Miracle-dz/UniFAR-FTUs huggingface dataset:
A U-shaped association between serum uric acid with all-cause mortality in normal-weight population

ABSTRACT Background It is uncertain how serum uric acid (SUA) associated with all-cause mortality among people with normal weight, hence was explored in this study. Methods We enrolled participants from 1999 to 2006 National Health and Nutrition Examination Survey (NHANES) that had mortality status through 31 December 2015. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality using Cox proportional hazard models, and propensity score analyses were performed. We also performed restricted cubic splines to demonstrate the nonlinear relationship, and used subgroup analysis to examine the effect modification. Results We enrolled 6169 participants (2905 men and 3264 women, mean age 42.3 ± 21.4 years) and 1060 (17.2%) cases of all-cause mortality occurred during the mean follow-up of 11.9 years. When using the lowest quartile of SUA as referent, the multivariable HRs for all-cause mortality increased in not parallel with the quartiles of SUA (HRs were 0.92 (95%CI: 0.68, 1.23), 1.10 (95%CI: 0.82, 1.47), and 1.08 (95%CI: 0.80, 1.45) from the second to the fourth quartiles, respectively. When treating SUA as continuous variable, the HRs for all-cause mortality were 1.07 (95%CI: 1.00, 1.15; P = 0.046), 1.03 (95%CI: 0.94, 1.12; P = 0.518) and 1.15 (95%CI: 1.01, 1.31; P = 0.032) in all population, male and female subjects, respectively. Elevated SUA was associated with all-cause mortality and the propensity scores analysis showed the similar results. Subgroup analysis showed SUA was an independent risk of all-cause mortality in female (HR1.17, 95%CI: 1.05, 1.31, P = 0.005), people aged <60 years (HR1.18, 95%CI: 1.03, 1.35, P = 0.018), non-diabetic population (HR1.10, 95%CI: 1.02, 1.18, P = 0.017) and people with eGFR<90 (HR1.10, 95%CI: 1.02, 1.19, P = 0.016). Smoothing spline plots suggested the optimal SUA for the lowest risk of all-cause mortality was approximately 4.7 mg/dl. Conclusion In normal-weight population, SUA was seemed to be a U-shaped relationship with all-cause mortality.
177Lu-DOTATATE Therapy of Advanced Pancreatic Neuroendocrine Tumors Heavily Pretreated with Chemotherapy: Analysis of Outcome, Safety, and Their Determinants

Objective: To retrospectively analyze toxicity, progression-free survival (PFS), overall survival (OS), and their determinants in patients with advanced pancreatic neuroendocrine tumors (PanNETs), previously pretreated with chemotherapy, undergoing peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. Methods: A total of 102 patients with advanced PanNETs, previously pretreated with one (67%) or several (33%) lines of chemotherapy, were included, of whom 90% had progressive disease and the majority (74.5%) had grade 2 tumors. 177Lu-DOTATATE, 7.4 GBq per cycle, was administered with 6- to 8-week intervals in 88% of patients utilizing a dosimetry-guided protocol until an absorbed dose of 23 Gy to the kidneys was reached. Results: A mean dose of 32 ± 10.9 GBq per patient was administered in 1–10 cycles starting a median of 36 months after PanNET diagnosis. The median follow-up was 34 months, the median PFS was 24 months, and the median OS was 42 months from start of PRRT. Independent risk factors for both progression and death were liver tumor burden >50%, more than one line of previous chemotherapy, and elevated alkaline phosphatase. Resection of the primary tumor was linked to longer survival. Bone marrow toxicity grade 3–4 occurred in 10.8%. One patient (1.0%) developed acute myeloid leukemia. Bone marrow toxicity was unrelated to type and length of previous chemotherapy, amount of administered activity, and absorbed dose to the bone marrow. Conclusion: 177Lu-DOTATATE therapy was feasible, highly effective, and safe in patients with advanced PanNETs heavily pretreated with chemotherapy. More than one line of chemotherapy was a therapy-related independent risk factor for shorter PFS and OS.
Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation

Key Points Question What outcomes are associated with combination therapy using oral anticoagulants (OAC) plus antiplatelet drugs in patients with newly diagnosed atrial fibrillation? Findings This cohort study of 24 436 patients with de novo atrial fibrillation found that, after adjusting for baseline characteristics and comedications, patients treated with OAC plus antiplatelet drugs had significantly higher incidence rates of stroke and any bleeding event than those receiving OAC alone. Use of OAC plus antiplatelet drugs was not associated with reduced risk of experiencing acute coronary syndromes. Meaning These findings suggest that patients with atrial fibrillation treated with OAC plus antiplatelet drugs may have significantly higher risk of stroke and bleeding compared with those receiving OAC alone.
Potential Role of Soluble Metal Impurities in the Acute Lung Inflammogenicity of Multi-Walled Carbon Nanotubes

Multi-walled carbon nanotubes (MWCNTs) have variable metal impurities, but little is known about the impact of soluble metal impurities on the toxicity of MWCNTs. Here, we evaluated the role of soluble metal impurities to the acute inflammogenic potential of MWCNTs, using five types of high purity MWCNTs (>95%). MWCNTs and their soluble fractions collected at 24 h after incubation in phosphate-buffered saline showed diverse metal impurities with variable concentrations. The fiber-free soluble fractions produced variable levels of reactive oxygen species (ROS), and the iron level was the key determinant for ROS production. The acute inflammation at 24 h after intratracheal instillation of MWCNTs to rats at 0.19, 0.63, and 1.91 mg MWCNT/kg body weight (bw) or fiber-free supernatants from MWCNT suspensions at 1.91 and 7.64 mg MWCNT/kg bw showed that the number of granulocytes, a marker for acute inflammation, was significantly increased with a good dose-dependency. The correlation study showed that neither the levels of iron nor the ROS generation potential of the soluble fractions showed any correlations with the inflammogenic potential. However, the total concentration of transition metals in the soluble fractions showed a good correlation with the acute lung inflammogenic potential. These results implied that metal impurities, especially transitional metals, can contribute to the acute inflammogenic potential of MWCNTs, although the major parameter for the toxicity of MWCNTs is size and shape.
Sodium channels implement a molecular leaky integrator that detects action potentials and regulates neuronal firing

Voltage-gated sodium channels play a critical role in cellular excitability, amplifying small membrane depolarizations into action potentials. Interactions with auxiliary subunits and other factors modify the intrinsic kinetic mechanism to result in new molecular and cellular functionality. We show here that sodium channels can implement a molecular leaky integrator, where the input signal is the membrane potential and the output is the occupancy of a long-term inactivated state. Through this mechanism, sodium channels effectively measure the frequency of action potentials and convert it into Na+ current availability. In turn, the Na+ current can control neuronal firing frequency in a negative feedback loop. Consequently, neurons become less sensitive to changes in excitatory input and maintain a lower firing rate. We present these ideas in the context of rat serotonergic raphe neurons, which fire spontaneously at low frequency and provide critical neuromodulation to many autonomous and cognitive brain functions.
Normative performance of older individuals on the Hopkins Verbal Learning Test-Revised (HVLT-R) according to ethno-racial group, gender, age and education level

Abstract Objective The Hopkins Verbal Learning Test-Revised (HVLT-R) provides a measure of verbal learning and memory. The aim of this study was to provide normative performance data on the HVLT-R for community-dwelling older individuals according to ethno-racial group, age, gender, and years of completed education, in Australia and the U.S. Method The ASPirin in Reducing Events in the Elderly (ASPREE) study recruited 19,114 generally healthy community dwelling individuals aged 70 years and over (65 years and over for U.S minorities), who were without a diagnosis of dementia and scored above 77 on the modified Mini-Mental State (3MS) examination. Included in the analysis presented here were 16,251 white Australians, and in the U.S. 1,082 white, 894 African American and 314 Hispanic/Latino individuals at baseline. Results Performance on each of the components of the HVLT-R (trials 1–3, total, learning, delayed recall, delayed recognition, percentage retention and recognition discrimination index [RDI]) differed by demographic variables. In country and ethno-racial stratified analyses, female gender, younger age and higher education were significantly associated with better total recall, delayed recall and RDI. Among white Australians these characteristics were also associated with better retention. Age, education and gender-specific reference values across ethno-racial categories were determined. Conclusions Ethno-racial, age, gender and education-stratified normative data from this large cohort of community-dwelling older individuals will serve as important reference standards in Australia and the U.S. to assess cognition in older individuals.
Understanding the human antibody repertoire

ABSTRACT The origins of the various elements in the human antibody repertoire have been and still are subject to considerable uncertainty. Uncertainty in respect of whether the various elements have always served a specific defense function or whether they were co-opted from other organismal roles to form a crude naïve repertoire that then became more complex as combinatorial mechanisms were added. Estimates of the current size of the human antibody naïve repertoire are also widely debated with numbers anywhere from 10 million members, based on experimentally derived numbers, to in excess of one thousand trillion members or more, based on the different sequences derived from theoretical combinatorial calculations. There are questions that are relevant at both ends of this number spectrum. At the lower bound it could be questioned whether this is an insufficient repertoire size to counter all the potential antigen-bearing pathogens. At the upper bound the question is rather simpler: How can any individual interrogate such an astronomical number of antibody-bearing B cells in a timeframe that is meaningful? This review evaluates the evolutionary aspects of the adaptive immune system, the calculations that lead to the large repertoire estimates, some of the experimental evidence pointing to a more restricted repertoire whose variation appears to derive from convergent ‘structure and specificity features’, and includes a theoretical model that seems to support it. Finally, a solution that may reconcile the size difference anomaly, which is still a hot subject of debate, is suggested.
Association of gout with CAD and effect of antigout therapy on CVD risk among gout patients

Hyperuricemia has been identified as an independent risk factor for coronary artery disease (CAD), with a dose–response association. In this study, we explored the causal association between gout and antigout medication and the risk of incidental CAD. We sampled data from the National Health Insurance Research Database and recruited 37,091 patients as the gout cohort, and 37,091 controls. Our primary endpoint was the diagnosis of CAD during follow-up. The overall study population was followed up until CAD diagnosis, withdrawal from the National Health Insurance program, or the end of the study. Cox proportional hazards regression models were used to examine the effect of gout on the risk of CAD, represented by the HR with the 95% CI. Patients with gout were at greater risk of CAD, compared with those without gout: HR=1.49 after adjusting for potential confounders. Non-steroidal anti-inflammatory drugs and prednisolone use was associated with a reduced risk of CAD: HR=0.63 and 0.50, respectively. Patients with gout, treated with antigout medication, exhibited a reduced risk of CAD compared with non-gout patients. Among patients with gout, those on antigout therapy had 32% lower risk compared with those not on antigout therapy: adjusted HR=0.68, 95% CI 0.63 to 0.73. Gout increases the risk of CAD, and the use of antigout medication reduces CAD risk. These results indicate that gout or hyperuricemia is a modifiable risk factor for CAD.
Crimean-Congo Hemorrhagic Fever Virus Endemicity in United Arab Emirates, 2019

We conducted a cross-sectional survey of Crimean-Congo hemorrhagic fever virus (CCHFV) in dromedary camels and attached ticks at 3 locations in the United Arab Emirates. Results revealed a high prevalence of CCHFV-reactive antibodies in camels and viral RNA in ticks and camel serum, suggesting the virus is endemic in this country.
Geomorphometric Methods for Burial Mound Recognition and Extraction from High-Resolution LiDAR DEMs

Archaeological topography identification from high-resolution DEMs (Digital Elevation Models) is a current method that is used with high success in archaeological prospecting of wide areas. I present a methodology through which burial mounds (tumuli) from LiDAR (Light Detection And Ranging) DEMS can be identified. This methodology uses geomorphometric and statistical methods to identify with high accuracy burial mound candidates. Peaks, defined as local elevation maxima are found as a first step. In the second step, local convexity watershed segments and their seeds are compared with positions of local peaks and the peaks that correspond or have in vicinity local convexity segments seeds are selected. The local convexity segments that correspond to these selected peaks are further fed to a Random Forest algorithm together with shape descriptors and descriptive statistics of geomorphometric variables in order to build a model for the classification. Multiple approaches to tune and select the proper training dataset, settings, and variables were tested. The validation of the model was performed on the full dataset where the training was performed and on an external dataset in order to test the usability of the method for other areas in a similar geomorphological and archaeological setting. The validation was performed against manually mapped, and field checked burial mounds from two neighbor study areas of 100 km2 each. The results show that by training the Random Forest on a dataset composed of between 75% and 100% of the segments corresponding to burial mounds and ten times more non-burial mounds segments selected using Latin hypercube sampling, 93% of the burial mound segments from the external dataset are identified. There are 42 false positive cases that need to be checked, and there are two burial mound segments missed. The method shows great promise to be used for burial mound detection on wider areas by delineating a certain number of tumuli mounds for model training.
Digital Commons @ Michigan Tech Digital Commons @ Michigan Tech Radiative absorption enhancements by black carbon controlled by Radiative absorption enhancements by black carbon controlled by particle-to-particle heterogeneity in composition particle-to-particle heterogeneity in composition

Black carbon (BC) absorbs solar radiation, leading to a strong but uncertain warming effect on climate. A key challenge in modeling and quantifying BC’s radiative effect on climate is pre- dicting enhancements in light absorption that result from internal mixing between BC and other aerosol components. Modeling and laboratory studies show that BC, when mixed with other aerosol components, absorbs more strongly than pure, uncoated BC; however, some ambient observations suggest more variable and weaker absorption enhancement. We show that the lower-than-expected enhancements in ambient measurements result from a combination of two factors. First, the often used spherical, concentric core-shell approximation generally overestimates the absorption by BC. Second, and more importantly, inadequate consideration of heterogeneity in particle-to-particle composition engenders substantial overestimation in absorption by the total particle population, with greater heterogeneity associated with larger model–measurement differences. We show that accounting for these two effects—variability in per-particle composition and deviations from the core-shell approximation— reconciles absorption enhancement predictions with laboratory and ﬁeld observations and resolves the apparent discrep- ancy. Furthermore, our consistent model framework provides a path forward for improving predictions of BC’s radiative effect on climate. Particle-Resolved
Maternal Consumption of a Low-Isoflavone Soy Protein Isolate Diet Accelerates Chemically Induced Hepatic Carcinogenesis in Male Rat Offspring

It has been reported that maternal nutrition determines the offspring’s susceptibility to chronic diseases including cancer. Here, we investigated the effects of maternal diets differing in protein source on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in adult rat offspring. Dams were fed a casein (CAS) diet or a low-isoflavone soy protein isolate (SPI) diet for two weeks before mating and throughout pregnancy and lactation. Offspring were weaned to and fed a chow diet throughout the study. From four weeks of age, hepatocellular carcinomas (HCC) were induced by intraperitoneal injection of DEN once a week for 14 weeks. The SPI/DEN group exhibited higher mortality rate, tumor multiplicity, and HCC incidence compared with the CAS/DEN group. Accordingly, altered cholesterol metabolism and increases in liver damage and angiogenesis were observed in the SPI/DEN group. The SPI/DEN group had a significant induction of the nuclear factor-κB-mediated anti-apoptotic pathway, as measured by increased phosphorylation of IκB kinase β, which may lead to the survival of precancerous hepatocytes. In conclusion, maternal consumption of a low-isoflavone soy protein isolate diet accelerated chemically induced hepatocarcinogenesis in male rat offspring in the present study, suggesting that maternal dietary protein source may be involved in DEN-induced hepatocarcinogenesis in adult offspring.
Short-Term Effect of the Inclusion of Silage Artichoke By-Products in Diets of Dairy Goats on Milk Quality

Simple Summary The use of artichoke by-products, both from the canning industry or from the stubble that remains in the field, provides a cheaper source of nutrients, suitable for ruminant feeding due to their ability to digest fibre-rich foods. The use of these by-products for animal feed is also a way to reduce waste caused by the canning industry and disposal costs, as well as the area and resources allocated to the production of food for livestock, contributing to the circular economy. Evaluating the effect of the inclusion of silage artichoke by-products (bracts and rest of crop plant) in dairy goat rations on the milk yield and composition, animal health status, mineral and lipid profile is an effective way to explore the suitability of these alternative feedstuffs for goat cattle. The use of artichoke bracts and whole plant silage in dairy goat diets does not lead to marked differences in the milk yield and quality or the animals’ health status. From a nutritional point of view for human health, slightly better mineral and lipid profiles are observed in milk from goats fed artichoke plant silage, due to its higher polyunsaturated fatty acids and conjugated linoleic acid contents. Abstract Artichoke by-products represent a high amount of waste whose removal entails several costs. Moreover, feed is the main cost in a farm. So, including these by-products in ruminant diets would lower feed costs. Two experiments were conducted to evaluate the effect of two levels of inclusion, 12.5% and 25.0%, of two silages of artichoke by-products (artichoke bracts, AB and artichoke plant, AP) in the diet of goats on the milk yield, composition and quality and on the metabolic profile of the animals. AB presented the lowest blood urea content and there were no differences in milk yield in the two experiments. However, with 25.0% of silage by-product in the diet, a higher fat content was observed in AB and of protein in AP, as well as this treatment showing a slightly higher Se content. Regarding the milk lipid profile, milk from 12.5% of AP treatment presented a higher PUFA content. In conclusion, the use of silage artichoke by-products in dairy goat diets does not jeopardise milk yield and quality and health status of animals and, from a nutritional point of view for human health, a slightly better mineral and lipid profile is observed in milk from AP treatments.
Single components of botanicals and nature-identical compounds as a non-antibiotic strategy to ameliorate health status and improve performance in poultry and pigs

Abstract In the current post-antibiotic era, botanicals represent one of the most employed nutritional strategies to sustain antibiotic-free and no-antibiotic-ever production. Botanicals can be classified either as plant extracts, meaning the direct products derived by extraction from the raw plant materials (essential oils (EO) and oleoresins (OR)), or as nature-identical compounds (NIC), such as the chemically synthesised counterparts of the pure bioactive compounds of EO/OR. In the literature, differences between the use of EO/OR or NIC are often unclear, so it is difficult to attribute certain effects to specific bioactive compounds. The aim of the present review was to provide an overview of the effects exerted by botanicals on the health status and growth performance of poultry and pigs, focusing attention on those studies where only NIC were employed or those where the composition of the EO/OR was defined. In particular, phenolic compounds (apigenin, quercetin, curcumin and resveratrol), organosulfur compounds (allicin), terpenes (eugenol, thymol, carvacrol, capsaicin and artemisinin) and aldehydes (cinnamaldehyde and vanillin) were considered. These molecules have different properties such as antimicrobial (including antibacterial, antifungal, antiviral and antiprotozoal), anti-inflammatory, antioxidant, immunomodulatory, as well as the improvement of intestinal morphology and integrity of the intestinal mucosa. The use of NIC allows us to properly combine pure compounds, according to the target to achieve. Thus, they represent a promising non-antibiotic tool to allow better intestinal health and a general health status, thereby leading to improved growth performance.