Miracle-dz/UniFAR-FTUs huggingface dataset:
Positive regulation of pyoluteorin biosynthesis in Pseudomonas sp. M18 by quorum-sensing regulator VqsR.

The biocontrol rhizobacterium Pseudomonas sp. M18 can produce two kinds of antibiotics, namely pyoluteorin (Plt) and phenazine-1-carboxylic acid (PCA), and is antagonistic against a number of soilborne phytopathogens. In this study, a luxR-type quorum-sensing regulatory gene, vqsR, was identified and characterized immediately downstream of the Plt gene cluster in strain M18. A vqsR-inactivated mutant led to a significant decrease in the production of Plt and its biosynthetic gene expression. However, this was restored when introducing the vqsR gene by cloning into the plasmid pME6032 in trans. The vqsR mutation did not exert any obvious influence on the production of PCA and its biosynthetic gene expression and the production of Nacylhomoserine lactones (C4 and C8-HSLs) and their biosynthetic gene rhlI expression. Accordingly, these results introduce VqsR as a regulator of Plt production in Pseudomonas spp. , and suggest that the regulatory mechanism of vqsR in strain M18 is distinct from that in P. aeruginosa. In addition, it was demonstrated that vqsR mutation did not have any obvious impact on the expression of Plt-specific ABC transporters and other secondary metabolic global regulators, including GacA, RpoS, and RsmA.
Qualitative Development and Content Validation of the PROMIS Pediatric Sleep Health Items

ABSTRACT Objective: To develop the Patient Reported Outcome Measurement Information System (PROMIS) Pediatric Sleep Health item pool and evaluate its content validity. Participants: Participants included 8 expert sleep clinician-researchers, 64 children ages 8–17 years, and 54 parents of children ages 5–17 years. Methods: We started with item concepts and expressions from the PROMIS Sleep Disturbance and Sleep Related Impairment adult measures. Additional pediatric sleep health concepts were generated by expert (n = 8), child (n = 28), and parent (n = 33) concept elicitation interviews and a systematic review of existing pediatric sleep health questionnaires. Content validity of the item pool was evaluated with item translatability review, readability analysis, and child (n = 36) and parent (n = 21) cognitive interviews. Results: The final pediatric Sleep Health item pool includes 43 items that assess sleep disturbance (children’s capacity to fall and stay asleep, sleep quality, dreams, and parasomnias) and sleep-related impairments (daytime sleepiness, low energy, difficulty waking up, and the impact of sleep and sleepiness on cognition, affect, behavior, and daily activities). Items are translatable and relevant and well understood by children ages 8–17 and parents of children ages 5–17. Conclusions: Rigorous qualitative procedures were used to develop and evaluate the content validity of the PROMIS Pediatric Sleep Health item pool. Once the item pool’s psychometric properties are established, the scales will be useful for measuring children’s subjective experiences of sleep.
Closure of the Cavity in Permethylated Cyclodextrins through Glucose Inversion, Flipping, and Kinking.

Glucose-flips in a small cycloamylose: the molecular structure of permethylated γ-cyclodextrin, which crystallizes as the dihydrate, is characterized by 180° flips of two diametrically opposed glucose residues. This leads to an elliptical distortion of the molecule and closure of the molecular cavity on one side so that it is no longer doughnut-shaped but is bowl-shaped. The hydrate water molecules are not located in the cavities!
A Machine Learning-Empowered System for Long-Term Motion-Tolerant Wearable Monitoring of Blood Pressure and Heart Rate With Ear-ECG/PPG

In this paper, we propose a fully ear-worn long-term blood pressure (BP) and heart rate (HR) monitor to achieve a higher wearability. Moreover, to enable practical application scenarios, we present a machine learning framework to deal with severe motion artifacts induced by head movements. We suggest situating all electrocardiogram (ECG) and photoplethysmography (PPG) sensors behind two ears to achieve a super wearability, and successfully acquire weak ear-ECG/PPG signals using a semi-customized platform. After introducing head motions toward real-world application scenarios, we apply a support vector machine classifier to learn and identify raw heartbeats from motion artifacts-impacted signals. Furthermore, we propose an unsupervised learning algorithm to automatically filter out residual distorted/faking heartbeats, for ECG-to-PPG pulse transit time (PTT) and HR estimation. Specifically, we introduce a dynamic time warping-based learning approach to quantify distortion conditions of raw heartbeats referring to a high-quality heartbeat pattern, which are then compared with a threshold to perform purification. The heartbeat pattern and the distortion threshold are learned by a K-medoids clustering approach and a histogram triangle method, respectively. Afterward, we perform a comparative analysis on ten PTT or PTT&HR-based BP learning models. Based on an acquired data set, the BP and HR estimation using the proposed algorithm has an error of −1.4±5.2 mmHg and 0.8±2.7 beats/min, respectively, both much lower than the state-of-the-art approaches. These results demonstrate the capability of the proposed machine learning-empowered system in ear-ECG/PPG acquisition and motion-tolerant BP/HR estimation. This proof-of-concept system is expected to illustrate the feasibility of ear-ECG/PPG-based motion-tolerant BP/HR monitoring.
Arrhythmogenic Effects of &bgr;2-Adrenergic Stimulation in the Failing Heart Are Attributable to Enhanced Sarcoplasmic Reticulum Ca Load

Ventricular tachycardia in heart failure (HF) can initiate by nonreentrant mechanisms such as delayed afterdepolarizations. In an arrhythmogenic rabbit model of HF, we have shown that isoproterenol induces ventricular tachycardia in vivo and aftercontractions and transient inward currents in HF myocytes. To determine whether &bgr;2-adrenergic receptor (&bgr;2-AR) stimulation contributes, we performed in vivo drug infusion, in vitro myocyte and biochemical studies. Intravenous zinterol (2.5 &mgr;g/kg) led to ventricular arrhythmias, including ventricular tachycardia up to 13 beats long in 4 of 6 HF rabbits (versus 0 of 5 controls, P<0.01), an effect blocked by &bgr;2-AR antagonist ICI-118,551 (0.2 mg/kg). In field-stimulated myocytes (0.5 to 4 Hz, 37°C), &bgr;2-AR stimulation (1 &mgr;mol/L zinterol+300 nmol/L &bgr;1-AR antagonist CGP-29712A) induced aftercontractions and Ca aftertransients in 88% of HF versus 0% of control myocytes (P<0.01). &bgr;2-AR stimulation in HF (but not control) myocytes increased Ca transient amplitude (by 29%), sarcoplasmic reticulum (SR) Ca load (by 28%), the rate of [Ca]i decline (by 28%; n=12, all P<0.05), and phospholamban phosphorylation at Ser16, but Ca current was unchanged. All of these effects in HF myocytes were blocked by ICI-118,551 (100 nmol/L). Although total &bgr;-AR expression was reduced by 47% in HF rabbit left ventricle, &bgr;2-AR number was unchanged, indicating more potent &bgr;2-AR–dependent SR Ca uptake and arrhythmogenesis in HF. Human HF myocytes showed similar &bgr;2-AR–induced aftercontractions, aftertransients, and enhanced Ca transient amplitude, SR Ca load and twitch [Ca]i decline rate. Thus, &bgr;2-AR stimulation is arrhythmogenic in HF, mediated by SR Ca overload-induced spontaneous SR Ca release and aftercontractions.
Multimodal Data Fusion: An Overview of Methods, Challenges, and Prospects

In various disciplines, information about the same phenomenon can be acquired from different types of detectors, at different conditions, in multiple experiments or subjects, among others. We use the term “modality” for each such acquisition framework. Due to the rich characteristics of natural phenomena, it is rare that a single modality provides complete knowledge of the phenomenon of interest. The increasing availability of several modalities reporting on the same system introduces new degrees of freedom, which raise questions beyond those related to exploiting each modality separately. As we argue, many of these questions, or “challenges,” are common to multiple domains. This paper deals with two key issues: “why we need data fusion” and “how we perform it. ” The first issue is motivated by numerous examples in science and technology, followed by a mathematical framework that showcases some of the benefits that data fusion provides. In order to address the second issue, “diversity” is introduced as a key concept, and a number of data-driven solutions based on matrix and tensor decompositions are discussed, emphasizing how they account for diversity across the data sets. The aim of this paper is to provide the reader, regardless of his or her community of origin, with a taste of the vastness of the field, the prospects, and the opportunities that it holds.
Gamma (40-100 Hz) oscillation in the hippocampus of the behaving rat

The cellular generation and spatial distribution of gamma frequency (40– 100 Hz) activity was examined in the hippocampus of the awake rat. Field potentials and unit activity were recorded by multiple site silicon probes (5- and 16-site shanks) and wire electrode arrays. Gamma waves were highly coherent along the long axis of the dentate hilus, but average coherence decreased rapidly in the CA3 and CA1 directions. Analysis of short epochs revealed large fluctuations in coherence values between the dentate and CA1 gamma waves. Current source density analysis revealed large sinks and sources in the dentate gyrus with spatial distribution similar to the dipoles evoked by stimulation of the perforant path. The frequency changes of gamma and theta waves positively correlated (40–100 Hz and 5–10 Hz, respectively). Putative interneurons in the dentate gyrus discharged at gamma frequency and were phase-locked to the ascending part of the gamma waves recorded from the hilus. Following bilateral lesion of the entorhinal cortex the power and frequency of hilar gamma activity significantly decreased or disappeared. Instead, a large amplitude but slower gamma pattern (25–50 Hz) emerged in the CA3-CA1 network. We suggest that gamma oscillation emerges from an interaction between intrinsic oscillatory properties of interneurons and the network properties of the dentate gyrus. We also hypothesize that under physiological conditions the hilar gamma oscillation may be entrained by the entorhinal rhythm and that gamma oscillation in the CA3-CA1 circuitry is suppressed by either the hilar region or the entorhinal cortex.
CHANGES IN CORNEAL ASTIGMATISM WITH AGE*

&NA; An analysis of the changes in corneal astigmatism over a mean period of 24.14 years was performed on data obtained by repeated keratometric measurements of the corneas of clinical patients. Patients aged 5 to 29 years at the time of their first measurement showed, as they aged, an increase in the amount of with‐the‐rule corneal astigmatism (or a decrease in againstthe‐rule) at an average rate of 0.0033 D a year. Those aged 30 and over showed a change in the direction of increasing against‐the‐rule at a mean rate of (0.0057 D) a year. However, the corneas of more than 70% of all these patients manifested a change of 0.25 D or less in their astigmatism in 10 years. Changes in the axis of corneal astigmatism averaged less than 4 degrees in 10 years. In over 70% of the subjects the axis was shifted closer to the 90th meridian and in 20% the axis shifted closer to the 180th meridian. The small size and random nature of these changes suggest that these statistical trends offer limited guidance for predicting changes in a specific patient's astigmatic error.
Spontaneous Theory of Mind and Its Absence in Autism Spectrum Disorders

Theory of mind, the cognitive capacity to infer others’ mental states, is crucial for the development of social communication. The impairment of theory of mind may relate to autism spectrum disorder (ASD), which is characterized by profound difficulties in social interaction and communication. In the current article, I summarize recent updates in theory of mind research utilizing the spontaneous false belief test, which assesses participants’ spontaneous tendency to attribute belief status to others. These studies reveal that young infants pass the spontaneous false belief test well before they can pass the same task when explicitly asked to answer. By contrast, high-functioning adults with ASD, who can easily pass the false belief task when explicitly asked to, do not show spontaneous false belief attribution. These findings suggest that the capacity for theory of mind develops much earlier than was previously thought, and the absence of spontaneous theory of mind may relate to impairment in social interaction and communication found in ASD.
Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes.

OBJECTIVE Conflicting evidence of a decline in incidence of microvascular complications in type 1 diabetes during the last decades has been reported. To assess recent trends in the cumulative incidence of diabetic microangiopathy in type 1 diabetes, we analyzed data from long-term prospective observational studies lasting >/=20 years. RESEARCH DESIGN AND METHODS A total of 600 Caucasian patients with onset of type 1 diabetes between 1965 and 1984 were followed until death or until the year 2000. Patients were divided into four groups based on the year of diabetes onset: group A, 1965-1969 (n = 113); group B, 1970-1974 (n = 130); group C, 1975-1979 (n = 113); and group D, 1979-1984 (n = 244). Group A, B, and C are prevalence cohorts identified in 1984; group D is an inception cohort. RESULTS In patients followed for >/=20 years, the cumulative incidence (95% CI) of diabetic nephropathy after 20 years of diabetes (urinary albumin excretion >300 mg/24 h) was reduced in patients with more recent diabetes onset (groups A-D): 31.1% (22.5-39.7) vs. 28.4% (19.8-37.0) vs. 18.9% (10.9-26.9) vs. 13.7% (6.2-21.2) (P = 0.015). Similarly, the cumulative incidence of proliferative retinopathy was as follows: 31.2% (22.2-39.8) vs. 30.3% (22.2-38.4) vs. 19.3% (11.2-27.4) vs. 12.5% (5.2-19.8) (P < 0.01). In the latter groups, antihypertensive treatment was started earlier, blood pressure and HbA(1c) were lower, and fewer patients smoked. CONCLUSIONS Our study demonstrates a decrease in the cumulative incidence of diabetic microangiopathy in type 1 diabetes over the past 35 years. Improved glycemic control, lower blood pressure (in part due to early aggressive antihypertensive treatment), and reduced prevalence of smoking rates were associated with the improved prognosis.
Traditional and commercial alcohols and esophageal cancer risk in Kenya

Squamous cell esophageal cancer is common throughout East Africa, but its etiology is poorly understood. We investigated the contribution of alcohol consumption to esophageal cancer in Kenya, based on a hospital‐based case–control study conducted from 08/2013 to 03/2018 in Eldoret, western Kenya. Cases had an endoscopy‐confirmed esophageal tumor whose histology did not rule out squamous cell carcinoma. Age and gender frequency‐matched controls were recruited from hospital visitors/patients without digestive diseases. Logistic regression was used to calculate odds ratios (ORs) and their 95% confidence intervals (CI) adjusting for tobacco (type, intensity) and 6 other potential confounders. A total of 422 cases (65% male, mean at diagnosis 60 (SD 14) years) and 414 controls were included. ORs for ever‐drinking were stronger in ever‐tobacco users (9.0, 95% CI: 3.4, 23.8, with few tobacco users who were never drinkers) than in never‐tobacco users (2.6, 95% CI: 1.6, 4.1). Risk increased linearly with number of drinks: OR for >6 compared to >0 to ≤2 drinks/day were 5.2 (2.4, 11.4) in ever‐tobacco users and 2.1 (0.7, 4.4) in never‐tobacco users. Although most ethanol came from low ethanol alcohols (busaa or beer), for the same ethanol intake, if a greater proportion came from the moonshine chang'aa, it was associated with a specific additional risk. The population attributable fraction for >2 drinks per day was 48% overall and highest in male tobacco users. Alcohol consumption, particularly of busaa and chang'aa, contributes to half of the esophageal cancer burden in western Kenya.
Hyperspectral imaging: innovative diagnostics to visualize hemodynamic effects of cold plasma in wound therapy

Abstract An important clinical potential of cold atmospheric plasma (CAP) lies in tumor and wound treatment, whereby the last-mentioned is well-referenced already. However, the underlying mechanisms of improved wound healing have not been sufficiently clarified yet, in particular the influence of CAP on microcirculation. Hyperspectral imaging (HSI) enables the visualization of microcirculation of large tissue areas, thus this technique seems to be a candidate to examine CAP effects on perfusion and oxygen saturation in wounds. During clinical wound management, one chronic wound caused by peripheral arterial occlusive disease and one acute wound after surgical removal of cervical lymph nodes were examined using HSI before and after CAP treatment. HSI was able to demonstrate CAP effects on microcirculation showing a relevant increase of superficial and deeper cutaneous oxygen saturation together with elevated hemoglobin concentration in treated and also surrounding wound area. For the first time, it was shown that CAP improves the superficial and deeper oxygenation and hemoglobin perfusion in and around the treated area of acute and chronic wounds. This effect may contribute to healing support by CAP in wounds. HSI seems suitable for evaluating and monitoring CAP effects in clinical settings.
Peyronie's disease intervention trials: methodological challenges and issues.

INTRODUCTION Peyronie's Disease (PD) has been studied for more than 260 years since Francois de la Peyronie's description in 1743. Based on the current literature, the prevalence of PD seems 3-9% with an average age of onset in the fifth life decade. Much effort has been spent on developing nonsurgical treatment options to cure or at least prevent disease progression. AIM The recent examination of drug trials for erectile dysfunction has led us to assess PD trial methodology more closely. METHODS An Iinternet search on PubMed was performed using MeSH words PD, clinical trials, oral, transdermal, intralesional and shock wave therapy focusing on 26 representing studies published over the last 15 years. Mean Outcome Measures. A comprehensive review of the current literature on nonsurgical treatment options for PD was conducted to address methodological issues and challenges in PD trials highlighting trial design, patient population, and symptom and sign assessment. RESULTS The majority of the reviewed studies are underpowered and the heterogeneity in the methodological approach and patient assessment between the studies is one of the remarkable findings from our review. Studies should use a uniform means of defining the degree and type of penile deformity and a large enough cohort of patients should be studied for adequate study power. An ideally designed PD intervention trial should comprise: (i) a randomized, placebo-controlled design; (ii) with a PD patient set representative of the general PD population; and (iii) a comprehensive symptom and sign assessment before and at the end of treatment which includes an assessment of at least deformity, pain, and sexual function. CONCLUSION A number of challenges exist for the design of PD intervention trials and deciphering the data generated from them. The field would benefit greatly from a consensus statement or guidelines development on the design and conduct of such trials.
Evidence for altered balance between matrix metalloproteinases and their inhibitors in human aortic diseases.

BACKGROUND Although abdominal aortic aneurysms (AAAs) exhibit increased expression of matrix metalloproteinases (MMPs), the functional balance between MMPs and their tissue inhibitors (TIMPs) remains uncertain. This report compares the proteolytic activity in normal aorta, aorto-occlusive disease (AOD), and AAA by use of a novel in situ zymographic technique. METHODS AND RESULTS Infrarenal aortic specimens were obtained from 25 patients undergoing surgery for AOD or AAA and were compared with normal aortic tissue (n = 7) obtained from cadavers. Immunohistochemical staining was performed for collagenase (MMP-1), gelatinase A (MMP-2), stromelysin (MMP-3), TIMP-1, and TIMP-2. Net proteolytic activity was determined with in situ zymography whereby aortic sections were incubated on fluorescently labeled substrate. Proteolytic activity was detected under epifluorescent examination. Compared with normal aortic tissue, AOD and AAA tissue demonstrated marked increases in MMP-1 and MMP-3 immunoreactivity, predominantly in the neointima, and modest increases in TIMP-1. MMP-2 was increased in the diseased aortas, and TIMP-2 was abundant in normal, AOD, and AAA samples. Zymography revealed proteolytic activity in AOD and AAA tissues with active digestion of casein and gelatin substrate, particularly on the luminal portion of the specimens. Normal specimens exhibited no lytic activity. Comparison of AOD and AAA specimens revealed no difference in MMP/TIMP immunoreactivity or net proteolytic activity. CONCLUSIONS MMP expression is markedly increased in AOD and AAA samples, and an imbalance between MMPs and their inhibitors results in similar proteolytic activity. The eventual formation of aneurysmal or occlusive lesions appears not to result from an ongoing difference in the proteolytic pattern.
Aminoindan and hydroxyaminoindan, metabolites of rasagiline and ladostigil, respectively, exert neuroprotective properties in vitro

The anti‐Parkinson, selective irreversible monoamine oxidase B inhibitor drug, rasagiline (Azilect), recently approved by the US Food and Drug Administration, has been shown to possess neuroprotective‐neurorescue activities in in vitro and in vivo models. Recent preliminary studies indicated the potential neuroprotective effect of the major metabolite of rasagiline, 1‐(R)‐aminoindan. In the current study, the neuroprotective properties of 1‐(R)‐aminoindan were assessed employing a cytotoxic model of human neuroblastoma SK‐N‐SH cells in high‐density culture‐induced neuronal death. We show that aminoindan (0.1–1 μmol/L) significantly reduced the apoptosis‐associated phosphorylated protein, H2A.X (Ser139), decreased the cleavage of caspase 9 and caspase 3, while increasing the anti‐apoptotic proteins, Bcl‐2 and Bcl‐xl. Protein kinase C (PKC) inhibitor, GF109203X, prevented the neuroprotection, indicating the involvement of PKC in aminoindan‐induced cell survival. Aminoindan markedly elevated pPKC(pan) and specifically that of the pro‐survival PKC isoform, PKCε. Additionally, hydroxyaminoindan, a metabolite of a novel bifunctional drug, ladostigil [(N‐propargyl‐(3R) aminoindan‐5yl)‐ethyl methyl carbamate], combining cholinesterase and monoamine oxidase inhibitor activity, exerted similar neuroprotective properties. Aminoindan and hydroxyaminoindan also protected rat pheochromacytoma PC‐12 cells against the neurotoxin, 6‐hydroxydopamine. Our findings suggest that both metabolites may contribute to the overall neuroprotective activity of their respective parent compounds, further implicating rasagiline and ladostigil as potentially valuable drugs for treatment of a wide variety of neurodegenerative disorders of aging.
Effects of conjugated oestrogen and droloxifene on the renin–angiotensin system, blood pressure and renal blood flow in postmenopausal women

objective The aim of this study was to evaluate the effect of conjugated equine oestrogen (CEE), and droloxifene, a selective oestrogen receptor modulator (SERM) on individual components of renin–angiotensin–aldosterone (RAAS) and blood pressure (BP) in postmenopausal women.