future clinical trials.
Major changes in domain arrangements are associated with the evolution of termite castes
Authors: Mikhailova Alina A. , Dohmen Elias , Harrison Mark C. 
Published: May 2023

AbstractDomains as functional protein units and their rearrangements along the phylogeny can shed light on the functional changes of proteomes associated with the evolution of complex traits like eusociality. This complex trait is associated with sterile soldiers and workers, and long-lived, highly fecund reproductives. Unlike in Hymenotpera (ants, bees, and wasps), the evolution of eusociality within Blattodea, where termites evolved from within cockroaches, was accompanied by a reduction in proteome size, raising the question of whether functional novelty was achieved with existing rather than novel proteins. To address this, we investigated the role of domain rearrangements during the evolution of termite eusociality. Analysing domain rearrangements in the proteomes of three solitary cockroaches and five eusocial termites, we inferred more than 5000 rearrangements over the phylogeny of Blattodea. The 90 novel domain arrangements that emerged at the origin of termites were enriched for several functions related to longevity, such as protein homeostasis, DNA repair, mitochondrial activity, and nutrient sensing. Many domain rearrangements were related to changes in developmental pathways, important for the emergence of novel castes. Along with the elaboration of social complexity, including permanently sterile workers and larger, foraging colonies, we found 110 further domain arrangements with functions related to protein glycosylation and ion transport. We found an enrichment of caste-biased expression and splicing within rearranged genes, highlighting their importance for the evolution of castes. Furthermore, we found increased levels of DNA methylation among rearranged compared to non-rearranged genes suggesting fundamental differences in their regulation. Our findings indicate an importance of domain rearrangements in the generation of functional novelty necessary for termite eusociality to evolve.