Miracle-dz/UniFAR-FTUs huggingface dataset:
Generation of Highly Efficient Equine-Derived Antibodies for Post-Exposure Treatment of Ricin Intoxications by Vaccination with Monomerized Ricin

Ricin, a highly lethal toxin derived from the seeds of Ricinus communis (castor beans) is considered a potential biological threat agent due to its high availability, ease of production, and to the lack of any approved medical countermeasure against ricin exposures. To date, the use of neutralizing antibodies is the most promising post-exposure treatment for ricin intoxication. The aim of this work was to generate anti-ricin antitoxin that confers high level post-exposure protection against ricin challenge. Due to safety issues regarding the usage of ricin holotoxin as an antigen, we generated an inactivated toxin that would reduce health risks for both the immunizer and the immunized animal. To this end, a monomerized ricin antigen was constructed by reducing highly purified ricin to its monomeric constituents. Preliminary immunizing experiments in rabbits indicated that this monomerized antigen is as effective as the native toxin in terms of neutralizing antibody elicitation and protection of mice against lethal ricin challenges. Characterization of the monomerized antigen demonstrated that the irreversibly detached A and B subunits retain catalytic and lectin activity, respectively, implying that the monomerization process did not significantly affect their overall structure. Toxicity studies revealed that the monomerized ricin displayed a 250-fold decreased activity in a cell culture-based functionality test, while clinical signs were undetectable in mice injected with this antigen. Immunization of a horse with the monomerized toxin was highly effective in elicitation of high titers of neutralizing antibodies. Due to the increased potential of IgG-derived adverse events, anti-ricin F(ab’)2 antitoxin was produced. The F(ab’)2-based antitoxin conferred high protection to intranasally ricin-intoxicated mice; ~60% and ~34% survival, when administered 24 and 48 h post exposure to a lethal dose, respectively. In line with the enhanced protection, anti-inflammatory and anti-edematous effects were measured in the antitoxin treated mice, in comparison to mice that were intoxicated but not treated. Accordingly, this anti-ricin preparation is an excellent candidate for post exposure treatment of ricin intoxications.
Is the Montreal Cognitive Assessment (MoCA) screening superior to the Mini-Mental State Examination (MMSE) in the detection of mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) in the elderly?

ABSTRACTObjective:To compare the accuracy of Mini-Mental State Examination (MMSE) and of the Montreal Cognitive Assessment (MoCA) in tracking mild cognitive impairment (MCI) and Alzheimer's Disease (AD). METHOD A Systematic review of the PubMed, Bireme, Science Direct, Cochrane Library, and PsycInfo databases was conducted. Using inclusion and exclusion criteria and staring with 1,629 articles, 34 articles were selected. The quality of the selected research was evaluated through the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2). RESULT More than 80% of the articles showed MoCA to be superior to MMSE in discriminating between individuals with mild cognitive impairment and no cognitive impairment. The area under the curve varied from 0.71 to 0.99 for MoCA, and 0.43 to 0.94 for MMSE, when evaluating the ability to discriminate MCI in the cognitively healthy elderly individuals, and 0.87 to 0.99 and 0.67 to 0.99, respectively, when evaluating the detection of AD. The AUC mean value for MoCA was significantly larger compared to the MMSE in discriminating MCI from control [0.883 (CI 95% 0.855-0.912) vs MMSE 0.780 (CI 95% 0.740-0.820) p < 0.001]. CONCLUSION The screening tool MoCA is superior to MMSE in the identification of MCI, and both tests were found to be accurate in the detection of AD.
Comparative Assessment of Tungsten Toxicity in the Absence or Presence of Other Metals

Tungsten is a refractory metal that is used in a wide range of applications. It was initially perceived that tungsten was immobile in the environment, supporting tungsten as an alternative for lead and uranium in munition and military applications. Recent studies report movement and detection of tungsten in soil and potable water sources, increasing the risk of human exposure. In addition, experimental research studies observed adverse health effects associated with exposure to tungsten alloys, raising concerns on tungsten toxicity with questions surrounding the safety of exposure to tungsten alone or in mixtures with other metals. Tungsten is commonly used as an alloy with nickel and cobalt in many applications to adjust hardness and thermal and electrical conductivity. This review addresses the current state of knowledge in regard to the mechanisms of toxicity of tungsten in the absence or presence of other metals with a specific focus on mixtures containing nickel and cobalt, the most common components of tungsten alloy.
Clinical correlates of sluggish cognitive tempo in adolescents with autism spectrum disorder

Adolescents with autism spectrum disorder frequently experience social communication difficulties, executive functioning deficits, and anxiety and depressive symptoms, which are similar to the symptoms and correlates of sluggish cognitive tempo. Although sluggish cognitive tempo is related to, but distinct from, the inattentive and hyperactive-impulsive symptoms of attention-deficit/hyperactivity disorder that commonly co-occur with autism spectrum disorder, few studies have examined sluggish cognitive tempo in autism spectrum disorder. We examined whether sluggish cognitive tempo and attention-deficit/hyperactivity disorder were differentially associated with autism symptomatology, daily life executive functioning, and internalizing and externalizing symptoms in 51 adolescents (ages 13–18 years) with autism spectrum disorder without intellectual disability. Regression analyses controlling for age and IQ showed that sluggish cognitive tempo symptoms, but not attention-deficit/hyperactivity disorder symptoms, were associated with increased autism symptomatology and internalizing symptoms. Attention-deficit/hyperactivity disorder symptoms, but not sluggish cognitive tempo symptoms, were associated with increased externalizing behaviors and behavior regulation deficits. Both sluggish cognitive tempo and attention-deficit/hyperactivity disorder were independently associated with increased metacognitive deficits. This study provides preliminary evidence that sluggish cognitive tempo symptoms are elevated in autism spectrum disorder and associated with key clinical correlates, with implications for the assessment and treatment in adolescents with autism spectrum disorder.
Primary and Repeated Respiratory Viral Infections Among Infants in Rural Nepal

Abstract Background Respiratory viruses cause significant morbidity and death in infants; 99% of such deaths occur in resource-limited settings. Risk factors for initial and repeated respiratory viral infections in young infants in resource-limited settings have not been well described. Methods From 2011 to 2014, a birth cohort of infants in rural Nepal was enrolled and followed with weekly household-based active surveillance for respiratory symptoms until 6 months of age. Respiratory illness was defined as having any of the following: fever, cough, wheeze, difficulty breathing, and/or a draining ear. We tested nasal swabs of infants with respiratory illness for multiple respiratory viruses by using a reverse transcription polymerase chain reaction assay. The risk of primary and repeated infections with the same virus was evaluated using Poisson regression. Results Of 3528 infants, 1726 (49%) had a primary infection, and 419 (12%) had a repeated infection. The incidences of respiratory viral infection in infants were 1816 per 1000 person-years for primary infections and 1204 per 1000 person-years for repeated infection with the same virus. Exposure to other children and male sex were each associated with an increased risk for primary infection (risk ratios, 1.13 [95% confidence interval (CI), 1.06–1.20] and 1.14 [95% CI, 1.02–1.27], respectively), whereas higher maternal education was associated with a decreased risk for both primary and repeated infections (risk ratio, 0.96 [95% CI, 0.95–0.98]). The incidence of subsequent infection did not change when previous infection with the same or another respiratory virus occurred. Illness duration and severity were not significantly different in the infants between the first and second episodes for any respiratory virus tested. Conclusions In infants in rural Nepal, repeated respiratory virus infections were frequent, and we found no decrease in illness severity with repeated infections and no evidence of replacement with another virus. Vaccine strategies and public health interventions that provide durable protection in the first 6 months of life could decrease the burden of repeated infections by multiple respiratory viruses, particularly in low-resource countries.
Multiple object tracking and pupillometry reveal deficits in both selective and intensive attention in unilateral spatial neglect

ABSTRACT Introduction: Unilateral spatial neglect is typically associated with a spatial attention deficit, as neglect patients fail to respond to objects in their contralesional hemispace. However, growing evidence suggests that also nonspatial attention impairments (e.g., arousal) play a role and influences the recovery from this syndrome. Method: Nonspatial and spatial attentional functions were assessed in 13 right-hemisphere stroke patients with neglect, 13 right-hemisphere stroke patients without neglect, and 26 healthy control participants, by investigating pupillary responses and performance on a multiple object tracking task (MOT)—that is, a dynamic task of divided attention where cognitive load can be manipulated precisely. The task was alternately presented in the left and right hemispace to assess spatial attention functioning. Results: Results revealed smaller pupillary dilations in both patient groups than in controls, suggesting reduced attentional resources or arousal, and while patients without neglect and controls revealed significant effects of cognitive load on their pupillary responses, neglect patients did not. Both MOT and visual search (VS) tasks revealed spatial symptoms of neglect, while MOT performance measures additionally indicated reduced cognitive functioning in the ipsilateral hemispace. Moreover, the MOT task revealed severely reduced divided attention in neglect patients, as they only managed to track one target in the contralesional hemispace and occasionally two targets at the time in the ipsilesional hemispace. Conclusion: Our results suggest that a stroke may lead to reduced attentional resources. Furthermore, as neglect patients showed no indications in their pupillary responses that they were able to regulate the allocation of resources in accordance with the varying task demands, it appears they additionally had impaired mechanisms for adjusting arousal levels. Our findings suggest that neglect involves nonspatial as well as spatial attention impairments, as also ipsilesional performance was reduced in this group.
Characteristics of Indoor PM2.5 Concentration in Gers Using Coal Stoves in Ulaanbaatar, Mongolia

Coal combustion in ger areas is the main source of ambient air pollution in Ulaanbaatar (Mongolia). This study determined the characteristics of indoor PM2.5 concentrations in gers using coal stoves during winter. The study population consisted of 60 gers in the Chingeltei district of Ulaanbaatar. The indoor particle number concentration (PNC) in each ger was measured using a Dylos DC1700 particle counter for 24 h in January and February 2016. The PNC by Dylos was converted into the mass concentration using a calibration equation developed using a collocated real-time light scattering monitor adjusted by gravimetric measurement. The average 24 h PM2.5 concentration was 203.9 ± 195.1 μg/m3 in gers with traditional stoves (n = 29) and 257.5 ± 204.4 μg/m3 in those with improved stoves (n = 31). In the daily profile, concentrations were lower at night, increased in the early morning, and peaked up to noon. The temperature in gers was slightly higher than that recommended in winter. Many development-assistance programs have supported the installation of improved energy-efficient stoves. Better control measures are needed to improve the indoor air quality of gers.
Factors Affecting Trailer Thermal Environment Experienced by Market Pigs Transported in the US

Simple Summary Transport conditions can be a challenge for pigs being transported to market. In this study, 40 trips of commercial market pigs transported from the farms to an abattoir were monitored for thermal conditions including temperature and relative humidity in order to better understand thermal variability within the trailer during transport. Variation in thermal environment inside the pig transport trailer was used as an indicator of ventilation pattern during various weather conditions. During cold weather, the front top and bottom zones were warmer than in the rest of the trailer, indicating less ventilation toward the front of the trailer. Conditions were more uniform throughout the trailer for hot temperatures, indicating sufficient ventilation to limit temperature rise. Misting showed the potential to alleviate high temperatures, but resulted in higher THI conditions. No effect of boarding and bedding combination was observed for spatial distribution of trailer interior temperatures. Abstract Extreme weather conditions challenge pig thermoregulation during transport and are addressed by the National Pork Board (NPB) Transport Quality Assurance® (TQA) program that provides guidelines for trailer boarding, bedding, and misting. These guidelines are widely applied, yet very little is known about the microenvironment within the trailer. In this study, TQA guidelines (V4) were evaluated via extensive thermal environment measurements during transport in order to evaluate spatial variability and implications on ventilation pattern. Effects of trailer management strategies including bedding, boarding, and misting were examined and the trailer was monitored for interior temperature rise and THI responses within six separate zones. The trailer thermal environment was not uniformly distributed in the colder trips with the top front and bottom zones were the warmest, indicating these zones had the majority of outlet openings and experienced air with accumulated sensible and latent heat of the pigs. Relatively enhanced thermal environment uniformity was observed during hot trips, suggesting that ventilation patterns and ventilation rate were different for colder vs. warmer weather conditions. Misting applied prior to transport cooled interior air temperature, but also created high THI conditions in some cases. Neither boarding and bedding combinations in the TQA nor boarding position showed impacts on trailer interior temperature rise or spatial distribution of temperature inside the trailer.
Pretreatment of Lignocellulosic Materials as Substrates for Fermentation Processes

Lignocellulosic biomass is an abundant and renewable resource that potentially contains large amounts of energy. It is an interesting alternative for fossil fuels, allowing the production of biofuels and other organic compounds. In this paper, a review devoted to the processing of lignocellulosic materials as substrates for fermentation processes is presented. The review focuses on physical, chemical, physicochemical, enzymatic, and microbiologic methods of biomass pretreatment. In addition to the evaluation of the mentioned methods, the aim of the paper is to understand the possibilities of the biomass pretreatment and their influence on the efficiency of biofuels and organic compounds production. The effects of different pretreatment methods on the lignocellulosic biomass structure are described along with a discussion of the benefits and drawbacks of each method, including the potential generation of inhibitory compounds for enzymatic hydrolysis, the effect on cellulose digestibility, the generation of compounds that are toxic for the environment, and energy and economic demand. The results of the investigations imply that only the stepwise pretreatment procedure may ensure effective fermentation of the lignocellulosic biomass. Pretreatment step is still a challenge for obtaining cost-effective and competitive technology for large-scale conversion of lignocellulosic biomass into fermentable sugars with low inhibitory concentration.
Polyamidoamine Nanoparticles for the Oral Administration of Antimalarial Drugs

Current strategies for the mass administration of antimalarial drugs demand oral formulations to target the asexual Plasmodium stages in the peripheral bloodstream, whereas recommendations for future interventions stress the importance of also targeting the transmission stages of the parasite as it passes between humans and mosquitoes. Orally administered polyamidoamine (PAA) nanoparticles conjugated to chloroquine reached the blood circulation and cured Plasmodium yoelii-infected mice, slightly improving the activity of the free drug and inducing in the animals immunity against malaria. Liquid chromatography with tandem mass spectrometry analysis of affinity chromatography-purified PAA ligands suggested a high adhesiveness of PAAs to Plasmodium falciparum proteins, which might be the mechanism responsible for the preferential binding of PAAs to Plasmodium-infected erythrocytes vs. non-infected red blood cells. The weak antimalarial activity of some PAAs was found to operate through inhibition of parasite invasion, whereas the observed polymer intake by macrophages indicated a potential of PAAs for the treatment of certain coinfections such as Plasmodium and Leishmania. When fluorescein-labeled PAAs were fed to females of the malaria mosquito vectors Anopheles atroparvus and Anopheles gambiae, persistent fluorescence was observed in the midgut and in other insect’s tissues. These results present PAAs as a versatile platform for the encapsulation of orally administered antimalarial drugs and for direct administration of antimalarials to mosquitoes, targeting mosquito stages of Plasmodium.
Synthesis and In Vitro Antitumor Activity of Novel Bivalent β-Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target

A series of novel bivalent β-carboline derivatives were designed and synthesized, and in vitro cytotoxicity, cell apoptosis, and DNA-binding affinity were evaluated. The cytotoxic results demonstrated that most bivalent β-carboline derivatives exhibited stronger cytotoxicity than the corresponding monomer against the five selected tumor cell lines (A549, SGC-7901, Hela, SMMC-7721, and MCF-7), indicating that the dimerization at the C3 position could enhance the antitumor activity of β-carbolines. Among the derivatives tested, 4B, 6i, 4D, and 6u displayed considerable cytotoxicity against A549 cell line. Furthermore, 4B, 6i, 4D, and 6u induced cell apoptosis in a dose-dependent manner, and caused cell cycle arrest at the S and G2/M phases. Moreover, the levels of cytochrome C in mitochondria, and the expressions of bcl-2 protein, decreased after treatment with β-carbolines, which indicated that 6i and 6u could induce mitochondria-mediated apoptosis. In addition, the results of UV-visible spectral, thermal denaturation, and molecular docking studies revealed that 4B, 6i, 4D, and 6u could bind to DNA mainly by intercalation.
Sonographic Volumetric Assessment Is a More Accurate Measure Than Maximum Diameter Alone in Papillary Thyroid Cancer

Abstract Background Tumor size is an important prognostic factor in papillary thyroid cancer (PTC). Management guidelines, staging systems, and pathological definitions use maximum diameter (Dmax) as a surrogate marker of tumor size. However, PTC nodules are three-dimensional (3D) structures, with behavior reflective of tumor cell count, which is directly proportional to volume. We explored the relationship between sonographically determined Dmax, volume, and lymph node status (LNS) in a cohort of patients with PTC. Methods All patients treated for PTC between 2003 and 2015 in our institution who had sonographic 3D nodule measurements available were evaluated. We examined the relationship between diameter, volume, and LNS. Results A total of 159 nodules in 153 patients met the inclusion criteria. Mean nodule dimensions were 2.4 × 1.9 × 1.5 cm, giving “ideal” nodule dimensions of y × 0.78y × 0.62y, where y is the Dmax. Observed volumes differed from predicted nodule volumes by an average of 26.2%. For PTC ≤2 cm, the coefficient of variation was 26.7%. Dmax did not correlate with the presence of lymph node metastases (Pearson coefficient 0.08), whereas volume very weakly correlated with LNS (Pearson coefficient 0.22). However, both Dmax and volume correlated very strongly with the number of nodal metastases (Pearson coefficients 0.93 and 0.89, respectively). Conclusions PTC nodules demonstrated significant volume heterogeneity, rendering Dmax an inaccurate marker of true tumor size. Although there was little difference between Dmax and volume in predicting nodal status or nodal disease burden, we propose that a prospective, randomized trial might demonstrate a clear clinical advantage of 3D sonographic nodule measurement over Dmax alone.
The Remarkable Role of Similarity in Redundancy-based Program Repair

Recently, there have been original attempts to use the concept of "code similarity" in program repair, suggesting that similarity analysis has an important role in the repair process. However, there is no dedicated work to characterize and quantify the role of similarity in redundancy-based program repair, where the patch is composed from source code taken from somewhere else. This is where our paper makes a major contribution: we perform a deep and systematic analysis of the role of code similarity during the exploration of the repair search space. We define and set up a large-scale experiment based on four code similarity metrics that capture different similarities: character, token, semantic and structure similarity. Overall, we have computed 56 million similarity score over 15 million source code components. We show that with similarity analysis, at least 90% of search space can be ignored to find the correct patch. Code similarity is capable of ranking the correct repair ingredient first in 4 - 33 % of the considered cases.