Miracle-dz/UniFAR-FTUs huggingface dataset:
High-Density Lipoprotein Anti-Inflammatory Capacity and Incident Cardiovascular Events

Supplemental Digital Content is available in the text. Background: The role of high-density lipoprotein (HDL) function in cardiovascular disease represents an important emerging concept. The present study investigated whether HDL anti-inflammatory capacity is prospectively associated with first cardiovascular events in the general population. Methods: HDL anti-inflammatory capacity was determined as its ability to suppress TNFα (tumor necrosis factor α)–induced VCAM-1 (vascular cell adhesion molecule-1) mRNA expression in endothelial cells in vitro (results expressed as achieved percent reduction by individual HDL related to the maximum TNFα effect with no HDL present). In a nested case-control design of the PREVEND (Prevention of Renal and Vascular End Stage Disease) study, 369 cases experiencing a first cardiovascular event (combined end point of death from cardiovascular causes, ischemic heart disease, nonfatal myocardial infarction, and coronary revascularization) during a median of 10.5 years of follow-up were identified and individually matched to 369 controls with respect to age, sex, smoking status, and HDL cholesterol. Baseline samples were available in 340 cases and 340 matched controls. Results: HDL anti-inflammatory capacity was not correlated with HDL cholesterol or hsCRP (high-sensitivity C-reactive protein). HDL anti-inflammatory capacity was significantly lower in cases compared with controls (31.6% [15.7–44.2] versus 27.0% [7.4–36.1]; P<0.001) and was inversely associated with incident CVD in a fully adjusted model (odds ratio [OR] per 1 SD, 0.74 [CI, 0.61–0.90]; P=0.002). Furthermore, this association was approximately similar with all individual components of the cardiovascular disease end point. The HDL anti-inflammatory was not correlated with cholesterol efflux capacity (r=−0.02; P>0.05). When combining these 2 HDL function metrics in 1 model, both were significantly and independently associated with incident cardiovascular disease in a fully adjusted model (efflux: OR per 1 SD, 0.74; P=0.002; anti-inflammatory capacity: OR per 1 SD, 0.66; P<0.001). Adding HDL anti-inflammatory capacity improved risk prediction by the Framingham risk score, with a model likelihood-ratio statistic increase from 10.50 to 20.40 (P=0.002). Conclusions: The HDL anti-inflammatory capacity, reflecting vascular protection against key steps in atherogenesis, was inversely associated with incident cardiovascular events in a general population cohort, independent of HDL cholesterol and HDL cholesterol efflux capacity. Adding HDL anti-inflammatory capacity to the Framingham risk score improves risk prediction.
Rigid reduced successor representation as a potential mechanism for addiction

Difficulty in cessation of drinking, smoking, or gambling has been widely recognized. Conventional theories proposed relative dominance of habitual over goal‐directed control, but human studies have not convincingly supported them. Referring to the recently suggested “successor representation (SR)” of states that enables partially goal‐directed control, we propose a dopamine‐related mechanism that makes resistance to habitual reward‐obtaining particularly difficult. We considered that long‐standing behavior towards a certain reward without resisting temptation can (but not always) lead to a formation of rigid dimension‐reduced SR based on the goal state, which cannot be updated. Then, in our model assuming such rigid reduced SR, whereas no reward prediction error (RPE) is generated at the goal while no resistance is made, a sustained large positive RPE is generated upon goal reaching once the person starts resisting temptation. Such sustained RPE is somewhat similar to the hypothesized sustained fictitious RPE caused by drug‐induced dopamine. In contrast, if rigid reduced SR is not formed and states are represented individually as in simple reinforcement learning models, no sustained RPE is generated at the goal. Formation of rigid reduced SR also attenuates the resistance‐dependent decrease in the value of the cue for behavior, makes subsequent introduction of punishment after the goal ineffective, and potentially enhances the propensity of nonresistance through the influence of RPEs via the spiral striatum‐midbrain circuit. These results suggest that formation of rigid reduced SR makes cessation of habitual reward‐obtaining particularly difficult and can thus be a mechanism for addiction, common to substance and nonsubstance reward.
Psychological distress in patients with cardiovascular disease: time to do something about it?

and as risk factors for quality of life and a prognosis in patients with cardiovascular disease professionals in clinical practice, as and physiotherapists, in cardiac rehabilitation, are in the to to patients with psychosocial risk factors. to be to such professionals need effective tools. This research that focuses on to do about psychological distress. to on the prevalence, relationships to, and effects of psychological distress in CVD patients and studies on interventions are A argue that there are studies that have evaluated such interventions. this is certain-ly true. There are studies that evaluate intervention in patients with psychological distress in CVD, however many of these studies have not been able to support the benefits of intervention. There are im-portant lessons to be learned from these studies
Expression of Rasd1 in mouse endocrine pituitary cells and its response to dexamethasone

Abstract Dexamethasone-induced Ras-related protein 1 (Rasd1) is a member of the Ras superfamily of monomeric G proteins that have a regulatory function in signal transduction. Rasd1, also known as Dexras1 or AGS1, is rapidly induced by dexamethasone (Dex). While prior data indicates that Rasd1 is highly expressed in the pituitary and that the gene may function in regulation of corticotroph activity, its exact cellular localization in this tissue has not been delineated. Nor has it been determined which endocrine pituitary cell type(s) are responsive to Dex-induced expression of Rasd1. We hypothesized that Rasd1 is primarily localized in corticotrophs and furthermore, that its expression in these cells would be upregulated in response to exogenous Dex administration. Rasd1 expression in each pituitary cell type both under basal conditions and 1-hour post Dex treatment were examined in adult male mice. While a proportion of all endocrine pituitary cell types expressed Rasd1, a majority of corticotrophs and thyrotrophs expressed Rasd1 under basal condition. In vehicle treated animals, approximately 50–60% of corticotrophs and thyrotrophs cells expressed Rasd1 while the gene was detected in only 15–30% of lactotrophs, somatotrophs, and gonadotrophs. In Dex treated animals, Rasd1 expression was significantly increased in corticotrophs, somatotrophs, lactotrophs, and gonadotrophs but not thyrotrophs. In Dex treated animals, Rasd1 was detected in 80–95% of gonadotrophs and corticotrophs. In contrast, Dex treatment increased Rasd1 expression to a lesser extent (55–60%) in somatotrophs and lactotrophs. Corticotrophs of the pars intermedia, which lack glucocorticoid receptors, failed to display increased Rasd1 expression in Dex treated animals. Rasd1 is highly expressed in corticotrophs under basal conditions and is further increased after Dex treatment, further supporting its role in glucocorticoid negative feedback. In addition, the presence and Dex-induced expression of Rasd1 in endocrine pituitary cell types, other than corticotrophs, may implicate Rasd1 in novel pituitary functions.
The efficacy of therapeutic cervical cerclage in singleton pregnancies: a retrospective study

Abstract Objectives We compared the pregnancy prolongation effect attributable to cervical cerclage to that achieved by conservative management, and determined the cervical length for which cervical cerclage is effective. Methods We retrospectively examined medical records of 281 women admitted to our hospital between January 2013 and December 2017 for management of threatened preterm birth at 22−28 weeks of gestation. Obstetricians determined suitability for cervical cerclage, which was performed using the McDonald procedure in all cases. Of the 281 subjects, 71 underwent cervical cerclage (cerclage group); the other 210 received conservative therapy (non-cerclage group). We recorded maternal and neonatal characteristics of all patients. The two groups were compared in terms of length of extension of pregnancy and weeks of gestation at delivery. Multivariate analysis was performed to identify factors associated with extension of time to delivery. Results Our analyses revealed that the cerclage group was hospitalized earlier in pregnancy than the non-cerclage group (23.7 ± 1.5 weeks vs. 26.4 ± 1.9 weeks, p < .001) and had shorter cervixes (6.0 ± 9.4 mm vs. 16.9 ± 13.0 mm, p < .001). The two groups did not differ significantly in terms of gestational weeks at delivery. Multivariate analysis regarding extension of pregnancy revealed significant differences in extension of pregnancy related with cervical cerclage (26.65 days, 95% CI 17.0 − 36.3, p < .001) and cervical length <10 mm (−27.4 days, 95% CI −36.0–−18.8, p < .001). While the time to delivery was extended by cervical cerclage in women with short cervixes (<25 mm), the two groups did not differ when cervical length was ≥15 mm. Conclusions Cervical cerclage was a significant positive factor and short cervix was a significant negative factor for elongating pregnancy. In primigravida and multigravida women with no history of preterm birth, when the cervix is short (<10 mm), cervical cerclage should be recommended.
Efficacy and safety of crizotinib plus bevacizumab in ALK/ROS-1/c-MET positive non-small cell lung cancer: an open-label, single-arm, prospective observational study.

BACKGROUND Crizotinib is a tyrosine kinase inhibitor (TKI) effective in ALK/ROS-1/c-MET positive non-small cell lung cancer (NSCLC) patients. Bevacizumab is an antiangiogenic monoclonal antibody, and improves clinical benefit of NSCLC in combination with EGFR-TKIs or chemotherapy. However, the efficacy and safety of crizotinib plus bevacizumab in treating naive ALK/ROS-1/c-MET positive NSCLC patients have not been studied. METHODS In this open-label, single-arm, prospective observational study, locally advanced or metastatic ALK rearrangement/ROS-1 fusion/c-MET amplification NSCLC patients were treated with crizotinib (250 mg orally twice daily) and bevacizumab (7.5 mg/kg intravenous every three weeks) until disease progression or intolerant toxicity or death. Primary end point was progressive free survival (PFS), secondary end points were duration of response (DOR), overall response rate (ORR), disease control rate (DCR) and safety. Patients receiving ≥1 cycle of treatment were evaluated. FINDINGS Fourteen patients were eligible for analyzing between June 2016 and October 2017. There were 12 patients with ALK rearrangement, 1 patient with ROS-1 fusion, and 1 patient with c-MET amplification. The median follow-up time was 42.8 months. The median PFS and DOR of the patients with ALK rearrangement were 13.9 and 14.8 months respectively. Of the 12 patients, 7 gained partial response, 5 gained stable disease. The ORR and DCR were 58.3% and 100%. The PFS were 12.9 months and 1.9 months for patient with ROS-1 fusion or c-MET amplification. The most two common treatment-related adverse events were fatigue (28.6%) and rash (21.4%). 3 patients discontinued therapy because of liver damage or hemoptysis. INTERPRETATION This study demonstrated that crizotinib plus bevacizumab showed benefit in treating naive ALK rearrangement NSCLC patients, and the toxicity was relatively tolerant. Our results suggested that crizotinib plus bevacizumab might be a promising treatment strategy in ALK/ROS-1/c-MET positive NSCLC patients.
Lung cancers and pulmonary nodules detected by computed tomography scan: a population-level analysis of screening cohorts

Background An increasing number and proportion of younger lung cancer patients have been observed worldwide, raising concerns on the optimal age to begin screening. This study aimed to investigate the association between age and findings in initial CT scans. Methods We searched for low-dose CT screening cohorts from electronic databases. Single-arm syntheses weighted by sample size were performed to calculate the detection rates of pulmonary nodules, lung cancers (all stages and stage I), and the proportion of stage I diseases in lung cancers. In addition, we included patients who underwent chest CT in our center as a supplementary cohort. The correlation between the detection rates and age was evaluated by the Pearson Correlation Coefficient. Results A total of 37 studies involving 163,442 participants were included. We found the detection rates of pulmonary nodules and lung cancers increased with age. However, the proportion of stage I diseases in lung cancers declined with increased starting age and was significantly higher in the 40-year group than in other groups (40 vs. 45, 50, 55, P<0.001). In addition, the ratio of early-stage lung cancer to the number of nodules declined with age. Similarly, in our center, the detection rates of nodules (R2=0.86, P≤0.001), all lung cancer (R2=0.99, P≤0.001) and stage I diseases (R2=0.87, P=0.001) increased with age, while the proportion of stage I diseases consistently declined with age (R2=0.97, P≤0.001). Conclusions Starting lung cancer screening at an earlier age is associated with a higher probability of identifying a curable disease, urging future research to determine the optimal starting age.
Sleep Health in Male-dominated Workplaces: A Qualitative Study Examining the Perspectives of Male Employees

ABSTRACT Objective The purpose of this qualitative study was to explore working men’s perspectives about sleep health and the intersecting influences of gender and work, describing participant’s views on current and potential programming and organizational support to promote sleep health. Methods Twenty men employed in male-dominated industries in the north-central region of Alberta, Canada, participated in 4 consultation group discussions addressing motivators, facilitators and barriers to sleep health. Results Participants reported sleeping an average of 6.36 (SD ±1.1) hours per night, and the majority worked more than 40 hours per week. Data were analyzed using an inductive approach. The findings provided important insights. In normalizing sleep deprivation and prioritizing the need to “just keep going” on six or less hours of sleep, the men subscribed to masculine ideals related to workplace perseverance, stamina and resilience. Workplace cultures and practices were implicated including normative dimensions of overtime and high productivity and output, amid masculine cultures constraining emotions and conversations about sleep, the sum of which muted avenues for discussing, let alone promoting sleep. Challenges to good sleep were primarily constructed around time constraints, and worry about meeting work and home responsibilities. Men’s preferences for workplace support included providing and incentivizing the use of sleep health resources, designing work for sleep health (e.g., shift schedules, overtime policies) and getting advice from experienced coworkers and experts external to the workplace organization. Conclusion These findings hold potential for informing future gender-sensitive programming and organizational practices to support sleep health among working men.
The anatomical basis behind the neuromodulation effects associated with pulmonary vein isolation

The anatomical basis underlying the neuromodulation effects seen with pulmonary vein (PV) isolation (PVI) is not fully understood. Left atrial (LA) electro‐anatomical maps of 38 patients who underwent catheter cardioneuroablation for vagally mediated bradycarrhythmias were studied. During the procedure, LA ganglionic plexi (GPs) were systematically identified and ablated. Design PVI lines were created on these maps by a blinded observer, and the degree of overlap between four GPs and individual PVs was assessed. Here, 1.7 ± 7 (35.5 ± 17.0%) of the total 31.6 ± 10 GP ablation sites per patient were found to overlap with the design PVI lines. The overlap was higher for the right‐sided GPs, p < . 001. The degree of GP–PV overlap varied: 1 PV in 5 (13.2%) patients, 2 PVs in 15 (39.2%), 3 PVs in 16 (42.1%), and all 4 PVs in 2 (5.3%). No patient had zero GP–PV overlap. A vagal response was most commonly observed during ablation at the left superior GP (89.5%), while a sympathetic response was observed most often during the right superior GP ablation (97.4%). Some degree of GP–PV antral overlap is the norm, and this is more pronounced for the right‐sided PVs. There is significant individual variability in the degree of overlap which may explain why neuromodulation effects are not seen universally following PVI.
An artificial intelligence platform for the diagnosis and surgical planning of strabismus using corneal light-reflection photos

Background Strabismus affects approximately 0.8–6.8% of the world’s population and can lead to abnormal visual function. However, Strabismus screening and measurement are laborious and require professional training. This study aimed to develop an artificial intelligence (AI) platform based on corneal light-reflection photos for the diagnosis of strabismus and to provide preoperative advice. Methods An AI platform consisting of three deep learning (DL) systems for strabismus diagnosis, angle evaluation, and operation plannings based on corneal light-reflection photos was trained and retrospectively validated using a retrospective development data set obtained between Jan 1, 2014, and Dec 31, 2018. Corneal light-reflection photos were collected to train the DL systems for strabismus screening and deviation evaluations in the horizontal strabismus while concatenated images (each composed of two photos representing different gaze states) were procured to train the DL system for operative advice regarding exotropia. The AI platform was further prospectively validated using a prospective development data set captured between Sep 1, 2019, and Jun 10, 2020. Results In total, 5,797 and 571 photos were included in the retrospective and prospectively development data sets, respectively. In the retrospective test sets, the screening system detected strabismus with a sensitivity of 99.1% [95% confidence interval (95% CI), 98.1–99.7%], a specificity of 98.3% (95% CI, 94.6–99.5%), and an AUC of 0.998 (95% CI, 0.993–1.000, P<0.001). Compared to the angle measured by the perimeter arc, the deviation evaluation system achieved a level of accuracy of ±6. 6º (95% LoA) with a small bias of 1. 0º. Compared to the real design, the operation advice system provided advice regarding the target angle within ±5. 5º (95% LoA). Regarding strabismus in the prospective test set, the AUC was 0.980. The platform achieved a level of accuracy of ±7. 0º (95% LoA) in the deviation evaluation and ±6. 1º (95% LoA) in the target angle suggestion. Conclusions The AI platform based on corneal light-reflection photos can provide reliable references for strabismus diagnosis, angle evaluation, and surgical plannings.
SPAG6-silencing enhances decitabine-induced apoptosis and demethylation of PTEN in SKM-1 cells and in a xenograft mouse model

Abstract Myelodysplastic syndromes (MDS) are a group of malignant diseases that are characterized by disordered hematopoiesis with a high risk of transforming into leukemia. In the present study, SPAG6-knockdown and decitabine (DAC) treatment resulted in a decreased DNA methyltransferases and methyl-CpG-binding domain protein expression. In addition, DAC and LBH589 were shown to promote apoptosis in SKM-1 cells, and SPAG6-knockdown to enhance the pro-apoptotic effect of DAC. DAC could reduce PTEN methylation and increase PTEN expression in SKM-1 cells. SPAG6-knockdown and LBH589 treatment could increase DAC-mediated demethylation of PTEN promoter. Finally, a mouse model was constructed, and an enhanced efficacy of DAC following SPAG6-knockdown was confirmed in vivo. In conclusion, DAC-mediated apoptosis and PTEN promoter demethylation may be synergistically enhanced by SPAG6-silencing. Therefore, in the present study it was indicated that SPAG6 may be a potential target for demethylation therapy in MDS.
Risk factors for cognitive impairment in patients with first-time ischemic stroke.

OBJECTIVE To determine the risk factors for cognitive impairment (CI) in patients with first-time ischemic stroke. METHODS The clinical data of 180 patients with ischemic stroke who were admitted to our hospital from January 2018 to December 2019 was retrospectively analyzed. Patients with MMSE score ≤24 were included into the CI group and the rest of the patients were placed into the normal group. Multivariate logistic regression was applied to describe risk factors for CI in patients with first-time ischemic stroke. RESULTS Among the patients with first-time ischemic stroke, 96 cases (53%) developed CI, 84 cases (47%) were normal. In different subtypes of TOAST classifications, patients with large-artery atherosclerosis had the highest CI incidence (66.96%). For different infarction sites, the highest CI incidence occurred in the frontal lobe (82.35%), and the lowest was from cerebellar infarction (37.50%). The difference of CI incidences in the frontal lobe, parietal lobe, temporal lobe and occipital lobe was significant between the two groups (P<0.05). Logistic regression analysis indicated that independent risk factors for CI in patients with first ischemic stroke include age ≥60 years old, diabetes history, CRP >6.53 mg/L, Hcy >13.84 μmol/L, NIHSS score >4.37, VD <45.16 nmol/L, and the difference was statistically significant (P<0.05). CONCLUSION The study showed a high CI incidence in patients with preexisting ischemic stroke. Age ≥60 years old, history of diabetes mellitus, CRP >6.53 mg/L, Hcy >13.84 μmol/L, NIHSS score >4.37 score, VD <45.16 nmol/L are independent risk factors for CI in patients with first-time ischemic stroke.