bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-Sectional Study of Resident-Reported Surgical Experience in Female Pelvic Medicine and Reconstructive Surgery
Authors: Ward Sarah A. , Mendiola Monica , Royce Celeste S. , Anand Mallika , Gompers Annika , Hacker Michele R. , Winkelman William D. 
Published: January 2023

Importance
Comprehensive surgical training is an essential component of obstetrics and gynecology residency, yet subspecialty experience may be declining.

Objective
The objective of this study was to describe trends in reported obstetrics and gynecology resident experience in female pelvic medicine and reconstructive surgery (FPMRS).

Study Design
This study was a retrospective analysis of national case log reports from the Accreditation Council for Graduate Medical Education (ACGME) for obstetrics and gynecology residents.

Results
From 2013 through 2019, ACGME collected data from a median of 241 programs (range, 239–242) with a median of 1,259 residents (range, 1,213–1,286) reporting annually. There was a 26% decrease in resident-reported experience with incontinence and pelvic floor procedures from 74 ± 38 in 2013 to 55 ± 34 in 2019 (P < 0.001). Cystoscopy increased by 19% from 43 ± 25 in 2013 to 51 ± 29 in 2019 (P < 0.001). From 2014 to 2019, vaginal hysterectomy cases decreased by 12% (P < 0.001).

Conclusions
There was a significant decrease in resident-reported FPMRS surgical experience from 2013 to 2019, while cystoscopy numbers increased. After laparoscopic and vaginal hysterectomies were unbundled in 2013, resident vaginal hysterectomy cases decreased from 2014 to 2019. Given that the ACGME Incontinence and Pelvic Floor designation comprises a wide range of procedures, future investigation is needed to elucidate the gaps in FPMRS-specific surgical training during residency and its implication in comprehensive resident surgical training.
Pregnancy and Outcomes After Prolapse Surgery: A Case Series
Authors: Boyd Brittni , Buono Kristen , Novin Atieh , Whitcomb Emily 
Published: January 2023

Importance
There are limited data on whether pelvic organ prolapse (POP) surgery is durable after subsequent delivery.

Objectives
The aims of this study were to evaluate the safety and durability of POP surgery after delivery and to describe the medical decision-making and clinical outcomes of patients who gave birth after POP surgery.

Study Design
This study is a retrospective case series of patients who underwent surgery for symptomatic POP between 2007 and 2017, and subsequently had a live birth.

Results
Twenty patients were identified. Seventeen patients underwent posterior colporrhaphy, 10 anterior colporrhaphy, and 5 apical suspensions. The mean interval between POP surgery and the first delivery was 28.6 months. One patient endorsed recurrent POP symptoms before pregnancy, and none of the remaining 19 patients reported recurrent POP symptoms before or during pregnancy. There were no pregnancy complications related to the POP surgery. Nine patients underwent cesarean delivery (CD). Four patients were counseled to have a CD due to their prior POP surgery, 3 patients had an elective primary CD due to the POP surgery, 1 patient chose an elective repeat CD, and 1 patient had a CD due to obstructed labor. Urogynecologists were consulted for delivery recommendations for 6 patients and recommended CD for 3 of them. Eleven patients had spontaneous vaginal delivery. Three patients reported recurrent POP symptoms after delivery.

Conclusions
Our findings corroborate previous case series demonstrating the safety and durability of POP surgery during and after pregnancy. More than 75% of patients gave birth by CD, which was due to physician or patient concerns regarding the prior POP surgery.
Double Pretransplant Positivity for Autoantibodies to LG3 and Angiotensin II Type 1 Receptor Is Associated With Alloimmune Vascular Injury in Kidney Transplant Recipients
Authors: Carroll Robert , Turgeon Julie , Deayton Sue , Emery Tim , Bilogrevic Fiona , Jahan Sadia , Rimbaud Annie Karakeussian , Georges Barbara , Tavares-Brum Alexandre , Hébert Marie-Josée , Cardinal Héloïse 
Published: January 2023

Background.
Both angiotensin II receptor autoantibodies (ATRabs) and autoantibodies to LG3 have been linked to kidney graft rejection with alloimmune vascular injury (AVI). We aimed to examine whether positivity for both anti-LG3 and ATRabs is associated with rejection with AVI in kidney transplant recipients.

Methods.
We performed a retrospective cohort study including consecutive kidney transplant recipients between 2013 and 2017 at a single center. The primary outcome was acute rejection with AVI (Banff grade 2 or 3 T-cell-mediated rejection and/or antibody-mediated rejection) in the first 3 mo posttransplant. The secondary outcome was death-censored allograft loss. The independent variables, anti-LG3 and ATRab, were measured pretransplant.

Results.
Among the 328 study participants, 68 experienced acute rejection with AVI and 23 experienced graft loss over a median follow-up of 4.5 y. In a multivariable model, double pretransplant positivity for anti-LG3/ATRab was associated with acute rejection with AVI (odds ratio: 2.73, 95% confidence interval: 1.06-7.05). We did not observe an association between double positivity for anti-LG3/ATRab and death-censored graft loss.

Conclusions.
Double positivity for anti-LG3/ATRabs pretransplant is associated with a higher risk of acute rejection with AVI. Whether therapies that remove antibodies could decrease that risk remains to be studied.
Supplemental Visual Abtract: http://links.lww.com/TXD/A494.
Clinical Decision Support with a Comprehensive in-EHR Patient Tracking System Improves Genetic Testing Follow Up
Authors: Campbell Ian M. , Karavite Dean J. , McManus Morgan L. , Cusick Fred C. , Junod David C. , Sheppard Sarah E. , Lourie Eli M. , Shelov Eric D. , Hakonarson Hakon , Luberti Anthony A. , Muthu Naveen , Grundmeier Robert W. 
Published: January 2023

AbstractObjectiveWe sought to develop and evaluate an electronic health record (EHR) genetic testing tracking system to address the barriers and limitations of existing spreadsheet-based workarounds.Materials and MethodsWe evaluated the spreadsheet-based system using mixed effects logistic regression to identify factors associated with delayed follow up. These factors informed the design of an EHR-integrated genetic testing tracking system. After deployment we assessed the system in two ways. We analyzed EHR access logs and note data to assess patient outcomes and performed semi-structured interviews with users to identify impact of the system on work.ResultsWe found that patient-reported race was a significant predictor of documented genetic testing follow up, indicating a possible inequity in care. We implemented a CDS system including a patient data capture form and management dashboard to facilitate important care tasks. The system significantly speeded review of results and significantly increased documentation of follow-up recommendations. Interviews with system users identified key team members ensuring success and revealed that the system addresses a number of sociotechnical factors that collectively result in safer and more efficient care.DiscussionOur new tracking system ended decades of workarounds for identifying and communicating test results and improved clinical workflows. Interview participants related that the system decreased cognitive and time burden which allowed them to focus on direct patient interaction.ConclusionBy assembling a multidisciplinary team, we designed a novel patient tracking system that improves genetic testing follow up. Similar approaches may be effective in other clinical settings.
Incident autoimmune diseases in association with a SARS-CoV-2 infection: A matched cohort study
Authors: Tesch Falko , Ehm Franz , Vivirito Annika , Wende Danny , Batram Manuel , Loser Friedrich , Menzer Simone , Jacob Josephine , Roessler Martin , Seifert Martin , Kind Barbara , König Christina , Schulte Claudia , Buschmann Tilo , Hertle Dagmar , Ballesteros Pedro , Baßler Stefan , Bertele Barbara , Bitterer Thomas , Riederer Cordula , Sobik Franziska , Reitzle Lukas , Scheidt-Nave Christa , Schmitt Jochen 
Published: January 2023

AbstractObjectivesTo investigate whether the risk of developing an incident autoimmune disease is increased in patients with previous COVID-19 disease compared to people without COVID-19.MethodA cohort was selected from German routine health care data covering 38.9 million individuals. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through December 31, 2020. Patients were matched 1:3 to control patients without COVID-19. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyze the onset of autoimmune diseases during the post-acute period. Incidence rates (IR) per 1000 person-years were calculated for each outcome and patient group. Poisson models were deployed to estimate the incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding diagnosis of COVID-19.ResultsIn total, 641,704 patients with COVID-19 were included. Comparing the incidence rates in the COVID-19 (IR=15.05, 95% CI: 14.69-15.42) and matched control groups (IR=10.55, 95% CI: 10.25-10.86), we found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID-19. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR was observed for autoimmune disease of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune diseases.ConclusionsSARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection.
Evidence for Cytokine Dysregulation in Schizophrenia Spectrum Disorders: A Comparison of Cerebrospinal Fluid and Blood Samples
Authors: Gallego Juan A. , McNamara Robert K. , Castaneda Santiago , Jimenez Laura D. , Alvarez-Lesmes Santiago , Blanco Emily A. , Lencz Todd , Malhotra Anil K. 
Published: January 2023

AbstractIntroductionAbnormalities in immune function have been described in schizophrenia. Cytokines, key signaling molecules of the immune system, have been investigated in peripheral blood samples of patients with schizophrenia though few studies have investigated cytokines in cerebrospinal fluid (CSF). Moreover, very few studies with schizophrenia subjects have investigated the relationships between CSF and blood cytokine levels or investigated sex differences.MethodsIn this cross-sectional study, subjects with schizophrenia spectrum disorder (SSD) diagnosis and healthy volunteers (HV) underwent a lumbar puncture, a blood draw, and psychopathology ratings. CSF and plasma levels of IL-1ß, IL-2, IL-4, IL-6, IL-8 and TNFα were determined by enzyme-linked immunosorbent assay (ELISA) and a high-sensitivity MilliplexTM Multiplex kit. Cytokine levels were square root transformed and compared between both groups using bivariate tests and a multivariate regression analysis. CSF and plasma cytokine levels were compared as were the effects of sex.ResultsThirty SSD and 23 HV were included in the study. In bivariate analysis, CSF TNFα and IL-4 levels were significantly increased in SSD subjects compared to HV. Multivariate regression analysis also showed increases in TNFα and IL-4 after adjusting for sex, age and body mass index. There were no significant differences in plasma cytokine levels between groups, and there were no correlations between CSF and plasma cytokine levels. CSF levels of TNFα and IL-4 were negatively correlated with speed of processing. Stratified analysis by sex showed significantly increased levels of TNFα and IL-4 in SSD vs. HV in males but not in females, although sample sizes were small after stratification.DiscussionThe present findings provide evidence of dysregulation of TNFα and IL-4 in CSF of schizophrenia and suggest that peripheral cytokine levels are not reflective of CSF levels. We also provide further evidence of the association between cytokine levels and impairment of certain cognitive domains. These results identify elevated CSF TNFα levels as a potential biomarker relevant to the neuropathophysiology of schizophrenia.
SRC-mediated and TKS5-enabled podosome formation is an inherent property of IPF fibroblasts, promoting ECM invasion and pulmonary fibrosis
Authors: Barbayianni Ilianna , Kanellopoulou Paraskevi , Fanidis Dionysios , Ntouskou Eleftheria-Dimitra , Nastos Dimitris , Galaris Apostolos , Harokopos Vaggelis , Hatzis Pantelis , Tsitoura Eliza , Homer Robert , Kaminski Naftali , Antoniou Katerina M. , Crestani Bruno , Tzouvelekis Argyrios , Aidinis Vassilis 
Published: January 2023

AbstractThe activation and accumulation of lung fibroblasts (LFs), resulting in aberrant deposition of collagens and other extracellular matrix (ECM) components, is a pathogenic hallmark of Idiopathic Pulmonary Fibrosis (IPF), a lethal and incurable disease. In this report, increased expression of TKS5, a scaffold protein essential for the formation of podosomes, was detected in the lung tissue of IPF patients and bleomycin (BLM)-treated mice, correlating with increased collagen type I alpha 1 chain (COL1A1) expression. The profibrotic milieu, TGFβ, as well as a stiff Col1a1-rich acellular fibrotic ECM, were found to induceTKS5expression and the formation of prominent podosome rosettes in LFs, culminating in increased ECM invasion. Podosomes were retainedex vivoin the absence of any stimulation, indicating that the formation of TKS5-enabled podosomes is an inherent property of IPF LFs. Remarkably, haploinsufficientTks5+/-mice were relatively resistant to BLM-induced pulmonary fibrosis. Disease protection was largely attributable to diminished podosome formation in LFs and decreased ECM invasion, thus indicating TKS5-enabled and podosome-mediated ECM invasion as a major pathogenic mechanism in pulmonary fibrosis. Expression profiling revealed an ECM-podosome cross talk, and pharmacologic connectivity map analysis suggested several inhibitors that could prevent podosome formation and thus pulmonary fibrosis. Among them, inhibition of src kinase was shown to potently attenuate podosome formation in LFs, ECM invasion, as well as pulmonary fibrosis in post BLM precision cut lung slices, suggesting that pharmacological targeting of TKS5-enabled podosome formation is a very promising therapeutic option in pulmonary fibrosis.
Microbiome modulates immunotherapy response in cutaneous squamous cell carcinoma
Authors: Voigt Anita Y. , Walter Andrew , Young Timothy , Graham John P. , Batista Bittencourt Bruna M. , de Mingo Pulido Alvaro , Prieto Karol , Tsai Kenneth Y. , Sundberg John P. , Oh Julia 
Published: January 2023

ABSTRACTThe gut microbiome is increasingly recognized to alter cancer risk, progression, and response to treatments such as immunotherapy, especially in cutaneous melanoma. However, whether the microbiome influences immune checkpoint inhibitor (ICI) immunotherapy response to non-melanoma skin cancer has not yet been defined. As squamous cell carcinomas (SCC) are in closest proximity to the skin microbiome, we hypothesized that the skin microbiome, which regulates cutaneous immunity, might affect SCC-associated anti-PD1 immunotherapy treatment response. We used ultraviolet radiation to induce SCC in SKH1 hairless mice. We then treated the mice with broad-band antibiotics to deplete the microbiome, followed by colonization by candidate skin and gut bacteria or persistent antibiotic treatment, all in parallel with ICI treatment. We longitudinally monitored skin and gut microbiome dynamics by 16S rRNA gene sequencing, and tumor burden by periodic tumor measurements and histologic assessment. Our study revealed that antibiotics-induced abrogation of the microbiome reduced tumor burden, suggesting a functional role of the microbiome in non-melanoma skin cancer therapy response.
Dormancy-inducing 3D-engineered matrix uncovers mechanosensitive and drug protective FHL2-p21 signaling axis
Authors: Bakhshandeh Sadra , Heras Unai , Taïeb Hubert M. , Varadarajan Adithi R. , Lissek Susanna M. , Hücker Sarah M. , Lu Xin , Garske Daniela S. , Young Sarah A. E. , Abaurrea Andrea , Caffarel Maria M , Riestra Ana , Bragado Paloma , Contzen Jörg , Gossen Manfred , Kirsch Stefan , Warfsmann Jens , Honarnejad Kamran , Klein Christoph A. , Cipitria Amaia 
Published: January 2023

AbstractResected tumors frequently relapse with distant metastasis, despite systemic treatment. Cellular dormancy has been identified as an important mechanism underlying such drug resistance enabling late relapse. Nonetheless, hurdles associated with detection and isolation of disseminated cancer cells (DCCs) in disease-free patients urge the need forin vitromodels of dormant cells suited for drug discovery. Here, we explore dormancy-inducing 3D-engineered matrices, which generate mechanical confinement and induce growth arrest and survival against chemotherapy in cancer cells. We characterized the dormant phenotype of solitary cells by P-ERKlow:P-p38highdormancy signaling ratio, along with Ki67-expression. As underlying mechanism, we identified stiffness-dependent nuclear localization of the four-and-a-half LIM domains 2 (FHL2) protein, leading to p53-independent high p21Cip1/Waf1nuclear expression, validated in murine and human tissue. Suggestive of a resistance-causing role, cells in the dormancy-inducing matrix became sensitive against chemotherapy upon FHL2 downregulation. Thus, our biomaterial-based approach will enable systematic screens for novel compounds suited to eradicate potentially relapsing, dormant cancer cells.TeaserUsing semi-synthetic bioengineered hydrogels, we reveal a mechanosensitive and drug protective mechanism of dormant cancer cells in tissues
Selective recruitment: Evidence for task-dependent gating of inputs to the cerebellum
Authors: Shahshahani Ladan , King Maedbh , Nettekoven Caroline , Ivry Richard , Diedrichsen Jörn 
Published: January 2023

SummaryfMRI studies have documented cerebellar activity across a wide array of tasks. However, the functional contribution of the cerebellum within these task domains remains unclear because cerebellar activity is often studied in isolation. This is problematic, as cerebellar fMRI activity may simply reflect the transmission of neocortical activity through fixed connections. Here we present a new approach that addresses this problem. Rather than focus on task-dependent activity changes in the cerebellum alone, we ask if neocortical inputs to the cerebellum are gated in a task-dependent manner. We hypothesize that input is upregulated when the cerebellum functionally contributes to a task. We first validated this approach using a finger movement task, where the integrity of the cerebellum has been shown to be essential for the coordination of rapid alternating movements but not for force generation. While both neocortical and cerebellar activity increased with increasing speed and force, the speed-related changes in the cerebellum were larger than predicted by an optimized cortico-cerebellar connectivity model. We then applied the same approach in a cognitive domain, assessing how the cerebellum supports working memory. Enhanced gating was associated with the encoding of items in working memory, but not with the manipulation or retrieval of the items. Focusing on task-dependent gating of neocortical inputs to the cerebellum offers a promising approach for using fMRI to understand the specific contributions of the cerebellum to cognitive function.
Hacking brain development to test models of sensory coding
Authors: Ahmed Maria , Rajagopalan Adithya E. , Pan Yijie , Li Ye , Williams Donnell L. , Pedersen Erik A. , Thakral Manav , Previero Angelica , Close Kari C. , Christoforou Christina P. , Cai Dawen , Turner Glenn C. , Clowney E. Josephine 
Published: January 2023

AbstractAnimals can discriminate myriad sensory stimuli but can also generalize from learned experience. You can probably distinguish the favorite teas of your colleagues while still recognizing that all tea pales in comparison to coffee. Tradeoffs between detection, discrimination, and generalization are inherent at every layer of sensory processing. During development, specific quantitative parameters are wired into perceptual circuits and set the playing field on which plasticity mechanisms play out. A primary goal of systems neuroscience is to understand how material properties of a circuit define the logical operations— computations--that it makes, and what good these computations are for survival. A cardinal method in biology—and the mechanism of evolution--is to change a unit or variable within a system and ask how this affects organismal function. Here, we make use of our knowledge of developmental wiring mechanisms to modify hard-wired circuit parameters in theDrosophila melanogastermushroom body and assess the functional and behavioral consequences. By altering the number of expansion layer neurons (Kenyon cells) and their dendritic complexity, we find that input number, but not cell number, tunes odor selectivity. Simple odor discrimination performance is maintained when Kenyon cell number is reduced and augmented by Kenyon cell expansion.
The memory of pathogenic IgE is contained within CD23+IgG1+memory B cells poised to switch to IgE in food allergy
Authors: Ota Miyo , Hoehn Kenneth B. , Ota Takayuki , Aranda Carlos J. , Friedman Sara , Braga Weslley F. , Malbari Alefiyah , Kleinstein Steven H. , Sicherer Scott H. , Curotto de Lafaille Maria A. 
Published: January 2023

AbstractFood allergy is caused by allergen-specific IgE antibodies but little is known about the B cell memory of persistent IgE responses. Here we describe in human pediatric peanut allergy CD23+IgG1+memory B cells arising in type 2 responses that contain peanut specific clones and generate IgE cells on activation. These ‘type2-marked’ IgG1+memory B cells differentially express IL-4/IL-13 regulated genesFCER2/CD23, IL4R, and germlineIGHEand carry highly mutated B cell receptors (BCRs). Further, high affinity memory B cells specific for the main peanut allergen Ara h 2 mapped to the population of ‘type2-marked’ IgG1+memory B cells and included convergent BCRs across different individuals. Our findings indicate that CD23+IgG1+memory B cells transcribing germlineIGHEare a unique memory population containing precursors of pathogenic IgE.One-Sentence SummaryWe describe a unique population of IgG+memory B cells poised to switch to IgE that contains high affinity allergen-specific clones in peanut allergy.
Evolutionary loss of the ß1-adrenergic receptor in salmonids
Authors: Joyce William 
Published: January 2023

AbstractWhole-genome duplications (WGDs) have been at the heart of the diversification of ß-adrenergic receptors (ß-ARs) in vertebrates. Non-teleost jawed vertebrates typically possess three ß-AR genes:adrb1(ß1-AR),adrb2(ß2-AR), andadrb3(ß3-AR), originating from the ancient 2R (two rounds) WGDs. Teleost fishes, owing to the teleost-specific WGD, have five ancestraladrbparalogs (adrb1, adrb2a, adrb2b, adrb3aandadrb3b). Salmonids are particularly intriguing from an evolutionary perspective as they experienced an additional WGD after separating from other teleosts. Moreover, adrenergic regulation in salmonids, especially rainbow trout, has been intensively studied for decades. However, the repertoire ofadrbgenes in salmonids has not been yet characterized. An exhaustive genome survey of diverse salmonids, spanning five genera, complemented by phylogenetic sequence analysis, revealed each species has sevenadrbparalogs: twoadrb2a, twoadrb2b, twoadrb3aand oneadrb3b. Surprisingly, salmonids emerge as the first known jawed vertebrate lineage to lackadrb1. adrb1is nevertheless highly expressed in the hearts of non-salmonid teleosts, indicating that the wealth of data on adrenergic regulation in salmonids should be generalised to other teleost fishes with caution. It is hypothesised that the loss ofadrb1could have been viable because of the evolutionary radiation ofadrb2andadrb3genes attributable to the salmonid WGD.