Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipoprotein(a) and coronary artery disease in Chinese postmenopausal female patients: a large cross-sectional cohort study

Background It has been reported that lipoprotein(a) (Lp(a)) is associated with the risk of cardiovascular disease. The present study aimed to examine the association of Lp(a) levels with the presence and severity of coronary artery disease (CAD) in female patients. Methods A total of 3712 female patients who received coronary angiography were consecutively enrolled. The levels of Lp(a) were measured and compared among patients with or without CAD, myocardial infarction and menopause. Spearman correlation analysis and logistic regression analysis were used to examine the association of Lp(a) with the presence of CAD and the severity of coronary atherosclerosis assessed by Gensini score (GS). Results The average of Lp(a) levels was elevated as age increased in female subjects. Notably, women after menopause had higher Lp(a) levels compared with that before menopause (16.8 mg/dL (IQR 7.54–41.12 mg/dL) vs 14.7 mg/dL (IQR 6.72–30.82 mg/dL), p=0.002). Furthermore, multiple logistic regression analysis identified that Lp(a)>30 mg/dL was an independent risk factor of CAD in the postmenopausal females (OR: 1.33, 95% CI: 1.08 to 1.63, p=0.007). Finally, Lp(a) had a positive correlation with GS (r=0.11, p<0.001), and Lp(a)>30 mg/dL was an independent risk factor for high GS (OR: 1.43, 95% CI: 1.14 to 1.79, p=0.02) in the postmenopausal females. Conclusion Circulating Lp(a) levels were independently associated with the presence and severity of CAD in the postmenopausal females, suggesting that Lp(a) may be useful for prevention and risk-stratification of CAD in female individuals.
Nivo-lution in Mesothelioma

The MERIT study was a single-arm, phase II clinical trial of nivolumab for the second- or third-line treatment of patients with malignant pleural mesothelioma in Japan. MERIT confirmed that PD-1 inhibition has activity in mesothelioma and led to the regulatory approval of nivolumab for the treatment of mesothelioma in Japan. See related article by Okada et al., p. 5485
Improved performance of the 2017 McDonald criteria for diagnosis of multiple sclerosis in children in a real-life cohort

Objective: To compare the performance of the 2017 McDonald criteria with that of the 2010 criteria for the diagnosis of multiple sclerosis (MS) in children in the clinical setting. Methods: In this retrospective, multi-centre study, we identified children who presented with symptoms suggestive of a clinically isolated syndrome (CIS) and were followed up for at least 2 years or until their second attack. Results: Of 156 children with CIS followed up for a median of 4.17 years, 94 (60.3%) were diagnosed with MS. In all, 83 (88.3%) of these fulfilled the 2010 dissemination in space (DIS) criteria at onset. Three additional children fulfilled the 2017 DIS criteria because of the inclusion of symptomatic lesions. Of the 59 children with MS who underwent post-gadolinium magnetic resonance imaging (MRI), 44 (74.6%) fulfilled the 2010 dissemination in time (DIT) criteria at baseline. When the presence of oligoclonal bands (OCBs) was used to substitute DIT, an additional 35 children (79/94, 84.0%) were diagnosed with MS according to the 2017 criteria. The 2017 criteria had higher accuracy (87.2% vs 66.7%), higher sensitivity (84.0% vs 46.8%), but reduced specificity (91.9% vs 96.8%) when compared to the 2010 criteria. Conclusion: The improved performance of the 2017 criteria when compared to the 2010 criteria was predominantly due to the inclusion of intrathecal OCBs.
Bingeing, Purging, and Suicidal Ideation in Clinical and Non-Clinical Samples of Youth

ABSTRACT Suicidal ideation is a serious mental health concern reported by adolescents. Despite understanding of increased suicidal ideation in patients with eating disorders (EDs) and obesity, few studies have compared how disordered eating (bingeing, vomiting and over exercising) is associated with suicidal ideation in clinical and non-clinical samples of youth across the ED and weight spectrum. The present study aimed to 1) comparatively examine rates of suicidal ideation and disordered eating behaviors in clinical samples of youth with EDs, complex obesity, or from the community, and 2) examine whether disordered eating was associated with suicidal ideation above and beyond age, body mass index, diagnosis, treatment-seeking status, and depressive symptoms in large samples of males vs. females in an attempt to understand whether these behaviors should lead to concern regarding suicidal ideation. Data from charts on treatment-seeking adolescents diagnosed with either an ED (N = 315), severe complex obesity (N = 212), and from the community (N = 3036) were pooled together for comparative purposes. Results showed that suicidal ideation was higher in youth seeking treatment for an ED (50.2%) and obesity (23.7%) as compared to youth from the community (13%). Binary logistic regression analyses revealed that vomiting (OR = 1.73 for females, 8.17 for males) and over-exercising (OR = 1.47 for females, 1.68 for males) was significantly associated with suicidal ideation in both males and females. Findings underscore the importance of screening for suicidal ideation in youth who report vomiting or over-exercising despite diagnostic presentation, age, weight, or treatment setting.
Constructing a Total Cost of Ownership supplier selection methodology based on Activity-Based Costing and mathematical programming

Abstract In this paper we elaborate on a Total Cost of Ownership (TCO) supplier selection methodology that we have constructed using real life case studies of three different industrial components groups in a firm. These case studies are presented in this article. Analysing the value chain of the firm, data on the costs generated by the purchasing policy and on supplier performance are collected using Activity-Based Costing (ABC). Since a spreadsheet cannot encompass all these costs, let alone optimise the supplier selection and inventory management policy, a mathematical programming model is used. For a specific component group the combination of suppliers is selected that minimises the TCO. TCO takes into account all costs that the purchase and the subsequent use of a component entail in the entire value chain of the company. The TCO approach goes beyond minimising purchase price and studies all costs that occur during the entire life cycle of the item in the organisation. Possible savings of between 6% and 14% of the total cost of ownership of the current purchasing policy are obtained for the three cases. ABC is not an optimisation tool as such, but provides important accurate input to the optimising mathematical program, whereas the Operations Research literature usually only distinguishes between variable and fixed costs. We show that the integration of both delivers better results in the setting we have studied.
Trait-based plant ecology a flawed tool in climate studies? The leaf traits of wild olive that pattern with climate are not those routinely measured

Climate-related studies have generally focussed upon physiologically well-defined ‘mechanistic’ traits rather than ‘functional’ ones relating indirectly to resource capture. Nevertheless, field responses to climate are likely to typically include both ‘mechanistic’ specialization to climatic extremes and ‘functional’ strategies that optimize resource acquisition during less climatically-severe periods. Here, this hypothesis was tested. Seventeen traits (six ‘functional’, six ‘mechanistic’ and five ‘intermediate’) were measured from 19 populations of oleaster (wild olive) along a climatic gradient in Morocco. Principal components analysis of the trait dataset identified size and the ‘worldwide leaf economics spectrum’ as PCA axes 1 and 2. However, contrary to our prediction, these axes, and commonly-measured ‘functional’ traits, were little correlated with climate. Instead, PCA 3, perhaps relating to water-use and succulence, together stomatal density, specific leaf water content and leaf shape, patterned with altitude, aridity, rainfall and temperature. We concluded that, at least for slow-growing species, such as oleaster, ‘mechanistic’ traits are key to identifying mechanisms of climatic restriction. Meaningful collaboration between ‘mechanistic’ and ‘functional’ disciplines provides the best way of improving our understanding of the global impacts of climate change on species distribution and performance.
CD69 Targeting Enhances Anti-vaccinia Virus Immunity

In this study, we demonstrate the influence of human and mouse anti-CD69 therapies on the immune response to VACV infection. We report that targeting CD69 increases the leukocyte numbers in the secondary lymphoid organs during infection and improves the capacity to clear the viral infection. Targeting CD69 increases the numbers of gamma interferon (IFN-γ)- and tumor necrosis factor alpha (TNF-α)-producing NK and T cells. In mice expressing human CD69, treatment with an anti-CD69 MAb produces increases in cytokine production, survival, and proliferation mediated in part by mTOR signaling. These results, together with the fact that we have mainly worked with a human-CD69 transgenic model, reveal CD69 as a treatment target to enhance vaccine protectiveness. ABSTRACT CD69 is highly expressed on the leukocyte surface upon viral infection, and its regulatory role in the vaccinia virus (VACV) immune response has been recently demonstrated using CD69−/− mice. Here, we show augmented control of VACV infection using the anti-human CD69 monoclonal antibody (MAb) 2.8 as both preventive and therapeutic treatment for mice expressing human CD69. This control was related to increased natural killer (NK) cell reactivity and increased numbers of cytokine-producing T and NK cells in the periphery. Moreover, similarly increased immunity and protection against VACV were reproduced over both long and short periods in anti-mouse CD69 MAb 2.2-treated immunocompetent wild-type (WT) mice and immunodeficient Rag2−/− CD69+/+ mice. This result was not due to synergy between infection and anti-CD69 treatment since, in the absence of infection, anti-human CD69 targeting induced immune activation, which was characterized by mobilization, proliferation, and enhanced survival of immune cells as well as marked production of several innate proinflammatory cytokines by immune cells. Additionally, we showed that the rapid leukocyte effect induced by anti-CD69 MAb treatment was dependent on mTOR signaling. These properties suggest the potential of CD69-targeted therapy as an antiviral adjuvant to prevent derived infections. IMPORTANCE In this study, we demonstrate the influence of human and mouse anti-CD69 therapies on the immune response to VACV infection. We report that targeting CD69 increases the leukocyte numbers in the secondary lymphoid organs during infection and improves the capacity to clear the viral infection. Targeting CD69 increases the numbers of gamma interferon (IFN-γ)- and tumor necrosis factor alpha (TNF-α)-producing NK and T cells. In mice expressing human CD69, treatment with an anti-CD69 MAb produces increases in cytokine production, survival, and proliferation mediated in part by mTOR signaling. These results, together with the fact that we have mainly worked with a human-CD69 transgenic model, reveal CD69 as a treatment target to enhance vaccine protectiveness.
Succinate induces skeletal muscle fiber remodeling via SUNCR1 signaling

The conversion of skeletal muscle fiber from fast twitch to slow‐twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber‐type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss‐of‐function models generated by phospholipase Cβ antagonists, SUCNR1 global knockout, or SUCNR1 gastrocnemius‐specific knockdown, we found that the effects of succinate on skeletal muscle fiber‐type remodeling are mediated by SUCNR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUCNR1 signaling pathway. These findings suggest the potential beneficial use of succinate‐based compounds in both athletic and sedentary populations.
Quantitative Measurements of Codeine and Fentanyl on a Surface-Enhanced Raman-Active Pad

The USA is in the midst of an opioid crisis that included over 60,000 overdose fatalities in 2017, mostly unintentional. This is due to excessive use of prescription opioids and the use of very strong synthetic opioids, such as fentanyl, mixed with illicit street drugs. The ability to rapidly determine if people or packages entering the country have or contain drugs could reduce their availability, and thereby decrease the use of illicit drugs. In an effort to address this problem, we have been investigating the ability of surface-enhanced Raman spectroscopy to detect trace amounts of opioids on clothing and packages. Here, we report the measurement of codeine and fentanyl at 100 ng/mL for 5 min on a pad impregnated with gold colloids, as well as a preliminary measurement of 500 pg of fentanyl on a glass surface using one of these pads. The calculated limit of detection for this measurement was 40 pg. This data strongly suggests that these pads, used with portable Raman analyzers, would be invaluable to airport security, drug raids, crime scenes, and forensic analysis.
Musculoskeletal Impairment: Causes of Pain with Breastfeeding Insight into 11 Cases

Abstract Objective: To determine the possible relationship between pain experienced by mothers with breastfeeding and musculoskeletal impairment commonly seen in physiotherapy practice. Evidence-based principles of the evaluation and treatment of musculoskeletal impairment used in physiotherapy practice were applied and adapted to manage pain experienced by mothers with breastfeeding. Subjects and Methods: This report describes 11 mothers referred to a breastfeeding clinic for pain with breastfeeding. Mothers were initially assessed by a physician and a nurse clinician, both International Board-Certified Lactation Consultants, to rule out causes of breast or nipple pain. When the cause remained unexplained, it was deemed musculoskeletal, and mothers were referred to a physiotherapist for assessment and treatment with manual orthopedic therapy and mobilization of the myofascial system. Results: The physiotherapist's objective musculoskeletal assessment and mothers' impression showed an improvement in the overall clinical picture after the first appointment in most mothers. Pain was resolved or alleviated by 80% in five mothers after 1–3 weekly treatments. The most useful therapeutic approach was to make afflicted mothers aware of their posture to maintain spinal alignment and avoid shear posture (lateral displacement of the trunk). Shear posture is a consequence of sitting leaning to one side. This posture is exacerbated by thoracic rotation and flexion, for example, when turning the trunk and bending over the baby while giving the breast. Conclusion: Treating musculoskeletal impairment referred pain to the breast or nipple with physiotherapy practices used in a nonbreastfeeding clientele can help alleviate or resolve pain with breastfeeding.
Dilated cardiomyopathy and arrhythmogenic left ventricular cardiomyopathy: a comprehensive genotype-imaging phenotype study.

AIMS Myocardial scar detected by cardiovascular magnetic resonance has been associated with sudden cardiac death in dilated cardiomyopathy (DCM). Certain genetic causes of DCM may cause a malignant arrhythmogenic phenotype. The concepts of arrhythmogenic left ventricular (LV) cardiomyopathy (ALVC) and arrhythmogenic DCM are currently ill-defined. We hypothesized that a distinctive imaging phenotype defines ALVC. METHODS AND RESULTS Eighty-nine patients with DCM-associated mutations [desmoplakin (DSP) n = 25, filamin C (FLNC) n = 7, titin n = 30, lamin A/C n = 12, bcl2-associated athanogene 3 n = 3, RNA binding motif protein 20 n = 3, cardiac sodium channel NAv1.5 n = 2, and sarcomeric genes n = 7] were comprehensively phenotyped. Clustering analysis resulted in two groups: 'DSP/FLNC genotypes' and 'non-DSP/FLNC'. There were no significant differences in age, sex, symptoms, baseline electrocardiography, arrhythmia burden, or ventricular volumes between the two groups. Subepicardial LV late gadolinium enhancement with ring-like pattern (at least three contiguous segments in the same short-axis slice) was observed in 78.1% of DSP/FLNC genotypes but was absent in the other DCM genotypes (P < 0.001). Left ventricular ejection fraction (LVEF) and global longitudinal strain were lower in other DCM genotypes (P = 0.053 and P = 0.015, respectively), but LV regional wall motion abnormalities were more common in DSP/FLNC genotypes (P < 0.001). DSP/FLNC patients with non-sustained ventricular tachycardia (NSVT) had more LV scar (P = 0.010), whereas other DCM genotypes patients with NSVT had lower LVEF (P = 0.001) than patients without NSVT. CONCLUSION DSP/FLNC genotypes cause more regionality in LV impairment. The most defining characteristic is a subepicardial ring-like scar pattern in DSP/FLNC, which should be considered in future diagnostic criteria for ALVC.
ATVB IN FOCUS: Clinically Available Immunotherapies: Expected Impact on Cardiovascular Disease

Atherosclerosis is a lipid-driven chronic inflammatory disease that is modulated by many immune cell subsets, including B cells. Therefore, targeting the inflammatory component of cardiovascular disease represents a promising therapeutic strategy. In the past years, immunotherapy has revolutionized the treatment of autoimmunity and cancer. Many of these clinically used strategies target B cells. Given the multifaceted role of B cells in atherogenesis, it is conceivable that B-cell–directed therapies can modulate disease development. Here, we review clinically available B-cell–targeted therapies and the possible benefits or detrimental effects on cardiovascular disease. VISUAL OVERVIEW: An online visual overview is available for this article.
The lack of mitochondrial thioredoxin TRXo1 affects in vivo alternative oxidase activity and carbon metabolism under different light conditions.

The alternative oxidase (AOX) constitutes a non-phosphorylating pathway of electron transport in the mitochondrial respiratory chain that provides flexibility to energy and carbon primary metabolism. Its activity is regulated in vitro by the mitochondrial thioredoxin (TRX) system which reduces conserved cysteines residues of AOX. However, in vivo evidence for redox regulation of the AOX activity is still scarce. In the present study, the redox state, protein levels and in vivo activity of the AOX in parallel to photosynthetic parameters were determined in Arabidopsis knock out mutants lacking mitochondrial trxo1 under moderate (ML) and high light (HL) conditions, known to induce in vivo AOX activity. In addition, 13C- and 14C-labeling experiments together with metabolite profiling were performed to better understand the metabolic coordination between energy and carbon metabolism in the trxo1 mutants. Our results show that the in vivo AOX activity is higher in the trxo1 mutants at ML while the AOX redox state is apparently unaltered. These results suggest that mitochondrial thiol redox systems are responsible for maintaining AOX in its reduced form rather than regulating its activity in vivo. Moreover, the negative regulation of the TCA cycle by the TRX system is coordinated with the increased input of electrons into the AOX pathway. Under HL conditions, while AOX and photosynthesis displayed similar patterns in the mutants, photorespiration is restricted at the level of glycine decarboxylation most likely as a consequence of redox imbalance.
Ischemic Stroke in Adults With Congenital Heart Disease: A Population‐Based Cohort Study

Background Congenital heart disease (CHD) is associated with risk factors for ischemic stroke including cardiac arrhythmias and heart failure. However, few long‐term follow‐up data exist on ischemic stroke risk and associated mortality in adults with CHD. Methods and Results Using Danish nationwide registries, we identified individuals aged ≥18 years diagnosed with CHD, at any age, from 1963 to 2017 and a sex and birth year‐matched (1:10) general population comparison cohort. We computed risks, as well as sex and birth year‐adjusted hazard ratios (aHRs) for ischemic stroke and 30‐day post‐stroke mortality in CHD adults compared with the general population. Analyses were stratified according to age <60 years (young) and ≥60 years (older). We identified 16 836 adults with CHD. The risk of ischemic stroke at age 60 years was 7.4% in the CHD cohort and 2.9% in the general population cohort. The adjusted hazard ratios for ischemic stroke compared with the general population was 3.8 (95% CI: 3.3–4.3) in young CHD adults and 1.6 (95% CI: 1.4–1.9) in older CHD adults. The adjusted hazard ratios for post‐stroke mortality compared with the general population was 2.3 (95% CI: 1.2–4.4) in young CHD adults and 1.3 (95% CI: 0.9–1.9) in older CHD adults. Conclusions Both younger and older CHD adults have an increased risk of ischemic stroke and by 60 years of age 7.4% of CHD adults will have had an ischemic stroke. Post‐stroke mortality was also increased in CHD adults compared with the general population.
The Role of Mitochondria in Sex-Dependent Differences in Hepatic Steatosis and Oxidative Stress in Response to Cafeteria Diet-Induced Obesity in Mice

Female mice fed a cafeteria diet (FCaf) develop higher liver steatosis and oxidative stress than males (MCaf) as a consequence of unresolved ER stress. Here, we investigated whether mitochondria play a role in this sex difference. The isolated mitochondria from FCaf showed more signs of oxidative stress than those of MCaf, correlated with a reduced content of GSH, increased amount of reactive oxygen species (ROS), and lower activities of enzymes involved in ROS neutralisation. Mitochondria from FCaf and MCaf livers exhibited lower rates of succinate-driven state III respiration and reduced ATPase activity in intact coupled mitochondria compared to their controls fed a standard diet (FC and MC), with no differences between the sexes. Fatty acid oxidation in mitochondria and peroxisomes was higher in MCaf and FCaf compared to their respective controls. In the intact perfused liver, there was no difference between sex or diet regarding the fatty acid oxidation rate. These results indicated that cafeteria diet did not affect mitochondrial energy metabolism, even in FCaf livers, which have higher steatosis and cellular oxidative stress. Nevertheless, the increase in mitochondrial ROS generation associated with a decrease in the antioxidant defence capacity, probably contributes to inducing or reinforcing the ER stress in FCaf livers.