Miracle-dz/UniFAR-FTUs huggingface dataset:
The renal resistive index is associated with microvascular remodeling in patients with severe obesity

Background: Renal hemodynamics is impaired since the early stage of cardiometabolic disease. However, in obesity, its noninvasive ultrasound assessment still fails to provide pathophysiologic and clinical meaningfulness. We aimed to explore the relationship between peripheral microcirculation and renal hemodynamics in severe obesity. Methods: We enrolled fifty severely obese patients with an indication for bariatric referring to our outpatient clinic. Patients underwent an extensive reno-metabolic examination, paired with Doppler ultrasound and measurement of the renal resistive index (RRI). On the day of the surgery, visceral fat biopsies were collected to perform an ex-vivo complete microcirculatory assessment. Media-to-lumen ratio (M/L) and vascular response to acetylcholine (ACh), alone or co-incubated with NG-nitro arginine methyl ester (L-NAME), were measured. Results: Patients were stratified according to their normotensive (NT) or hypertensive (HT) status. HT had lower estimated glomerular filtration rate and higher RRI compared to NT, while the presence and extent of albuminuria were similar between the two groups. Concerning microcirculatory assessment, there were no differences between groups as regards the microvascular structure, while the vasorelaxation to ACh was lower in HT (P = 0.042). Multivariable analysis showed a relationship between M/L and RRI (P = 0.016, St. β 0.37) and between albuminuria and the inhibitory response of L-NAME to Ach vasodilation (P = 0.036, St. β = −0.34). Notably, all these correlations were consistent also after adjustment for confounding factors. Conclusions: The RRI and albuminuria relationship with microvascular remodeling in patients affected by severe obesity supports the clinical implementation of RRI to improve risk stratification in obesity and suggests a tight pathophysiologic connection between renal haemodynamics and microcirculatory disruption.
Gendered Relationships Between Adverse Childhood Experiences, Negative Emotional States, and Violent Delinquency

Adverse childhood experiences (ACEs) have been linked to a host of negative health and behavioral outcomes, including crime, delinquency, and violence. Recent work on ACEs suggests that the impact of ACEs differs by gender, but research is unclear on the mechanisms of this relationship and how they impact violent delinquency. To explore whether and how the impact of ACEs on violent delinquency varies by gender, this study draws on Broidy and Agnew’s gendered expansion of general strain theory (GST), which proposes that a key explanation for the gendered impact of strain on crime lies in gender differences in the negative emotional states that mediate the relationship. Using longitudinal data on a sample of 979 at-risk youth (558 girls and 421 boys) from the Longitudinal Studies on Child Abuse and Neglect, this study examines the impact of ACEs (sexual abuse, physical abuse, emotional abuse, physical neglect, supervisory neglect, parent mental illness, parent intimate partner violence, parent substance use, parent criminality, and family trauma) on violent delinquency by gender with consideration of the three negative emotional states hypothesized by GST—anger, depression, and anxiety. Results indicate that ACEs increase the odds of violent delinquency for both boys and girls, but that this relationship is significantly stronger for boys. Mediation models suggest that anger mediates the link between ACEs and violent delinquency for girls. Implications for research and policy centering on ACEs are discussed.
The inner magnetosphere ion composition and local time distribution over a solar cycle

Using the Cluster/Composition and Distribution Function (CODIF) analyzer data set from 2001 to 2013, a full solar cycle, we determine the ion distributions for H+, He+, and O+ in the inner magnetosphere (L < 12) over the energy range 40 eV to 40 keV as a function magnetic local time, solar EUV (F10.7), and geomagnetic activity (Kp). Concentrating on L = 6–7 for comparison with previous studies at geosynchronous orbit, we determine both the average flux at 90° pitch angle and the pitch angle anisotropy as a function of energy and magnetic local time. We clearly see the minimum in the H+ spectrum that results from the competition between eastward and westward drifts. The feature is weaker in O+ and He+, leading to higher O+/H+ and He+/H+ ratios in the affected region, and also to a higher pitch angle anisotropy, both features expected from the long‐term effects of charge exchange. We also determine how the nightside L = 6–7 densities and temperatures vary with geomagnetic activity (Kp) and solar EUV (F10.7). Consistent with other studies, we find that the O+ density and relative abundance increase significantly with both Kp and F10.7. He+ density increases with F10.7, but not significantly with Kp. The temperatures of all species decrease with increasing F10.7. The O+ and He+ densities increase from L = 12 to L ~ 3–4, both absolutely and relative to H+, and then drop off sharply. The results give a comprehensive view of the inner magnetosphere using a contiguous long‐term data set that supports much of the earlier work from GEOS, ISEE, Active Magnetospheric Particle Tracer Explorers, and Polar from previous solar cycles.
Programmed ageing: decline of stem cell renewal, immunosenescence, and Alzheimer's disease

The characteristic maximum lifespan varies enormously across animal species from a few hours to hundreds of years. This argues that maximum lifespan, and the ageing process that itself dictates lifespan, are to a large extent genetically determined. Although controversial, this is supported by firm evidence that semelparous species display evolutionarily programmed ageing in response to reproductive and environmental cues. Parabiosis experiments reveal that ageing is orchestrated systemically through the circulation, accompanied by programmed changes in hormone levels across a lifetime. This implies that, like the circadian and circannual clocks, there is a master ‘clock of age’ (circavital clock) located in the limbic brain of mammals that modulates systemic changes in growth factor and hormone secretion over the lifespan, as well as systemic alterations in gene expression as revealed by genomic methylation analysis. Studies on accelerated ageing in mice, as well as human longevity genes, converge on evolutionarily conserved fibroblast growth factors (FGFs) and their receptors, including KLOTHO, as well as insulin‐like growth factors (IGFs) and steroid hormones, as key players mediating the systemic effects of ageing. Age‐related changes in these and multiple other factors are inferred to cause a progressive decline in tissue maintenance through failure of stem cell replenishment. This most severely affects the immune system, which requires constant renewal from bone marrow stem cells. Age‐related immune decline increases risk of infection whereas lifespan can be extended in germfree animals. This and other evidence suggests that infection is the major cause of death in higher organisms. Immune decline is also associated with age‐related diseases. Taking the example of Alzheimer's disease (AD), we assess the evidence that AD is caused by immunosenescence and infection. The signature protein of AD brain, Aβ, is now known to be an antimicrobial peptide, and Aβ deposits in AD brain may be a response to infection rather than a cause of disease. Because some cognitively normal elderly individuals show extensive neuropathology, we argue that the location of the pathology is crucial – specifically, lesions to limbic brain are likely to accentuate immunosenescence, and could thus underlie a vicious cycle of accelerated immune decline and microbial proliferation that culminates in AD. This general model may extend to other age‐related diseases, and we propose a general paradigm of organismal senescence in which declining stem cell proliferation leads to programmed immunosenescence and mortality.
Plasmablasts in previously immunologically naïve COVID-19 patients express markers indicating mucosal homing and secrete antibodies cross-reacting with SARS-CoV-2 variants and other beta-coronaviruses

Abstract Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin β1, only some integrin β7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S) and nucleocapsid (N) proteins of the Wuhan strain as well as later variants of concern, but also bind S proteins from endemic and non-circulating betacoronaviruses. In contrast, after recovery, antibodies produced from memory B cells target variants of SARS-CoV-2 and SARS-CoV-1 but compared to previously non-infected individuals do not show increased binding to endemic coronaviruses. This suggests that the early antibody response to a large extent stems from pre-existing cross-reactive class-switched memory B cells, and that although newly formed memory cells target the novel SARS-CoV-2 virus the numbers of broadly cross-reactive memory B cells do not increase extensively. The observations give insight into the role of pre-existing memory B cells in early antibody responses to novel pathogens and may explain why class-switched antibodies are detected early in the serum of COVID-19 patients.
The utility of quantitative MRI parameters in discriminating progressive supranuclear palsy from Parkinson’s disease

ABSTRACT Objective We sought to re-evaluate the utility of all the quantitative neuroimaging parameters attributed to progressive supranuclear palsy (PSP) in discrimination between PSP and Parkinson’ s disease (PD) subjects in our cohort. We aimed to propose some practical clinical remarks in this field. Methods In our retrospective study, 19 patients with ‘probable’ PSP and 37 patients with PD were enrolled. The radiological measurements of PSP, described in the previous reports, have been calculated in all subjects. The comparisons between the groups were performed and the measures regarding the accuracy of these parameters in the differentiation of PSP from PD subjects were analyzed. Results We found that the values of magnetic resonance parkinsonism index-2 (MRPI-2), pontine-to-midbrain area (P/M) ratio, P/M 2 ratio, and 3rdV/bifrontal width ratio had high AUC values and very good discriminative powers. The analyses revealed that; for the discrimination of PSP from PD subjects, a 3rdvent/bifrontal width cut-off value of 0.30 had 42.1 % sensitivity and 97.3 % specificity; a P/M cut-off value of 6.03 had a 52.6 % sensitivity and 97.3 % specificity; and an MRPI-2 cut-off value of 7.43 had 57.9 % sensitivity and 97.3 % specificity. Remarkably, we also found that the presence of high values for both P/M and 3rdV/bifrontal ventricle rate had a positive predictive value of 100% for the diagnosis of PSP. Conclusion Our study results support the utility of previously defined neuroimaging parameters in distinguishing PSP and PD subjects. Besides, combined use of a high P/M ratio and 3rdV/bifrontal width may be practical and present strictly high evidence for the diagnosis of PSP.
Gaming disorder and stigma-related judgements of gaming individuals: An online randomized controlled trial.

BACKGROUND AND AIMS The inclusion of gaming disorder (GD) in the ICD-11 has generated scholarly debate, including claims about its potential stigmatizing effects on the wider gaming population. The present study aimed to estimate the effect of addiction-based and non-addiction-based conceptualizations of problem gaming on stigma of gamers DESIGN: This preregistered experiment involved a 2 (health information: addiction-related or non-addiction-related) x 3 (vignette: problem, regular, or casual gamer) randomized, between-subjects design SETTING: An international sample of participants were recruited via Prolific in June and July 2021 PARTICIPANTS: Participants were eligible (N=1,228) if they were aged 35-50 years, played video games for no more than 6 hours per week, and did not endorse DSM-5 or ICD-11 criteria for GD. Intervention and comparator Participants were provided with an explanation of PG as related to either an addictive disorder (i.e., 'addiction' explanation) or personal choice and lifestyle factors (i.e., 'non-addiction' explanation). MEASUREMENTS The Attribution Questionnaire (AQ) and Universal Stigma Scale (USS) assessed stigma towards each gamer vignette. Vignettes described a problem gamer (with features of GD); a regular gamer (frequent gaming; some life interference); and a casual gamer (infrequent gaming; no life interference) FINDINGS: Problem gamer vignettes (mean [M] = 113.3; 95% confidence interval [CI] = 111.5-115.4) received higher AQ stigma ratings than regular (M = 94.0; 95% CI = 91.9-95.9) and casual gamers (M = 80.1; 95% CI = 78.2-82.1). While significant, the effect of health information type on AQ stigma ratings was negligible (addiction group [M = 97.6; 95% CI = 95.9-99.1], non-addiction group [M = 94.1; 95% CI = 92.6-95.8]). However, the addiction information lowered on USS blame and responsibility to non-addiction information with at least a small effect (99.1% confidence) CONCLUSIONS: Framing of problem gaming as an addictive disorder or non-addictive activity appears to have a negligible effect on stigma of different gamers among middle-aged adults with minimal gaming experience. The concept of 'gaming addiction' seems unlikely to be an important influence on public stigma of gaming.
The standard Instrumentation Feedthrough System for the LHC cryomagnets

For the LHC, 1232 dipole magnets and about 400 quadrupole magnets operating at 1.9 K are installed in arcs and dispersion suppressors. Each cryo-magnet assembly comprises the main magnet and several small corrector magnets. Each assembly is equipped with voltage taps, quench heaters and cryogenic instrumentation. The number of instrumentation wires serving each magnet assembly and passing from cold to ambient is between 36 and 40. An Instrumentation Feedthrough System (IFS) will electrically and mechanically connect the instrument wires to the outside of the vacuum vessel. The IFS has to satisfy several requirements: simplicity of integration, optimal access during tests and commissioning, voltage withstand and reliability during the lifetime of the machine. The heat load to superfluid helium must be minimized, and the long-term stability of the insulation vacuum should be preserved. The solution foresees an open stainless steel tube housing the wire's connected between the magnet and the outside of the vacuum vessel and terminated by a leak tight connector. The IFS is assembled from different standard components designed to fulfill the electrical, mechanical and thermal requirements and will be integrated by the industries that build the magnets. The standardization of the IFS for all types of cryo-magnet assemblies permits the same hardware interfaces and procedures to be used from the integration to commissioning and operation of the machine. This paper describes the main parameters, the technical choices, the performance and the integration techniques of the IFS system.
Pro‐inflammatory cytokines IL‐1α, IL‐6 and TNF‐α in major depressive disorder: Sex‐specific associations with psychological symptoms

The pro‐inflammatory cytokines IL‐1α, IL‐6 and TNF‐α are associated with major depressive disorder, psychological distress, cardiovascular health and obesity. However, there is limited research that has examined multiple associations between these variables, particularly among individuals with major depressive disorder who are treatment free, in comparison with a control cohort, and including analyses of sex differences. In this study, data were analysed from 60 individuals with major depressive disorder and 60 controls, including plasma IL‐1α, IL‐6 and TNF‐α, adiposity measures (body mass index, waist circumference), cardiovascular health indices (blood pressure, heart rate) and psychological symptoms (depressive severity, anxiety, hostility, stress). The cytokines were compared by group and sex and correlated with measures of adiposity, cardiovascular health indices and psychological health. Plasma IL‐1α and IL‐6 were higher in major depressive disorder group versus control, but with a sex interaction for IL‐6, with this group difference only among females. TNF‐α did not differ between groups. IL‐1α and IL‐6 correlated with depressive severity, anxiety, hostility and stress, whereas TNF‐α correlated only with anxiety and hostility. Psychopathology was associated with IL‐1α in males only and with IL‐6 and TNF‐α in females only. None of the cytokines correlated with body mass index, waist circumference, blood pressure or heart rate. The result of group by sex interaction for IL‐6 and sex‐specific associations between pro‐inflammatory cytokines and psychometrics could be aetiologically important in depression interventions and treatments for females versus males, warranting further investigation.
Online calculators for predicting the risk of anastomotic stricture after hepaticojejunostomy for bile duct injury after cholecystectomy: a multicenter retrospective study

Background: Anastomotic stricture is a common underlying cause of long-term morbidity after hepaticojejunostomy (HJ) for bile duct injury (BDI) following cholecystectomy. However, there are no methods for predicting stricture risk. This study was aimed at establishing two online calculators for predicting anastomotic stricture occurrence (ASO) and stricture-free survival (SFS) in this patient population. Methods: The clinicopathological characteristics and follow-up information of patients who underwent HJ for BDI after cholecystectomy from a multi-institutional database were reviewed. Univariate and multivariate analyses of the risk factors of ASO and SFS were performed in the training cohort. Two nomogram-based online calculators were developed and validated by internal bootstrapping resamples (n=1000) and an external cohort. Results: Among 220 screened patients, 41 (18.64%) experienced anastomotic strictures after a median follow-up of 110.7 months. Using multivariate analysis, four variables, including previous repair, sepsis, HJ phase, and bile duct fistula, were identified as independent risk factors associated with both ASO and SFS. Two nomogram models and their corresponding online calculators were subsequently developed. In the training cohort, the novel calculators achieved concordance indices (C-indices) of 0.841 and 0.763 in predicting ASO and SFS, respectively, much higher than those of the above variables. The predictive accuracy of the resulting models was also good in the internal (C-indices: 0.867 and 0.821) and external (C-indices: 0.852 and 0.823) validation cohorts. Conclusions: The two easy-to-use online calculators demonstrated optimal predictive performance for identifying patients at high risk for ASO and with dismal SFS. The estimation of individual risks will help guide decision-making and long-term personalized surveillance.
The effect of frailty in older community-dwelling outpatients with atrial fibrillation: a new score HAS-BLED-F (rail).

OBJECTIVE This study aims to determine the effect of frailty on thromboembolic events (TEE) and bleeding in older patients with non-valvular atrial fibrillation (AF). PATIENTS AND METHODS Patients aged ≥65 years who were diagnosed as having non-valvular AF in a geriatric outpatient clinic between June 2015 and February 2021 were included in the study. Frailty, the risk of thrombosis secondary to AF, and the risk of bleeding as a complication of AF treatment were evaluated using the FRAIL scale, and CHA2DS2-VASc and HAS-BLED scores, respectively. RESULTS Out of 83 patients included in the study, 72.3% were frail and 21.7% were pre-frail. TEE was observed in 14.5% (n=12) and bleeding was observed in 25.3% (n=21) of the patients. A total of 21 (25.3%) patients had a history of bleeding. There was no difference between the normal, pre-frail, and frail groups in terms of TEE and bleeding history (p=0.112 and p=0.571, respectively). In multivariate analysis, mortality decreased with the use of apixaban; frailty and malnutrition were found to increase mortality (p=0.014, p=0.023, and p=0.020, respectively). HAS-BLED-F score was obtained as a result of the sum of the patients' HAS-BLED and FRAIL scores to predict the bleeding risk. A HAS-BLED-F score of ≥6 predicted the risk of bleeding with 90.5% sensitivity and 40.3% specificity. CONCLUSIONS Frailty is not associated with a statistically significant increase in the risk of thromboembolic events or bleeding in patients with non-valvular AF. HAS-BLED-F score can be used to better predict the risk of bleeding in frail patients.
Long-term hemodynamic changes in cerebral proliferative angiopathy presenting with intracranial hemorrhage: illustrative case

BACKGROUND Cerebral proliferative angiopathy (CPA) is a rare vascular proliferative disease; however, long-term follow-up reports are scarce. The authors report a rare case and document a patient’s medical history over 20 years. OBSERVATIONS A 5-year-old girl developed left frontal lobe hemorrhage, presenting with headache. At 8 years of age, angiography showed diffuse capillary ectasia without an arteriovenous shunt. Single-photon emission computed tomography (SPECT) showed normal cerebral blood flow (CBF). She had normal growth without systemic disease. At 25 years of age, an intraventricular hemorrhage occurred, presenting with sudden headache. Angiography revealed vascular lesion enlargement, increased feeding arteries, dural supply to the nidus and peri-nidal lesion, and flow-related aneurysm. SPECT showed remarkable decreases in CBF in the nidus and peri-nidal lesion. Cerebral proliferative angiopathy (CPA) was diagnosed, and the aneurysm arising at the lateral posterior choroidal artery caused the hemorrhage. Coil embolization of the aneurysm was performed with a flow-guide catheter and extremely soft platinum coils. New aneurysms were not noted 1.5 years after the procedure. LESSONS This is the first report to demonstrate hemodynamic changes in CPA on angiography and SPECT over 17 years. The development of endovascular devices has enabled the embolization of ruptured aneurysms at the peripheral cerebral artery.
Floquet operators with singular spectrum. II

Floquet operators for time-periodic perturbation of discrete Hamiltonians with increasing gaps between eigenvalues have no absolutely continuous spectrum. An example is −d 2 /dx 2 +q(x)+v(x, t) with Dirichlet boundary conditions on [O, π], where q(x) is bounded and v(x, t) is C 2 and periodic in t Les operateurs de Floquets pour des perturbations periodiques d'hamiltoniens discrets ayant des distances entre valeurs propres successives croissantes n'ont pas de spectre absolument continu. Un exemple est donne par l'operateur −d 2 /dx 2 +q(x)+v(x, t) avec conditions de Dirichlet sur [O, π], ou q(x) est borne et v(x, t) est C 2 et periodique en t