bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitrectomy and All-Cause and Cause-Specific Mortality in Elderly Patients With Vitreoretinal Diseases: A Nationwide Cohort Study
Authors: Kim Yoon Jeon , Lee Ji Sung , Lee Yunhan , Lee Hun , Kim Jae Yong , Tchah Hungwon 
Published: April 2022

PurposeTo determine the all-cause and cause-specific mortality in elderly patients with vitreoretinal diseases based on vitrectomy status.MethodsElderly patients (aged ≥ 60 years) diagnosed with vitreoretinal diseases between 2003 and 2012 using the Korean National Health Insurance Service-Senior cohort (2002–2015) were included in this nationwide population-based retrospective cohort study. The exposure of interest was vitrectomy, and information on mortality from patient inclusion until December 2015 was obtained. Cox regression modeling was used to assess the association between vitrectomy and mortality. An additional subgroup analysis was performed to investigate the effects of the underlying retinal disease characteristics and comorbidities on mortality.ResultsThe study cohort included 152,283 patients (3,313 and 148,970 in the vitrectomy and non-vitrectomy groups, respectively). The adjusted model showed vitrectomy was associated with a decreased risk of pulmonary-cause mortality [hazard ratio (HR), 0.51; P &lt; 0.001]; however, no association was observed for all-cause mortality (HR, 0.93; P = 0.325). Vitrectomy was associated with increased mortality risk (all-cause: HR, 1.26; P &lt; 0.001 and vascular causes: HR, 1.41; P = 0.003) among patients with retinal vascular diseases and decreased mortality risk (all-cause: HR, 0.64; P &lt; 0.001 and pulmonary causes: HR, 0.35; P = 0.011) among patients with macular diseases. There were significant interactions between age and vitrectomy with respect to all-cause mortality among patients with either vitreoretinal disease.ConclusionsIn elderly patients with retinal diseases, the vitrectomy group showed the lower mortality from pulmonary causes with no association for all-cause mortality.
Medical Student Experiences of Uncertainty Tolerance Moderators: A Longitudinal Qualitative Study
Authors: Stephens Georgina C. , Sarkar Mahbub , Lazarus Michelle D. 
Published: April 2022

IntroductionUncertainty tolerance (UT), a construct explicating individuals' response to perceived uncertainty, is increasingly considered a competency for effective medical practice. Lower UT among physicians is linked with negative outcomes, including less favorable attitudes toward patient-centered care, and increased burnout risk. Despite decades of research, as yet few have engaged methodological approaches aiming to understand the factors that may influence medical students' UT (so-called moderators). Such knowledge, though, could inform teaching practices for fostering learners' skills for managing uncertainties. Accordingly, we asked “What factors do medical students in their clinical years perceive as moderating their perceptions of, and responses to, uncertainty?”MethodsWe conducted a qualitative study with forty-one medical students in clinical years at an Australian medical school, with data collected throughout 2020. Participants described their experiences of uncertainty through both in-semester reflective diary entries (n= 230) and end of semester group or individual semi-structured interviews (n= 40). Data were analyzed using a team-based framework analysis approach.ResultsFour major themes of UT moderators were identified: (1) Individual factors, (2) Sociocultural factors, (3) Academic factors and (4) Reflective learning. Aspects of individual, sociocultural and academic factors were perceived as having either positive or negative influences on students' perceptions of uncertainty. By contrast, reflective learning was described as having a predominantly positive influence on students' perceptions of uncertainty, with students noting learning opportunities and personal growth afforded through uncertain experiences.ConclusionsAs healthcare becomes increasingly complex, a future challenge is equipping our medical students with strategies and skills to manage uncertainties. Our study identified multiple moderators of medical students' UT, key among them being reflective learning. We also identified UT moderators that contemporary and future medical educators may be able to harness in order to develop learner UT as a healthcare graduate attribute, especially through teaching practices such as intellectual candor. Further research is now required to evaluate the impact of proposed educational interventions, and to develop effective assessments of students' skills for managing clinical uncertainties.
A Glycolysis-Related Gene Signature Correlates With the Characteristics of the Tumor Immune Microenvironment and Predicts Prognosis in Patients With Hepatocellular Carcinoma
Authors: Yang Jun , Zhang Yuening , Duan Jin , Huang Xiaojie , Yu Haibin , Hu Zhongjie 
Published: April 2022

Aim: To develop a glycolysis-related gene signature that correlated with the characteristics of the tumor immune microenvironment and had good predictive power for overall survival (OS) in hepatocellular carcinoma (HCC).Methods: Gene expression profiles, RNA sequencing data, clinical characteristics and survival information for 407 patients with HCC and 58 healthy controls were downloaded from the TCGA database. GSEA 4.1.0 software was used to evaluate the glycolysis-related pathways enriched in HCC compared to normal liver tissue. Univariate Cox, Least Absolute Shrinkage, Selection Operator, and two-step multivariate Cox analyses were used to construct a glycolysis-related gene signature for prognostic prediction. The glycolysis-related gene signature was combined with clinical characteristics to generate a nomogram. Tumor-infiltrating immune cell profiles and PD-L1 protein expression in HCC tissues were investigated.Results: The gene expression profiles of HCC tissues were enriched in glycolysis-related pathways. A glycolysis-related gene signature was used to categorize patients as high-risk or low-risk, where high-risk patients had significantly worse OS. Receiver operating characteristic curves confirmed the predictive capability of the glycolysis-related gene signature for OS (AUC &gt;0.80). There was a significant difference in M0 macrophage (p = 0.017), dendritic cell (p = 0.043), B cell (p = 0.0018), CD4 T cell (p = 0.003), Treg (p = 0.01) and mast cell (p = 0.02) content and PD-L1 protein expression (p = 0.019) between HCC tissues in patients in the high-risk and low-risk groups.Conclusion: We established a glycolysis-related gene signature for OS in HCC that was predictive in training and test TCGA cohorts and correlated with the characteristics of the HCC tumor immune microenvironment. The glycolysis-related gene signature may guide clinical decision-making concerning patient selection for immunotherapy in HCC.
Longitudinal Variations of CDC42 in Patients With Acute Ischemic Stroke During 3-Year Period: Correlation With CD4+ T Cells, Disease Severity, and Prognosis
Authors: Cheng Xiao , Ye Jianxin , Zhang Xiaolei , Meng Kun 
Published: April 2022

ObjectiveCell division cycle 42 (CDC42) modulates CD4+ T-cell differentiation, blood lipids, and neuronal apoptosis and is involved in the pathogenesis of acute ischemic stroke (AIS); however, the clinical role of CDC42 in AIS remains unanswered. This study aimed to evaluate the expression of CDC42 in a 3-year follow-up and its correlation with disease severity, T helper (Th)1/2/17 cells, and the prognosis in patients with AIS.MethodsBlood CDC42 was detected in 143 patients with AIS at multiple time points during the 3-year follow-up period and in 70 controls at admission by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, blood Th1, Th2, and Th17 cells and their secreted cytokines (interferon-γ (IFN-γ), interleukin-4 (IL-4), and interleukin-17A (IL-17A)) in patients with AIS were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively.ResultsCompared with controls (p &lt; 0.001), CDC42 was reduced in patients with AIS. CDC42 was negatively correlated with the National Institutes of Health Stroke Scale (NIHSS) score (p &lt; 0.001), whereas, in patients with AIS (all p &lt; 0.050), it was positively associated with Th2 cells and IL-4 but negatively correlated with Th17 cells and IL-17A. CDC42 was decreased from admission to 3 days and gradually increased from 3 days to 3 years in patients with AIS (P&lt;0.001). In a 3-year follow-up, 24 patients with AIS recurred and 8 patients died. On the 3rd day, 7th day, 1st month, 3rd month, 6th month, 1st year, 2nd year, and 3rd year, CDC42 was decreased in recurrent patients than that in non-recurrent patients (all p &lt; 0.050). CDC42 at 7 days (p = 0.033) and 3 months (p = 0.023) was declined in reported deceased patients than in survived patients.ConclusionCDC42 is used as a biomarker to constantly monitor disease progression and recurrence risk of patients with AIS.
The Clinical Differences of Patients With Traumatic Brain Injury in Plateau and Plain Areas
Authors: Yang Yongxiang , Peng Yuping , He Siyi , Wu Jianping , Xie Qingyun , Ma Yuan 
Published: April 2022

ObjectiveTraumatic brain injury (TBI) is a leading cause of death and disability, which tends to have a worse clinical recovery if it occurs in plateau areas than in plain areas. To explore the underlying cause of this outcome preliminarily, this retrospective study was conducted to compare the clinical differences of patients with TBI in plateau and plain areas.MethodsIn this study, 32 patients with TBI in plateau areas (altitude ≥ 4,000 m) and 32 in plain areas (altitude ≤ 1,000 m) were recruited according to the inclusion and exclusion criteria from June 2020 to December 2021. The collected data and compared parameters include clinical features, head CT presentations and Marshall classifications, hematology profile, lipid profile, coagulation profile, and multiorgan (cardiac, liver, renal) function within 24 h of hospital admission, as well as the treatment method and final outcome.ResultsThere were no obvious differences in demographic characteristics, including gender, age, height, and weight, between patients with TBI in plateau and plain areas (all P &gt; 0.05). Compared to patients with TBI in plain areas, the time before hospital admission was longer, heartbeat was slower, systolic blood pressure (SBP) was lower, and hospital stays were longer in patients with TBI in plateau areas (all P &lt; 0.05). More importantly, elevated red blood cells (RBCs) count and hemoglobin (HGB) level, enhanced coagulation function, and higher rates of multiorgan (cardiac, liver, and renal) injury were found in patients with TBI in plateau areas (all P &lt; 0.05).ConclusionPatients with TBI in plateau areas presented with altered clinical characteristics, enhanced coagulation function, and aggravated predisposition toward multiorgan (cardiac, liver, and renal) injury, compared to patients with TBI in plain areas. Future prospective studies are needed to further elucidate the influences of high altitude on the disease course of TBI.
Impact of Socio-Economic Factors on Nutrition Efficiency: An Application of Data Envelopment Analysis
Authors: Pakravan-Charvadeh Mohammad Reza , Flora Cornelia Butler , Emrouznejad Ali 
Published: April 2022

BackgroundPaying particular attention to sustainable food consumption in low-income households is essential for increasing human health. Due to the growing population globally, this concept will likely become more serious soon.MethodsFollowing the importance of optimizing food consumption for sustainability, in this study, a novel methodology is introduced for calculating nutrient intake efficiency and determining choices of food in different locations. The impact of socio-economic factors on nutrition efficiency is assessed. Data Envelopment Analysis (DEA) as a well-known linear programming (LP) and a Tobit model are used to achieve the goals. Household Consumption and Expenditure Surveys (HCESs) of 30,000 rural and urban Iranian households in all provinces in 2016 are analyzed. A Nutrient Efficiency Map (NEM) of Iran was depicted by GIS software.ResultsThe results showed that many townships had nutrient efficiency scores of less than 70%. Northeast townships had the lowest scores, with an efficiency score of less than 50%. Overall, townships have lower efficiency in the North (seaside cities), East (desert cities), and North East (isolated cities) when compared with other areas.ConclusionTherefore, it is suggestible that the government should modify the support policies and the protection packages based on social, geographical, and cultural status.
Arteriovenous Cerebral High Flow Shunts in Children: From Genotype to Phenotype
Authors: Tas Berivan , Starnoni Daniele , Smajda Stanislas , Vivanti Alexandre J. , Adamsbaum Catherine , Eyries Mélanie , Melki Judith , Tawk Marcel , Ozanne Augustin , Revencu Nicole , Soubrier Florent , Siala Selima , Vikkula Miikka , Deiva Kumaran , Saliou Guillaume 
Published: April 2022

ObjectiveTo study the genotypes and phenotypes of cerebral arteriovenous fistulas that drain or do not drain through the vein of Galen, and true vein of Galen aneurysmal malformations, in order to determine whether genotyping could help improve classification of these malformations and their management.MethodsWe carried out a retrospective review of genetic and phenotypic data in databases of four centers. All children with cerebral arteriovenous fistula or vein of Galen aneurysmal malformations aged below 18 years at onset were included. We recorded the nature of the genetic variant or absence of variant, age at onset, type of malformation, symptoms at onset (hemorrhage, neurological deficit, hydrocephalus, incidental, and heart failure), type of venous drainage and the long-term outcome.ResultsOne hundred and fifteen children were included. Autosomal dominant variants were identified in 39% of patients. The most frequent variant affected was the RASA1 gene (25%) followed by EPHB4 (8%) and the HHT-associated genes (5%). HHT gene variants were only observed in pial arteriovenous fistula not draining into the vein of Galen; on the contrary, EPHB4 variants were only seen in genuine vein of Galen aneurysmal malformation. RASA1 variants were identified in all types of shunts.ConclusionsEPHB4 variants seem specific to the vein of Galen aneurysmal malformation, RASA1 variants are associated with either pial arteriovenous fistulas or with genuine VGAM and HHT gene variants seem specific to pial arteriovenous fistulas. The genetic data helps to classify these malformations and to guide treatment toward lowest risk of post-operative cerebral ischemic-hemorrhagic complications.
Bilirubin Improves Gap Junction to Alleviate Doxorubicin-Induced Cardiotoxicity by Regulating AMPK-Axl-SOCS3-Cx43 Axis
Authors: Zhang Siqi , Fan Yixin , Zheng Binbin , Wang Yu , Miao Chen , Su Yue , Li Kun , E. Yan , Wang Xueli , He Xueming , Wu Xuefeng , Xu Chenjie , Tang Yulin , Liu Wen-Tao , Kong Xiangqing , Hu Liang 
Published: April 2022

Doxorubicin induces severe cardiotoxicity, accompanied by the high level of bilirubin in the blood. The conventional wisdom is that bilirubin is considered as a marker of liver damage. By contrast, here we aim to explore the potential protective effect of bilirubin on doxorubicin-induced cardiotoxicity, and investigate the mechanism for drug development. Doxorubicin was used to establish cardiotoxicity model in vitro and in vivo. The electrocardiogram (ECG), echocardiography and molecular biological methods were used to detect the effects of bilirubin on doxorubicin-induced cardiotoxicity. Consecutive intraperitoneal injection of bilirubin for 7 days significantly attenuated doxorubicin-induced arrhythmia, prolonged survival time and reduced the levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB) and α-hydroxybutyrate dehydrogenase (α-HBDH) in mice. Bilirubin also markedly inhibited doxorubicin-induced phosphorylation of c-Jun N-terminal kinase (JNK) and connexin 43 (Cx43), and improved gap junction function in vitro and in vivo. In addition, bilirubin activated adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) and induced suppressor of cytokine signaling 3 (SOCS3) expression, which was abolished by Axl inhibition. Moreover, pretreatment with AMPK agonist or AMPK inhibitor could mimic or abolish the cardioprotective effect of bilirubin on H9C2 cells in vitro, respectively. Altogether, bilirubin upregulates gap junctions’ function to protect against doxorubicin-induced cardiotoxicity by activating AMPK-Axl-SOCS3 signaling axis. We enrich the physiological function of bilirubin, and provide theoretical support for drug development.
REL-1017 (Esmethadone), A Novel NMDAR Blocker for the Treatment of MDD is Not Neurotoxic in Sprague-Dawley Rats
Authors: Bifari Francesco , Pappagallo Marco , Bleavins Michael , Traversa Sergio , Folli Franco , Manfredi Paolo L. 
Published: April 2022

REL-1017 (esmethadone; dextromethadone; (S)-methadone) is the opioid-inactive dextro-isomer of the racemic mixture, (R, S)-methadone. REL-1017 acts as a low affinity, low potency N-methyl-D-aspartate receptor (NMDAR) channel blocker with rapid, robust, and sustained therapeutic effects in patients with major depressive disorder (MDD). Systemic administration of NMDAR blockers may cause transient and reversible pathomorphological alterations in brain cortical neurons characterized by cytoplasmic vacuolization, which are called Olney’s lesions, and may also lead to irreversible neuronal necrosis. We determined whether REL-1017 administration via oral gavage for 1–4 days to Sprague-Dawley rats could produce Olney’s lesions and cortical neuronal death and microgliosis as compared with MK-801, a known neurotoxic potent NMDAR blocker. As previously reported, MK-801 produced Olney’s lesions, neuronal necrosis and cortical microgliosis, and impaired behavior and activity. In contrast, administration of REL-1017 at low (20–31.25 mg/kg in females and males), medium (40–62.5 mg/kg) or high (80–110 mg/kg) doses did not cause pathomorphological changes in brain neurons and did not cause impaired behavior and activity. In conclusion, REL-1017 did not produce initial or cumulative neurotoxic effects or other evidence of damage to cortical neurons, further encouraging the development of REL-1017 as a potentially safe novel candidate for rapid treatment of MDD.
Radical Acceptance of Reality: Putting DBT®-A Skill Groups Online During the COVID-19 Pandemic: A Qualitative Study
Authors: Bock Mercedes M. , Graf Theres , Woeber Verena , Kothgassner Oswald D. , Buerger Arne , Plener Paul L. 
Published: April 2022

IntroductionEmotion dysregulation is a common challenge pertaining to numerous psychiatric disorders in adolescence and is associated with increased morbidity and mortality. Dialectical Behavior Therapy for Adolescents (DBT®-A) has been shown to be an effective treatment, especially in the reduction of self-harm and suicidality. Measures in relation to the COVID-19 pandemic set strict limits on physical contacts with patients. In order to continuously provide evidence-based specialized care to patients suffering from emotion dysregulation, we offered two online DBT®-A skill groups in a video-group-call format.ObjectiveWe aimed at assessing our online DBT®-A skills groups, collect according up- and downsides, and form a basis for advancement of this form of treatment provision. Also, the impact of the COVID-19 pandemic on patients was assessed.MethodsA physical DBT®-A skill group was switched to a video-group-call format and a second group was initiated de novo online. After five sessions, patients engaged in structured group discussions to reflect experiences. Discussion content was analyzed via Inductive Category Formation within the Framework of Qualitative Content Analysis.ResultsPatients unanimously found the COVID-19 pandemic challenging, but also reported differentially on its impact. Downsides were balanced by subjective “gains” in time and a perceived reduction in stress. Technical problems of the online format were discussed, but did not limit the positive experience of still receiving treatment. Patients of both online DBT®-A skill groups valued the offer, felt connected, and reported benefits from the treatment. The transition group additionally discussed changes in structure and content of the group sessions after the switch to online meetings and reflected differential functions of the group.DiscussionAlthough the sample size is small, and conclusions are drawn from Inductive Qualitative Content Analysis, the presented results are of interest. In our investigation, video-group-calls were both safe and beneficial for patients. This alternative to physical meetings is not only interesting for further waves of the current pandemic but also for service provision in remote areas with limited access to specialized care. Further research is needed to challenge and refine our results and to explore extensions to “basic” video-group-calls, such as “break-out sessions,” blended therapy, or real-time supervision within an online session.
The Effect of Physical Activity on Neurotrophin Concentrations and Cognitive Control in Patients With a Depressive Episode
Authors: Jasińska-Mikołajczyk Anna , Drews Katarzyna , Domaszewska Katarzyna , Kolasa Grzegorz , Konofalska Marta , Jowik Katarzyna , Skibińska Maria , Rybakowski Filip 
Published: April 2022

BackgroundCognitive deficits occur in most patients with affective disorders. The role of neurotrophic factors (e.g., BDNF) as modulators of brain plasticity affecting neurocognitive abilities has been emphasized. Neurotrophin concentrations may change under the influence of various interventions, including physical activity. Selected studies have shown that cognitive function may also be affected by exercise.AimThe aim of the study was to determine whether physical activity changes the concentration of neurotrophins and their receptors in patients with an episode of depression. It was also examined how one session of aerobic exercise affects cognitive control.MethodsThe study included 41 participants. The subjects were asked to exercise on a cycloergometer for 40 min with individually selected exercise loads (70% VO2max). Before and shortly after the exercise blood samples were acquired to perform blood assays (proBDNF, BDNF, TrkB, NGFR). The participants also performed a Stroop test twice—before the exercise and 10 min after its cessation.ResultsThe single bout of physical exercise did not cause any significant changes in the concentration of neurotrophic factors. The SCWT results: both the mean reading time (29.3 s vs. 47.8 s) and the color naming time (36.7 s vs. 50.7 s) increased. The patients made more mistakes after physical exercise, both in part A (0.2 vs. 1.5) and B (0.6 vs. 1.5). The so-called interference effect decreased—the difference between naming and reading times was smaller after exercise (6.2 s vs. 2.4 s). No significant correlations were found between the concentrations of the studied neurotrophic factors and the Stroop test results.ConclusionsThe results did not confirm changes in neurotrophin concentration under the influence of a single session of physical activity. The shortening of the interference time after exercise may be caused by practice effects. A significant limitation of the study is the use of the Stroop test twice in short intervals.