bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intraoperative Neurophysiological Monitoring in Tethered Cord Syndrome Surgery: Predictive Values and Clinical Outcome
Authors: Squintani Giovanna , Basaldella Federica , Badari Andrea , Rasera Andrea , Tramontano Vincenzo , Pinna Giampietro , Moscolo Fabio , Soda Christian , Ricci Umberto , Ravenna Giorgio , Sala Francesco 
Published: June 2024

Introduction:
“Tethered cord syndrome” (TCS) refers to a congenital abnormality associated with neurological signs and symptoms. The aim of surgery is to prevent or arrest their progression. This study reports a retrospective case series of tethered cord syndrome surgeries, supported by intraoperative neurophysiological monitoring.

Methods:
The case series comprises 50 surgeries for tethered cord syndrome in which multimodal intraoperative neurophysiological monitoring was performed using motor evoked potentials (transcranial motor evoked potentials [TcMEPs]), tibial nerve somatosensory evoked potentials (TNSEPs), and pudendal-anal reflex (PAR). The intraoperative neurophysiological monitoring results are reported and correlated with clinical outcomes.

Results:
Sensitivity, specificity, and negative predictive value were high for TcMEPs and TNSEPs, while PAR exhibited low sensitivity and positive predictive value but high specificity and negative predictive value. Fisher's exact test revealed a significant correlation between changes in TcMEPs, TNSEPs, and clinical outcome (P < 0.000 and P = 0.049 respectively), but no correlation was detected between PAR and urinary/anal function (P = 0.497).

Conclusions:
While TcMEPs and TNSEPs were found to be reliable intraoperative neurophysiological monitoring parameters during tethered cord syndrome surgery, PAR had low sensitivity and positive predictive value probably because the reflex is not directly related to bladder function and because its multisynaptic pathway may be sensitive to anesthetics. New onset muscle weakness and sensory deficits were related to postoperative changes in TcMEPs and TNSEPs, whereas changes in PAR did not predict bladder/urinary impairment. Urinary deficits may be predicted and prevented with other neurophysiological techniques, such as the bladder–anal reflex.
Are We Supporting Surgical Quality Improvement in Training and Beyond? A Qualitative Study of Surgical Trainees and Practicing Surgeons
Authors: Peters Xane D , Waddle Shelbie D , Shah Tejen , Reilly Eileen , Valek Sarah , Modla Lynn , Langenscheidt Ulrike , Pollitt Karen , Johnson Julie K , Ko Clifford Y 
Published: June 2024

BACKGROUND:
We conducted a qualitative study to describe surgeon and surgical trainee perspectives of quality improvement (QI) in training and practice to elucidate how surgeons and trainees interact with barriers and leverage facilitators to learn and conduct QI.

STUDY DESIGN:
Surgeons and surgical trainees of the American College of Surgeons were recruited via email and snowball sampling to participate in focus groups. Eligible individuals were English speaking surgical trainees or practicing surgeons. We developed a semistructured focus group protocol to explore barriers and facilitators of quality training and improvement. An inductive thematic approach was used to identify actionable items.

RESULTS:
Thirty-two surgical trainees and surgeons participated in 6 focus groups. A total of 28% of participants were trainees (8 residents, 1 fellow) and 72% were practicing surgeons, representing practice settings in university, community, and Veterans Affairs hospitals in urban and suburban regions. Thematic analysis revealed that the central theme among trainees was that they lacked necessary support to effectively learn and conduct QI. Dominant subthemes included lack of formal education, insufficient time, inconsistent mentorship, and maximizing self-sufficiency to promote success. The central theme among surgeons was that effective QI initiatives require adequate resources and institutional support; however, surgeons in this study were ultimately constrained by institutional limitations. Subthemes included difficulties in data acquisition and interpretation, financial limitations, workforce and staffing challenges, misaligned stakeholder priorities, and institutional culture.

CONCLUSIONS:
This qualitative evaluation further details gaps in QI demonstrated by previous quantitative studies. There is an opportunity to address these gaps with dedicated QI training and mentorship for surgical trainees and by creating a supportive environment with ample resources for surgeons.
Astrocyte-Derived Exosomes Regulate Sperm miR-34c Levels to Mediate the Transgenerational Effects of Paternal Chronic Social Instability Stress
Authors: Champroux Alexandre , Sadat-Shirazi Mitra , Chen Xuan , Hacker Jonathan , Yang Yongjie , Feig Larry A. 
Published: June 2024

ABSTRACTThe effects of chronically stressing male mice can be transmitted across generations by stress-specific changes in their sperm miRNA content that induce stress-specific phenotypes in their offspring. But how each stress paradigm alters the levels of distinct sets of sperm miRNAs is not understood. Here we describe evidence forastrocyte-derivedexosomes (A-Exos) containing miR-34c mediating how chronic social instability (CSI) stress suppesses levels of miR-34c in sperm, which we showed previously contributes to how this stress protocol leads to both elevated anxiety and defective sociability in their female offspring and reduced sperm miR-34c in their male offspring. In particular, we found that CSI stress decreases content of miR-34c in A-Exos isolated from the prefrontal cortex and amygdala, as well as in blood of CSI-stressed males. Strikingly, miR-34c content is also reduced in A-Exos isolated from these tissues of their F1 male offspring, who also display reduced sperm miR-34c levels despite never being directly exposed to stress and transmit these stress related traits to their offspring. In addition, restoring A-Exos miR-34c content in the blood of CSI-stressed males by IV injection of miR-34c-containing A-Exos restores miR-34c levels in their sperm. These findings reveal a surprising role for A-Exos in maintaining sperm miR-34c levels by a process that when suppressed by CSI stress mediates this example of transgenerational epigenetic inheritance.
Surviving Medical School During a Pandemic: Experiences of New York Medical Students During the Height of SARS-CoV-2
Authors: Knight L. M. , Seth Divya , Zuckerman David A. , Rogers Eli J. , Talukdar Zain , Holloway Robert , Gómez-Di Cesare Caroline , Henshaw Mariluz , Privitera Michael , Dowling Frank 
Published: June 2024

AbstractBackgroundThe COVID-19 pandemic dramatically altered the landscape of medical education. While patients overwhelmed hospital systems, lockdowns and social distancing recommendations took priority, and medical education was pushed online. Early in 2020, New York State (NYS) was hit especially hard by COVID-19.ObjectiveThis study sought to understand the effect of the COVID-19 pandemic on medical students well-being and education.MethodsNYS medical students responded to a six-question survey during April and May 2020. Questions assessed self-reported changes in stress levels, academic performance, and board preparation efforts. Open-ended data was analyzed using a modified grounded theory approach.Results488 responses across 11 medical schools were included (response rate of 5.8%). Major themes included: standardized test-related stressors (23%), study-related changes (19%), education and training concerns (17%), financial stressors (12%), and additional family obligations (12%).Second year students reported more stress/anxiety than students in other years (95.9%,p-value< 0.00001). Reported stress/anxiety, effects on exam preparation, and anticipated academic effect varied by geographics.ConclusionsWhile all NYS medical students reported being greatly affected, those closest to the NY City pandemic epi-center and closest to taking the Step 1 exam were the most distressed. Lack of flexibility of the medical education system during this public health emergency contributed to worsened student well-being. It is time to make plans for supporting the long-term mental health needs of these physicians-in-training and to examine ways the academic medical community can better adapt to the needs of students affected by a large public health emergency in the future.
RUNX1 Isoforms Regulate RUNX1 and Target-Genes Differentially in Platelets-Megakaryocytes: Association with Clinical Cardiovascular Events
Authors: Guan Liying , Voora Deepak , Myers Rachel , Del Carpio-Cano Fabiola , Rao A. Koneti 
Published: June 2024

AbstractBackgroundHematopoietic transcription factor RUNX1 is expressed from proximal P2 and distal P1 promoter to yield isoforms RUNX1 B and C, respectively. The roles of these isoforms in RUNX1 autoregulation and downstream-gene regulation in megakaryocytes and platelets are unknown.ObjectivesTo understand the regulation of RUNX1 and its target genes by RUNX1 isoforms.MethodsWe performed studies on RUNX1 isoforms in megakaryocytic HEL cells and HeLa cells (lack endogenous RUNX1), in platelets from 85 healthy volunteers administered aspirin or ticagrelor, and on the association of RUNX1 target genes with acute events in 587 patients with cardiovascular disease (CVD).ResultsIn chromatin immunoprecipitation and luciferase promoter assays, RUNX1 isoforms B and C bound and regulated P1 and P2 promoters. In HeLa cells RUNX1B decreased and RUNX1C increased P1 and P2 activities, respectively. In HEL cells, RUNX1B overexpression decreased RUNX1C and RUNX1A expression; RUNX1C increased RUNX1B and RUNX1A. RUNX1B and RUNX1C regulated target genes (MYL9, F13A1, PCTP, PDE5Aand others) differentially in HEL cells. In platelets RUNX1B transcripts (by RNAseq) correlated negatively with RUNX1C and RUNX1A; RUNX1C correlated positively with RUNX1A. RUNX1B correlated positively withF13A1, PCTP, PDE5A, RAB1B, and others, and negatively withMYL9. In our previous studies, RUNX1C transcripts in whole blood were protective against acute events in CVD patients. We found that higher expression of RUNX1 targetsF13A1andRAB31associated with acute events.ConclusionsRUNX1 isoforms B and C autoregulate RUNX1 and regulate downstream genes in a differential manner and this associates with acute events in CVD.Scientific categoryPlateletsEssentialsRUNX1 is expressed from 2 promoters (P1 and P2) to yield isoforms RUNX1C and RUNX1B.RUNX1B and RUNX1C regulate RUNX1 and target genes differentially in megakaryocytes/platelets.In platelets RUNX1B and RUNX1C expression is inversely related and ticagrelor increases RUNX1CRUNX1 target gene (F13A1, RAB31) expression in blood is associated with death or MI in cardiac disease.
The bacterial Bmt methionine synthase is involved in lag phase shortening
Authors: Narváez-Barragán Delia A. , Sperfeld Martin , Segev Einat 
Published: June 2024

AbstractBacteria can shorten their lag phase by utilizing methyl groups from compounds such as dimethylsulfoniopropionate (DMSP). These methyl groups are then incorporated into cellular building blocks via the methionine cycle. However, the specific contribution of bacterial methionine synthesis, which is critical for assimilating and incorporating methyl groups, remains unclear.In this study, we employed transcriptomics, genetic manipulation and biochemical assays to explore the involvement of methionine synthesis in lag phase shortening using the model marine bacteriumPhaeobacter inhibens. We mapped the expression profiles of the MetH-like methionine synthase components—an enzyme complex that is encoded by three genes—in response to DMSP during the lag phase. Our findings revealed transcriptional decoupling of the three genes. The deletion of the homocysteine-binding component of the MetH-like complex, namelybmt, disrupted lag phase shortening in response to DMSP. Through heterologous expression of thebmtgene product, we show that the individual Bmt enzyme produces methionine by directly demethylating DMSP and betainein vitro. These findings reveal a metabolic route that was not previously described in marine bacteria. Since Bmt does not require tetrahydrofolate or cobalamin as co-factors for methionine synthesis, its potential to act alone as a demethylase and a methionine synthase represents a cost-effective metabolic shortcut for methyl group assimilation, which could be specifically beneficial under limiting conditions. Indeed, we show that under stress conditions, Bmt allows cells to shorten their lag phase in response to DMSP.This study enhances our understanding of the enzymatic mechanisms underlying bacterial lag phase shortening, revealing microbial adaptation strategies in response to environmental conditions.
Distribution of informal caregiving for older adults living with or at risk of cognitive decline within and beyond family in rural South Africa
Authors: Matina Sostina S , Manderson Lenore , Brear Michelle , Rusere Farirai , Gómez-Olivé F. Xavier , Kahn Kathleen , Harling Guy 
Published: June 2024

ABSTRACTObjectivesAging populations in rural areas of low and middle-income countries will increasingly need care. However, formal support is severely limited and adult children are frequently unavailable due to morbidity, early mortality, employment and migration. We aimed to describe how care is shared within and between households for older adults in a rural South African setting.MethodsWe conducted quantitative interviews with 1012 household members and non-household caregivers of 106 older adults living with or at risk of cognitive decline in rural Mpumalanga, South Africa. Using descriptive statistics and regression analysis, we described how care is shared, with particular attention to generational patterns of care.ResultsInformal care for older persons was spread among family, friends, and neighbours, with minimal paid support. This care was mostly provided by female relatives one or two generations younger than the recipient, and unemployed. However, a smaller number of paid caregivers, also mostly female, provided the most intensive care. Spouses commonly took on the role of primary caregiver for their partner.DiscussionIn our study, care mainly came from household members due to close family ties and practical considerations, with support from outside the household. This reflects shared history, reciprocal relationships, and easy access to care tasks within the household. A deeper understanding of how informal care for older adults is shared in low- and middle-income countries is essential for developing targeted interventions.
Investigating the relationship between the immune response and the severity of COVID-19: a large-cohort retrospective study
Authors: Margiotta Riccardo Giuseppe , Sozio Emanuela , Del Ben Fabio , Beltrami Antonio Paolo , Cesselli Daniela , Fabris Martina , Curcio Francesco , Tascini Carlo , Sanguinetti Guido 
Published: June 2024

AbstractThe COVID-19 pandemic has left an indelible mark globally, presenting numerous challenges to public health. This crisis, while disruptive and impactful, has provided a unique opportunity to gather precious clinical data extensively. In this observational, case-control study, we utilized data collected at the Azienda Sanitaria Universitaria Friuli Centrale, Italy, to comprehensively characterize the immuno-inflammatory features in COVID-19 patients. Specifically, we employed multicolor flow cytometry, cytokine assays, and inflammatory biomarkers to elucidate the interplay between the infectious agent and the host’s immune status. We characterized immuno-inflammatory profiles within the first 72 hours of hospital admission, stratified by age, disease severity, and time elapsed since symptom onset. Our findings indicate that patients admitted to the hospital shortly after symptom onset exhibit a distinct pattern compared to those who arrive later, characterized by a more active immune response and heightened cytokine activity, but lower markers of tissue damage. We used univariate and multivariate logistic regression models to identify informative markers for outcome severity. Predictors incorporating the immuno-inflammatory features significantly outperformed standard baselines, identifying up to 59% of patients with positive outcomes while maintaining a false omission rate as low as 4%. Overall, our study sheds light on the immuno-inflammatory aspects observed in COVID-19 patients prior to vaccination, providing insights for guiding the clinical management of first-time infections by a novel virus.
An Algorithm to Predict the Need for Magnetic Resonance Imaging to Support Disease Monitoring in Multiple Sclerosis
Authors: Robinette Michael S. , Gray-Roncal Karla , Fitzgerald Kathryn C. , Ferryman Kadija , Overby Taylor Casey , Scott John , Sotirchos Elias S. , Calabresi Peter A. , Mowry Ellen M. , Gray-Roncal William 
Published: June 2024

AbstractPeople with multiple sclerosis (MS), a chronic neurologic disease, typically undergo brain magnetic resonance imaging (MRI) to assess for new disease activity or to evaluate response to disease-modifying therapy. The required frequency of these imaging studies has not yet been determined, and clinicians rely on expert panel recommendations or intuition to select the interval length for their patients. These former recommendations are often broad and lack the incorporation of individualized information (i.e., age, presence of recent disease activity, type of disease modifying therapy) into the synthesis of their assessment. We developed an algorithm that can predict new disease activity (i.e., lesions) on the next MRI scan. Multiple data sources from the electronic health records of 1045 patients were used to train and test the algorithm which resulted in an accurate solution with an area under the curve (AUC) of 0.8 that minimizes missed lesions while accurately identifying two-thirds of patients as not having a new lesion in subsequent MRI. We believe that this algorithm can be developed into a clinical decision support tool as input into a clinician-patient assessment of the appropriate interval length between MRIs for a specific patient.
Comparative analysis of culture- and ddPCR-based wastewater surveillance for carbapenem-resistant bacteria
Authors: Zhou Siyi , Lou Esther G. , Schedler Julia , Ensor Katherine B. , Hopkins Loren , Stadler Lauren B. 
Published: June 2024

AbstractWith the widespread use of last-resort antibiotics, carbapenems, clinical reports of infections associated with carbapenem-resistantEnterobacterales(CRE) have increased. Clinical surveillance for CRE involves susceptibility testing and/or whole genome sequencing of resistant isolates, which is laborious, resource intensive, and requires expertise. Wastewater surveillance can potentially complement clinical surveillance of CRE, and population-level antibiotic resistance (AR) surveillance more broadly. In this study, we quantitatively and qualitatively compared two widely used methods for AR wastewater surveillance: (1) a culture-based approach for quantifying carbapenem-resistant bacteria and (2) a digital droplet PCR (ddPCR) assay targeting five major carbapenemase genes. We developed a multiplexed ddPCR assay to detect five carbapenemase genes and applied it to wastewater samples from three sites over 12 weeks. In parallel, we quantified carbapenem resistant bacteria and carbapenemase-producing bacteria using culture-based methods. We assessed associations between the concentrations of carbapenemase genes and resistant bacteria. Although both approaches showed similar trends in the overall abundance of dominant carbapenem-resistant bacteria and genes, there were weak correlations between the quantitative levels of resistance. Nanopore sequencing of the resistome of the carbapenem-resistant bacteria revealed that discrepancies arose from differences in the sensitivity and specificity of the methods. This study enhances our understanding of the application of wastewater surveillance in tracking carbapenem resistance and highlights how method choice impacts the results from AR wastewater surveillance.
PPTC7 acts as an essential co-factor of the SCFFBXL4ubiquitin ligase complex to restrict BNIP3/BNIP3L-dependent mitophagy
Authors: Xu Xiayun , Chen Yingji , Li Yao , Zhao Shi-Min , Wang Chenji 
Published: June 2024

ABSTRACTMitophagy is a selective process that targets damaged, dysfunctional, or superfluous mitochondria for degradation through autophagy. The SCFFBXL4ubiquitin ligase complex suppresses basal mitophagy by targeting BNIP3 and BNIP3L, two key mitophagy cargo receptors, for ubiquitin-proteasomal degradation.FBXL4loss-of-function mutations lead to excessive BNIP3/3L-dependent mitophagy, thereby causing a devasting multi-system disorder called mitochondrial DNA depletion syndrome, type 13 (MTDPS13). PPTC7, a mitochondrial matrix phosphatase, is essential for proper mitochondrial function and biogenesis. Here, we show that a proportion of PPTC7 is located on the outer mitochondrial membrane, where it interacts with FBXL4 and BNIP3/3L. PPTC7 decreases BNIP3/3L protein stability in a protein phosphatase activity-independent manner. Usingin vitrocell culture andPptc7knockout mice models, we demonstrate that PPTC7 deficiency activates high levels of basal mitophagy in a BNIP3/3L-dependent manner. Mechanistically, PPTC7 facilitates SCFFBXL4-mediated ubiquitin-proteasomal degradation of BNIP3/3L. Overall, these findings establish PPTC7 as an essential co-factor of the SCFFBXL4complex and a suppressor of BNIP3/3L-dependent mitophagy.
Cell wall melanin impedes growth of theCryptococcus neoformanspolysaccharide capsule by sequestering calcium
Authors: Baker Rosanna P. , Liu Amy Z. , Casadevall Arturo 
Published: June 2024

AbstractCryptococcus neoformanshas emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival ofC. neoformanswithin the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated with the cell wall, we were interested to explore possible cooperative or competitive interactions between these two virulence factors. Whereas capsule thickness had no effect on the rate at which cells became melanized, build-up of the melanin pigment layer resulted in a concomitant loss of polysaccharide material, leaving melanized cells with significantly thinner capsules than their non-melanized counterparts. When melanin was provided exogenously to cells in a transwell culture system we observed a similar inhibition of capsule growth and maintenance. Our results show that melanin sequesters calcium thereby limiting its availability to form divalent bridges between polysaccharide subunits required for outer capsule assembly. The decreased ability of melanized cells to incorporate exported polysaccharide into the growing capsule correlated with the amount of shed polysaccharide, which could have profound negative impacts on the host immune response.Significance StatementCryptococcus neoformansis an opportunistic fungal pathogen that presents a significant health risk for immunocompromised individuals. We report an interaction between the two major cryptococcal virulence factors, the polysaccharide capsule and melanin. Melanin impacted the growth and maintenance of the polysaccharide capsule, resulting in loss of capsular material during melanization. Our results suggest that melanin can act as a sink for calcium, thereby limiting its availability to form ionic bridges between polysaccharide chains on the growing surface of the outer capsule. As polysaccharide is continuously exported to support capsule growth, failure of melanized cells to incorporate this material results in a higher concentration of shed polysaccharide in the extracellular milieu, which is expected to interfere with host immunity.