bluuebunny/crossref_metadata_2025_split huggingface dataset:
A longitudinal cohort study observed increasing perfectionism and declining resilience, ambiguity tolerance and calling during medical school which is not explained by student personality
Authors: Eley Diann S. , Leung Janni , Cloninger Kevin M. 
Published: November 2022

AbstractBackgroundThe medical degree is a long and challenging program, not just academically, but regarding the expectations engrained in the culture of medical education. The recent proliferation of literature on the poor mental well-being among students suggests a dilemma that often lays the onus on students to improve their health. The link between personality and vulnerability to psychological distress is acknowledged. This longitudinal study looked at personality in 1st-year and changes in levels of certain psychological traits, as proxy indicators of well-being, in 4th-year. We aimed to determine to what extent changes in psychological traits over time may be attributed to personality.MethodsMedical students completed surveys at the start (1st-year: baseline) and finish (4th-year: follow-up) of their medical degree (N = 154). Temperament and character personality, Perfectionism-Concern over mistakes (CoM), Ambiguity Tolerance, Resilience, Calling to medicine, and demographic variables were measured. Paired t-tests compared changes in psychological traits from baseline to follow-up. Linear regression examined whether personality at baseline would predict levels of psychological traits at follow-up.ResultsThe temperament and character profile of the sample was as expected, and congruent with previous studies, which describe a mature personality. Over four years, levels of Perfectionism-CoM significantly increased, while Resilience, Ambiguity Tolerance and Calling to medicine decreased. Harm Avoidance, Persistence, Self-Directedness and Cooperativeness at baseline significantly predicted levels of these traits at follow-up, but effect sizes were weak. Correlations were in the expected direction and weak.ConclusionsMost commencing medical students, including this cohort, have mature personalities with an industrious temperament and an adaptable character. Yet over four years of medicine, Ambiguity Tolerance, Resilience and Calling declined while Perfectionism-CoM, already elevated at baseline, continued to increase to the final year. Of concern is the increased perfectionism that is strongly associated with poor mental health and psychological distress. The findings suggest a closer look at the entirety of the education environment and how its culture, including secondary school and the medical school admissions processes may influence these trends in students. As medical educators we should question why the pathway to medicine places such unhealthy pressure on students who aspire to be doctors.
College competitiveness and medical school exam performance
Authors: Levy Joshua , Kausar Hiba , Patel Deepal , Andersen Shaun , Simanton Edward 
Published: November 2022

Abstract
Background
In medical school, students are tested through periodic USMLE Step 1 and 2 examinations before obtaining a medical license. Traditional predictors of medical school performance include MCAT scores, undergraduate grades, and undergraduate institutional selectivity. Prior studies indicate that admissions committees might unfairly discriminate against applicants who graduated from less competitive universities. However, there is limited literature to determine whether those who attended competitive colleges perform better on USMLE Step 1 and 2 examinations.

Objective
The purpose of our study is to determine if students who attended competitive undergraduate colleges outperform those who did not on medical school benchmarks.

Methods
We defined a Competitive College as having greater than 10% of its student body scoring 1400 or higher (on a 1600 scale) on the SAT. If this criteria was not met, colleges would be categorized as Non-Competitive. Descriptive statistics and unpaired t-tests were calculated to analyze average test scores on the MCAT, Phase 1 NBME, USMLE Step 1, Phase 2 NBME, and USMLE Step 2.

Results
Our findings suggest there are no statistically significant differences between students who do or do not attend competitive undergraduate colleges on these medical school benchmark examinations following the MCAT.

Conclusion
Admissions committees should use this data to aid in their student selection as our research indicates that institutional selectivity accurately predicts MCAT scores, but not performance on standardized medical school examinations once admitted.
Two-year change in latent classes of comorbidity among high-risk Veterans in primary care: a brief report
Authors: Hutchins Franya , Thorpe Joshua , Zhao Xinhua , Zhang Hongwei , Rosland Ann-Marie 
Published: November 2022

Abstract
Background
Segmentation models such as latent class analysis are an increasingly popular approach to inform group-tailored interventions for high-risk complex patients. Multiple studies have identified clinically meaningful high-risk segments, but few have evaluated change in groupings over time.

Objectives
To describe population-level and individual change over time in latent comorbidity groups among Veterans at high-risk of hospitalization in the Veterans Health Administration (VA).

Research design
Using a repeated cross-sectional design, we conducted a latent class analysis of chronic condition diagnoses. We compared latent class composition, patient high-risk status, and patient class assignment in 2018 to 2020.

Subjects
Two cohorts of eligible patients were selected: those active in VA primary care and in the top decile of predicted one-year hospitalization risk in 2018 (n = 951,771) or 2020 (n = 978,771).

Measures
Medical record data were observed from January 2016–December 2020. Latent classes were modeled using indicators for 26 chronic health conditions measured with a 2-year lookback period from study entry.

Results
Five groups were identified in both years, labeled based on high prevalence conditions: Cardiometabolic (23% in 2018), Mental Health (18%), Substance Use Disorders (16%), Low Diagnosis (25%), and High Complexity (10%). The remaining 8% of 2018 patients were not assigned to a group due to low predicted probability. Condition prevalence overall and within groups was stable between years. However, among the 563,725 patients identified as high risk in both years, 40.8% (n = 230,185) had a different group assignment in 2018 versus 2020.

Conclusions
In a repeated latent class analysis of nearly 1 million Veterans at high-risk for hospitalization, population-level groups were stable over two years, but individuals often moved between groups. Interventions tailored to latent groups need to account for change in patient status and group assignment over time.
Clinical parameters obtained during tear film examination in domestic rabbits
Authors: Corsi Francesca , Arteaga Kevin , Corsi Flavia , Masi Marco , Cattaneo Alexia , Selleri Paolo , Crasta Manuela , Peruccio Claudio , Guandalini Adolfo 
Published: November 2022

AbstractBackgroundOne of the contributing factors to ocular surface health is a stable precorneal tear film. Considering the increasing interest in rabbits as pets and the limited literature available on domestic rabbit tearing, the aim of this study was to establish normative data for examination of the tear film in domestic rabbits.ResultsThe study included 75 client-owned domestic Holland Lop rabbits (150 eyes). The following examinations were performed in each eye: Schirmer tear test-1, tear osmometry, interferometry, tear meniscus height measurement and meibography (quantifying meibomian gland loss as a percentage). The resulting median (95% central range) values were 10.0 (5.0–17.3) mm/min for the Schirmer tear test-1, 345.0 (280.5–376.1) mOsm/L for tear osmolarity, grade 2 (1–4) of interferometry, 0.28 (0.20–0.47) mm for tear meniscus height and 0.0 (0.0–67.6) % meibomian gland loss. A significant association was found between tear osmolarity and age, with an estimated decrease of − 4.0 mOsm/L with each additional year of age (p < 0.001). The distributions of interferometry grades were significantly different between males and females (p < 0.001), with grade 1 and grade 2 being the most frequent in females and males, respectively. A weak negative correlation was also observed between interferometry grade and the percentage of meibomian gland loss (r = − 0.22,p = 0.006).ConclusionsThis is an original study that documents extensive tear film parameters in healthy Holland Lop rabbits. The results can be used as normative data for the examination of the tear film in this lagomorph breed.
Glycemic control is independently associated with rapid progression of coronary atherosclerosis in the absence of a baseline coronary plaque burden: a retrospective case–control study from the PARADIGM registry
Authors: Won Ki-Bum , Lee Byoung Kwon , Lin Fay Y. , Hadamitzky Martin , Kim Yong-Jin , Sung Ji Min , Conte Edoardo , Andreini Daniele , Pontone Gianluca , Budoff Matthew J. , Gottlieb Ilan , Chun Eun Ju , Cademartiri Filippo , Maffei Erica , Marques Hugo , de Araújo Gonçalves Pedro , Leipsic Jonathon A. , Lee Sang-Eun , Shin Sanghoon , Choi Jung Hyun , Virmani Renu , Samady Habib , Chinnaiyan Kavitha , Berman Daniel S. , Narula Jagat , Shaw Leslee J. , Bax Jeroen J. , Min James K. , Chang Hyuk-Jae 
Published: November 2022

Abstract
Background
The baseline coronary plaque burden is the most important factor for rapid plaque progression (RPP) in the coronary artery. However, data on the independent predictors of RPP in the absence of a baseline coronary plaque burden are limited. Thus, this study aimed to investigate the predictors for RPP in patients without coronary plaques on baseline coronary computed tomography angiography (CCTA) images.

Methods
A total of 402 patients (mean age: 57.6 ± 10.0 years, 49.3% men) without coronary plaques at baseline who underwent serial coronary CCTA were identified from the Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry and included in this retrospective study. RPP was defined as an annual change of ≥ 1.0%/year in the percentage atheroma volume (PAV).

Results
During a median inter-scan period of 3.6 years (interquartile range: 2.7–5.0 years), newly developed coronary plaques and RPP were observed in 35.6% and 4.2% of the patients, respectively. The baseline traditional risk factors, i.e., advanced age (≥ 60 years), male sex, hypertension, diabetes mellitus, hyperlipidemia, obesity, and current smoking status, were not significantly associated with the risk of RPP. Multivariate linear regression analysis showed that the serum hemoglobin A1c level (per 1% increase) measured at follow-up CCTA was independently associated with the annual change in the PAV (β: 0.098, 95% confidence interval [CI]: 0.048–0.149; P < 0.001). The multiple logistic regression models showed that the serum hemoglobin A1c level had an independent and positive association with the risk of RPP. The optimal predictive cut-off value of the hemoglobin A1c level for RPP was 7.05% (sensitivity: 80.0%, specificity: 86.7%; area under curve: 0.816 [95% CI: 0.574–0.999]; P = 0.017).

Conclusion
In this retrospective case–control study, the glycemic control status was strongly associated with the risk of RPP in patients without a baseline coronary plaque burden. This suggests that regular monitoring of the glycemic control status might be helpful for preventing the rapid progression of coronary atherosclerosis irrespective of the baseline risk factors. Further randomized investigations are necessary to confirm the results of our study.

Trial registration
ClinicalTrials.gov NCT02803411.
The association between fibrinogen-to-albumin ratio (FAR) and adverse prognosis in patients with acute decompensated heart failure at different glucose metabolic states
Authors: Huang Rong , Dai Qing , Chang Lei , Wang Ziyan , Chen Jianzhou , Gu Rong , Zheng Hongyan , Hu Lei , Xu Biao , Wang Lian 
Published: November 2022

Abstract
Background
Circulating fibrinogen-to-albumin ratio (FAR) has been proposed as a novel inflammatory biomarker and a cardiovascular disease risk predictor. However, its prognostic value in patients with acute decompensated heart failure (ADHF) and different glycemic metabolic states remains ambiguous.

Methods
A total of 1031 hospitalized patients with ADHF from January 2018 to May 2021 were included in the study. The primary endpoints were the major adverse cardiac and cerebral events (MACCEs). Patients were categorized into high-level FAR (FAR-H) and low-level FAR (FAR-L) groups based on the optimal cut-off value of FAR obtained from restricted cubic spline function analysis. The Kaplan–Meier plots and three multivariate-adjusted Cox proportional hazard models were used to determine the association between FAR and the risk of developing MACCEs in patients with ADHF at different glycemic metabolic states.

Results
MACCEs occurred in 483 (46.8%) patients during a median follow-up time of 520 days. The optimal FAR cut-off value was 0.079. Upon analyzing the Kaplan–Meier plots, the incidence of MACCEs was significantly different between the FAR groups in all patients and patients with diabetes mellitus (p < 0.05). After adjusting for the confounding factors, the hazard ratio (HR) for MACCEs in the FAR-H group was 1.29 compared with the FAR-L group in all patients (Model 3: 95% CI 1.07–1.56, p = 0.007). Additionally, high FAR was associated with MACCEs in three multivariate Cox models (Model 1, HR = 1.52, 95% CI 1.17–1.96, p = 0.002; Model 2, HR = 1.46, 95% CI 1.13–1.89, p = 0.004; Model 3, HR = 1.48, 95% CI 1.14–1.92, p = 0.003) in DM patients. But no significant differences were found between the FAR groups for prediabetes mellitus (Pre-DM) and normal glucose regulation (NGR) using the three Cox models (all p-values were > 0.05).

Conclusions
Elevated FAR was independently associated with poor prognosis in patients with ADHF and DM and thus could be used as a risk stratification tool and a potential therapeutic target in the future.
Risk factors for cardiovascular disease in patients with metabolic-associated fatty liver disease: a machine learning approach
Authors: Drożdż Karolina , Nabrdalik Katarzyna , Kwiendacz Hanna , Hendel Mirela , Olejarz Anna , Tomasik Andrzej , Bartman Wojciech , Nalepa Jakub , Gumprecht Janusz , Lip Gregory Y. H. 
Published: November 2022

Abstract
Background
Nonalcoholic fatty liver disease is associated with an increased cardiovascular disease (CVD) risk, although the exact mechanism(s) are less clear. Moreover, the relationship between newly redefined metabolic-associated fatty liver disease (MAFLD) and CVD risk has been poorly investigated. Data-driven machine learning (ML) techniques may be beneficial in discovering the most important risk factors for CVD in patients with MAFLD.

Methods
In this observational study, the patients with MAFLD underwent subclinical atherosclerosis assessment and blood biochemical analysis. Patients were split into two groups based on the presence of CVD (defined as at least one of the following: coronary artery disease; myocardial infarction; coronary bypass grafting; stroke; carotid stenosis; lower extremities artery stenosis).
The ML techniques were utilized to construct a model which could identify individuals with the highest risk of CVD. We exploited the multiple logistic regression classifier operating on the most discriminative patient’s parameters selected by univariate feature ranking or extracted using principal component analysis (PCA). Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were calculated for the investigated classifiers, and the optimal cut-point values were extracted from the ROC curves using the Youden index, the closest to (0, 1) criteria and the Index of Union methods.

Results
In 191 patients with MAFLD (mean age: 58, SD: 12 years; 46% female), there were 47 (25%) patients who had the history of CVD. The most important clinical variables included hypercholesterolemia, the plaque scores, and duration of diabetes. The five, ten and fifteen most discriminative parameters extracted using univariate feature ranking and utilized to fit the ML models resulted in AUC of 0.84 (95% confidence interval [CI]: 0.77–0.90, p < 0.0001), 0.86 (95% CI 0.80–0.91, p < 0.0001) and 0.87 (95% CI 0.82–0.92, p < 0.0001), whereas the classifier fitted over 10 principal components extracted using PCA followed by the parallel analysis obtained AUC of 0.86 (95% CI 0.81–0.91, p < 0.0001). The best model operating on 5 most discriminative features correctly identified 114/144 (79.17%) low-risk and 40/47 (85.11%) high-risk patients.

Conclusion
A ML approach demonstrated high performance in identifying MAFLD patients with prevalent CVD based on the easy-to-obtain patient parameters.
Hidden in plain sight: urinary Cryptococcus neoformans missed by routine diagnostics in a patient with acute leukemia
Authors: Weiss Zoe F. , DiCarlo James E. , Basta David W. , Kent Stephanie , Liakos Alexis , Baden Lindsey , Brigl Manfred , Kanjilal Sanjat , Cañete-Gibas Connie , Wiederhold Nathan P. , Basu Sankha S. 
Published: November 2022

AbstractCryptococcuria is a rare manifestation of localized cryptococcal disease. We present a case of Cryptococcus neoformans urinary tract infection in an immunocompromised host missed by routine laboratory workup. The patient had negative blood cultures, a negative serum cryptococcal antigen (CrAg), and “non-Candida yeast” growing in urine culture that was initially dismissed as non-pathogenic. The diagnosis was ultimately made by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) from a repeat urine culture after transfer to a tertiary care center. Cryptococcus should be considered in the differential of refractory urinary tract infections growing non-Candida yeast.
Differential regulation of TNFα and IL-6 expression contributes to immune evasion in prostate cancer
Authors: Deichaite Ida , Sears Timothy J. , Sutton Leisa , Rebibo Daniel , Morgan Kylie , Nelson Tyler , Rose Brent , Tamayo Pablo , Ferrara Napoleone , Asimakopoulos Fotis , Carter Hannah 
Published: November 2022

Abstract
Background
The role of the inflammatory milieu in prostate cancer progression is not well understood. Differences in inflammatory signaling between localized and metastatic disease may point to opportunities for early intervention.

Methods
We modeled PCa disease progression by analyzing RNA-seq of localized vs. metastatic patient samples, followed by CIBERSORTx to assess their immune cell populations. The VHA CDW registry of PCa patients was analyzed for anti-TNF clinical outcomes.

Results
We observed statistically significant opposing patterns of IL-6 and TNFα expression between localized and metastatic disease. IL-6 was robustly expressed in localized disease and downregulated in metastatic disease. The reverse was observed with TNFα expression. Metastatic disease was also characterized by downregulation of adhesion molecule E-selectin, matrix metalloproteinase ADAMTS-4 and a shift to M2 macrophages whereas localized disease demonstrated a preponderance of M1 macrophages. Treatment with anti-TNF agents was associated with earlier stage disease at diagnosis.

Conclusions
Our data points to clearly different inflammatory contexts between localized and metastatic prostate cancer. Primary localized disease demonstrates local inflammation and adaptive immunity, whereas metastases are characterized by immune cold microenvironments and a shift towards resolution of inflammation and tissue repair. Therapies that interfere with these inflammatory networks may offer opportunities for early intervention in monotherapy or in combination with immunotherapies and anti-angiogenic approaches.
Celastrol elicits antitumor effects by inhibiting the STAT3 pathway through ROS accumulation in non-small cell lung cancer
Authors: Zhao Zhucheng , Wang Yanmao , Gong Yuyan , Wang Xian , Zhang Luyao , Zhao Haiyang , Li Jifa , Zhu Jiandong , Huang Xiaoying , Zhao Chengguang , Yang Lehe , Wang Liangxing 
Published: November 2022

Abstract
Background
Non-small cell lung cancer (NSCLC) is the most common lung cancer with high mortality across the world, but it is challenging to develop an effective therapy for NSCLC. Celastrol is a natural bioactive compound, which has been found to possess potential antitumor activity. However, the underlying molecular mechanisms of celastrol activity in NSCLC remain elusive.

Methods
Cellular function assays were performed to study the suppressive role of celastrol in human NSCLC cells (H460, PC-9, and H520) and human bronchial epithelial cells BEAS-2B. Cell apoptosis levels were analyzed by flow cytometry, Hoechst 33342, caspase-3 activity analysis, and western blot analysis. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometry and fluorescence microscope. Expression levels of endoplasmic reticulum (ER) stress-related proteins and phosphorylated signal transducer and activator of transcription 3 (P-STAT3) were identified via western blot analysis. A heterograft model in nude mice was employed to evaluate the effect of celastrol in vivo.

Results
Celastrol suppressed the growth, proliferation, and metastasis of NSCLC cells. Celastrol significantly increased the level of intracellular ROS; thus, triggering the activation of the ER stress pathway and inhibition of the P-STAT3 pathway, and eventually leading to cell apoptosis, and the effects were reversed by the pre-treatment with N-Acetyl-l-cysteine (NAC). Celastrol also suppressed tumor growth in vivo.

Conclusion
The outcomes revealed that celastrol plays a potent suppressive role in NSCLC in vitro and in vivo. Celastrol induces apoptosis via causing mitochondrial ROS accumulation to suppress the STAT3 pathway. Celastrol may have potential application prospects in the therapy of NSCLC.
Ca2+ dysregulation in cardiac stromal cells sustains fibro-adipose remodeling in Arrhythmogenic Cardiomyopathy and can be modulated by flecainide
Authors: Maione Angela S. , Faris Pawan , Iengo Lara , Catto Valentina , Bisonni Luca , Lodola Francesco , Negri Sharon , Casella Michela , Guarino Anna , Polvani Gianluca , Cerrone Marina , Tondo Claudio , Pompilio Giulio , Sommariva Elena , Moccia Francesco 
Published: November 2022

Abstract
Background
Cardiac mesenchymal stromal cells (C-MSC) were recently shown to differentiate into adipocytes and myofibroblasts to promote the aberrant remodeling of cardiac tissue that characterizes arrhythmogenic cardiomyopathy (ACM). A calcium (Ca2+) signaling dysfunction, mainly demonstrated in mouse models, is recognized as a mechanism impacting arrhythmic risk in ACM cardiomyocytes. Whether similar mechanisms influence ACM C-MSC fate is still unknown.
Thus, we aim to ascertain whether intracellular Ca2+ oscillations and the Ca2+ toolkit are altered in human C-MSC obtained from ACM patients, and to assess their link with C-MSC-specific ACM phenotypes.

Methods and results
ACM C-MSC show enhanced spontaneous Ca2+ oscillations and concomitant increased Ca2+/Calmodulin dependent kinase II (CaMKII) activation compared to control cells. This is manly linked to a constitutive activation of Store-Operated Ca2+ Entry (SOCE), which leads to enhanced Ca2+ release from the endoplasmic reticulum through inositol-1,4,5-trisphosphate receptors. By targeting the Ca2+ handling machinery or CaMKII activity, we demonstrated a causative link between Ca2+ oscillations and fibro-adipogenic differentiation of ACM C-MSC. Genetic silencing of the desmosomal gene PKP2 mimics the remodelling of the Ca2+ signalling machinery occurring in ACM C-MSC. The anti-arrhythmic drug flecainide inhibits intracellular Ca2+ oscillations and fibro-adipogenic differentiation by selectively targeting SOCE.

Conclusions
Altogether, our results extend the knowledge of Ca2+ dysregulation in ACM to the stromal compartment, as an etiologic mechanism of C-MSC-related ACM phenotypes. A new mode of action of flecainide on a novel mechanistic target is unveiled against the fibro-adipose accumulation in ACM.