Miracle-dz/UniFAR-FTUs huggingface dataset:
Change in NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) Level and Risk of Dementia in Multi-Ethnic Study of Atherosclerosis (MESA)

Supplemental Digital Content is available in the text. Cross-sectionally measured NT-proBNP (N-terminal pro-B-type natriuretic peptide) is related to incident dementia. However, data linking changes in NT-proBNP to risk of future dementia are lacking. We aimed to examine the association of change in NT-proBNP over 3.2 years with incident dementia. We included 4563 participants in MESA (Multi-Ethnic Study of Atherosclerosis) prospective cohort who were free of cardiovascular disease at enrollment, had NT-proBNP level measured at MESA exams 1 (baseline, 2000–2002) and 3 (2004–2005), and had no diagnosis of dementia before exam 3. The association of change in NT-proBNP level between MESA exams 1 through 3 and all-cause hospitalized dementia (by International Classification of Diseases, Ninth Revision, codes) after MESA exam 3 (2004–2005) through 2015 was assessed using competing-risks Cox proportional hazard regression analysis. During 45 522 person-years of follow-up, 223 dementia cases were documented. Increase in log-NT-proBNP from MESA exams 1 through 3 was positively associated with incidence of dementia (multivariable hazard ratio, 1.28 [95% CI, 1.001–1.64]; P=0.049). An increase of at least 25% in NT-proBNP level from MESA exam 1 through 3 was associated with a 55% (P=0.02) increase in the risk of dementia in multivariable analysis. Addition of temporal NT-proBNP change to a model including risk factors and baseline NT-proBNP improved the prediction of dementia (Harrell C statistic from 0.85 to 0.87, P=0.049). Increase in NT-proBNP is independently associated with future all-cause hospitalized dementia and offers a moderately better predictive performance for risk of dementia compared with risk factors and baseline NT-proBNP. Clinical Trial Registration— URL: https://www.clinicaltrials. gov. Unique identifier: NCT00005487.
Optical constants of sputtered beryllium thin films determined from photoabsorption measurements in the spectral range 20.4-250 eV.

In this work, the refractive index of beryllium in the photon energy range 20.4-250 eV was experimentally determined. The initial data include measurements of the transmittance of two free-standing Be films with thicknesses of 70 nm and 152 nm, as well as reflectometric measurements of similar films on a substrate. Measurements were carried out at the optics beamline of the BESSY II synchrotron radiation source. The absorption coefficient β was found directly from the transmission coefficient of the films, and the real part of the polarizability δ was calculated from the Kramers-Kronig relations. A comparison is carried out with results obtained 20 years ago at the ALS synchrotron using a similar methodology.
High Blood Pressure and Cardiovascular Disease

Fragmented investigation has masked the overall picture for causes of cardiovascular disease (CVD). Among the risk factors for CVD, high blood pressure (BP) is associated with the strongest evidence for causation and it has a high prevalence of exposure. Biologically, normal levels of BP are considerably lower than what has typically been characterized as normal in research and clinical practice. We propose that CVD is primarily caused by a right-sided shift in the population distribution of BP. Our view that BP is the predominant risk factor for CVD is based on conceptual postulates that have been tested in observational investigations and clinical trials. Large cohort studies have demonstrated that high BP is an important risk factor for heart failure, atrial fibrillation, chronic kidney disease, heart valve diseases, aortic syndromes, and dementia, in addition to coronary heart disease and stroke. In multivariate modeling, the presumed attributable risk of high BP for stroke and coronary heart disease has increased steadily with progressive use of lower values for normal BP. Meta-analysis of BP-lowering randomized controlled trials has demonstrated a benefit which is almost identical to that predicted from BP risk relationships in cohort studies. Prevention of age-related increases in BP would, in large part, reduce the vascular consequences usually attributed to aging, and together with intensive treatment of established hypertension would eliminate a large proportion of the population burden of BP-related CVD.
Exendin-4 Protects Human Retinal Pigment Epithelial Cells from H2O2-Induced Oxidative Damage via Activation of NRF2 Signaling

Aims: Oxidative damage plays a vital role in the pathogenesis of age-related macular degeneration (AMD). Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, possesses several pharmacological functions, such as anti-inflammatory and antioxidative properties. However, the effects and mechanism of EX4 on oxidative stress in retinal pigment epithelial (RPE) cells induced by hydrogen peroxide (H2O2) remain unclear. The present study aimed to investigate the protective mechanism of EX4 on human RPE cells subjected to oxidative stress. Methods: Human RPE ARPE-19 cells were treated with H2O2 to induce oxidative damage. Cell viability was determined by Cell Counting Kit-8 and lactate dehydrogenase assay. Levels of intracellular reactive oxygen species (ROS), malonyldialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH) were measured using commercial kits. The expression of nuclear factor erythroid 2-related factor-2 (NRF2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO-1) was measured using reverse transcription quantitative polymerase chain reaction assay and western blot, respectively. Results: H2O2 significantly induced oxidative stress to reduce viability of RPE cells and increased intracellular ROS generation. EX4 significantly ameliorated H2O2-induced oxidative damage by reducing intracellular ROS generation, decreasing MDA concentration, and increasing antioxidant enzymes activities (SOD and GSH). In addition, EX4 markedly increased expression of NRF2, HO-1, and NQO-1 and significantly improved protein expression of NRF2 and HO-1 in H2O2-treated ARPE-19 cells, caused by increased nuclear NRF2 protein expression. NRF2 knockdown by targeted siRNA alleviated EX4-mediated HO-1 expression and significantly nullified EX4-mediated RPE cell protection against H2O2. Conclusions: EX4 attenuated oxidative damage induced by H2O2 in ARPE-19 cells through the activation of the NRF2 signaling pathway. The findings suggested that EX4 may be a potential therapeutic agent for the treatment of AMD.
Effectiveness of training program combining chakrayoga and meditation

Abstract Background This study was designed to examine the effectiveness of program combining chakrayoga and meditation on the physical health and disease-related factors and psychological factors of people. Methods Ninety-seven subjects (32–83 years old) who had free from prior experiences in meditation programs or Chakrayoga training courses were assigned to either the experimental group (EXP) (45 subjects; 13 male subjects and 32 female subjects; average age of 60.67 years, SD=11.09 years) or the control group (CONT) of remaining subjects (52 subjects; 14 male subjects and 38 female subjects; average age of 61.58 years, SD=9.70 years). Subjects in the EXP participated in the Chakrayoga Meditation Program for twice a week for 2 h during 6 weeks in each session consisted of 1 h of Chakrayoga and 1 h of meditation. The measurements in this study included the mindfulness, stress response, subjective quality of life, medical symptom checklist, difficulty in emotional regulation and objective of life and sense of control. Results Results revealed that participants in the EXP reported significantly more relief of mindfulness, stress response, subjective quality of life and medical symptom checklist than those in the CONT. Conclusions These findings provide evidence that the Chakrayoga Meditation Program can help relieve the physical health and disease-related factors and psychological factors.
Single-molecule measurements in microwells for clinical applications

Abstract The ability to detect and analyze proteins, nucleic acids, and other biomolecules is critical for clinical diagnostics and for understanding the underlying mechanisms of disease. Current detection methods in clinical and research laboratories rely upon bulk measurement techniques such as immunoassays, polymerase chain reaction, and mass spectrometry to detect these biomarkers. However, many potentially useful protein or nucleic acid biomarkers in blood, saliva, or other biofluids exist at concentrations well below the detection limits of current methods, necessitating the development of more sensitive technologies. Single-molecule measurements are poised to address this challenge, vastly improving sensitivity for detecting low abundance biomarkers and rare events within a population. Microwell arrays have emerged as a powerful tool for single-molecule measurements, enabling ultrasensitive detection of disease-relevant biomolecules in easily accessible biofluids. This review discusses the development, fundamentals, and clinical applications of microwell-based single-molecule methods, as well as challenges and future directions for translating these methods to the clinic.
Examining the initial usability, acceptability and feasibility of a digital mental health intervention for college students in India.

Generalised anxiety disorder (GAD) is prevalent among college students in India; however, barriers like stigma, treatment accessibility and cost prevent engagement in treatment. Web- and mobile-based, or digital, mental health interventions have been proposed as a potential solution to increasing treatment access. With the ultimate goal of developing an engaging digital mental health intervention for university students in India, the current study sought to understand students' reactions to a culturally and digitally adapted evidence-based cognitive behavioural therapy (CBT) for GAD intervention. Specifically, through theatre testing and focus groups with a non-clinical sample of 15 college students in India, the present study examined initial usability, acceptability and feasibility of the "Mana Maali Digital Anxiety Program. " Secondary objectives comprised identifying students' perceived barriers to using the program and eliciting recommendations. Results indicated high usability, with the average usability rating ranking in the top 10% of general usability scores. Participants offered actionable changes to improve usability and perceived acceptability among peers struggling with mental health issues. Findings highlight the benefits of offering digital resources that circumvent barriers associated with accessing traditional services. Results build on existing evidence that digital interventions can be a viable means of delivering mental healthcare to large, defined populations.
Atrial fibrillation progression risk factors and associated cardiovascular outcome in well-phenotyped patients: data from the AF-RISK study.

AIMS Atrial fibrillation (AF) is a progressive disease, but identifying patients at risk for AF progression is challenging. We aimed to identify factors associated with AF progression. METHODS AND RESULTS Atrial fibrillation progression was assessed in 392 patients with recent-onset paroxysmal or persistent AF included in the prospective, observational, multicentre identification of a risk profile to guide atrial fibrillation (AF-RISK) study. Progression of AF was assessed by Holter monitoring and 2-week event recorder at baseline and 1-year follow-up. AF progression was defined as: (i) doubling in AF burden at 1 year compared to baseline with a minimum AF burden of 10% in paroxysmal AF; or (ii) transition from paroxysmal to persistent or permanent AF; or (iii) persistent to permanent AF. Age was 60 ± 11 years, 62% were men, and 83% had paroxysmal AF. At 1 year, 52 (13%) had AF progression (11% in paroxysmal; 26% in persistent AF). Multivariable logistic regression showed that left atrial volume [odds ratio (OR) per 10 mL 1.251, 95% confidence interval (CI) 1.078-1.450; P < 0.001], N-terminal pro-B-type natriuretic peptide (NT-proBNP; OR per standard deviation increase 1.583, 95% CI 1.099-2.281; P = 0.014), and plasminogen activator inhibitor-1 (PAI-1; OR per standard deviation increase 0.660, 95% CI 0.472-0.921; P = 0.015) were associated with AF progression. In an additional follow-up of 1.9 (0.9-3.3) years patients with AF progression developed more cardiovascular events and all-cause mortality (12.4%/year vs. 2.3%/year, P < 0.001). CONCLUSION Atrial fibrillation progression occurred in 13% of patients with recent-onset AF during 1-year follow-up. Left atrial volume, NT-proBNP, and PAI-1 were associated with AF progression. Patients with AF progression had a higher event rate. TRIAL REGISTRATION NUMBER Clinicaltrials.gov NCT01510210.
Magnetic hybrid wax nanocomposites as externally controlled theranostic vehicles: high MRI enhancement and synergistic magnetically-assisted thermo/chemo therapy.

To fight against cancer, smarter drugs and drug delivery systems are required both to boost the efficiency of current treatments while reducing deleterious side effects, and combine diagnosis/monitoring with therapy (theranosis) in the search for the final goal of personalized medicine. This work presents the design, preparation and proof-of-principle validation of a novel hybrid organic-inorganic nanocomposite joining together non-invasive imaging capabilities by magnetic resonance imaging and externally actuated therapeutic properties through a combination of chemo- and thermo-therapy. The lipidic matrix of the nanocomposite was composed of carnauba wax, which was simultaneously dual loaded with magnetite nanoparticles and the anticancer drug Oncocalyxone A. Obtained formulations were fully characterized and showed outstanding performance as T 2 -contrast agents in magnetic resonance imaging ( r 2 > 800 mM -1 s -1 ), heat generating sources in magnetic hyperthermia (SAR > 200 Wg -1 Fe ) and magnetically responsive drug delivery vehicles. The potential of the designed formulations as theranostic agents was validated in vitro and results indicated a synergistic thermo/chemo-therapeutic effect derived from heat generation and controlled drug delivery over cancer growth. Thereby, this external control over the drug delivery profile and the integrated imaging capability open the door to personalized cancer medicine and real-time monitoring of tumor progression.
Effects of dynamic lycra orthosis as an adjunct to rehabilitation after botulinum toxin-A injection of the upper-limb in adults following stroke: A single-blinded randomized controlled pilot study

ABSTRACT Background Dynamic lycra splints are proposed to modify hypertonicity due to their characteristics – neutral warmth, circumferential pressure, and creating a low-intensity prolonged stretch on hypertonic muscles – to contribute to increased sensory awareness of the involved limb. Objectives The aim of this study was to investigate the effects of dynamic lycra orthosis as an adjunct to botulinum toxin-A injection and rehabilitation of the upper-limb in adults following stroke. Methods Patients who had suffered a stroke more than three months previously were randomized into two groups: lycra sleeve plus rehabilitation (n = 10) and only-rehabilitation group (n = 10). After botulinum toxin injection, both groups underwent an upper-limb rehabilitation program. The intervention group wore a lycra sleeve for eight hours a day, five days a week for three weeks in addition to the rehabilitation program. Fugl Meyer upper-limb motor score, Motricity index, Modified Ashworth scale, Box and Block test, Stroke Impact Scale and change in touch-detection thresholds of the fingers measured via Semmes-Weinstein monofilaments were assessed by blinded investigators at before treatment, post-treatment (at 3 weeks) and three months post-treatment. This trial is registered with Clinicaltrials.gov, number NCT03546959. Results There were no differences between groups in terms of Fugl Meyer upper-limb motor score, Motricity Index, Modified Ashworth scale, Box and Block test, Stroke Impact Scale and change in light touch threshold at any follow-up time points. Conclusions Using lycra splints as an adjunct to an upper-limb rehabilitation program after stroke did not provide additional benefit in spasticity, upper-limb motor function, light touch threshold of fingers or stroke-specific quality-of-life.
Can the efficacy of subacromial corticosteroid injection be improved using a single-session mobilization treatment in subacromial impingement syndrome? A randomized single-blind controlled trial

Background/aim The objective in this study is to assess the short-term effects of a single-session mobilization in addition to subacromial corticosteroid (SACS) injection in impingement syndrome. Materials and methods The study was designed as a prospective randomized controlled single-blind, parallel group clinical trial. Patients (totally 84) were divided randomly into two groups equally. Forty-two patients in Group 1 received mobilization and SACS injection, whereas 42 patients in Group 2 only received SACS injections. A single SACS injection was applied in all patients. Mobilization was administered as a single session right after SACS injection. Patients’ evaluations were performed measuring active range of motion (AROM), visual analogue scale (VAS) during activity and rest, and Disabilities of Arm, Shoulder, and Hand Score (DASH) prior to treatment and in the first and fourth weeks following the treatment. Results Both groups showed significant improvement in terms of AROM, VAS, and DASH scores in each evaluation step (P < 0.05). Visual analogue scale activity in the first week was significantly better in Group 1 (P = 0.028). Also, flexion and abduction degrees showed significantly better outcomes in Group 1 (P = 0.007, P = 0.036). Conclusion Addition of single-session mobilization might provide rapid improvement in flexion and abduction as well as early pain relief following SACS injections.
Double-balloon enteroscopy for retrieving retained small-bowel video capsule endoscopes: a systematic review

Abstract Background and aim: Capsule retention is the most common adverse event associated with video capsule endoscopy. The use of double-balloon enteroscopy-assisted capsule endoscope retrieval has been increasingly reported in recent years. However, evidence is limited regarding its success rate, associated factors, and subsequent clinical outcomes. Methods: A systematic review of relevant studies published before January 2019 was performed. Successful retrieval rate and associated factors, rate of endoscopic balloon dilation, and outcomes after double-balloon enteroscopy were summarized and pooled. Results: Within 154 associated original articles, 12 including 150 cases of capsule retrieval by double-balloon enteroscopy were included. The estimated pooled successful retrieval rate was 86.5% (95% confidence interval, 75.6–95.1%). Anterograde approach and capsules retained in the jejunum or trapped by malignant strictures were associated with a higher successful retrieval rate than the retrograde approach (62/83 [74.7%] vs. 10/38 [26.3%], p < .001) and capsules retained in the ileum (41/41 [100.0%] vs. 43/58 [74.1%], p < .001) or trapped by benign strictures (21/21 [100.0%] vs. 65/83 [78.3%], p = .043). Endoscopic balloon dilation was performed in 38.8% (95% confidence interval, 22.3–56.3%) of patients with benign strictures. Two perforations (1.3%) were reported as severe adverse events after double-balloon enteroscopy. A significantly lower surgery rate was found among cases with successful video capsule removal compared with unsuccessful cases (7.2% vs. 38.5%, p = .002). Conclusions: Double-balloon enteroscopy is feasible and safe for removing retained video capsule endoscopes, and its use could decrease the need for surgery in patients with benign strictures and facilitate subsequent surgery in patients with malignant strictures.
Measurement of the penetration of 56 cosmetic relevant chemicals into and through human skin using a standardized protocol

OECD test guideline 428 compliant protocol using human skin was used to test the penetration of 56 cosmetic‐relevant chemicals. The penetration of finite doses (10 μL/cm2) of chemicals was measured over 24 hours. The dermal delivery (DD) (amount in the epidermis, dermis and receptor fluid [RF]) ranged between 0.03 ± 0.02 and 72.61 ± 8.89 μg/cm2. The DD of seven chemicals was comparable with in vivo values. The DD was mainly accounted for by the amount in the RF, although there were some exceptions, particularly of low DD chemicals. While there was some variability due to cell outliers and donor variation, the overall reproducibility was very good. As six chemicals had to be applied in 100% ethanol due to low aqueous solubility, we compared the penetration of four chemicals with similar physicochemical properties applied in ethanol and phosphate‐buffered saline. Of these, the DD of hydrocortisone was the same in both solvents, while the DD of propylparaben, geraniol and benzophenone was lower in ethanol. Some chemicals displayed an infinite dose kinetic profile; whereas, the cumulative absorption of others into the RF reflected the finite dosing profile, possibly due to chemical volatility, total absorption, chemical precipitation through vehicle evaporation or protein binding (or a combination of these). These investigations provide a substantial and consistent set of skin penetration data that can help improve the understanding of skin penetration, as well as improve the prediction capacity of in silico skin penetration models.
Long-Term Outcomes of Active Surveillance for Prostate Cancer - The Memorial Sloan Kettering Cancer Center Experience.

PURPOSE To report oncologic outcomes for men with Grade Group 1 prostate cancer managed with active surveillance (AS) at a tertiary cancer center. MATERIALS AND METHODS 2,907 patients were managed with AS between 2000-2017 of whom 2,664 were Grade Group 1. Patients were recommended confirmatory biopsy to verify eligibility and were followed semi-annually with prostate-specific antigen (PSA), digital rectal examination (DRE) and review of symptoms. Magnetic resonance imaging (MRI) was increasingly used in recent years. Biopsy was repeated every 2-3 years or after a sustained PSA increase or changes in MRI/DRE. The Kaplan-Meier method was used to estimate probabilities of treatment, progression, and development of metastasis. RESULTS The median age at diagnosis was 62 years. For men with Grade Group 1 prostate cancer, the treatment-free probability at 5, 10, and 15 years was 76% (95% CI 74%-78%), 64% (95% CI 61%-68%), and 58% (95% CI 51%-64%), respectively. At 5, 10, and 15 years, there were 1,146, 220, and 25 men at risk for metastasis, respectively. The median follow-up for those without metastasis was 4.3 years (95% CI 2.3-6.9). Five men developed distant metastasis. Upon case note review, only two of these men were deemed to have disease that could have been cured on immediate treatment. The risk of distant metastasis was 0.6% (95% CI 0.2%-2.0%) at 10 years. CONCLUSIONS AS is a safe strategy over longer follow-up for appropriately selected patients with Grade Group 1 following a well-defined monitoring plan.