bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal muscle thickness as an independent prognostic imaging marker in newly diagnosed glioblastoma patients: A validation study
Authors: Broen Martinus P G , Beckers Rueben , Willemsen Anna C H , Huijs Sandra M H , Pasmans Raphael C O S , Eekers Daniëlle B P , Ackermans Linda , Beckervordersandforth Jan , van Raak Elisabeth P M , Verduin Maikel , Anten Monique H M E , Hoeben Ann , Postma Alida A 
Published: March 2022

Abstract

Background
Previous studies have recognized temporal muscle thickness (TMT) as a prognostic marker in glioblastoma, but clinical implementation is hampered due to studies’ heterogeneity and lack of established cutoff values. The aim of this study was to assess the validity of recent proposed sex-specific TMT cutoff values in a real-world population of genotyped primary glioblastoma patients.

Methods
We measured TMT in preoperative MR images of 328 patients. Sex-specific TMT cutoff values were used to divide patients into “at risk of sarcopenia” or “normal muscle status”. Kaplan-Meier analyses and stepwise multivariate Cox-Regression analyses were used to assess the association with overall survival (OS) and progression-free survival (PFS). The association with occurrence of complications and discontinuation of glioblastoma treatment was investigated using odds ratios (OR).

Results
Patients at risk of sarcopenia had a significantly higher risk of progression and death than patients with normal muscle status, which remained significant in the multivariate analyses (OS HR = 1.437; 95%CI: 1.046–1.973; P = .025 and PFS HR = 1.453; 95%CI: 1.037–2.036; P = .030). Patients at risk of sarcopenia also had a significantly higher risk of early discontinuation of treatment (OR = 2.45; 95%CI: 1.011–5.952; P = .042) and a significantly lower chance of receiving second-line treatment (OR = 0.23; 95%CI: 0.09–0.60; P = .001). There was no association with the occurrence of complications.

Conclusions
Our study confirms external validity of the use of proposed sex-specific TMT cutoff values as an independent prognostic marker in newly diagnosed glioblastoma patients. This simple, noninvasive marker could improve patient counseling and aid in treatment decision processes or trial stratification.
Atypical Conjunctival Lesion as the Initial Presentation of Granulomatosis With Polyangiitis in an Adolescent Male
Authors: Sripawadkul Wathanee , Zein Mike , Galor Anat , Rivas-Chacon Rafael , Khzam Rayan Abou , Dubovy Sander R. , Karp Carol L. 
Published: March 2022

Purpose:
The purpose of this study was to report the first case of a conjunctival granulomatous lesion as the presenting sign of granulomatous polyangiitis (GPA) in a pediatric patient.

Methods:
This study is a case report.

Results:
A 14-year-old Hispanic boy presented with a conjunctival lesion on the inferior bulbar conjunctiva of the right eye associated with diffuse conjunctival injection. The mass progressively grew and became painful over the course of 6 weeks. No retinal or orbital abnormalities were noted on examination. The lesion was excised, and histopathological analysis was consistent with granulomatous inflammation. The lesion recurred after 15 months, and a second excisional biopsy was performed. The lesion again slowly recurred, and on presentation to our clinic, an elevated lesion in the inferior limbal/bulbar conjunctiva of the right eye was noted from 4 to 8 o'clock with accompanying forniceal shortening. Five months after the second excision, the patient developed flu-like symptoms with polyarthralgia. A full diagnostic workup revealed multiple pulmonary nodules on chest imaging, proteinuria on urinalysis, and a positive c-antineutrophil cytoplasmic antibody on serological studies. Based on these findings, the patient underwent a kidney biopsy which showed pauci-immune crescentic glomerulonephritis, consistent with a diagnosis of GPA. The patient achieved disease remission with rituximab. Despite treatment, the conjunctival lesion did not regress and remained unchanged in size for 3 years with periodic episodes of inflammation.

Conclusions:
This is the first documented case of a conjunctival mass as the initial presenting feature of pediatric GPA. The presence of granulomatous inflammation on histopathology and recurrences after excision should raise suspicion for GPA in children and adults.
Guiding Fellows to Independent Practice
Authors: Kou Maybelle , Baghdassarian Aline , Khanna Kajal , Jamal Nazreen , Carney Michele , Fein Daniel M. , Kim In , Langhan Melissa L. , Rose Jerri A. , Zuckerbraun Noel S. , Roskind Cindy G. ,   On behalf of the AAP Section on Emergency Medicine Fellowship Program Director's Committee
Published: March 2022

Background
Recent studies highlight the importance of physician readiness to practice beyond graduate training. The Accreditation Council for Graduate Medical Education mandates that pediatric emergency medicine (PEM) fellows be prepared for independent practice by allowing “progressive responsibility for patient care.” Prior unpublished surveys of program directors (PDs) indicate variability in approaches to provide opportunities for more independent practice during fellowship training.

Objectives
The aims of the study were to describe practices within PEM fellowship programs allowing fellows to work without direct supervision and to identify any barriers to independent practice in training.

Design/Methods
An anonymous electronic survey of PEM fellowship PDs was performed. Survey items were developed using an iterative modified Delphi process and pilot tested. Close-ended survey responses and demographic variables were summarized with descriptive statistics. Responses to open-ended survey items were reviewed and categorized by theme.

Results
Seventy two of 84 PDs (88%) responded to the survey; however, not all surveys were completed. Of the 68 responses to whether fellows could work without direct supervision (as defined by the Accreditation Council for Graduate Medical Education) during some part of their training, 31 (45.6%) reported that fellows did have this opportunity. In most programs, clinical independence was conditional on specific measures including the number of clinical hours completed, milestone achievement, and approval by the clinical competency committee. Reported barriers to fellow practice without direct oversight included both regulatory and economic constraints.

Conclusions
Current training practices that provide PEM fellows with conditional clinical independence are variable. Future work should aim to determine best practices of entrustment, identify ideal transition points, and mitigate barriers to graduated responsibility.
Deimplementation of Polycythemia Screening in Asymptomatic Infants in a Level 1 Nursery
Authors: Johnson Scarlett C. , Bigus Elizabeth , Thompson Patricia L. , Bundy David G. , Amaya Michelle I. 
Published: March 2022

Introduction:
Polycythemia (venous hematocrit >65%) is rare in healthy newborns (incidence: 0.4%–5%), with serious outcomes (stroke, bowel ischemia) of unknown incidence in asymptomatic infants. No national guidelines address screening or management of asymptomatic infants with polycythemia. Our nursery screened “high risk” (HR) newborns (small for gestational age, large for gestational age, twin, infant of diabetic mother) with poor adherence and low yield. We aimed to decrease polycythemia screening of asymptomatic HR infants by 80% within 6 months.

Methods:
We conducted an improvement project at a tertiary children’s hospital using the Model for Improvement. Eligible infants had an HR ICD-10 code on their problem list, were asymptomatic, over 35 weeks gestational age, and remained in the nursery for >6 hrs. Interventions included discontinuation of prior protocol, education for staff, bimonthly feedback on project performance, and visual reminders. Our primary outcome measure was the proportion of asymptomatic infants who received a hematocrit screen. Secondary measures were screening costs. Balancing measures were the length of stay, detected/symptomatic polycythemia, transfers to ICU/wards, and readmissions within 1 week of discharge.

Results:
The Nursery unit screened 80% of HR infants at baseline. This decreased to 7.3% after PDSA1, 0% after PDSA2, and 1% after PDSA3. There was no symptomatic polycythemia or statistically significant increase in readmissions/transfers. One month of monitoring revealed persistent changes.

Conclusion:
Simple quality improvement interventions such as education, reminders, and feedback can facilitate the deimplementation of low-value practices.
Effect of a Multispecialty Faculty Handoff Initiative on Safety Culture and Handoff Quality
Authors: Fitzgerald Katie M. , Banerjee Taruna R. , Starmer Amy J. , Caplan Gregory H. , Alkuwari Mohammed , Hillier Debra F. , Stack Anne M. 
Published: March 2022

Introduction:
Structured handoffs at transitions of care are vital components of patient safety. A safety culture survey showed that “handoffs and transitions” were among the lowest scoring dimensions at our hospital. We sought to improve physician handoffs and safety culture scores by implementing standardized handoff communication across multiple divisions of an academic pediatric department.

Methods:
We used a modified learning collaborative model to implement an I-PASS program, including training, standardized verbal handoff processes, observation and feedback, and sustainment. The setting was the Department of Pediatrics (DoP) within a tertiary academic children’s hospital encompassing 13 clinical divisions. The primary outcome was a change in the DoP staff physician “handoffs and transitions” score on the Agency for Healthcare Quality (AHRQ) Hospital Survey on Patient Safety Culture. Process measures included handoff duration and proportion of handoffs using the complete I-PASS mnemonic.

Results:
Five hundred sixty-seven physicians from clinical divisions participated over 14 months. One hundred percent of eligible physicians completed an introductory online I-PASS training module. The “handoffs and transitions” score improved from 46% to 54% from 2018 to 2020. From May 2019 to February 2020, the proportion of observed handoffs with all five elements of the I-PASS mnemonic improved from 62% to 100%, and the duration of handoffs per patient did not change.

Conclusions:
We successfully implemented an I-PASS program across an academic department of pediatrics. The departmental staff physician safety culture “handoff and transitions” score improved. The adherence to the I-PASS mnemonic improved. The duration of handoffs did not change over the study period.
Engagement and Bundle Compliance during COVID-19: A Virtual Strategy
Authors: Reinhart Richelle M. , Fink Alia , Bhattarai Sopnil , Cheng Jenhao Jacob , Saha Anit , Worten Katherine , Cronin Jessica , Shah Rahul 
Published: March 2022

Introduction:
COVID-19 forced industries to change work processes; this was no different for those working to improve patient outcomes in healthcare. Due to competing priorities, many hospitals struggled with the upkeep of hospital-acquired condition (HAC) auditing and engagement. Children’s National hospital developed a three-pronged approach for virtual engagement and sustainment of the processes necessary to achieve and maintain goal auditing and bundle compliance in three HACs: unplanned extubation, central line-associated bloodstream infections, and employee staff safety overexertion injuries.

Methods:
The overall goal was to create a flexible approach to maintaining engagement while relying on virtual communication.

Aim:
To maintain, without a decrease of more than 20%, the baseline bundle compliance per month for each HAC (unplanned extubation, central line-associated bloodstream infections, and employee staff safety) from March 2020 to March 2021. Our approach to increasing bundle compliance (primary outcome measure) and audits (process measure) included: regular leadership meetings using multiple virtual modalities, improving the audit process, and ensuring fidelity to bundle elements.

Results:
Qualitatively, we have found that microsystem leaders regularly engage with quality improvement staff and their teams using virtual touchpoints and ongoing communication. We exceeded the goal of maintaining our monthly bundle compliance, and we saw a significant positive change in the rate of audits after COVID-19.

Conclusions:
In a time of change during a pandemic, increased engagement in HAC work can adapt structure and processes. Our results are generalizable by increasing touchpoints using multiple virtual modalities.
Ectopic Gallbladder in the Left Upper Abdomen Shown on Hepatobiliary Scintigraphy
Authors: Bai Xia , Zhuang Hongming 
Published: March 2022

Abstract
The gallbladder is normally located in the right upper abdomen below the undersurface of the liver. We reported an ectopically located gallbladder, which was located in the left upper abdomen on hepatobiliary scintigraphy in an 18-year-old woman.
Heterogeneous Head and Neck Paraganglioma With Distinct Features on 123I-MIBG and 68Ga-DOTATATE Images
Authors: Lu Yang 
Published: March 2022

Abstract
A 37-year-old man has palpable bilateral carotid body paragangliomas, larger on the right. The right-sided tumor is avid on both 123I-MIBG and 68Ga-DOTATATE PET/CT images. The left-sided tumor is only avid on 68Ga-DOTATATE PET/CT, but not 123I-MIBG scan. This case illustrates the heterogeneous features of carotid body paragangliomas.
Fast model-free standardization and integration of single-cell transcriptomics data
Authors: Xu Yang , Kramann Rafael , McCord Rachel Patton , Hayat Sikander 
Published: March 2022

AbstractSingle-cell transcriptomics datasets from the same anatomical sites generated by different research labs are becoming mainstream. However, fast, and computationally inexpensive tools for standardization of cell-type annotation and data integration are still needed to increase research inclusivity. To standardize cell-type annotation and integrate single-cell transcriptomics datasets, we have built a fast, model-free integration method called MASI (Marker-Assisted Standardization and Integration). MASI can run integrative annotation on a personal laptop for approximately one million cells, providing a cheap computational alternative for the single-cell data analysis community. MASI has an average macro F1/overall accuracy of 0.79/0.89 over the 4 benchmark datasets. We demonstrate that MASI outperforms other methods based on speed, and its performance for the tasks of data integration and cell-type annotation is comparable or even superior to other existing methods. We apply MASI for integrative lineage analysis and show that it preserves the underlying biological signal in datasets tested. Finally, to harness knowledge from single-cell atlases, we demonstrate three case studies that cover integration across research groups, biological conditions, and surveyed participants, respectively.
Profiling the proximal proteome of the mu opioid receptor identifies novel regulators of receptor signaling and trafficking
Authors: Polacco Benjamin J. , Lobingier Braden T. , Blythe Emily E. , Abreu Nohely , Khare Prachi , Howard Matthew K. , Gonzalez-Hernandez Alberto J. , Xu Jiewei , Li Qiongyu , Novy Brandon , Chi Naing Zun Zar , Shoichet Brian K. , Coyote-Maestas Willow , Levitz Joshua , Krogan Nevan J. , Zastrow Mark Von , Hüttenhain Ruth 
Published: March 2022

AbstractThe mu opioid receptor (μOR), a prototypic member of the large G protein-coupled receptor (GPCR) family, represents an important target of therapeutic and abused drugs. To date, most of our understanding of μOR activity has focused on signal transducers and regulatory molecules including G proteins, GPCR kinases, and beta-arrestins. Yet it is clear that signaling through the μOR is coordinated by additional proteins recruited into the proximal interaction network of the activated receptor, which have largely remained invisible given the lack of technologies to interrogate these networks systematically.Here, we implement a quantitative proteomics pipeline leveraging the chemical diversity of μOR agonists and APEX-based proximity labeling to investigate the protein networks that underlie μOR signaling. We leverage a novel computational framework to extract subcellular location, trafficking, and functional partners of GPCR activity from the proximity labeling datasets. Applying this unbiased, systematic approach to the μOR, we demonstrate that opioid agonists exert differences in the μOR proximal proteome mediated by endocytosis and subsequent endosomal sorting, exemplified by VPS35 and COMMD3. Moreover, we identify two novel μOR network components, EYA4 and KCTD12, that are recruited into the receptor proximal network irrespective of the activating ligand and independent of receptor trafficking but based on receptor-triggered G protein activation. We provide functional evidence that these network components form a previously unrecognized buffering system for G protein activity which broadly modulates cellular GPCR signaling.
Reference-based cell type matching of spatial transcriptomics data
Authors: Zhang Yun , Miller Jeremy A. , Park Jeongbin , Lelieveldt Boudewijn P. , Long Brian , Abdelaal Tamim , Aevermann Brian D. , Biancalani Tommaso , Comiter Charles , Dzyubachyk Oleh , Eggermont Jeroen , Langseth Christoffer Mattsson , Petukhov Viktor , Scalia Gabriele , Vaishnav Eeshit Dhaval , Zhao Yilin , Lein Ed S. , Scheuermann Richard H. 
Published: March 2022

AbstractWith the advent of multiplex fluorescence in situ hybridization (FISH) and in situ RNA sequencing technologies, spatial transcriptomics analysis is advancing rapidly. Spatial transcriptomics provides spatial location and pattern information about cells in tissue sections at single cell resolution. Cell type classification of spatially-resolved cells can also be inferred by matching the spatial transcriptomics data to reference single cell RNA-sequencing (scRNA-seq) data with cell types determined by their gene expression profiles. However, robust cell type matching of the spatial cells is challenging due to the intrinsic differences in resolution between the spatial and scRNA-seq data. In this study, we systematically evaluated six computational algorithms for cell type matching across four spatial transcriptomics experimental protocols (MERFISH, smFISH, BaristaSeq, and ExSeq) conducted on the same mouse primary visual cortex (VISp) brain region. We find that while matching results of individual algorithms vary to some degree, they also show agreement to some extent. We present two ensembl meta-analysis strategies to combine the individual matching results and share the consensus matching results in the Cytosplore Viewer (https://viewer.cytosplore.org) for interactive visualization and data exploration. The consensus matching can also guide spot-based spatial data analysis using SSAM, allowing segmentation-free cell type assignment.
A DEAD-box helicase drives the partitioning of a pro-differentiation NAB protein into nuclear foci
Authors: Doi Akiko , Suarez Gianmarco D. , Droste Rita , Horvitz H. Robert 
Published: March 2022

AbstractHow cells regulate gene expression in a precise spatiotemporal manner during organismal development is a fundamental question in biology. Recent studies have demonstrated the role of transcriptional condensates in gene regulation1–5. However, little is known about the function and regulation of these transcriptional condensates in the context of animal development and physiology. We found that the evolutionarily conserved DEAD-box helicase DDX-23 controls stem cell fate in C. elegans at least in part by binding to and facilitating the condensation of MAB-10, the C. elegans homolog of mammalian NAB protein. MAB-10 is a transcriptional cofactor that functions with the EGR protein LIN-29 to regulate the transcription of genes required for exiting the cell cycle, terminal differentiation, and the larval-to-adult transition6. We suggest that DEAD-box helicase proteins function more generally during animal development to control the condensation of NAB proteins important in cell-fate decisions and that this mechanism is evolutionarily conserved. In mammals, a comparable mechanism might underlie terminal cell differentiation and when misregulated might promote cancerous growth.
Application of B cell immortalization for the isolation of antibodies and B cell clones from vaccine and infection settings
Authors: Boswell Kristin L. , Watkins Timothy , Cale Evan M. , Samsel Jakob , Andrews Sarah F. , Ambrozak David R. , Driscoll Jefferson I. , Messina Michael A. , Narpala Sandeep , Hopp Christine S. , Cagigi Alberto , Casazza Joseph P. , Yamamoto Takuya , Zhou Tongqing , Schief William R. , Crompton Peter D. , Ledgerwood Julie E. , Connors Mark , Gama Lucio , Kwong Peter D. , McDermott Adrian , Mascola John R. , Koup Richard A. 
Published: March 2022

AbstractThe isolation and characterization of neutralizing antibodies from infection and vaccine settings will inform future vaccine design, and methodologies that streamline the isolation of antibodies and the generation of B cell clones are of great interest. Retroviral transduction to express Bcl-6 and Bcl-xL in primary B cells has been shown to promote long-term B cell survival and antibody secretion in vitro, and can be used to isolate antibodies from memory B cells. The application of this methodology to B cell subsets from tissues and to B cells from individuals with chronic infection has not been extensively characterized. Here, we characterize Bcl-6/Bcl-xL B cell immortalization across multiple tissue types and B cell subsets in healthy and HIV-1 infected individuals, as well as individuals recovering from malaria. In HIV-1- and malaria-uninfected donors, naïve and memory B cell subsets from PBMC and tonsil tissue transformed with similar efficiencies, and displayed similar characteristics after transformation with respect to their longevity and immunoglobulin secretion. In HIV-1-viremic individuals or in individuals after malaria infection, the CD27-CD21- memory B cell subsets transformed with lower efficiencies compared to the CD27+CD21+ populations, but following transformation B cells expanded and secreted IgG with similar efficiency. Using B cells from HIV-1-infected individuals, we combined Bcl-6/Bcl-xL B cell immortalization with a HIV-1 microneutralization assay to isolate broadly neutralizing antibodies related to VRC13 and VRC38.01. Overall, Bcl-6/Bcl-xL B cell immortalization can be used to isolate antibodies and generate B cell clones from multiple different B cell populations, albeit with different efficiencies.