bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Structure Theorem on Intersections of General Doubling Measures and Its Applications
Authors: Anderson Theresa C , Hu Bingyang 
Published: March 2022

Abstract
In this paper, we construct an explicit family of measures that are $p$-adic doubling for any given pair of primes, yet not doubling. This generalizes the construction by Boylan, Mills, and Ward on a structure theorem on the intersection of dyadic doubling measures and tri-adic doubling measures. As some byproducts, we apply these results to show analogous statements about the reverse Hölder and Muckenhoupt $A_p$ classes of weights.
Engineering a self-eliminating transgene in the yellow fever mosquito,Aedes aegypti
Authors: Chae Keun , Dawson Chanell , Valentin Collin , Contreras Bryan , Zapletal Josef , Myles Kevin M , Adelman Zach N 
Published: March 2022

AbstractPromising genetics-based approaches are being developed to reduce or prevent the transmission of mosquito-vectored diseases. Less clear is how such transgenes can be removed from the environment, a concern that is particularly relevant for highly invasive gene drive transgenes. Here, we lay the groundwork for a transgene removal system based on single-strand annealing (SSA), a eukaryotic DNA repair mechanism. An SSA-based rescuer strain (kmoRG) was engineered to have direct repeat sequences (DRs) in the Aedes aegypti kynurenine 3-monooxygenase (kmo) gene flanking the intervening transgenic cargo genes, DsRED and EGFP. Targeted induction of DNA double-strand breaks (DSBs) in the DsRED transgene successfully triggered complete elimination of the entire cargo from the kmoRG strain, restoring the wild-type kmo gene, and thereby, normal eye pigmentation. Our work establishes the framework for strategies to remove transgene sequences during the evaluation and testing of modified strains for genetics-based mosquito control.
Left/Right Judgment Task for the Chest Region, Part 1: Performance Outcomes in Healthy Women Compared to Women Post Breast Cancer Treatment
Authors: Boyd Benjamin S. , Smoot Betty J. , Nee Robert J. 
Published: March 2022

Background:
Movement planning and execution involve using our internal representations within motor and sensory areas of our brain. Left/right judgment tasks (LRJTs) are behavioral tests that involve determining the side of the body when shown an image, without performing the movement. Individuals theoretically need to use their working body schemas to complete LRJTs.

Objectives:
To develop a chest LRJT testing protocol and document performance in healthy women and women post breast cancer (BrCA) treatment.

Design:
Observational, cohort study.

Method:
We recruited women with and without a history of unilateral BrCA. Participants provided demographic and health history information online, followed by hand, shoulder, and chest LRJTs. Images were digitally mirrored to create equal numbers of left and right images. Images were presented in random order within each body region. We measured accuracy and response time for LRJTs.

Results:
A total of 316 healthy women and 160 women post-BrCA treatment competed all testing. The BrCA group was consistently slower and less accurate at performing LRJTs for all 3 regions. The side of the image presented was not associated with performance.

Conclusions:
We successfully developed a chest LRJT testing method. Performance on LRJT of the upper quarter is diminished after BrCA treatment. We established tolerance intervals for anticipated performance in healthy women for future clinical and research comparisons.
Mental Health Disclosure Questions on Medical Licensure Applications: Implications for Medical Students, Residents, and Physicians
Authors: Taylor Nicki W. , Porter Cheryl , Rivera-Rodriguez Melanis , Miller I.S. Keino , Desmarais Nathaly 
Published: March 2022

Medical trainees and physicians experience high rates of depression, anxiety, suicidal ideation, and burnout. The stigma surrounding mental health may deter help-seeking behaviors and increase informal treatment to maintain anonymity. Invasive health history questions on state medical licensure applications regarding mental health diagnoses and treatment likely increase stigma, reduce help-seeking, and consequently may motivate some applicants to report an inaccurate history to the state medical board. Research on physician mental health, suicide rates, and lack of help-seeking have led to recommendations for changes to licensure questions. In this article, the authors review the language of health history questions, disclosure requirements for applicants, and the potential consequences of disclosing mental health or substance abuse history on state medical licensure applications. They review recent changes to some states’ health history questions, using the changes to Florida’s licensure application in 2021 as an example, and explore the implications of these changes for reducing stigma and encouraging help-seeking.
The authors recommend that state medical boards review and refine licensure applications’ health history questions regarding mental health disclosure in ways that strategically address concerns related to stigma, bias, and unwarranted scrutiny. They call for research to examine the impact of such question changes on applicant response accuracy, help-seeking behaviors, and mental health outcomes and stigma. They also recommend that medical schools offer and promote access to mental health services, encourage faculty to normalize help-seeking behaviors, and provide students with information about state licensure processes. Reducing stigma, normalizing trainee and physician experiences, and promoting help-seeking are preliminary steps to promote a culture in academic medicine that prioritizes mental health. In turn, this will encourage trainees and physicians to care for themselves and cultivate physicians who are better equipped to heal and support their patients.
Analysis of the Frequency, Characteristics, and Reasons for Termination of Spine-related Clinical Trials
Authors: Caruana Dennis L. , Nam-Woo Kim David , Galivanche Anoop R. , David Wyatt B. , Justen Marissa A. , Moushey Alexander M. , Sheth Amar H. , Paranjpe Manish D. , Grauer Jonathan N. 
Published: March 2022

Study Design:
Cross-sectional analysis of completed and terminated spine-related clinical trials in the ClinicalTrials.gov registry.

Objective:
The aim was to quantify completed and terminated spine-related clinical trials, assess reasons for termination, and determine predictors of termination by comparing characteristics of completed and terminated trials.

Summary of Background Data:
Clinical trials are key to the advancement of products and procedures related to the spine. Unfortunately, trials may be terminated before completion. ClinicalTrials.gov is a registry and results database maintained by the National Library of Medicine that catalogs trial characteristics and tracks overall recruitment status (eg, ongoing, completed, terminated) for each study as well as reasons for termination. Reasons for trial termination have not been specifically evaluated for spine-related clinical trials.

Methods:
The ClinicalTrials.gov database was queried on July 20, 2021 for all completed and terminated interventional studies registered to date using all available spine-related search terms. Trial characteristics and reason for termination, were abstracted. Univariate and multivariate analyses were performed determine predictors of trial termination.

Results:
A total of 969 clinical trials were identified and characterized (833 completed, 136 terminated). Insufficient rate of participant accrual was the most frequently reported reason for trial termination, accounting for 33.8% of terminated trials.
Multivariate analysis demonstrated increased odds of trial termination for industry-sponsorship [odds ratio (OR)=1.59] relative to sponsorship from local groups, device studies (OR=2.18) relative to investigations of drug or biological product(s), and phase II (OR=3.07) relative to phase III studies (P<0.05 for each).

Conclusions:
Spine-related clinical trials were found to be terminated 14% of the time, with insufficient accrual being the most common reason for termination. With significant resources put into clinical studies and the need to advance scientific objectives, predictors, and reasons for trial termination should be considered and optimized to increase the completion rate of trials that are initiated.
Effect of Bronchoscopic Spray Cryotherapy and Ultra-low Temperature on Physical Properties of Metallic and Silicone Airway Stents
Authors: Sharma Deepankar , Kang Le , Shepherd Ray W. 
Published: March 2022

Background:
Bronchoscopic spray cryotherapy (SCT) is utilized in the field of interventional pulmonology for treating benign and malignant airway stenosis as a standard tool to maintain airway patency. Stent-related complications include tumor overgrowth, granulation tissue, and epithelialization. Thermal ablation can have a limited role in such scenarios due to the risk of airway fire and damage to the existing stent. SCT is a potential therapy using ultra-low temperatures that can allow stents to remain in place during treatment. However, there has been no study demonstrating the safety of SCT on the integrity and physical properties of tracheobronchial stents. We report the results of the first study demonstrating the safety of SCT utilized to treat stent-associated granulation or malignant airway disease. The aim of this study was to demonstrate the effects of SCT on the physical properties of airway stents in an ex vivo environment.

Methods:
Various types of airway stents were subjected to multiple intervals of SCT for up to 30 seconds, and then the cycle was repeated 3 times. After every cycle, we compressed the stents to 60% of their original size, and compression and expansion force data was collected immediately after, at 3-minute and 5-minute intervals, and compared with the baseline readings.

Results:
There was no significant change in the association between diameter and compression/expansion force, including any derangement in returning to the original diameter or any physical damage to any of the stents even after 3 prolonged SCT sessions of 30 seconds.

Conclusion:
Our study provides the first evidence that the use of SCT in conjunction with existing silicone/metal stents is feasible and does not cause any physical damage to the stents or alters their ability to maintain the original diameter.
Economic Evaluation
Authors: Smith David H. , O’Keeffe-Rosetti Maureen , Leo Michael C. , Mayhew Meghan , Benes Lindsay , Bonifay Allison , Deyo Richard A. , Elder Charles R. , Keefe Francis J. , McMullen Carmit , Owen-Smith Ashli , Trinacty Connie M. , Vollmer William M. , DeBar Lynn 
Published: March 2022

Background:
Chronic pain is prevalent and costly; cost-effective nonpharmacological approaches that reduce pain and improve patient functioning are needed.

Objective:
Report the incremental cost-effectiveness ratio (ICER), compared with usual care, of cognitive behavioral therapy aimed at improving functioning and pain among patients with chronic pain on long-term opioid treatment.

Design:
Economic evaluation conducted alongside a pragmatic cluster randomized trial.

Subjects:
Adults with chronic pain on long-term opioid treatment (N=814).

Intervention:
A cognitive behavioral therapy intervention teaching pain self-management skills in 12 weekly, 90-minute groups delivered by an interdisciplinary team (behaviorists, nurses) with additional support from physical therapists, and pharmacists.

Outcome Measures:
Cost per quality adjusted life year (QALY) gained, and cost per additional responder (≥30% improvement on standard scale assessment of Pain, Enjoyment, General Activity, and Sleep). Costs were estimated as-delivered, and replication.

Results:
Per patient intervention replication costs were $2145 ($2574 as-delivered). Those costs were completely offset by lower medical care costs; inclusive of the intervention, total medical care over follow-up was $1841 lower for intervention patients. Intervention group patients also had greater QALY and responder gains than did controls. Supplemental analyses using pain-related medical care costs revealed ICERs of $35,000, and $53,000 per QALY (for replication, and as-delivered intervention costs, respectively); the ICER when excluding patients with outlier follow-up costs was $106,000.

Limitations:
Limited to 1-year follow-up; identification of pain-related utilization potentially incomplete.

Conclusion:
The intervention was the optimal choice at commonly accepted levels of willingness-to-pay for QALY gains; this finding was robust to sensitivity analyses.
Racial Disparities in the Emergency Department Evaluation of Adolescent Girls
Authors: Polhemus Samuel , Pickett Michelle L. , Liu Xuerong (Joy) , Fraser Raphael , Ferguson Catherine C. , Drendel Amy L. 
Published: March 2022

Objective
Racial disparities and differences exist in emergency care. Obtaining a sexual history is standard of care for adolescents with abdominal pain. Testing for sexually transmitted infections (STIs) and pregnancy should be based on historical findings. The objective of this study was to determine whether differential care was provided to adolescent female patients with abdominal pain based on patient race or healthcare provider characteristics by evaluating the documentation of sexual history, STI testing, and pregnancy testing.

Methods
This was a retrospective chart review of female patients between the ages of 14 and 18 years with abdominal pain presenting to a pediatric emergency department. Patient and provider characteristics, sexual history documentation, STI, and pregnancy testing were abstracted. Data were analyzed using χ2 test and logistic regression model.

Results
Eight hundred eighty-six encounters were included in the analysis. Median patient age was 16 years (range, 14–18 years); 359 (40.5%) were non-White. Differential care was provided. Non-White patients compared with White patients were more likely to have a documented sexual history (59.9% vs 44.0%, P < 0.001), STI testing (24.8% vs 7.8%, P < 0.001), and pregnancy testing (76.6% vs 66.2%, P < 0.001). Among sexually active female patients, the racial disparity for STI testing persisted (P = 0.010). Provider type and sex did not result in differences in sexual history documentation, STI, or pregnancy testing for non-White compared with White patients (P > 0.05).

Conclusions
Differential care was provided to non-White adolescents with abdominal pain compared with White adolescents. They were more likely to have a documented sexual history, STI testing, and pregnancy testing. Healthcare provider characteristics did not impact patient care. This racial disparity resulted in better medical care for non-White adolescents, but this may be the consequence of underlying implicit bias.
De-escalation of High-flow Respiratory Support for Children Admitted with Bronchiolitis: A Quality Improvement Initiative
Authors: Hoefert Jennifer A. , Molina Adolfo L. , Gardner Hannah M. , Miller Kevin H. , Wu Chang L. , Grizzle Karisa , Miller Kylee N. , Orr Mary M. 
Published: March 2022

Introduction:
Bronchiolitis is the most common cause for hospitalization in the first year of life, with hypoxemia and acute respiratory failure as major determinants leading to hospitalization. In addition, the lack of existing guidelines for weaning and discontinuing supplemental oxygen, including high-flow nasal cannula, may contribute to prolonged hospitalization and increased resource utilization.

Methods:
This single-center quality improvement initiative assessed the effect of implementing a standardized care process for weaning and discontinuing high-flow oxygen for patients hospitalized with bronchiolitis. Patients aged 1–24 months with bronchiolitis admitted to the general wards or ICU step-down unit from February 1, 2018, and January 31, 2020 were included in the study. Primary outcomes included length of stay and time on supplemental oxygen, with time on high-flow oxygen and length of time in ICU step-down unit as secondary outcomes. Balancing measures included transfer rate to Pediatric Intensive Care Unit, intubation rate, 7- and 30-day readmission rates, and 7- and 30-day ED visits after discharge.

Results:
Following the standardized care process implementation, the mean length of stay decreased from 60.7 hours to 46.7 hours (P < 0.01). In addition, the mean time on any supplemental oxygen decreased by 47% (P < 0.01), the mean time on high-flow oxygen decreased by 45% (P < 0.01), and the mean time in the ICU step-down unit decreased by 27% (P =< 0.01). Balancing measures remained unchanged with no statistically significant differences.

Conclusion:
Implementing a standardized care process for weaning and discontinuing high-flow oxygen may reduce the length of stay and resource utilization for patients hospitalized with bronchiolitis.
Schmorl Node Can Cause Increased 68Ga-FAPI Activity on PET/CT
Authors: Wu Junhao , Tang Wenxin , Wang Yingwei , Gong Weidong , Zhang Chunyin 
Published: March 2022

Abstract

68Ga-FAPI is a newly developed tumor imaging agent with promising clinical applications. However, benign lesions may also show increased FAPI activity. We accidentally discovered that Schmorl node expressed FAPI activity in a patient with sweat gland cancer. Thus, greater awareness is needed that Schmorl nodes are a potential reason for false-positive uptake on 68Ga-FAPI PET/CT.
Uncommon Metastases From Occult Breast Cancer Revealed by 18F-FDG and 68Ga-FAPI PET/CT
Authors: Xu Weizhi , Meng Tinghua , Shang Qihang , Pang Yizhen , Chen Haojun 
Published: March 2022

Abstract
Metastases to gastrointestinal tract from breast cancer are very rare and can be diagnostically challenging. In this case, we reported 18F-FDG and 68Ga-FAPI PET/CT findings in a 54-year-old women with such uncommon metastases from breast cancer. Although the primary tumor of breast cancer remained radiologically occult, 68Ga-FAPI PET/CT showed a far better tumor-to-background ratio than 18F-FDG PET/CT for detecting the metastatic lesions, especially for detecting the retroperitoneal lymph node and rectal metastases.
Synthesis of genetic association studies on autism spectrum disorders using a genetic model-free approach
Authors: Mpoulimari Ioanna , Zintzaras Elias 
Published: March 2022

Background
Autism spectrum disorder (ASD) is a clinically and genetically heterogeneous group of neurodevelopmental disorders. Despite the extensive efforts of scientists, the etiology of ASD is far from completely elucidated. In an effort to enlighten the genetic architecture of ASDs, a meta-analysis of all available genetic association studies (GAS) was conducted.

Methods
We searched in the Human Genome Epidemiology Navigator (HuGE Navigator) and PubMed for available case–control GAS of ASDs. The threshold for meta-analysis was two studies per genetic variant. The association between genotype distribution and ASDs was examined using the generalized linear odds ratio (ORG). For variants with available allele frequencies, the examined model was the allele contrast.

Results
Overall, 57 candidate genes and 128 polymorphisms were investigated in 159 articles. In total 28 genetic polymorphisms have been shown to be associated with ASDs, that are harbored in 19 genes. Statistically significant results were revealed for the variants of the following genes adenosine deaminase (ADA), bone marrow stromal cell antigen-1 (CD157/BST1), Dopamine receptor D1 (DRD1), engrailed homolog 2 (EN2), met proto-oncogene (MET), methylenetetrahydrofolate reductase (MTHFR), solute carrier family 6 member 4 (SLC6A4), Synaptosomal-associated protein, 25kDa (SNAP-25) and vitamin D receptor (VDR). In the allele contrast model of cases versus healthy controls, significant associations were observed for Adrenoceptor Alpha 1B (ADRA1B), acetyl serotonin O - methyltransferase (ASMT), complement component 4B (C4B), dopamine receptor D3 (DRD3), met proto-oncogene (MET), neuroligin 4, X-linked (NLGN4), neurexin 1 (NRXN1), oxytocin receptor (OXTR), Serine/Threonine-Protein Kinase PFTAIRE-1 (PFTK1), Reelin (RELN) and Ras-like without CAAX 2 (RIT2).

Conclusion
These significant findings provide further evidence for genetic factors’ implication in ASDs offering new perspectives in means of prevention and prognosis.
Neuron-specific transcriptomic signatures indicate neuroinflammation and altered neuronal activity in ASD temporal cortex
Authors: Zhang Pan , Omanska Alicja , Ander Bradley P. , Gandal Michael J. , Stamova Boryana , Schumann Cynthia M. 
Published: March 2022

AbstractAutism spectrum disorder (ASD) is a highly heterogeneous disorder, yet transcriptomic profiling of bulk brain tissue has identified substantial convergence among dysregulated genes and pathways in ASD. However, this approach lacks cell-specific resolution. We performed comprehensive transcriptomic analyses on bulk tissue and laser-capture microdissected (LCM) neurons of 59 postmortem human brains (27 ASD and 32 matched controls) in the superior temporal gyrus (STG) ranging from 2-73 years of age. In bulk tissue, synaptic signaling, heat shock protein-related pathways and RNA splicing were significantly altered in ASD. There was age-dependent dysregulation of genes involved in GABA (GAD1 and GAD2) and glutamate (SLC38A1) signaling pathways. In LCM neurons, AP-1 mediated neuroinflammation and insulin/IGF-1 signaling pathways were upregulated in ASD, while mitochondrial function, ribosome and spliceosome components were downregulated. GABA synthesizing enzymes GAD1 and GAD2 were both downregulated in ASD neurons. Alterations in small nucleolar RNAs (snoRNAs) associated with splicing events suggested interplay between snoRNA dysregulation and splicing disruption in neurons of individuals with ASD. Our findings supported the fundamental hypothesis of altered neuronal communication in ASD, demonstrated that inflammation was elevated at least in part in ASD neurons, and may reveal windows of opportunity for biotherapeutics to target the trajectory of gene expression and clinical manifestation of ASD throughout the human lifespan.