Miracle-dz/UniFAR-FTUs huggingface dataset:
Real-world comparison of all-cause hospitalizations, hospitalizations due to stroke and major bleeding, and costs for non-valvular atrial fibrillation patients prescribed oral anticoagulants in a US health plan

Abstract Aims: To compare the risk of all-cause hospitalization and hospitalizations due to stroke/systemic embolism (SE) and major bleeding, as well as associated healthcare costs for non-valvular atrial fibrillation (NVAF) patients initiating apixaban, dabigatran, rivaroxaban, or warfarin. Materials and methods: NVAF patients initiating apixaban, dabigatran, rivaroxaban, or warfarin were selected from the OptumInsight Research Database from January 1, 2013–September 30, 2015. Propensity score matching (PSM) was performed between apixaban and each oral anticoagulant. Cox models were used to estimate the risk of stroke/SE and major bleeding. Generalized linear and 2-part models were used to compare healthcare costs. Results: Of the 47,634 eligible patients, 8,328 warfarin-apixaban pairs, 3,557 dabigatran-apixaban pairs, and 8,440 rivaroxaban-apixaban pairs were matched. Compared to apixaban, warfarin patients were associated with a significantly higher risk of all-cause (hazard ratio [HR] = 1.30; 95% confidence interval [CI] = 1.21–1.40) as well as stroke/SE-related (HR = 1.60; 95% CI = 1.23–2.07) and major bleeding-related (HR = 1.95; 95% CI = 1.60–2.39) hospitalization; rivaroxaban patients were associated with a higher risk of all-cause (HR = 1.15; 95% CI = 1.07–1.24) and major bleeding-related hospitalization (HR = 1.71; 95% CI = 1.39–2.10); and dabigatran patients were associated with a higher risk of major bleeding hospitalization (HR = 1.46, 95% CI = 1.02–2.10). Warfarin patients had significantly higher major bleeding-related and total all-cause healthcare costs compared to apixaban patients. Rivaroxaban patients had significantly higher major bleeding-related costs compared to apixaban patients. No significant results were found for the remaining comparisons. Limitations: No causal relationships can be concluded, and unobserved confounders may exist in this retrospective database analysis. Conclusions: This study demonstrated a significantly higher risk of hospitalization (all-cause, stroke/SE, and major bleeding) associated with warfarin, a significantly higher risk of major bleeding hospitalization associated with dabigatran or rivaroxaban, and a significantly higher risk of all-cause hospitalization associated with rivaroxaban compared to apixaban. Lower major bleeding-related costs were observed for apixaban patients compared to warfarin and rivaroxaban patients.
Affective and cooperative social interactions modulate effective connectivity within and between the mirror and mentalizing systems

Decoding the meaning of others’ actions, a crucial step for social cognition, involves different neural mechanisms. While the “mirror” and “mentalizing” systems have been associated with, respectively, the processing of biological actions versus more abstract information, their respective contribution to intention understanding is debated. Processing social interactions seems to recruit both neural systems, with a different weight depending on cues emphasizing either shared action goals or shared mental states. We have previously shown that observing cooperative and affective social interactions elicits stronger activity in key nodes of, respectively, the mirror (left posterior superior temporal sulcus (pSTS), superior parietal cortex (SPL), and ventral/dorsal premotor cortex (vPMC/dPMC)) and mentalizing (ventromedial prefrontal cortex (vmPFC)) systems. To unveil their causal organization, we investigated the effective connectivity underlying the observation of human social interactions expressing increasing cooperativity (involving left pSTS, SPL, and vPMC) versus affectivity (vmPFC) via dynamic causal modeling in 36 healthy human subjects. We found strong evidence for a model including the pSTS and vPMC as input nodes for the observed interactions. The extrinsic connectivity of this model undergoes oppositely valenced modulations, with cooperativity promoting positive modulations of connectivity between pSTS and both SPL (forward) and vPMC (mainly backward), and affectivity promoting reciprocal positive modulations of connectivity between pSTS and vmPFC (mainly backward). Alongside fMRI data, such divergent effective connectivity suggests that different dimensions underlying the processing of social interactions recruit distinct, although strongly interconnected, neural pathways associated with, respectively, the bottom–up visuomotor processing of motor intentions, and the top–down attribution of affective/mental states.
Regulation of Appetite in Chronic Renal Failure

Anorexia, nausea and vomiting in patients with severe renal failure may cause or contribute to development of protein-energy malnutrition, which is associated with increased morbidity and mortality. However, the specific mechanisms that cause appetite suppression in uremia are poorly understood. This review summarizes the general mechanisms by which appetite is regulated. Various factors are discussed that may potentially be involved in appetite suppression in chronic renal failure.
Targeting phosphodiesterase 5 as a therapeutic option against myocardial ischaemia/reperfusion injury and for treating heart failure

Phosphodiesterase type 5 (PDE5) selectively hydrolyses the second messenger cGMP into 5′‐GMP, thereby regulating its intracellular concentrations. Dysregulation of the cGMP‐dependent pathway plays a significant role in various cardiovascular diseases. Therefore, its modulation by drugs, such as PDE5 inhibitors, may represent an effective therapeutic approach. There are currently four PDE5 inhibitors available for the treatment of erectile dysfunction: sildenafil, vardenafil, tadalafil and avanafil. Sildenafil and tadalafil have also received Food and Drug Administration approval for the treatment of pulmonary arterial hypertension. This review summarizes the pharmacological aspects and clinical potential of PDE5 inhibition for the treatment of myocardial ischaemia/reperfusion injury and heart failure.
Preoperative Risk Factors for Subsyndromal Delirium in Older Adults Who Undergo Joint Replacement Surgery.

BACKGROUND Older adults with subsyndromal delirium have similar risks for adverse outcomes following joint replacement surgery as those who suffer from delirium. PURPOSE This study examined relationships among subsyndromal delirium and select preoperative risk factors in older adults following major orthopaedic surgery. METHODS Delirium assessments of a sample of 62 adults 65 years of age or older were completed on postoperative Days 1, 2, and 3 following joint replacement surgery. Data were analyzed for relationships among delirium symptoms and the following preoperative risk factors: increased comorbidity burden, cognitive impairment, fall history, and preoperative fasting time. RESULTS Postoperative subsyndromal delirium occurred in 68% of study participants. A recent fall history and a longer preoperative fasting time were associated with delirium symptoms (p ≤ .05). CONCLUSIONS Older adults with a recent history of falls within the past 6 months or a longer duration of preoperative fasting time may be at higher risk for delirium symptoms following joint replacement surgery.
An exploration of weekly patterns in HIV-related behaviors: implications for successful interventions and future research

Recent studies have indicated weekly patterns of health behaviors and information seeking in areas such as diet and smoking cessation, but little information is available on whether similar patterns may exist in HIV. If such patterns do exist, there could be important implications for the timing of interventions for both prevention and care. This review provides a summary of the available literature on weekly patterns in HIV-relevant behaviors and existing interventions (including prevention and antiretroviral therapy [ART] adherence), and provides recommendations for additional research. Data were collected from published reports indexed from database inception through December 2014 and identified through PubMed and EBSCO. Only English language reports were included. Evidence of weekly patterns was found in information-seeking behaviors, risk behaviors, screening and care, and structuring of existing interventions, including ART adherence interventions. These patterns included increased interest in HIV-related information early in the week, weekend patterns of risk behavior among some populations, and interest in weekend and evening clinic hours. Literature on text messaging for ART adherence indicates that weekly short message service messages are the most effective. Implications for prevention and adherence interventions are discussed, and recommendations for future research are given.
Comparison of trace element levels after cardiopulmonary bypass between cyanotic and acyanotic patients

Abstract Trace elements are essential micronutrients for the human body. In this study, we evaluated the alterations in copper, chromium, manganese, selenium, magnesium, zinc, iron, arsenic, boron, and silicon levels in children with cyanotic and acyanotic CHD who underwent cardiac surgery with cardiopulmonary bypass. Participants were divided into the following three groups: patients acyanotic CHDs (n=34), patients with cyanotic CHDs (n=30), and healthy controls (n=30). Blood samples were collected before the surgery and 1 hour after the sternum was closed. Serum trace elements were determined by Inductively Coupled Plasma Optical Emission Spectrometer-ICAP 6000. The baseline serum arsenic, manganese, and zinc levels of both patient groups were lower compared with controls, but there was no significant difference between baseline serum trace element levels of cyanotic and acyanotic patients. In both the patient groups, there was a significant decrease in postoperative serum arsenic, boron, copper, and zinc levels, and a significant increase in postoperative serum iron and magnesium levels. Silicon levels increased in cyanotic patients. Alterations in trace element levels were in the same direction in cyanotic and acyanotic patients. Copper, zinc, and manganase replacement may be needed after on-pump cardiac surgery.
An audit on technical quality of root fillings performed by undergraduate students

AIM To evaluate radiographically the technical quality of root fillings performed by undergraduate dental students and to assess whether students were exposed to an appropriate endodontic case mix during their clinical training. METHODOLOGY A retrospective audit was undertaken evaluating the clinical records of patients who underwent endodontic procedures during the period from September 2015 to June 2016 in the Dental School at Queen's University Belfast, UK. Two final-year dental students were trained and calibrated to evaluate postoperative intra-oral periapical radiographs of completed root canal treatments using specific assessment criteria. Data were presented as frequencies, percentage and mean ± standard deviation (SD). Comparisons of treatment outcomes between groups (posterior and anterior teeth) were calculated using Fisher's exact test, and the level of significance was set at P < 0.05. Intra- and interexaminer reproducibility was assessed by Kappa statistics. RESULTS A total of 222 teeth and 381 canals were assessed, and of those, 253 (66%) of the root fillings were found to be acceptable in all the assessment parameters, namely taper, length and lateral adaptation of the root filling. Subanalysis of individual root filling parameters revealed that 372 canals (97%) exhibited good taper, and 275 canals (72%) were considered to be of an appropriate length, with 89 canals (23%) found to be underfilled and 17 canals (5%) overfilled. Overall 346 (91%) of canals had good lateral condensation. Students treated both single and multirooted teeth, and there was no significant association between tooth type and the quality of root filling provided (P > 0.05). CONCLUSIONS In the majority of the teeth treated by undergraduate students at Queen's University Belfast, the technical quality of the root filling was acceptable and students were exposed to an appropriate case mix for endodontic training.
Adolescent Tobacco Use: The Protective Effects of Developmental Assets

Purpose. To examine the effects of 10 youth developmental assets on adolescent tobacco use. Design. Survey of a randomly selected sample using in-home interviewing methodology. Setting. Inner-city areas of two midsized Midwestern cities. Subjects. The researchers studied 1,350 teen-parent pairs. Measures. Demographic information, adolescent self-reported tobacco use, eight developmental asset Likert scales, and two one-item developmental asset measures. Results. The response rate was 51%. Logistic regression results indicate that youth who possess nine of 10 developmental assets examined are significantly less likely to report tobacco use than youth with low levels of assets. Adjusting for youth age, race, gender, parental income and education, and family structure, significant odds ratios include the following: nonparental adult role model, 2.09 (95% confidence interval [CI] = 1.45, 3.02); peer role models, 2.48 (95% CI = 1.87, 3.29); family communication, 1.73 (95% CI = 1.29, 2.31); use of time (organized groups), 1.77 (95% CI = 1.28, 2.44); use of time (religion), 2.49 (95% CI = 1.86, 3.33); good health practices (exercise/nutrition), 1.61 (95% CI = 1.21, 2.14); community involvement, 1.66 (95% CI = 1.07, 2.58); future aspirations, 2.06 (95% CI = 1.42, 2.99); and responsible choices, 2.21 (95% CI = 1.55, 3.15). Conclusions. The findings of this study support the view that certain developmental assets may serve to protect youth from risk-taking behaviors, particularly tobacco use. Limitations include cross-sectional data and three scales with alphas below . 7.
Pharmacokinetics and Clinical Outcomes of Generic Tacrolimus (Hexal) Versus Branded Tacrolimus in De Novo Kidney Transplant Patients: A Multicenter, Randomized Trial

Background Scrupulous comparison of the pharmacokinetic and clinical characteristics of generic tacrolimus formulations versus the reference drug (Prograf) is essential. The pharmacokinetics of the Tacrolimus Hexal (TacHexal) formulation is similar to Prograf in stable renal transplant patients, but data in de novo patients are lacking. Methods De novo kidney transplant patients were randomized to generic tacrolimus (TacHexal) or Prograf in a 6-month open-label study. Results The primary end point, the dose-normalized area under the curve0-12h at month 1 posttransplant, was similar with TacHexal or Prograf; back-transformed geometric means of adjusted log-transformed values (analysis of variance) were 18.99 ng·h·L−1 (TacHexal) and 20.48 ng·h·L−1 (Prograf) (ratio, 1.08; 90% confidence interval, 0.84-1.38; P = 0.605). The dose-normalized peak concentration geometric means at month 1 was also comparable between treatments (ratio, 1.16; 90% confidence interval, 0.88-1.54; P = 0.377). There were no relevant differences in other pharmacokinetic parameters at month 1 or in area under the curve0-4h and trough concentration when measured at months 3 and 6. The adjusted change in mean estimated glomerular filtration rate from baseline to month 6 (Nankivell) was noninferior for TacHexal versus Prograf using observed values (47.7 vs 38.6 mL/min per 1.73 m2, P < 0.001) and was superior based on observed values (P = 0.044) but not using last observation-carried forward method. Rates of biopsy-proven acute rejection (5.7% vs 7.9%), adverse events, and serious adverse events were similar with TacHexal or Prograf. Conclusion Tacrolimus pharmacokinetics is similar with TacHexal and Prograf early after kidney transplantation. Efficacy and safety in this limited data set were comparable, with at least equivalent graft function under TacHexal.
Cerebral haemodynamic response to somatosensory stimulation in neonatal lambs

Cerebral haemodynamic response to neural stimulation has been extensively studied in adults, but little is known about cerebral haemodynamic response in the fetal and neonatal brain. The present study describes the cerebral haemodynamic response measured by near infrared spectroscopy to somatosensory stimulation in newborn lambs, in comparison to recent findings in fetal sheep. The cerebral haemodynamic responses in the newborn lamb brain can involve an increase in oxyhaemoglobin (oxyHb), or a decrease of oxyHb suggestive of reduced perfusion and oxygenation. Positive correlations between changes in oxyHb and mean arterial blood pressure were found in newborn but not fetal sheep, which suggests the result is unlikely to be due to immature autoregulation alone. In contrast to adult studies, hypercapnia increased the changes in cerebral blood flow and oxyHb in most of the lambs in response to somatosensory stimulation.
Aberrant astrocyte Ca2+ signals “AxCa signals” exacerbate pathological alterations in an Alexander disease model

Alexander disease (AxD) is a rare neurodegenerative disorder caused by gain of function mutations in the glial fibrillary acidic protein (GFAP) gene. Accumulation of GFAP proteins and formation of Rosenthal fibers (RFs) in astrocytes are hallmarks of AxD. However, malfunction of astrocytes in the AxD brain is poorly understood. Here, we show aberrant Ca2+ responses in astrocytes as playing a causative role in AxD. Transcriptome analysis of astrocytes from a model of AxD showed age‐dependent upregulation of GFAP, several markers for neurotoxic reactive astrocytes, and downregulation of Ca2+ homeostasis molecules. In situ AxD model astrocytes produced aberrant extra‐large Ca2+ signals “AxCa signals”, which increased with age, correlated with GFAP upregulation, and were dependent on stored Ca2+. Inhibition of AxCa signals by deletion of inositol 1,4,5‐trisphosphate type 2 receptors (IP3R2) ameliorated AxD pathogenesis. Taken together, AxCa signals in the model astrocytes would contribute to AxD pathogenesis.
Genomic analysis of a cardinalfish with larval homing potential reveals genetic admixture in the Okinawa Islands

Discrepancies between potential and observed dispersal distances of reef fish indicate the need for a better understanding of the influence of larval behaviour on recruitment and dispersal. Population genetic studies can provide insight on the degree to which populations are connected, and the development of restriction site‐associated sequencing (RAD‐Seq) methods has made such studies of nonmodel organisms more accessible. We applied double‐digest RAD‐Seq methods to test for population differentiation in the coral reef‐dwelling cardinalfish, Siphamia tubifer, which based on behavioural studies, have the potential to use navigational cues to return to natal reefs. Analysis of 11,836 SNPs from fish collected at coral reefs in Okinawa, Japan, from eleven locations over 3 years reveals little genetic differentiation between groups of S. tubifer at spatial scales from 2 to 140 km and between years at one location: pairwise FST values were between 0.0116 and 0.0214. These results suggest that the Kuroshio Current largely influences larval dispersal in the region, and in contrast to expectations based on studies of other cardinalfishes, there is no evidence of population structure for S. tubifer at the spatial scales examined. However, analyses of outlier loci putatively under selection reveal patterns of temporal differentiation that indicate high population turnover and variable larval supply from divergent source populations between years. These findings highlight the need for more studies of fishes across various geographic regions that also examine temporal patterns of genetic differentiation to better understand the potential connections between early life‐history traits and connectivity of reef fish populations.
Modification, validation and implementation of a protocol for post‐thyroidectomy hypocalcaemia

INTRODUCTION The management of post‐thyroidectomy hypocalcaemia should facilitate early discharge, and reduce risks of hypocalcaemia, readmission and treatment related hypercalcaemia. This paper describes the implementation, evaluation and revision a protocol for the optimal management of this condition. METHODS Day 1 parathyroid hormone (PTH) measurements in addition to calcium measurements were commenced following review of the unit's outcomes and literature on post‐thyroidectomy hypocalcaemia. Outcomes from a three‐year cohort of patients undergoing thyroid surgery helped amend this protocol (revision 1) to reduce biochemical tests, stipulate the need, nature and dose of vitamin D/calcium supplements, and encourage early discharge. This was further validated over seven months to assess compliance, episodes of hyper and/or hypocalcaemia after discharge, readmissions and need for treatment changes. Further revisions were made (revision 2) and implemented. RESULTS The temporary and long‐term postoperative hypocalcaemia rates were 29.1% and 3.2% respectively. Repeat calcium measurements on the first day altered management in only 1.4% of cases. The revised protocol was adhered to in 90% of cases. One patient had hypocalcaemia (due to non‐compliance) and one had hypercalcaemia. Revision 2 involved reducing the dose of calcium. CONCLUSIONS This is a good example of a unit protocol for post‐thyroidectomy hypocalcaemia being developed and modified on the basis of the literature and local experience. Day 1 PTH and calcium levels determine the need for treatment and frequency of follow‐up visits, facilitate early discharge, reduce risk of over and/or undertreatment, and are good indicators of permanent hypocalcaemia.
Going Off Script: Effects of Awe on Memory for Script-Typical and -Irrelevant Narrative Detail

People often filter their experience of new events through knowledge they already have; for example, encoding new events by relying on prototypical event “scripts” at the expense of actual details. Previous research suggests that positive affect often increases this tendency. Three studies assessed whether awe—an emotion elicited by perceived vastness, and thought to promote cognitive accommodation—has the opposite effect, reducing rather than increasing reliance on event scripts. True/false questions on details of a short story about a romantic dinner were used to determine whether awe (a) reduces the tendency to impute script-consistent but false details into memory, and/or (b) promotes memory of unexpected details. Across studies we consistently found support for the first effect; evidence for the second was less consistent. Effects were partially mediated by subjective awe, and independent of other aspects of subjective affect. Results suggest that awe reduces reliance on internal knowledge in processing new events.