bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teprotumumab for Thyroid Eye Disease-related Strabismus
Authors: Dallalzadeh Liane O. , Villatoro George A. , Chen Lillian , Sim Myung S. , Movaghar Mansoor , Robbins Shira L. , Karlin Justin N. , Khitri Monica R. , Velez Federico G. , Korn Bobby S. , Demer Joseph L. , Rootman Daniel B. , Granet David B. , Kikkawa Don O. 
Published: February 2024

Purpose:
To assess and quantify teprotumumab’s effect on thyroid eye disease-related strabismus by change in measured horizontal and vertical deviations and change in extraocular motility.

Methods:
We reviewed a series of patients with thyroid eye disease-related strabismus treated with teprotumumab. Exclusion criteria included age under 18 years, strabismus of alternate etiology, or thyroid eye disease-related reconstructive surgery during the treatment course. Primary outcomes were absolute (prism diopters) and relative (%) differences in horizontal and vertical deviations in primary position at distance, as well as change in ductions of the more affected eye. Secondary outcomes included incidence and timing of strabismus surgery postteprotumumab.

Results:
Thirty-one patients were included, with mean age 63 years and thyroid eye disease duration 10 months. After teprotumumab, there was 6 prism diopters (39%) mean reduction in vertical deviation (p < 0.001), without significant change in mean horizontal deviation (p = 0.75). Supraduction, abduction, adduction, and infraduction significantly improved in the more restricted eye (p < 0.01, p < 0.01, p = 0.04, and p = 0.01, respectively). Thirty-five percent of patients underwent strabismus surgery posttreatment, at an average 10 months after last infusion.

Conclusions:
Teprotumumab produced a statistically significant reduction in vertical but not horizontal strabismus angles in primary position at distance. Extraocular motility in all 4 ductions also improved. A substantial minority of patients still required strabismus surgery following teprotumumab.
Nonsurgical risk factors for marginal ulcer following Roux-en-Y gastric bypass for obesity: a systematic review and meta-analysis of 14 cohort studies
Authors: Liang Yi , Wang Chunyun , Yang Lebin , Yang Kewei , Zhang Shulun , Xie Wenbiao 
Published: February 2024

Backgrounds:
Marginal ulcer (MU) is a common complication of Roux-en-Y Gastric Bypass (RYGB). The primary goal of this meta-analysis was to identify potential risk factors for MU post-RYGB.

Methods:
A comprehensive literature search was conducted on four databases (PubMed, Embase, Web of Science, and the Cochrane Library) to identify articles published from inception to 23 May 2023 that reported risk factors linked to ulcer occurrence post-RYGB. Hazard Ratio (HR) and Odds Ratio (OR) with respective 95% CI were calculated to estimate the impact of selected risk factors on MU. The risk factors were evaluated through multivariate analyses. The estimated risk factors were subjected to a random-effects model. Subgroup analysis based on study baseline characteristics and leave-one-out sensitivity analysis were also performed to investigate the potential sources of heterogeneity and assess the robustness of the findings.

Result:
Herein, 14 observational studies involving 77 250 patients were included. Diabetes, smoking, and steroid use were identified to be risk factors of MU, with pooled ORs of (1.812; 95% CI: 1.226–2.676; P=0.003), (3.491; 95% CI: 2.204–5.531; P<0.001), and (2.804; 95% CI: 1.383–5.685; P=0.004), respectively. Other risk factors, such as alcohol consumption, male sex, and PPI use, were deemed not significant due to differences in data acquisition and effect estimates.

Conclusion:
Diabetes, smoking, and steroid use were identified as independent risk factors of MU. Enhancing awareness of these identified risk factors will lead to more effective preoperative prevention and targeted postoperative interventions for patients undergoing RYGB.
Beyond competence and retention: Developing a comprehensive evaluation framework for a rural primary care nurse practitioner residency program
Authors: Hillman JoAnna L. , Gowgiel Janelle C. , Price Paula S. , Robertson Bethany 
Published: February 2024

ABSTRACTWith the rise in nurse practitioner (NP) residency programs, evaluations have largely focused on retention and competency completion for residents. There is a need for expanded evaluation to ensure the sustainability of NP residency programs, to ensure timely adaptations to address resident satisfaction, and to solidify a long-term pathway of NPs well prepared for rural practice. We created a family nurse practitioner (FNP) residency program with a comprehensive evaluation framework to prepare residents for practice in rural settings. The evaluation framework was developed through collaborative engagement of an external evaluation team, program leadership, and clinical site representatives. The evaluation framework of the FNP residency program combined resident assessment and holistic program evaluation, using a rapid continuous quality improvement (QI) approach. The evaluation considered three distinct perspectives: the resident, the peer coach, and the clinical site. The rapid continuous QI approach allowed program leadership to respond swiftly to programmatic challenges, improve the residency program in response to residents' reported experiences, and emphasize sustainability for continued program impact, while assessing residents' learning and performance. The program's data-driven evaluation approach has demonstrated its success in meeting the goals of the Health Resources and Services Administration funding by increasing the number of primary care providers in rural settings. The program's expansion and continued success have further validated the efficacy of this evaluation framework in assessing, improving, and ensuring the sustainability of APRN residency programs. This article calls for the adoption of similar evaluation strategies in future residency programs to promote their long-term success and impact in rural health care settings.
Mapping Cumulative Risk in Delaware: Approach and Implications for Health Equity
Authors: Brooks Madeline M. , Salvatore Alicia L. , Khanal Pragyan , Curriero Frank C. 
Published: February 2024

Background:
Addressing health equity requires attention to upstream determinants of health, including environmental and social factors that act in tandem to increase communities' exposure to and vulnerability to toxicants. Cumulative risk assessment, which evaluates combined risks from environmental and social factors, is a useful approach for estimating potential drivers of health disparities. We developed a cumulative risk score of multiple indices of environmental and social conditions and assessed block group–level differences in New Castle County, Delaware.

Methods:
This cross-sectional study used choropleth maps to visualize the distribution of environmental, social, and cumulative risks and Moran's I statistics to assess spatial clustering of cumulative risk across the county and among individual block groups.

Results:
Findings indicate that environmental risk rarely occurs without social risk and that environmental and social risks co-occur in distinct areas, resulting in large-scale clustering of cumulative risk. Areas of higher cumulative risk had more Black residents and people of lower socioeconomic status.

Conclusions:
Replicable measures of cumulative risk can show how environmental and social risks are inequitably distributed by race and socioeconomic status, as seen here in New Castle County. Such measures can support upstream approaches to reduce health disparities resulting from histories of environmental racism.
Effect of Robotic Rehabilitation on Hand Functions and Quality of Life in Children With Cerebral Palsy
Authors: Adar Sevda , Keskin Duygu , Dündar Ümit , Toktaş Hasan , Yeşil Hilal , Eroğlu Selma , Eyvaz Nuran , Beştaş Ersin , Demircan Ali 
Published: February 2024

Objective
This study aimed to examine the impact of robotic hand rehabilitation on hand function and quality of life in children with cerebral palsy.

Design
Children with cerebral palsy aged 7–16 yrs were divided into robotic rehabilitation (n = 9) or conventional rehabilitation (n = 10) groups for hand rehabilitation of 30 sessions. The primary outcomes were the Fugl-Meyer Assessment for Upper Extremity and Box and Block Test. The secondary outcomes were the Manual Ability Classification System, modified Ashworth scale, hand grasp and finger strengths, ABILHAND-Kids, Functional Independence Measure for Children, and PedsQL Quality of Life Inventory–CP Module.

Results
In the robotic rehabilitation group, a significant improvement was found in all parameters after treatment (P < 0.05), except for the Functional Independence Measure (P = 0.081). In the conventional rehabilitation group, there was significant improvement after treatment in the modified Ashworth scale, Fugl-Meyer Assessment for Upper Extremity, hand grasp strength, Box and Block Test, ABILHAND-Kids, and PedsQL Quality of Life Inventory–CP Module (P < 0.05). Before and after treatment, all outcome parameters in the groups were similar (P > 0.05).

Conclusions
Robotic hand rehabilitation is effective in improving motor function, manual dexterity, spasticity, and quality of life in children with cerebral palsy. However, it was not demonstrated to be superior to conventional rehabilitation.
Antimicrobial Stewardship and Improved Antibiotic Utilization in the Pediatric Cardiac Intensive Care Unit
Authors: Hillyer Margot M. , Jaggi Preeti , Chanani Nikhil K. , Fernandez Alfred J. , Zaki Hania , Fundora Michael P. 
Published: February 2024

Background:
We developed a multidisciplinary antimicrobial stewardship team to optimize antimicrobial use within the Pediatric Cardiac Intensive Care Unit. A quality improvement initiative was conducted to decrease unnecessary broad-spectrum antibiotic use by 20%, with sustained change over 12 months.

Methods:
We conducted this quality improvement initiative within a quaternary care center. PDSA cycles focused on antibiotic overuse, provider education, and practice standardization. The primary outcome measure was days of therapy (DOT)/1000 patient days. Process measures included electronic medical record order-set use. Balancing measures focused on alternative antibiotic use, overall mortality, and sepsis-related mortality. Data were analyzed using statistical process control charts.

Results:
A significant and sustained decrease in DOT was observed for vancomycin and meropenem. Vancomycin use decreased from a baseline of 198 DOT to 137 DOT, a 31% reduction. Meropenem use decreased from 103 DOT to 34 DOT, a 67% reduction. These changes were sustained over 24 months. The collective use of gram-negative antibiotics, including meropenem, cefepime, and piperacillin-tazobactam, decreased from a baseline of 323 DOT to 239 DOT, a reduction of 26%. There was no reciprocal increase in cefepime or piperacillin-tazobactam use. Key interventions involved electronic medical record changes, including automatic stop times and empiric antibiotic standardization. All-cause mortality remained unchanged.

Conclusions:
The initiation of a dedicated antimicrobial stewardship initiative resulted in a sustained reduction in meropenem and vancomycin usage. Interventions did not lead to increased utilization of alternative broad-spectrum antimicrobials or increased mortality. Future interventions will target additional broad-spectrum antimicrobials.
The Effect of Obesity on Vaginoplasty Outcomes
Authors: Berger Lauren E. , Lava Christian X. , Spoer Daisy L. , Huffman Samuel S. , Martin Taylor , Bekeny Jenna C. , Fan Kenneth L. , Lisle David M. , Del Corral Gabriel A. 
Published: February 2024

Background
Some surgeons use body mass index criteria within the patient selection processes before vaginoplasty, thereby limiting access to select obese patients. We sought to better characterize the effect of obesity on postoperative outcomes across multiple vaginoplasty techniques.

Methods
A single-center retrospective review of all transfeminine patients undergoing primary vaginoplasty procedures from December 2018 to July 2022 was conducted. Patients were stratified into cohorts according to the World Health Organization Obesity Class criteria. Data regarding demographics, comorbidities, operative details, postoperative complications, and all-cause revision were collected.

Results
A total of 237 patients met the inclusion criteria. Average follow-up duration was 9.1 ± 4.7 months. Multivariate regression revealed that patients with class I and class II/III obesity were associated with higher odds of developing vaginal stenosis (class I: odds ratio [OR], 7.1 [P = 0.003]; class II/III: OR, 3.4 [P = 0.018]) and all-cause revision (class I: OR, 3.7 [P = 0.021]; class II/III: OR, 4.8 [P = 0.027]). Undergoing either robotic peritoneal or robotic intestinal vaginoplasty was associated with lower odds of delayed wound healing (peritoneal: OR, 0.2 [P < 0.001]; intestinal: OR, 0.2 [P = 0.011]). Lastly, adherence to dilation regimen was negatively associated with development of vaginal stenosis (OR, 0.04; P < 0.001).

Conclusions
Patients with obesity may be at a higher risk of developing vaginal stenosis after vaginoplasty, which may ultimately necessitate operative revision. Although patients with obesity may remain surgical candidates, proper preoperative counseling and adherence to postoperative vaginal dilation regimens are critical to optimizing outcomes.
Positional Skull Deformities and Neurodevelopmental Delay: Study on 449 Infants
Authors: Pinyot Joan , Lacambra David , Garriga Maria , Pinyot Maria , Niubó Josep Maria 
Published: February 2024

Objective:
Provide data on a cross-sectional study of neurodevelopmental delays (NDD) in patients with positional skull deformities (PSD), based on severity and gender, in early childhood.

Methods:
Neurodevelopment of 449 patients with PSD, with an age range of 3 to 59 months, was assessed with Battelle Developmental Inventory (BDI) tests during and after their cranial orthotic treatment. Data obtained were compared with the anthropometric measurements taken the same day the test was made, and results were grouped by diagnosis and severity, segmented by age group, and split by gender.

Results:
From 3983 patients with PSD and simple craniosynostosis, 526 accepted to participate and took a total of 1261 BDI tests. Premature patients, patients with neurological diseases or congenital malformations, and tests taken when PSD had been corrected were excluded. The resulting study group was 449 children (123 girls and 326 boys) and 972 BDI tests. Ninety-five percent of tests presented significant NDD (median value, expressed in months) in one or more BDI domains; male patients present larger NDD than do female patients; largest delays were found in brachycephaly and plagiocephaly combined (−7 mo at age range 48–59 mo), scaphocephaly (−3.5 mo at age range 12–17 mo), plagiocephaly (−3.2 mo at age range 12–17 mo). No significant NDD were found in the receptive or cognitive domains.

Conclusion:
When evaluating PSD, BDI tests, or similar, as well as mixed PSD classification should be considered. Patients with PSD should be monitored by a coordinated set of medical specialists.
The Patient Perspective on Colectomy for Recurrent Diverticulitis
Authors: Hawkins Alexander T. , Penson David F. , Geiger Timothy M. , Bonnet Kemberlee R. , Mutch Matthew G. , Maguire Lilias H. , Schlundt David G. , Rothman Russell L. 
Published: February 2024

Objective:
Understand the patient decision-making process regarding colectomy for recurrent diverticulitis.

Summary Background Data:
The decision to pursue elective colectomy for recurrent diverticulitis is highly preference sensitive. Little is known about the patient perspective in this decision-making process.

Methods:
We performed a qualitative study utilizing focus groups of patients with recurrent diverticulitis at three centers across the United States. Using an iterative inductive/deductive approach, we developed a conceptual framework to capture the major themes identified in the coded data.

Results:
From March 2019-July 2020, 39 patients were enrolled across three sites and participated in six focus groups. After coding the transcripts using a hierarchical coding system, a conceptual framework was developed. Major themes identified included: participants’ beliefs about surgery, such as normative beliefs (e.g., subjective, value placed on surgery), control beliefs (e.g., self-efficacy, stage of change) and anticipated outcomes (e.g., expectations, anticipated regret); the role of behavioral management strategies (e.g., fiber, eliminate bad habits); emotional experiences (e.g., depression, embarrassment); current symptoms (e.g., severity, timing); and quality of life (e.g., cognitive load, psychosocial factors). Three sets of moderating factors influencing patient choice were identified: clinical history (e.g., source of diagnosis, multiple surgeries), clinical protocols (e.g., pre- and post-op education) and provider-specific factors (e.g., specialty, choice of surgeon).

Conclusions:
Patients view the decision to undergo colectomy through three major themes- their beliefs about surgery, their psychosocial context and moderating factors that influence participant choice to undergo surgery. This knowledge is essential both for clinicians counseling patients who are considering colectomy and for researchers studying the process to optimize care for recurrent diverticulitis.
Single-cell multi-omics reveals insights into differentiation of rare cell types in mucinous colorectal cancer
Authors: Ladaika Christopher A. , Ghobashi Ahmed H. , Boulton William C. , Miller Samuel A. , O’Hagan Heather M. 
Published: February 2024

AbstractNeuroendocrine cells have been implicated in therapeutic resistance and worse overall survival in many cancer types. Mucinous colorectal cancer (mCRC) is uniquely enriched for enteroendocrine cells (EECs), the neuroendocrine cell of the normal colon epithelium, as compared to non-mucinous CRC. Therefore, targeting EEC differentiation may have clinical value in mCRC. Here, single cell multi-omics was used to uncover epigenetic alterations that accompany EEC differentiation, identify STAT3 as a novel regulator of EEC specification, and discover a rare cancer-specific cell type with enteric neuron-like characteristics. Further experiments demonstrated that lysine-specific demethylase 1 (LSD1) and CoREST2 mediate STAT3 demethylation and regulate STAT3 chromatin binding. Knockdown of CoREST2 in an orthotopic xenograft mouse model resulted in decreased primary tumor growth and lung metastases. In culmination, these results provide rationale for new LSD1 inhibitors that target the interaction between LSD1 with STAT3 or CoREST2, which may improve clinical outcomes for patients with mCRC.
SEraster: a rasterization preprocessing framework for scalable spatial omics data analysis
Authors: Aihara Gohta , Clifton Kalen , Chen Mayling , Atta Lyla , Miller Brendan F. , Fan Jean 
Published: February 2024

AbstractMotivationSpatial omics data demand computational analysis but many analysis tools have computational resource requirements that increase with the number of cells analyzed. This presents scalability challenges as researchers use spatial omics technologies to profile millions of cells.ResultsTo enhance the scalability of spatial omics data analysis, we developed a rasterization preprocessing framework called SEraster that aggregates cellular information into spatial pixels. We apply SEraster to both real and simulated spatial omics data prior to spatial variable gene expression analysis to demonstrate that such preprocessing can reduce resource requirements while maintaining high performance. We further integrate SEraster with existing analysis tools to characterize cell-type spatial cooccurrence. Finally, we apply SEraster to enable analysis of a mouse pup spatial omics dataset with over a million cells to identify tissue-level and cell-type-specific spatially variable genes as well as cooccurring cell-types that recapitulate expected organ structures.Availability and implementationSource code is available on GitHub (https://github.com/JEFworks-Lab/SEraster) with additional tutorials athttps://JEF.works/SEraster.
Optimal Performance Objectives in the Highly Conserved Bone Morphogenetic Protein Signaling Pathway
Authors: Shaikh Razeen , Larson Nissa J. , Hanjaya-Putra Donny , Zartman Jeremiah , Umulis David M. , Li Linlin , Reeves Gregory T. 
Published: February 2024

AbstractThroughout development, complex networks of cell signaling pathways drive cellular decision-making across different tissues and contexts. The transforming growth factor β (TGF-β) pathways, including the BMP/Smad pathway, play crucial roles in these cellular responses. However, as the Smad pathway is used reiteratively throughout the life cycle of all animals, its systems-level behavior varies from one context to another, despite the pathway connectivity remaining nearly constant. For instance, some cellular systems require a rapid response, while others require high noise filtering. In this paper, we examine how the BMP- Smad pathway balances trade-offs among three such systems-level behaviors, or “Performance Objectives (POs)”: response speed, noise amplification, and the sensitivity of pathway output to receptor input. Using a Smad pathway model fit to human cell data, we show that varying non-conserved parameters (NCPs) such as protein concentrations, the Smad pathway can be tuned to emphasize any of the three POs and that the concentration of nuclear phosphatase has the greatest effect on tuning the POs. However, due to competition among the POs, the pathway cannot simultaneously optimize all three, but at best must balance trade-offs among the POs. We applied the multi-objective optimization concept of the Pareto Front, a widely used concept in economics to identify optimal trade-offs among various requirements. We show that the BMP pathway efficiently balances competing POs across species and is largely Pareto optimal. Our findings reveal that varying the concentration of NCPs allows the Smad signaling pathway to generate a diverse range of POs. This insight identifies how signaling pathways can be optimally tuned for each context.
Defining the mechanisms and properties of post-transcriptional regulatory disordered regions by high-throughput functional profiling
Authors: Lobel Joseph H. , Ingolia Nicholas T. 
Published: February 2024

SummaryDisordered regions within RNA binding proteins are required to control mRNA decay and protein synthesis. To understand how these disordered regions modulate gene expression, we surveyed regulatory activity across the entire disordered proteome using a high-throughput functional assay. We identified hundreds of regulatory sequences within intrinsically disordered regions and demonstrate how these elements cooperate with core mRNA decay machinery to promote transcript turnover. Coupling high-throughput functional profiling with mutational scanning revealed diverse molecular features, ranging from defined motifs to overall sequence composition, underlying the regulatory effects of disordered peptides. Machine learning analysis implicated aromatic residues in particular contexts as critical determinants of repressor activity, consistent with their roles in forming protein-protein interactions with downstream effectors. Our results define the molecular principles and biochemical mechanisms that govern post-transcriptional gene regulation by disordered regions and exemplify the encoding of diverse yet specific functions in the absence of well-defined structure.