Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting shear gradient activated von Willebrand factor by the novel single-chain antibody A1 reduces occlusive thrombus formation in vitro

Intraluminal thrombus formation precipitates conditions such as acute myocardial infarction and disturbs local blood flow resulting in areas of rapidly changing blood flow velocities and steep gradients of blood shear rate. Shear rate gradients are known to be pro-thrombotic with an important role for the shear-sensitive plasma protein von Willebrand factor (VWF). Here, we developed a single-chain antibody (scFv) that targets a shear gradient specific conformation of VWF to specifically inhibit platelet adhesion at sites of shear rate gradients (SRG) but not in areas of constant shear. Microfluidic flow channels with stenotic segments were used to create SRG during blood perfusion. VWF-GPIbα interactions were increased at sites of SRG compared to constant shear rate of matched magnitude. The scFv-A1 specifically reduced VWF-GPIbα binding and thrombus formation at sites of SRG but did not block platelet deposition and aggregation under constant shear rate in upstream sections of the channels. Significantly, the scFv A1 attenuated platelet aggregation only in the later stages of thrombus formation. In the absence of shear, direct binding of scFv-A1 to VWF could not be detected and scFVA1 did not inhibit ristocetin induced platelet agglutination. We have exploited the pro-aggregatory effects of SRG on VWF dependent platelet aggregation and developed the shear gradient-sensitive scFv-A1 antibody that inhibits platelet aggregation exclusively at sites of SRG. The lack of VWF inhibition in non-stenosed vessel segments places scFV-A1 in an entirely new class of anti-platelet therapy for selective blockade of pathological thrombus formation while maintaining normal hemostasis.
Blood Pressure Lowering Decreases Intracerebral Hemorrhage Volume and Improves Behavioral Outcomes in Experimental Animals

Arterial blood pressure is often elevated in the acute phase of intracerebral hemorrhage (ICH). It is a predictor of a poor prognosis. The Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial II (INTERACT II) study revealed a strong tendency towards improved outcomes in ICH patients subjected to intensive blood pressure lowering, while the Antihypertensive Treatment of Acute Cerebral Hemorrhage Trial II (ATACH II) trial reported worse outcomes. So far, the pathophysiologic consequences of intensive blood pressure lowering in acute ICH are scarcely understood. Here we describe an experimental model with translational reference to the INTERACT II and ATACH II trials. Our study allows for rapid blood pressure lowering 30 minutes after ICH induction in rats. We aimed at assessing hematoma volume and functional outcome and evaluated histological and magnetic resonance imaging (MRI) parameters, including edema formation and blood-brain barrier dysfunction. For this study 84 spontaneously hypertensive rats (SHR) were used. A detailed methodical description can be found in Supplementary methods. In brief, striatal ICH was induced by stereotactic collagenase injection. SHR were then randomized into an interventional group (intensive blood pressure lowering by nifedipine orally to 126.0±8.8 mm Hg systolic) and a control group (saline orally; 186.0±9.8 mm Hg systolic) (Supplementary Figure 1). Hematoma volume as the primary endpoint was quantified photometrically 24 hours after ICH induction (end of main hematoma expansion phase). Neurological deficits were evaluated before sacrifice by a blinded rater using the modified Neurological Severity Score (mNSS). Additional histopathological analysis evaluated edema formation and blood brain barrier dysfunction at 24 and 72 hours after ICH induction (Supplementary Table 1). Ordinal histoscores were calculated using a semi-quantitative assessment (Supplementary methods 1). Intensive blood pressure lowering reduced hematoma volume 24 hours after ICH induction (nifedipine group 88.6±36.6 μL vs. control group 146.3±58.7 μL, P=0.023, n=9) (Figure 1A). This implicated a decrease in hematoma growth within the first 24 hours by nifedipine. Neurological deficits were significantly reduced 24 hours after ICH induction in the interventional group as compared to controls (median, 7 [interquartile range, IQR, 5.5 to 11] vs. 13 [IQR, 9.5 to 18]; P=0.011, n=9) (Figure 1B). Histopathological analyses revealed no differences in edema formation at 24 hours (histoscore: nifedipine median, 2 [IQR, 2 to 3] vs. control 3 [IQR, 2 to 3]; P=0.99, n=5) and 72 hours Blood Pressure Lowering Decreases Intracerebral Hemorrhage Volume and Improves Behavioral Outcomes in Experimental Animals
Prostate cancer detection rate and Gleason score in relation to prostate volume as assessed by magnetic resonance imaging cognitive biopsy and standard biopsy.

OBJECTIVE This study aimed to assess the relationship of the prostate cancer and Gleason scores (GSs) or ISUP Grade system with prostate volume (PV) as assessed by magnetic resonance imaging (MRI) cognitive biopsy and standard biopsy. MATERIAL AND METHODS Data were collected from 659 patients who underwent MRI cognitive biopsy and standard biopsy from January 2014 to January 2018. The biopsies were performed because of increased prostate-specific antigen (PSA) levels (>4 ng/mL) and/or abnormal digital rectal examination findings. Transrectal ultrasound was used to measure PV. RESULTS Prostate cancer detection rates in patients with increased PVs of ≤40 cc and >40 cc were 68.8% and 51.6% (p<0.001), respectively. ISUP Grade group ≥2 (Gleason score ≥3+4) detection rates for increased PVs of ≤40 cc and >40 cc were 68% and 73%, and 22.3% and 37.8%, respectively, for those with ISUP Grade group ≥4 (Gleason score ≥8) (p=0.003). Among the patients with PV>40 cc, univariate logistic regression showed a significant relationship between ISUP Grade group ≥2 and PSA, free/total PSA, PSA density, and MRI (p<0.05). On multivariable logistic regression, MRI (p=0.014) and PSA (p=0.039) predicted ISUP Grade group ≥2 in patients with PV>40 cc. CONCLUSION Although the detection rates of prostate cancer decreased as PV increased, the detection of prostate cancer aggressiveness increased as PV increased. This increase in high ISUP Grade lesions with the rise in PV is due to the use of MRI during prostate biopsy with standard biopsy.
Relationship between Vitamin B12 and Cobalt Metabolism in Domestic Ruminant: An Update

Simple Summary We review the role of cobalt and vitamin B12 in animals, especially in ruminants. Vitamin B12 is an essential part of the enzyme systems involved in multiple metabolic reactions and mainly in the formation of energy from ruminal fermentation. Signs of deficiency, as well as cobalt toxicity, in animals are described. The level of cobalt in ruminants can be assessed by measuring the blood or tissue concentrations of cobalt or vitamin B12, as well as the level of some metabolites such as malonate, homocysteine or transobolamine in blood or methylmalonic acid in urine. The requirement for cobalt (Co) is around 0.11 ppm (mg/kg) dry matter (DM) in the diet, although current recommendations advise supplementing the diet up to 0.20 mg Co/kg DM, which seems to increase animal production, especially in dairy cattle. Abstract Cobalt, as a trace element, is essential for rumen microorganisms for the formation of vitamin B12. In the metabolism of mammals, vitamin B12 is an essential part of two enzymatic systems involved in multiple metabolic reactions, such as in the metabolism of carbohydrates, lipids, some amino acids and DNA. Adenosylcobalamin and methylcobalamin are coenzymes of methylmalonyl coenzyme A (CoA) mutase and methionine synthetase and are essential for obtaining energy through ruminal metabolism. Signs of cobalt deficiency range from hyporexia, reduced growth and weight loss to liver steatosis, anemia, impaired immune function, impaired reproductive function and even death. Cobalt status in ruminant animals can be assessed by direct measurement of blood or tissue concentrations of cobalt or vitamin B12, as well as the level of methylmalonic acid, homocysteine or transcobalamin in blood; methylmalonic acid in urine; some variables hematological; food consumption or growth of animals. In general, it is assumed that the requirement for cobalt (Co) is expressed around 0.11 ppm (mg/kg) in the dry matter (DM) diet; current recommendations seem to advise increasing Co supplementation and placing it around 0.20 mg Co/kg DM. Although there is no unanimous criterion about milk production, fattening or reproductive rates in response to increased supplementation with Co, in some investigations, when the total Co of the diet was approximately 1 to 1.3 ppm (mg/kg), maximum responses were observed in the milk production.
Novel Molecular Markers in Glioblastoma—Benefits of Liquid Biopsy

Glioblastoma is a primary Central Nervous System (CNS) malignancy with poor survival. Treatment options are scarce and despite the extremely heterogeneous nature of the disease, clinicians lack prognostic and predictive markers to characterize patients with different outcomes. Certain immunohistochemistry, FISH, or PCR-based molecular markers, including isocitrate dehydrogenase1/2 (IDH1/2) mutations, epidermal growth factor receptor variant III (EGFRvIII) mutation, vascular endothelial growth factor overexpression (VEGF) overexpression, or (O6-Methylguanine-DNA methyltransferase promoter) MGMT promoter methylation status, are well-described; however, their clinical usefulness and accuracy is limited, and tumor tissue samples are always necessary. Liquid biopsy is a developing field of diagnostics and patient follow up in multiple types of cancer. Fragments of circulating nucleic acids are collected in various forms from different bodily fluids, including serum, urine, or cerebrospinal fluid in order to measure the quality and quantity of these markers. Multiple types of nucleic acids can be analyzed using liquid biopsy. Circulating cell-free DNA, mitochondrial DNA, or the more stable long and small non-coding RNAs, circular RNAs, or microRNAs can be identified and measured by novel PCR and next-generation sequencing-based methods. These markers can be used to detect the previously described alterations in a minimally invasive method. These markers can be used to differentiate patients with poor or better prognosis, or to identify patients who do not respond to therapy. Liquid biopsy can be used to detect recurrent disease, often earlier than using imaging modalities. Liquid biopsy is a rapidly developing field, and similarly to other types of cancer, measuring circulating tumor-derived nucleic acids from biological fluid samples could be the future of differential diagnostics, patient stratification, and follow up in the future in glioblastoma as well.
The application of artificial neural networks in modeling and predicting the effects of melatonin on morphological responses of citrus to drought stress

Drought stress as one of the most devastating abiotic stresses affects agricultural and horticultural productivity in many parts of the world. The application of melatonin can be considered as a promising approach for alleviating the negative impact of drought stress. Modeling of morphological responses to drought stress can be helpful to predict the optimal condition for improving plant productivity. The objective of the current study is modeling and predicting morphological responses (leaf length, number of leaves/plants, crown diameter, plant height, and internode length) of citrus to drought stress, based on four input variables including melatonin concentrations, days after applying treatments, citrus species, and level of drought stress, using different Artificial Neural Networks (ANNs) including Generalized Regression Neural Network (GRNN), Radial basis function (RBF), and Multilayer Perceptron (MLP). The results indicated a higher accuracy of GRNN as compared to RBF and MLP. The great accordance between the experimental and predicted data of morphological responses for both training and testing processes support the excellent efficiency of developed GRNN models. Also, GRNN was connected to Non-dominated Sorting Genetic Algorithm-II (NSGA-II) to optimize input variables for obtaining the best morphological responses. Generally, the validation experiment showed that ANN-NSGA-II can be considered as a promising and reliable computational tool for studying and predicting plant morphological and physiological responses to drought stress.
Impacts of the COVID-19 Pandemic on Food Security and Diet-Related Lifestyle Behaviors: An Analytical Study of Google Trends-Based Query Volumes

The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 disease (COVID)-19 is having profound effects on the global economy and food trade. Limited data are available on how this pandemic is affecting our dietary and lifestyle-related behaviors at the global level. Google Trends was used to obtain worldwide relative search volumes (RSVs) covering a timeframe from before the COVID-19 pandemic 1 June 2019 to 27 April 2020. Spearman’s rank-order correlation coefficients were used to measure relationships between daily confirmed cases and aforementioned RSVs between 31 December 2019 and 15 April 2020. RSV curves showed increased interest in multiple keywords related to dietary and lifestyle behaviors during the COVID-19 lockdown period in March and April 2020. Spearman’s correlation analysis showed that the strongest variables in each keyword category were (1) food security (food shortage: r = 0.749, food bank: r = 0.660, and free food: r = 0.555; all p < 0.001), (2) dietary behaviors (delivery: r = 0.780, restaurant: r = −0.731, take-away: r = 0.731, and food-delivery: r = 0.693; all p < 0.001), (3) outdoor-related behaviors (resort: r = −0.922, hotel: r = −0.913, cinema: r = −0.844, park: r = −0.827, fitness: r = −0.817, gym: r = −0.811; plant: r = 0.749, sunbathing: r = 0.668, and online: r = 0.670; all p < 0.001), and (4) immune-related nutrients/herbs/foods (vitamin C: r = 0.802, vitamin A: r = 0.780, zinc: r = 0.781, immune: r = 0.739, vitamin E: r = 0.707, garlic: r = 0.667, omega-3 fatty acid: r = −0.633, vitamin D: r = 0.549, and turmeric: r = 0.545; all p < 0.001). Restricted movement has affected peoples’ dietary and lifestyle behaviors as people tend to search for immune-boosting nutrients/herbs and have replaced outdoor activities with sedentary indoor behaviors.
ARTSCAN III: A Randomized Phase III Study Comparing Chemoradiotherapy With Cisplatin Versus Cetuximab in Patients With Locoregionally Advanced Head and Neck Squamous Cell Cancer

PURPOSE We performed an open-label randomized controlled phase III study comparing treatment outcome and toxicity between radiotherapy (RT) with concomitant cisplatin versus concomitant cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC; stage III-IV according to the Union for International Cancer Control TNM classification, 7th edition). MATERIALS AND METHODS Eligible patients were randomly assigned 1:1 to receive either intravenous cetuximab 400 mg/m2 1 week before start of RT followed by 250 mg/m2/wk, or weekly intravenous cisplatin 40 mg/m2, during RT. RT was conventionally fractionated. Patients with T3-T4 tumors underwent a second random assignment 1:1 between standard RT dose 68.0 Gy to the primary tumor or dose escalation to 73.1 Gy. Primary end point was overall survival (OS) evaluated using adjusted Cox regression analysis. Secondary end points were locoregional control, local control with dose-escalated RT, pattern of failure, and adverse effects. RESULTS Study inclusion was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. At 3 years, OS was 88% (95% CI, 83% to 94%) and 78% (95% CI, 71% to 85%) in the cisplatin and cetuximab groups, respectively (adjusted hazard ratio, 1.63; 95% CI, 0.93 to 2.86; P = .086). The cumulative incidence of locoregional failures at 3 years was 23% (95% CI, 16% to 31%) compared with 9% (95% CI, 4% to 14%) in the cetuximab versus the cisplatin group (Gray’s test P = .0036). The cumulative incidence of distant failures did not differ between the treatment groups. Dose escalation in T3-T4 tumors did not increase local control. CONCLUSION Cetuximab is inferior to cisplatin regarding locoregional control for concomitant treatment with RT in patients with locoregionally advanced HNSCC. Additional studies are needed to identify possible subgroups that still may benefit from concomitant cetuximab treatment.
Oxidation of Dichloromethane over Au, Pt, and Pt-Au Containing Catalysts Supported on γ-Al2O3 and CeO2-Al2O3

Au, Pt, and Pt-Au catalysts supported on Al2O3 and CeO2-Al2O3 were studied in the oxidation of dichloromethane (DCM, CH2Cl2). High DCM oxidation activities and HCl selectivities were seen with all the catalysts. With the addition of Au, remarkably lower light-off temperatures were observed as they were reduced by 70 and 85 degrees with the Al2O3-supported and by 35 and 40 degrees with the CeO2-Al2O3-supported catalysts. Excellent HCl selectivities close to 100% were achieved with the Au/Al2O3 and Pt-Au/Al2O3 catalysts. The addition of ceria on alumina decreased the total acidity of these catalysts, resulting in lower performance. The 100-h stability test showed that the Pt-Au/Al2O3 catalyst was active and durable, but the selectivity towards the total oxidation products needs improvement. The results suggest that, with the Au-containing Al2O3-supported catalysts, DCM decomposition mainly occurs via direct DCM hydrolysis into formaldehyde and HCl followed by the oxidation of formaldehyde into CO and CO2.
Cancer resection rates, socioeconomic deprivation, and geographical access to surgery among urban, suburban, and rural populations across Canada

High-risk cancer resection surgeries are increasingly being performed at fewer, more specialised, and higher-volume institutions across Canada. The resulting increase in travel time for patients to obtain treatment may be exacerbated by socioeconomic barriers to access. Focussing on five high-risk surgery types (oesophageal, ovarian/fallopian, liver, lung, and pancreatic cancers), this study examines socioeconomic trends in age-adjusted resection rates and travel time to surgery location for urban, suburban, and rural populations across Canada, excluding Québec, from 2004 to 2012. Significant differences in age-adjusted resection rates were observed between urban (14.9 per 100 000 person-years [95% CI: 12.2, 17.6]), suburban (40.7 [40.1, 41.2]), and rural (32.7 [29.6, 35.9]) populations, with higher rates in suburban and rural areas throughout the study period for all cancer types. Resection rates did not differ between the highest (Q1) and lowest (Q5) socioeconomic strata (Q1: 13.3 [12.2, 14.4]; Q5: 12.0 [10.7, 13.4]), with significantly higher rates among middle-SES patients (Q2: 27.3 [25.6, 29.0]; Q3: 39.6 [37.4, 41.8]; Q4: 37.5 [35.3, 39.7]). Travel times to treatment were consistently higher among the most socioeconomically deprived patients, most notably in suburban and rural areas. The results suggest that the conventional inclusion of suburbs with urban areas in health research may obfuscate important trends for public health policy and programmes.
Medicinal plants and bioactive natural compounds as inhibitors of HMG‐CoA reductase: A literature review

Cardiovascular diseases (CVDs) are one of the most important causes for mortality worldwide. Elevated levels of total cholesterol, and particularly LDL‐cholesterol (LDL‐C) are the main risk factor for acute myocardial infarction (AMI) and ischemic heart disease. The risk of CVDs could be reduced by decreasing the elevated cholesterol levels. β‐hydroxy β‐methylglutaryl‐CoA reductase (HMGCoAR) is the primary and rate‐limiting enzyme in the cholesterol biosynthesis pathway. Recently, the crucial role of nutraceuticals in maintaining normal physiological function was established. Nutraceuticals play an important role in preventing several non‐communicable diseases such as obesity, CVDs, cancer, diabetes, and reducing hyperlipidemia. Although the effect of nutraceuticals and herbal medicine on CVDs and dyslipidemia was previously investigated thoroughly, the effect of these natural products on HMGCoAR as one of the important enzymes involved in CVDs etiopathogenesis has not yet been investigated. Therefore, the major aim of this paper was to review the effects of nutraceuticals and medicinal plants on HMGCoAR. Results indicate that different types of natural foods, isolated nutrients, herbal products, and dietary supplements as nutraceuticals decrease the expression and activity of HMGCoAR. This review shows that medicinal plants and nutraceuticals could be used to decrease HMGCoAR activity as accessible and convenient and economical natural compounds to prevent dyslipidemia and CVDs.
Neural Encoding and Decoding With Distributed Sentence Representations

Building computational models to account for the cortical representation of language plays an important role in understanding the human linguistic system. Recent progress in distributed semantic models (DSMs), especially transformer-based methods, has driven advances in many language understanding tasks, making DSM a promising methodology to probe brain language processing. DSMs have been shown to reliably explain cortical responses to word stimuli. However, characterizing the brain activities for sentence processing is much less exhaustively explored with DSMs, especially the deep neural network-based methods. What is the relationship between cortical sentence representations against DSMs? What linguistic features that a DSM catches better explain its correlation with the brain activities aroused by sentence stimuli? Could distributed sentence representations help to reveal the semantic selectivity of different brain areas? We address these questions through the lens of neural encoding and decoding, fueled by the latest developments in natural language representation learning. We begin by evaluating the ability of a wide range of 12 DSMs to predict and decipher the functional magnetic resonance imaging (fMRI) images from humans reading sentences. Most models deliver high accuracy in the left middle temporal gyrus (LMTG) and left occipital complex (LOC). Notably, encoders trained with transformer-based DSMs consistently outperform other unsupervised structured models and all the unstructured baselines. With probing and ablation tasks, we further find that differences in the performance of the DSMs in modeling brain activities can be at least partially explained by the granularity of their semantic representations. We also illustrate the DSM’s selectivity for concept categories and show that the topics are represented by spatially overlapping and distributed cortical patterns. Our results corroborate and extend previous findings in understanding the relation between DSMs and neural activation patterns and contribute to building solid brain–machine interfaces with deep neural network representations.