Miracle-dz/UniFAR-FTUs huggingface dataset:
Seasonal Variation in Diurnal Rhythms of the Human Eye: Implications for Continuing Ocular Growth in Adolescents and Young Adults

Purpose To investigate the diurnal rhythms in the human eye in winter and summer in southeast Norway (latitude 60°N). Methods Eight measures (epochs) of intraocular pressure, ocular biometry, and optical coherence tomography were obtained from healthy participants (17–24 years of age) on a mid-winter's day (n = 35; 6 hours of daylight at solstice) and on a day the following summer (n = 24; 18 hours of daylight at solstice). Participants wore an activity monitor 7 days before measurements. The epochs were scheduled relative to the individual's habitual wake and sleep time: two in the day (morning and midday) and six in the evening (every hour until and 1 hour after sleep time). Saliva was collected for melatonin. A linear mixed-effects model was used to determine significant diurnal variations, and a sinusoid with a 24-hour period was fitted to the data with a nonlinear mixed-effects model to estimate rhythmic statistics. Results All parameters underwent significant diurnal variation in winter and summer (P < 0.002). A 1-hour phase advance was observed for melatonin and ocular axial length in the summer (P < 0.001). The degree of change in axial length was associated with axial length phase advance (R2 = 0.81, P < 0.001) and choroidal thickening (R2 = 0.54, P < 0.001) in summer. Conclusions Diurnal rhythms in ocular biometry appear to be synchronized with melatonin secretion in both winter and summer, revealing seasonal variation of diurnal rhythms in young adult eyes. The association between axial length and seasonal changes in the phase relationships between ocular parameters and melatonin suggests a between-individual variation in adaptation to seasonal changes in ocular diurnal rhythms.
Direct and indirect costs attributed to alcohol consumption in Brazil, 2010 to 2018

Introduction Alcohol consumption is the main risk factor for death and disability in the world population between 15 to 49 years old, is related to more than 200 causes of death, and has an important economic impact on the health and social security systems. In 2016, three million deaths were attributable to alcohol worldwide and 131.4 million DALYs. In Brazil, alcohol consumption per inhabitant was 7.8 liters in 2016; and the prevalence of abusive consumption was 17.1% in 2019. Objective Estimate the costs attributable of alcohol consumption in the Brazilian population 18 years-old and over, in the period 2010 to 2018. Methods This is a prevalence-based cost-of-illness study, with a top-down and retrospective approach, including direct costs (hospital and outpatient) and indirect costs (absenteeism from work) related to alcohol consumption. A list of diseases and conditions for which alcohol is a risk factor was used, and the Population Attributable Risk (PAR) was calculated to estimate what portion of the cost of these diseases is attributable to alcohol consumption. Prevalence was calculated by sex and level of alcohol consumption, based on data from the 2019 National Health Survey. Relative risk data were identified by disease/injury and level of daily consumption obtained from the Global Burden Disease study in 2017. The cost data used are from the Brazilian Unified Health System and social security system. All costs were adjusted for inflation for the period and converted to purchasing power parity. Results Prevalence data revealed that 73.6% of the Brazilian population reported not consuming alcoholic beverages, which included 62.9% of men and 83.0% of women. The lowest values for the PAR were found at the consumption range of 60 grams per day. Although the 12 grams per day consumption category is the least in terms of the quantity of alcohol consumed, it is one of the main ones in terms of PAR, given the higher prevalence of consumption. The total cost attributable to alcohol between 2010 and 2018 was Int$ 1,487,417,115.43, of which Int$ 737,834,696.89 was for hospital expenses, Int$ 416,052,029.75 for outpatient care, and Int$ 333,530,388.79 due to absenteeism from work. Conclusion Few comprehensive studies of alcohol-related costs have been developed, which suggests a knowledge gap in Brazil and worldwide and indicates the need for more research in this area. Understanding the economic impact of alcohol consumption is essential to help measure this public health problem in all its aspects and encourage implementation of public policies.
Minimally invasive sacroiliac fusion, a case series, and a literature review

Introduction: Non-autoimmune sacroiliac joint pain contributes to nearly a quarter of low back pain patients. Non-surgical management fails to satisfy patients. A new minimally invasive technique for sacroiliac stabilization has been introduced, defying the traditional rules of fusion. The results outside explanatory trials and in day-to-day practice have not been reported. Materials and methods: This case series includes 20 patients diagnosed with chronic sacroiliac pain resistant to conservative management for at least 6 months. The diagnosis was confirmed with a positive sacroiliac injection. Patients underwent stabilization using the iFuse® implant. Patients were followed up for a minimum of one year. The primary outcome was the functional outcomes, assessed using VAS, ODI, and SF36. Secondary procedure rates, complication rates, and radiological assessments of fusion were collected as secondary outcomes. Results: At one year, the mean VAS score improved from 81.25 ± 10.7 SD preoperatively to 52.5 ± 26.8, p-value 0.0013. The mean ODI improved from 54.8 ± 11.21 SD preoperatively to 41.315 ± 15.34, P value = 0.0079. The mean PCS and MCS of SF36 improved by 17 and 20 points, respectively. Only 55% of patients achieved the MCID for the VAS score. 35% of the cohort had secondary procedures. Discussion: Minimally invasive sacroiliac fusion resulted in an improvement in mean functional scores with a wide dispersion. Patients not achieving MCID are patients with either a malpositioned implant, an associated lumbar pathology, or an inaccurate diagnosis. Our results are underwhelming compared to similar work but are still better than conservative cohorts in comparative studies. Conclusion: Minimally invasive sacroiliac fusion can be used successfully in select patients. Attention to diagnosis and surgical technique can improve the reproducibility of results.
Effector Memory–Expressing CD45RA (TEMRA) CD8+ T Cells from Kidney Transplant Recipients Exhibit Enhanced Purinergic P2X4 Receptor–Dependent Proinflammatory and Migratory Responses

Significance Statement The pathogenic role of terminally differentiated effector memory (TEMRA) CD8+ T cells has been implicated in kidney transplant failure. The authors showed that humoral rejection of kidney allografts is associated with an accumulation of cytolytic TEMRA CD8+ T cells in blood and in kidney graft biopsies. They demonstrated that TEMRA CD8+ T cells from kidney transplant recipients exhibit enhanced migratory properties compared with effector memory CD8+ T cells and that the chemokine CXCL12 not only promotes migration of TEMRA CD8+ T cells toward nonlymphoid organs but also triggers a purinergic P2X4 receptor–dependent proinflammatory response. They also found that agents aimed at potential TEMRA CD8+ T cell–specific targets inhibited the migration of TEMRA CD8+ T cells from kidney transplant recipients, suggesting a possible strategy in treating kidney transplant failure. Visual Abstract Background The mechanisms regulating CD8+ T cell migration to nonlymphoid tissue during inflammation have not been fully elucidated, and the migratory properties of effector memory CD8+ T cells that re-express CD45RA (TEMRA CD8+ T cells) remain unclear, despite their roles in autoimmune diseases and allotransplant rejection. Methods We used single-cell proteomic profiling and functional testing of CD8+ T cell subsets to characterize their effector functions and migratory properties in healthy volunteers and kidney transplant recipients with stable or humoral rejection. Results We showed that humoral rejection of a kidney allograft is associated with an accumulation of cytolytic TEMRA CD8+ T cells in blood and kidney graft biopsies. TEMRA CD8+ T cells from kidney transplant recipients exhibited enhanced migratory properties compared with effector memory (EM) CD8+ T cells, with enhanced adhesion to activated endothelium and transmigration in response to the chemokine CXCL12. CXCL12 directly triggers a purinergic P2×4 receptor–dependent proinflammatory response of TEMRA CD8+ T cells from transplant recipients. The stimulation with IL-15 promotes the CXCL12-induced migration of TEMRA and EM CD8+ T cells and promotes the generation of functional PSGL1, which interacts with the cell adhesion molecule P-selectin and adhesion of these cells to activated endothelium. Although disruption of the interaction between functional PSGL1 and P-selectin prevents the adhesion and transmigration of both TEMRA and EM CD8+ T cells, targeting VLA-4 or LFA-1 (integrins involved in T cell migration) specifically inhibited the migration of TEMRA CD8+ T cells from kidney transplant recipients. Conclusions Our findings highlight the active role of TEMRA CD8+ T cells in humoral transplant rejection and suggest that kidney transplant recipients may benefit from therapeutics targeting these cells.
Risk factors for cardiovascular disease among individuals with hepatic steatosis

Cardiovascular disease (CVD) is the leading cause of mortality in adults with hepatic steatosis (HS). However, risk factors for CVD in HS are unknown. We aimed to identify factors associated with coronary artery disease (CAD) and incident major adverse cardiovascular events (MACE) in individuals with HS. We performed a nested cohort study of adults with HS detected on coronary computed tomography in the PROspective Multicenter Imaging Study for Evaluation of chest pain (PROMISE) trial. Obstructive CAD was defined as ≥50% coronary stenosis. MACE included hospitalization for unstable angina, nonfatal myocardial infarction, or all‐cause death. Multivariate modeling, adjusted for age, sex, atherosclerotic CVD (ASCVD) risk score and body mass index, identified factors associated with obstructive CAD. Cox regression, adjusted for ASCVD risk score, determined the predictors of MACE. A total of 959 of 3,756 (mean age 59.4 years, 55.0% men) had HS. Obstructive CAD was present in 15.2% (145 of 959). Male sex (adjusted odds ratio [aOR] = 1.83, 95% confidence interval [CI] 1.18–1.2.84; p = 0.007), ASCVD risk score (aOR = 1.05, 95% CI 1.03–1.07; p < 0.001), and n‐terminal pro‐b‐type natriuretic peptide (NT‐proBNP; aOR = 1.90, 95% CI 1.38–2.62; p < 0.001) were independently associated with obstructive CAD. In the 25‐months median follow‐up, MACE occurred in 4.4% (42 of 959). Sedentary lifestyle (adjusted hazard ratio [aHR] = 2.53, 95% CI 1.27–5.03; p = 0.008) and NT‐proBNP (aOR = 1.50, 95% CI 1.01–2.25; p = 0.046) independently predicted MACE. Furthermore, the risk of MACE increased by 3% for every 1% increase in ASCVD risk score (aHR = 1.03, 95% CI 1.01–1.05; p = 0.02). Conclusion: In individuals with HS, male sex, NT‐pro‐BNP, and ASCVD risk score are associated with obstructive CAD. Furthermore, ASCVD, NT‐proBNP, and sedentary lifestyle are independent predictors of MACE. These factors, with further validation, may help risk‐stratify adults with HS for incident CAD and MACE.
Generation of discord through a remote joint continuous variable measurement

In quantum mechanics, continuously measuring an observable steers the system into one eigenstate of that observable. This property has interesting and useful consequences when the observable is a joint property of two remotely separated qubits. In particular, if the measurement of the two-qubit joint observable is performed in a way that is blind to single-qubit information, quantum back-action generates correlation of the discord type even if the measurement is weak and inefficient. We demonstrate the ability to generate these quantum correlations in a circuit-QED setup by performing a weak joint readout of two remote, non-interacting, superconducting transmon qubits using the two non-degenerate modes of a Josephson Parametric Converter (JPC). Single-qubit information is erased from the output in the limit of large gain and with properly tailored cavity drive pulses. Our results of the measurement of discord are in quantitative agreement with theoretical predictions, and demonstrate the utility of the JPC as a which-qubit information eraser.
Risk of cardiovascular disease in patients with alcohol use disorder: A population-based retrospective cohort study

The complex effects of alcohol consumption on the cardiovascular system vary with mean daily consumption and duration of intake. This population-based retrospective cohort study aimed to explore the risk of cardiovascular disease (CVD) in patients with alcohol use disorder (AUD). Data was collected from the Taiwan National Health Insurance Research Database from 2000 to 2013. A total of 7,420 patients with AUD were included in our study group, and 29,680 age- and sex-matched controls without AUD in the control group. Cox proportional hazard regression analysis was used to investigate the effects of AUD on the risk of CVD. Most patients were men aged 25–44 years. At the end of the follow-up period, the AUD group had a significantly higher incidence of CVD (27.39% vs. 19.97%, P<0.001) and more comorbidities than the control group. The AUD group also exhibited a significantly higher incidence of CVD than the control group based on the Cox regression analysis and Fine and Gray’s competing risk model (adjusted hazard ratio [AHR] = 1.447, 95% confidence interval [CI] = 1.372–1.52 5, P<0.001). Furthermore, male sex, diabetes mellitus, hypertension, hyperlipidemia, chronic kidney disease, chronic obstructive pulmonary disease, anxiety, depression, and a high Charlson Comorbidity Index were also associated with an increased risk of CVD. Patients with AUD in different CVD subgroups, such as those with CVD, ischemic heart disease (IHD), and stroke, were at a significantly higher risk of disease than those without AUD; CVD (AHR = 1.447, 95% CI = 1.372–1.525, P<0.001), IHD (AHR = 1.304, 95% CI = 1.214–1.401, P<0.001), and stroke (AHR = 1.640, 95% CI = 1.519–1.770, P<0.001). The risk also significantly differed among patients in the different CVD subgroups. We observed an association between AUD and development of CVD even after adjusting for several comorbidities and medications in our nationwide population cohort.
Postdiagnosis body fatness, recreational physical activity, dietary factors and breast cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading

Based on the Global Cancer Update Programme, formally known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, we performed systematic reviews and meta‐analyses to investigate the association of postdiagnosis body fatness, physical activity and dietary factors with breast cancer prognosis. We searched PubMed and Embase for randomised controlled trials and longitudinal observational studies from inception to 31 October 2021. We calculated summary relative risks (RRs) and 95% confidence intervals (CIs) using random‐effects meta‐analyses. An independent Expert Panel graded the quality of evidence according to predefined criteria. The evidence on postdiagnosis body fatness and higher all‐cause mortality (RR per 5 kg/m2 in body mass index: 1.07, 95% CI: 1.05‐1.10), breast cancer‐specific mortality (RR: 1.10, 95% CI: 1.06‐1.14) and second primary breast cancer (RR: 1.14, 95% CI: 1.04‐1.26) was graded as strong (likelihood of causality: probable). The evidence for body fatness and breast cancer recurrence and other nonbreast cancer‐related mortality was graded as limited (likelihood of causality: limited‐suggestive). The evidence on recreational physical activity and lower risk of all‐cause (RR per 10 metabolic equivalent of task‐hour/week: 0.85, 95% CI: 0.78‐0.92) and breast cancer‐specific mortality (RR: 0.86, 95% CI: 0.77‐0.96) was judged as limited‐suggestive. Data on dietary factors was limited, and no conclusions could be reached except for healthy dietary patterns, isoflavone and dietary fibre intake and serum 25(OH)D concentrations that were graded with limited‐suggestive evidence for lower risk of the examined outcomes. Our results encourage the development of lifestyle recommendations for breast cancer patients to avoid obesity and be physically active.
Vasodilation in patients with calcium channel blocker poisoning treated with high-dose insulin: a comparison of amlodipine versus non-dihydropyridines

Abstract Background: High dose insulin (HDI), an inotrope and vasodilator, is a standard therapy for calcium channel blocker (CCB) poisoning. HDI causes vasodilation by stimulating endothelial nitric oxide synthase (eNOS). Most literature supporting HDI for CCB poisoning involves verapamil toxicity; however, amlodipine now causes more CCB poisonings. Unlike other CCBs, amlodipine stimulates eNOS and may cause synergistic vasodilation with HDI. The purpose of this study was to determine if amlodipine-poisoned patients treated with HDI had more evidence of vasodilation than similarly treated patients with non-dihydropyridine (non-DHP) poisoning. Methods: This was a retrospective study from a single poison center. Cases were identified via the generic code “Calcium Antagonists” in which the therapy “High Dose Insulin/Glucose” was “performed, whether or not recommended” from 2019–2021. Evidence of vasodilation was assessed via maximum number of vasopressor infusions per case, vasopressor doses, and use of rescue methylene blue to treat refractory vasoplegia. Results: Thirty-three patients were enrolled: 18 poisoned with amlodipine, 15 with non-DHPs (verapamil n = 10, diltiazem n = 5). The median number of maximum concomitant vasopressors in the amlodipine group was 3 (IQR: 2–5; range 0–6) and 2 in the non-DHP group (IQR: 1–3; range 0–5; p = 0.04); median difference in maximum concomitant vasopressors between groups was 1 (95% confidence interval: 0–2). Median maximum epinephrine dosing was higher in the amlodipine group (0.31 mcg/kg/min) compared to non-DHPs (0.09 mcg/kg/min; p = 0.03). Use of rescue methylene blue was more common in the amlodipine group (7/18 [39%]) than in the non-DHP group (0; p = 0.009). Conclusions: Amlodipine poisoned patients treated with HDI required more vasopressors, higher doses of epinephrine, and more often received rescue methylene blue than similarly treated patients with verapamil or diltiazem poisoning. These differences suggest amlodipine-poisoned patients had more evidence of vasodilation. Further study is warranted to determine if synergistic vasodilation occurs when HDI is used to treat amlodipine poisoning.
NACDDB: Nucleic Acid Circular Dichroism Database

Abstract The Nucleic Acid Circular Dichroism Database (NACDDB) is a public repository that archives and freely distributes circular dichroism (CD) and synchrotron radiation CD (SRCD) spectral data about nucleic acids, and the associated experimental metadata, structural models, and links to literature. NACDDB covers CD data for various nucleic acid molecules, including DNA, RNA, DNA/RNA hybrids, and various nucleic acid derivatives. The entries are linked to primary sequence and experimental structural data, as well as to the literature. Additionally, for all entries, 3D structure models are provided. All entries undergo expert validation and curation procedures to ensure completeness, consistency, and quality of the data included. The NACDDB is open for submission of the CD data for nucleic acids. NACDDB is available at: https://genesilico.pl/nacddb/.
Mediated awareness for intra-family communication

The research presented in this thesis has two objectives. The first objective is to investigate the current communication practices of family members to stay in touch with each other. Based on this investigation it elicits requirements for new pervasive communication systems, called awareness systems, which aim to support intra-family communication. The second objective is to develop those awareness systems based on the elicited requirements and evaluate them. In this thesis we focus on families who consist of working parents with dependent children living under the same roof. Awareness systems can be defined as a class of computer mediated communication systems that support individuals to maintain, with low effort, a peripheral awareness of each other’s activities and whereabouts. In the context of the research conducted, a variety of methods were used and several applications to conduct the research were developed. More specifically interviews, field studies of two prototypes, web surveys and an adapted version of the experience sampling study were used. The research endeavor started off with an interview study with twenty Dutch parents. The results of the interview were followed up with an online survey study and a prototype evaluation. A follow-up modified experience sampling study (Reconexp) helped in placing the previous findings into context. The objective of Reconexp was to find out the communication needs of busy parents under context. The two prototypes which were created, SchoolAware and FamilyAware embody the primary characteristics of awareness system according to the aforementioned definition. SchoolAware automatically communicated the presence of children in school as well as their schedule information to their parents. FamilyAware gathered multiple sources of awareness information such as place, calendar information, computer activity and automatically exchanged that information between busy parents. Moreover, it enabled parents to exchange messages and photos along with the automatically captured awareness information. This information was presented in mobile phones. The contributions of this thesis are twofold. First the thesis presents the intra-family communication needs that would drive the adoption of awareness systems. Moreover the thesis presents the implications for the design of such systems. Second the thesis examines a modification of the experience sampling method (ESM), the experience sampling and reconstruction method (ESRM). Evidence is presented which indicate the potential of the ESRM when compared to the ESM.
In vitro and in silico binding studies of phytochemical isochroman with calf thymus DNA using multi-spectroscopic and computational modelling techniques

Abstract A wide range of therapeutic molecules uses deoxyribonucleic acid (DNA) as an intracellular target. The interaction of small molecules to DNA is a key feature in pharmacology and plays a vital role in the development of novel and more efficient drugs with increased selective activity and enhanced therapeutic effectiveness. Isochroman (IC) is a constituent of Olea europea plant, which has been shown to exhibit several beneficial pharmacological activities. At present, its interaction studies using calf thymus DNA (ct-DNA) have not been explained. A set of multi-spectroscopic techniques has been performed to determine the interaction mechanism of isochroman with ct-DNA. Absorption spectra and quenching in fluorescence studies show that isochroman and ct-DNA form a complex. The static mode of quenching was determined by the Stern-Volmer plot. The value of binding constant, Kb = 4.0 × 103 M−1 revealed moderate type of binding. Effects of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) and ionic strength were studied to examine the isochroman binding to ct-DNA. Potassium iodide (KI) quenching effects and competitive binding studies clearly showed that isochroman binds in the minor groove of ct-DNA. Circular dichroic and DNA melting experiments also confirmed these results. The experimental outputs were further corroborated via in silico computational modelling studies. Lipinski’s rule of 5 and SwissADME showed drug-likeness and oral bioavailability scores. Protox ІІ online software predicts oral and organ toxicity. Communicated by Ramaswamy H. Sarma