Miracle-dz/UniFAR-FTUs huggingface dataset:
Association between cognitive impairment and criteria for frailty syndrome among older adults

Abstract The association between cognitive impairment and physical frailty has been studied in older adults. The criteria degree of frailty may be keys to associated cognitive impairment. Objective: To analyze the association between cognitive impairment and the criteria for frailty. Methods: We cross-sectionally examined data from 667 older adults (≥60 years of age) from a study entitled ‘Variables associated to cognition in elderly caregivers’ involving patients in an urban and rural primary healthcare center. We defined cognitive impairment based on different groups of scores on the Mini Mental State Examination, and defined frailty and prefrailty using the criteria by the Cardiovascular Health Study. We performed multinomial regression models to analyze the association between levels of frailty and cognitive impairment. Results: Similar proportions of women (54.8%) and men (45.2%) participated in the study (mean age: 71 years old). We found cognitive impairment, prefrailty and frailty in 34, 54, and 24% of the participants, respectively. Concomitant cognitive impairment and frailty was found in 13% of them. The chances of cognitive impairment increased up to 330% ( Odds Ratio [OR]: 4.3; 95% confidence interval [95%CI] 2.4‒7.7; p<0.001) among frail individuals, and 70% (OR: 1.7; 95%CI 1.0‒2.8; p=0.033) among prefrail individuals compared to robust/non-frail individuals. After controlling for age, education, place of residence and functional dependence, slowness and fatigue criteria were significantly associated with cognitive impairment. Conclusion: Older adults with frailty have a greater likelihood of concomitant cognitive impairment than prefrail and robust older adults. The prevalence of cognitive impairment and frailty is consistent with data reported in literature. The present findings contribute to the investigation of cognitive frailty.
The Clinical Observation of Midodrine United with Shenfu Injection in Treating with Hemodialysis-related Hypopiesia

【Objective】 Observe a rice many gentlemans to unite the clinical curative effect that three remarks shoot the liquid treatment blood dialysis relativity low blood pressure. 【Methods】 Treatment set and matched control sufferer all in dialysis the rice taking orally hydrochloric acid 30 minutes ago is many gentlemans 5 mgses,2 sets are 10 to is dialysis before the blood pressure after selecting a sufferer to distinguish to observe it to use a medicine in a row to each one under the unified dialysis condition,in the dialysis process the lowest blood pressure and the dialysis empress blood pressure,when the sufferer appeared IDH the matched control lowered super filtered speed,raised a dialysate sodium density,lowered dialysate temperature,lost to note physiology brine or Gao Shen glucose etc.,the treatment set gave three remarks to shoot the liquid 40 mL intravenous injection.Observe the variety of blood pressure in two sets of the front and back of treatments,heart rate. 【Results】 The low blood pressure happens to treatment set sufferer totally 62 times,after processing show an effect 43,always efficient is 91.94%;The low blood pressure happens to matched control totally 65 times,after processing show an effect 31,always efficient is 69.23%,two sets of occurrence low blood pressure sufferer through processing after,the blood pressure all has different degree to heat up,the treatment set effect obviously surpasses a matched control,and the treatment set ALB,CRP and matched control relatively have obvious difference after the treatment. 【Conclusion】 Rice many gentlemans uniting three remarks to shoot a liquid application have already been in conjunction with a function,the curative effect obviously better than list is used many gentleman normal regulationses of rices treatment,worth at clinical up expand.
Relationship between TSH Levels and the Advanced Lipoprotein Profile in the Brazilian Longitudinal Study of Adult Health (ELSA–Brasil)

ABSTRACT Purpose/aims The relationship between thyroid-stimulating hormone (TSH) and lipoprotein subfractions by Vertical Auto Profile (VAP) is unclear. We aimed to evaluate lipoprotein profiles according to TSH levels in euthyroid individuals.Material and Methods: Cross-sectional analysis of 3,525 participants from the Brazilian Longitudinal Study of Adult Health (ELSA–Brasil) with no previous thyroid disease and who were not on lipid-lowering medication. Total-cholesterol and its fractions, lipoprotein subfractions, triglycerides, and triglyceride-rich lipoprotein cholesterol [TRL-C (VLDL1+2-C, VLDL3-C, IDL-C)] were determined by VAP. Associations between TSH quintiles and lipoprotein subfractions were evaluated by crude and adjusted linear regression models.Results: For the total sample, significant beta-coefficients in full adjusted models for the 5th quintile of TSH (compared to 1st) were found for the following VAP lipids and lipoproteins: IDL-C (β: 0.90; 0.11 to 1.69); VLDL-C (β: 2.80; 1.51 to 4.08), triglycerides (β: 18.66; 8.07 to 29.25), non-HDL-C (β: 4.63; 0.50 to 8.75 mg/dl), TRL-C (β:1.93;0.70 to 3.17), VLDL3-C (β: 1.04; 0.50 to 1.57), as well as, TC/HDL-C (β: 0.15; 0.03 to 0.26) and TG/HDL-C ratio (β: 0.49;0.21 to 0.77). In women, similar results were found for VLDL-C, triglycerides, non-HDL-C, TRL-C, VLDL3-C, TC/HDL-C and TG/HDL-C-ratios. In men, we also found positive associations between the highest quintile of TSH with VLDL-C, triglycerides, VLDL3-C and TG/HDL-C.Conclusions: In the ELSA-Brasil, the highest TSH levels were mostly positively associated with lipoprotein levels, particularly TG, TRL and their remnants. Notwithstanding, our findings suggest that TSH levels within the normal range have little impact on the atherogenic profile.
Investigating changes in estuarine ecosystem functioning under future scenarios.

Estuaries are subject to disturbance by land-based sediment and nutrient inputs, resulting in changes to the ecosystems and the functions and services that they support. Spatial mapping tools that identify how functional hotspots in the estuary may shift in location and intensity under different disturbance scenarios highlight to managers the trajectory of change and the value of active management and restoration, but to date these tools are only available in the most intensively researched ecosystems. Using empirical data derived from long-term monitoring and multi-habitat field experiments we developed future scenarios representing different impacts of environmental degradation on estuarine ecosystem functions that are important for supporting ecosystem services. We used the spatial prioritisation software Zonation in a novel fashion to assess effects of different disturbance scenarios on critical soft-sediment ecosystem processes (nutrient fluxes and sediment erodibility measures) that are influenced by macrofaunal communities and local environment conditions. We compared estimates of current conditions with three scenarios linked to changes in land-use and resulting downstream impacts on estuarine ecosystems to determine how disturbance influences the distribution of high value areas for ecosystem function. Scenarios investigated the implications of habitat degradation associated with sediment deposition and declines in large sediment-dwelling animal abundance whose behaviour has important influences on ecosystem function. Our analyses demonstrate decreases in the majority of ecosystem processes under scenarios associated with disturbances. These results suggest that it is important to restore biodiversity and ecosystem function and that the application of Zonation in this context offers a simple, rapid and cost-effective way of identifying priority actions and locations for restoration, and how these shift due to multiple impacts.
Long-Term Blood Pressure Lowering and cGMP Activating Actions of the Novel ANP Analogue MANP.

BACKGROUND Based on the cardiac hormone atrial natriuretic peptide (ANP) and its seminal role in blood pressure (BP) homeostasis, we investigated the chronic BP lowering actions of a novel ANP analogue currently entering clinical trials for hypertension. Previous reports demonstrate that this analogue MANP activates the guanylyl cyclase A receptor (GC-A) and results in more potent biological actions compared to ANP, and thus may represent a new therapeutic drug for hypertension. OBJECTIVES A major goal was to establish that chronic subcutaneous (SC) delivery of MANP is feasible and hypotensive together with cGMP effects. We investigated the BP lowering and cGMP-activating actions of acute and chronic SC delivery in normal and hypertensive rats. Further, we explored vascular mechanisms of MANP in human aortic smooth muscle cells (HASMC) and ex vivo in isolated arteries. METHODS AND RESULTS In normal rats with a single SC injection, MANP promoted robust dose-dependent BP lowering actions and natriuresis, together with cGMP activation. Most importantly in hypertensive rats, once a day SC injection of MANP for 7 days induced cGMP elevation and long-term BP reduction compared to Vehicle. Mechanistically, in HASMC, MANP activated cGMP and attenuated angiotensin II mediated increases in intracellular Ca2+ levels while directly vasorelaxing arterial rings. CONCLUSION Our study demonstrates for the first time the effectiveness of SC administration of MANP for 7 days and provides innovative, vascular mechanisms of BP regulation supporting its continued development as a novel therapeutic for hypertension.
Genetic Variation and Potential for Resistance Development to the tTA Overexpression Lethal System in Insects

Release of insect pests carrying the dominant lethal tetracycline transactivator (tTA) overexpression system has been proposed as a means for population suppression. High levels of the tTA transcription factor are thought to be toxic due to either transcriptional squelching or interference with protein ubiquitination. Here we utilized the Drosophila melanogaster Genetic Reference Panel (DGRP) to examine the influence of genetic variation on the efficacy of a female-specific tTA overexpression system. The level of female lethality between DGRP lines varied from 11 to 97% with a broad sense heritability of 0.89. A genome-wide association analysis identified 192 allelic variants associated with high or low lethality (P < 10−5), although none were significant when corrected for multiple testing. 151 of the variants fell within 108 genes that were associated with several biological processes including transcription and protein ubiquitination. In four lines with high female lethality, tTA RNA levels were similar or higher than in the parental tTA overexpression strain. In two lines with low lethality, tTA levels were about two fold lower than in the parental strain. However, in two other lines with low lethality, tTA levels were similar or approximately 30% lower. RNAseq analysis identified genes that were up or downregulated in the four low female lethal lines compared to the four high lethal lines. For example, genes associated with RNA processing and rRNA maturation were significantly upregulated in low lethal lines. Our data suggest that standing genetic variation in an insect population could provide multiple mechanisms for resistance to the tTA overexpression system.
The Relationships Among Work Related Stress, Health Status, and Physical Activity Participation of Nurses in Teaching Hospitals in Taipei, Taiwan

THE RELATIONSHIPS AMONG WORK RELATED STRESS, HEALTH STATUS, AND PHYSICAL ACTIVITY PARTICIPATION OF NURSES IN TEACHING HOSPITALS IN TAIPEI, TAIWAN Ming-Hui Yao Chair of Committee: Judith E. Beauford, Ph.D. University of the Incarnate Word, 2008 The purpose of this study was to investigate the relationship among work-related stress, health status, and physical activity participation of the nurses in teaching hospitals in Taipei, Taiwan. A quantitiative research design was used in this study. Participants were 420 female nurses systematically selected from 5 teaching hospitals. The participants were asked to complete a survey package including 4 instruments (Nurse Stress Scale (NSS), SF36 Health Survey, Stage of Exercise Scale (SOES), Seven-Day Physical Activity Recall Questionnaire and a demographic questionnaire. The results showed that among the 7 factors of nursing stress, work load was rated the highest by the participants. The result of MANOVA showed a relationship between age groups and levels of job-related stress. The nurses under 20 years old reported more stress than those who were over 21 years old. The nurse participants had evidenced negative correlation between nursing stress and nurse's physical (r = -.251) and mental (r = -.30) health status. This result showed that higher levels of nursing stress related to lower levels of mental and physical health. Logistic Regression showed that health was predicted by job related stress in nursing.
Annexin A3 is necessary for parallel artery‐vein alignment in the mouse retina

Annexin A3 (Anxa3) is a member of the calcium‐regulated, cell membrane‐binding family of annexin proteins. We previously confirmed that Anxa3 is expressed in the endothelial lineage in vertebrates and that loss of anxa3 in Xenopus laevis leads to embryonic blood vessel defects. However, the biological function of Anxa3 in mammals is completely unknown. In order to investigate Anxa3 vascular function in mammals, we generated an endothelial cell‐specific Anxa3 conditional knockout mouse model (Anxa3f/f;Tie2‐Cre).
Electrophysiologic Effects of Growth Hormone Post-Myocardial Infarction

Myocardial infarction remains a major health-related problem with significant acute and long-term consequences. Acute coronary occlusion results in marked electrophysiologic alterations that can induce ventricular tachyarrhythmias such as ventricular tachycardia or ventricular fibrillation, often heralding sudden cardiac death. During the infarct-healing stage, hemodynamic and structural changes can lead to left ventricular dilatation and dysfunction, whereas the accompanying fibrosis forms the substrate for re-entrant circuits that can sustain ventricular tachyarrhythmias. A substantial proportion of such patients present clinically with overt heart failure, a common disease-entity associated with high morbidity and mortality. Several lines of evidence point toward a key role of the growth hormone/insulin-like growth factor-1 axis in the pathophysiology of post-infarction structural and electrophysiologic remodeling. Based on this rationale, experimental studies in animal models have demonstrated attenuated dilatation and improved systolic function after growth hormone administration. In addition to ameliorating wall-stress and preserving the peri-infarct myocardium, antiarrhythmic actions were also evident after such treatment, but the precise underlying mechanisms remain poorly understood. The present article summarizes the acute and chronic actions of systemic and local growth hormone administration in the post-infarction setting, placing emphasis on the electrophysiologic effects. Experimental and clinical data are reviewed, and hypotheses on potential mechanisms of action are discussed. Such information may prove useful in formulating new research questions and designing new studies that are expected to increase the translational value of growth hormone therapy after acute myocardial infarction.
Geometry-Aware Cell Detection with Deep Learning

Automated diagnostic microscopy powered by deep learning is useful, particularly in rural areas. However, there is no general method for object detection of different cells. In this study, we developed GFS-ExtremeNet, a geometry-aware deep-learning method which is based on the detection of four extreme key points for each object (topmost, bottommost, rightmost, and leftmost) and its center point. A postprocessing step, namely, adjacency spectrum, was employed to measure whether the distances between the key points were below a certain threshold for a particular cell candidate. Our newly proposed geometry-aware deep-learning method outperformed other conventional object detection methods and could be applied to any type of cell with a certain geometrical order. Our GFS-ExtremeNet approach opens a new window for the development of an automated cell detection system. ABSTRACT Analyzing cells and tissues under a microscope is a cornerstone of biological research and clinical practice. However, the challenge faced by conventional microscopy image analysis is the fact that cell recognition through a microscope is still time-consuming and lacks both accuracy and consistency. Despite enormous progress in computer-aided microscopy cell detection, especially with recent deep-learning-based techniques, it is still difficult to translate an established method directly to a new cell target without extensive modification. The morphology of a cell is complex and highly varied, but it has long been known that cells show a nonrandom geometrical order in which a distinct and defined shape can be formed in a given type of cell. Thus, we have proposed a geometry-aware deep-learning method, geometric-feature spectrum ExtremeNet (GFS-ExtremeNet), for cell detection. GFS-ExtremeNet is built on the framework of ExtremeNet with a collection of geometric features, resulting in the accurate detection of any given cell target. We obtained promising detection results with microscopic images of publicly available mammalian cell nuclei and newly collected protozoa, whose cell shapes and sizes varied. Even more striking, our method was able to detect unicellular parasites within red blood cells without misdiagnosis of each other. IMPORTANCE Automated diagnostic microscopy powered by deep learning is useful, particularly in rural areas. However, there is no general method for object detection of different cells. In this study, we developed GFS-ExtremeNet, a geometry-aware deep-learning method which is based on the detection of four extreme key points for each object (topmost, bottommost, rightmost, and leftmost) and its center point. A postprocessing step, namely, adjacency spectrum, was employed to measure whether the distances between the key points were below a certain threshold for a particular cell candidate. Our newly proposed geometry-aware deep-learning method outperformed other conventional object detection methods and could be applied to any type of cell with a certain geometrical order. Our GFS-ExtremeNet approach opens a new window for the development of an automated cell detection system.
The IUPHAR Guide to Immunopharmacology: connecting immunology and pharmacology

Given the critical role that the immune system plays in a multitude of diseases, having a clear understanding of the pharmacology of the immune system is crucial to new drug discovery and development. Here we describe the International Union of Basic and Clinical Pharmacology (IUPHAR) Guide to Immunopharmacology (GtoImmuPdb), which connects expert‐curated pharmacology with key immunological concepts and aims to put pharmacological data into the hands of immunologists. In the pursuit of new therapeutics, pharmacological databases are a vital resource to researchers through providing accurate information on the fundamental science underlying drug action. This extension to the existing IUPHAR/British Pharmacological Society Guide to Pharmacology supports research into the development of drugs targeted at modulating immune, inflammatory or infectious components of disease. To provide a deeper context for how the resource can support research we show data in GtoImmuPdb relating to a case study on the targeting of vascular inflammation.
Determination of HMG-CoA reductase inhibitors by micellar electrokinetic chromatography

Abstract Objective: In this study we report the development of a simple, rapid and efficient capillary electrophoresis method for the simultaneous determination of atorvastatin, fluvastatin, lovastatin and simvastin. Methods: Capillary zone electrophoresis proved to be efficient for the simultaneous separation of atorvastatin and fluvastatin, but could not resolve the determination of lovastatin and simvastatin. The simultaneous separation of all four statins was achieved by applying a micellar electrokinetic chromatographic method, after transforming lovastatin and simvastatin in β-hydroxyl acid forms through alkaline hydrolysis. The optimum electrophoretic conditions and analytical parameters were investigated and the analytical performances of the method were verified with regard to linearity, precision, accuracy, LOD and LOQ. Results: The optimum electrophoretic separation conditions were: 25 mM sodium tetraborate with 25 mM sodium dodecyl sulphate buffer electrolyte at pH 9.5, applied voltage + 25 kV, separation temperature 25 °C, injection pressure/time 50 mbar/1 minutes, UV detection at 230 nm. Using the optimized electrophoretic conditions we succeeded in the simultaneous determination of the four statins in approximately 3 minutes, the order of migration being: atorvastatin, fluvastatin, lovastatin, simvastatin. The proposed method has been applied to the determination of the analytes in pharmaceutical tablets formulations. Conclusions: The capillary electrophoretic method developed in the present work proved to be suitable for the routine analysis of statins and can be adopted as quality control protocol in pharmaceutical analysis.
Statistical Design and Considerations of a Phase 3 Basket Trial for Simultaneous Investigation of Multiple Tumor Types in One Study

ASBTRACT The discovery of numerous molecular subtypes of common cancers leads to the investigation of biomarkers potentially predictive of treatment effect of an experimental treatment in multiple histologies. However, the prevalence of a putative predictive biomarker within a histology is often low, which makes it challenging to enroll adequate number of patients in a conventional histology-based confirmatory trial. An alternative approach is to study patients with a common biomarker signature in a “basket” trial across multiple histologies. This study design has previously been used to explore experimental therapies with potentially transformative effects. We present a general design concept of a Phase 3 basket trial broadly applicable to any effective therapy. The trial is designed with scientific and statistical rigor to enable the approval of an experimental treatment in multiple tumor indications based on the outcome from a single study. Given the difficulty in indication selection, the basic idea is to prune the inactive indications at an interim analysis and pool the active indications in the final analysis. A critical statistical issue of the basket design is Type I error control for the pooled analysis after pruning. While pruning may be seen as cherry-picking which tends to inflate the Type I error, it also shares similarity with a binding futility analysis which tends to deflate the Type I error if all indications are pruned. The net impact of pruning is complicated. The use of different endpoints for pruning and pooling further complicates the issue. This paper will provide statistical details on Type I error control for the general basket design concept under three sample size adjustment strategies after pruning. Power and sample size calculations are also provided. Comparisons are made to a straightforward design without pruning. Supplementary materials for this article are available online.
Assessing the validity of eyelid parameters to detect impairment due to benzodiazepines

Benzodiazepines impair driving ability and psychomotor function. Eyelid parameters accurately reflect drowsiness; however, the effects of benzodiazepines on these measures have not been extensively studied. The aim of this study was to investigate the effect of benzodiazepines on eyelid parameters and evaluate their accuracy for detecting psychomotor impairment.