Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacologic Characterization of ALD403, a Potent Neutralizing Humanized Monoclonal Antibody Against the Calcitonin Gene-Related Peptide

ALD403 is a genetically engineered, humanized immunoglobulin G1 monoclonal antibody that inhibits the action of human calcitonin gene-related peptide (CGRP). Clinical trial data indicate that ALD403 is effective as a preventive therapy for migraine and has an acceptable safety profile. For preclinical characterization of ALD403, rabbit antibodies targeting α-CGRP were humanized and modified to eliminate fragment crystallizable (Fc) γ receptor (FcγR) and complement interactions. The ability of ALD403 to inhibit CGRP-induced cAMP production was assessed using a cAMP bioassay (Meso Scale Discovery). The IC50 for inhibition of cAMP release was 434 and 288 pM with the rabbit-human chimera antibody and the humanized ALD403, respectively. ALD403 inhibited α-CGRP binding with an IC50 of 4.7 × 10−11 and 1.2 × 10−10 M for the α-CGRP and AMY1 receptors, respectively. ALD403 did not induce antibody-dependent cellular cytotoxicity or complement-dependent cytotoxicity and did not stably interact with any of the FcγR mediating these functions, exhibiting only weak binding to FcγRI. ALD403 significantly lowered capsaicin-induced blood flow responses in rodents at all time points starting at 5 minutes postapplication in a dose-dependent manner. In conclusion, ALD403 is a potent functional ligand inhibitor of α-CGRP‒driven pharmacology. SIGNIFICANCE STATEMENT α-Calcitonin gene-related peptide blockade by ALD403 was assessed via radiolabeled ligand displacement, in vitro inhibition of cell signaling, and in vivo inhibition of capsaicin-induced vasodilation. Lack of engagement of fragment crystallizable–mediated immune-effector functions by ALD403 was shown.
Poly(lysine) Dendrimers Form Complexes with siRNA and Provide Its Efficient Uptake by Myeloid Cells: Model Studies for Therapeutic Nucleic Acid Delivery

The disruption of the cellular pathways of protein biosynthesis through the mechanism of RNA interference has been recognized as a tool of great diagnostic and therapeutic significance. However, in order to fully exploit the potential of this phenomenon, efficient and safe carriers capable of overcoming extra- and intracellular barriers and delivering siRNA to the target cells are needed. Recently, attention has focused on the possibility of the application of multifunctional nanoparticles, dendrimers, as potential delivery devices for siRNA. The aim of the present work was to evaluate the formation of dendriplexes using novel poly(lysine) dendrimers (containing lysine and arginine or histidine residues in their structure), and to verify the hypothesis that the use of these polymers may allow an efficient method of siRNA transfer into the cells in vitro to be obtained. The fluorescence polarization studies, as well as zeta potential and hydrodynamic diameter measurements were used to characterize the dendrimer:siRNA complexes. The cytotoxicity of dendrimers and dendriplexes was evaluated with the resazurin-based assay. Using the flow cytometry technique, the efficiency of siRNA transport to the myeloid cells was determined. This approach allowed us to determine the properties and optimal molar ratios of dendrimer:siRNA complexes, as well as to demonstrate that poly(lysine) dendrimers may serve as efficient carriers of genetic material, being much more effective than the commercially available transfection agent Lipofectamine 2000. This outcome provides the basis for further research on the application of poly(lysine) dendrimers as carriers for nucleic acids in the field of gene therapy.
Highlights from the Paediatric and Congenital Interventional Cardiology Early-Career Society (PICES) 2019 Activities

Corresponding author: Sebastian Góreczny MD, PhD, Department of Cardiology, Polish Mother’s Memorial Hospital, Research Institute, 281/289 Rzgowska St, 93-338 Lodz, Poland, phone: +48 42 271 14 78, fax: +48 42 271 14 70, e-mail: sebastiangoreczny@yahoo.pl Received: 4.03. 2020, accepted: 4.03. 2020. Highlights from the Paediatric and Congenital Interventional Cardiology Early-Career Society (PICES) 2019 Activities
Survival prediction model for non‐small cell lung cancer based on somatic mutations

The 5‐year survival rate of non‐small cell lung cancer (NSCLC) is only 15%. Screening some combined gene mutations could predict the survival of NSCLC patients and also provide new ideas for the diagnosis and treatment of NSCLC. The present study aimed to identify signature mutations for survival prediction of NSCLC.
EFFECT OF REDUCED pH ON SECRETION, STABILITY AND ACTIVITY OF LISTERIA MONOCYTOGENES LISTERIOLYSIN O

The effect of environmental parameters on secretion, stability and activity of Listeria monocytogenes listeriolysin O (LLO) was examined. Increasing the initial glucose concentration in proteose peptone medium resulted in reduced LLO activity and lower final pH. Yield of LLO was substantially increased when the medium was buffered with s-glycerophosphate. Extended storage of active LLO in growth medium adjusted to pH 5.3 resulted in loss of only 10% LLO activity; however, up to 90% activity was lost during storage atpH < 4.5. In contrast, LLO activity was maximal at pH between 4.0 and 5.5. When the initial pH of culture medium was adjusted to give a final pH after growth of 5.3, as little as 10% of the maximum LLO activity was obtained. The results suggest that the degree of acidity may control both secretion and stability of LLO.
A new chemical race of Monarda fistulosa (Labiatae)

A race, chemically distinct but morphologically similar to the widespread Monarda fistulosa L. var. menthaefolia (Graham) Fern. , has been found to share the same habitat with the normal form in and around the Spruce Woods Forest Reserve in Manitoba.The foliage of the mutant form contained 0.7 to 1.1% oil on a fresh weight basis. This was about twice the quantity steam-distilled from the normal form. The oil from the mutant was 72 to 93% geraniol, previously unreported in Monarda. The mutant and normal forms cross readily, indicating no genetic isolating barriers have been established.
Influence of substrate age and quality on species diversity of lichens and bryophytes on stumps

Abstract Stumps from the last felling constitute a large proportion of dead wood in young managed forests. Yet, the knowledge of the diversity of stump-inhabiting organisms is poor. We studied the importance of substrate age and quality to lichen and bryophyte diversity on the cut surface of stumps in south-central Sweden. In total, we found 53 lichens and 35 bryophytes on 449 Norway spruce stumps in a forest stand chronosequence of four age classes: 4–5, 8–9, 12–13 and 16–18 years old stands. The influence of substrate age and substrate quality on species diversity differed between lichens and bryophytes. Lichen species richness was higher for age classes 2–4 compared to age class 1, whereas bryophyte richness was higher in age classes 3–4 than in 1. Further, lichen richness increased with increasing stump height and the presence of surface structural components (chairs and levels), which together with decay also influenced lichen species composition. Conversely, increasing stump height and the presence of levels decreased bryophyte richness, which in turn increased with increasing decay, surface area and number of surrounding trees and shrubs. Only decay explained differences in bryophyte species composition. Stumps in this region seem more important to overall lichen diversity, because there were on average more lichen species per stump and we only found common bryophytes but several uncommon lichens. The different responses of lichens and bryophytes to age and substrate variables indicates, however, the importance of including several organism groups in species diversity studies of dead wood.
Multiyear Links between Water Chemistry, Algal Chlorophyll, Drought-Flood Regime, and Nutrient Enrichment in a Morphologically Complex Reservoir

This investigation targeted the largest morphologically complex reservoir (Soyang) in South Korea during 1992–2013. It is a prominent source of domestic water supply, irrigation, flood control, and hydroelectric power generation. Therefore, this investigation focused on regional- to global-scale applications. We revealed the empirical links between chlorophyll (Chl-a) and total nitrogen (TN) and total phosphorus (TP), the impact of the monsoon regime on nutrients, and flood and drought regime. Further, we investigated the trophic status dynamics, tendencies of water chemistry factors, and valuation of zonal water chemistry by the application of a modified multimetric water pollution index (WPI). The physicochemical indicators illustrated significant disparities among the Lacustrine (Lz), Transition (Tz), and Riverine (Rz) zones. The solid contents (TSS) displayed a significant increase in the lake zones in the order of Lz (4.58 ± 13.7 mg/L), Tz (6.16 ± 16.2 mg/L), and Rz (7.38 ± 18.9 mg/L). However, TP and allied chemical species revealed an inverse relationship with the TN:TP ambient ratios. Nevertheless, Chl-a displayed sharp interzonal fluctuations from the Lz (2.90 ± 3.29 µg/L) to Tz (4.61 ± 4.98 µg/L). The seasonal deviations, however, exposed divergent heterogeneities among the TSS, TN, TP, and Chl-a. The regression plot between the observed and predicted Chl-a in the Soyang reservoir displayed a very strong relationship (R2 = 0.997). The seasonal and interannual variations of trophic status displayed a higher impact of precipitation, particularly in the case of TP and Chl-a. The flood years indicated phosphorus limitations, while drought years alluded to the non-algal light limitations (biogenic turbidity). Water temperature (WT), dissolved oxygen (DO), biological oxygen demand (BOD), TSS, TP, and Chl-a displayed decreasing trends in the ambient water. In contrast, pH, chemical oxygen demand (COD), electrical conductivity (EC), and TN displayed increasing tendencies by the application Mann–Kendall trend analysis. The WPI outcomes designated Lz with excellent water quality while Tz an Rz indicated good water quality. It also indicated impending sedimentation tendencies in the Rz. In conclusion, our findings indicated fluctuating rainfall patterns (drought and flood conditions) that significantly impacted the Soyang reservoir water quality, flood and drought severity, and trophic status of the reservoir. This study highlights the requirements of further studies to substantiate the drought and flood dynamics and their impacts on nutrients and overall water quality status.
The Influence of Very Thick and Fast Mashing Conditions on Wort Composition

The mashing process is of highest technological relevance for all following processes of wort and beer production. However, it is time consuming and therefore cost intensive. The influence of important mashing parameters on wort composition was investigated in order to shorten the mashing process by applying the thickest mashes without a negative influence on wort composition. The thickest mash leads to lower energy and water consumption in the brewhouse. On the other hand, the shortest mashing scheme results in the highest throughput. Finally, fine milling, mashing-in above gelatinization temperature, decreased mashing-in pH of 5.2, very thick mash of 1:2.3 malt:water ratio, and a holding time of 30–40 min at 64°C followed by 15–20 min at 72°C guarantees a high extract yield, normal attenuation limit, sufficient FAN level, required buffering capacity, and a reduced fatty acid oxidation. Lowering the pH to 5.2 at mashing-in results in lower glucose levels but the sum of fermentable sugar is not influenced due to a higher level of maltotriose and similar maltose levels. However, not all yeast strains assimilate maltotriose well in industrial fermentations. A mash pH of 5.2, positive for beer flavor stability, may result in a somewhat lower alcohol potential.
Green Tea and Pomegranate Extract Administered During Critical Moments of the Production Cycle Improves Blood Antiradical Activity and Alters Cecal Microbial Ecology of Broiler Chickens

Simple Summary Since the European Union’s (EU) antibiotic ban in 2006, interest in natural feed additives has largely increased. Natural feed additives are used to prevent diseases and promote growth in chickens, supporting animal health and modulating the development of the gut microflora during stressful situations. In the present study, a bioactive compound from plants belonging to the class of phytobiotics was assessed for its effects on production performance, antiradical activity and gut microflora in broiler chickens. The obtained results show how the tested compound is able to exert beneficial effects on the antiradical activity and gut microbial ecology of birds, even though the chickens’ performance was unaffected. Abstract Phytobiotics are usually tested in feed and throughout the production cycle. However, it could be beneficial to evaluate their effects when administered only during critical moments, such as changes in feeding phases. The aim of the trial was to investigate the effect of a commercial plant extract (PE; IQV-10-P01, InQpharm Animal Health, Kuala Lumpur, Malaysia) on growth performance, blood antiradical activity and cecal microbiome when administered in drinking water to broiler chickens during the post-hatching phase and at each change of diet. In the experiment, 480 1-day-old male broiler chicks were assigned to two groups in a 50-day trial. Broilers received drinking water (C) or drinking water plus PE (T) at a rate of 2 mL/L on days 0 to 4, 10–11 and 20–21. PE did not affect performance and water intake, while total antiradical activity was improved (p < 0.05). A greater abundance of lactic acid bacteria (false discovery rate (FDR) < 0.05) was found in the T group and the result was confirmed at a lower taxonomic level with higher Lactobacillaceae abundance (FDR < 0.05). Our findings suggest that PE administration during critical moments of the production cycle of broiler chickens may exert beneficial effects at a systemic level and on gut microbial ecology.
Genetic Diversity and Sequence Polymorphism of Two Genes Encoding Theileria parva Antigens Recognized by CD8+ T Cells among Vaccinated and Unvaccinated Cattle in Malawi

East Coast fever (ECF) is an acute fatal tick-borne disease of cattle caused by Theileria parva. It causes major losses in exotic and crossbreed cattle, but this could be prevented by a vaccine of T. parva if the vaccine is selected properly based on information from molecular epidemiology studies. The Muguga cocktail (MC) vaccine (Muguga, Kiambu 5 and Serengeti-transformed strains) has been used on exotic and crossbreed cattle. A total of 254 T. parva samples from vaccinated and unvaccinated cattle were used to understand the genetic diversity of T. parva in Malawi using partial sequences of the Tp1 and Tp2 genes encoding T. parva CD8+ antigens, known to be immunodominant and current candidate antigens for a subunit vaccine. Single nucleotide polymorphisms were observed at 14 positions (3.65%) in Tp1 and 156 positions (33.12%) in Tp2, plus short deletions in Tp1, resulting in 6 and 10 amino acid variants in the Tp1 and Tp2 genes, respectively. Most sequences were either identical or similar to T. parva Muguga and Kiambu 5 strains. This may suggest the possible expansion of vaccine components into unvaccinated cattle, or that a very similar genotype already existed in Malawi. This study provides information that support the use of MC to control ECF in Malawi.
Abundance and distribution patterns if Owls in Pieniny National Park, Southern Poland

Species composition, abundance and distribution of owls Strigiformes in the Pieniny National Park were studied during the years 2001-2002. The research area covered 23.25 km. Seven owl species were recorded. A total of 30-38 territories (16-17 Tawny Owl territories, six Eagle Owl territories, four Long-eared Owl territories, 2-4 Tengmalm’s Owl territories, 2-3 Ural Owl territories, three Pygmy Owl territories and one Little Owl territory) were found, giving a density of 12.9-16.3 territories per 10 km. The numbers and density of species in the Pieniny National Park differ from those of other mountainous regions in Poland. The density of the Tawny Owl is significantly higher than other figures given for mountainous areas. The density recorded for the Eagle Owl is the highest in Poland and one of the highest known for this species. A low density is seen for the Ural Owl, indicating a density gradient in the Carpathian Mountains. The Little Owl found here are the only ones presently known in this part of the Polish Carpathians.
Adipose Tissue Modification through Feeding Strategies and Their Implication on Adipogenesis and Adipose Tissue Metabolism in Ruminants

Dietary recommendations by health authorities have been advising of the importance of diminishing saturated fatty acids (SFA) consumption and replacing them by polyunsaturated fatty acids (PUFA), particularly omega-3. Therefore, there have been efforts to enhance food fatty acid profiles, helping them to meet human nutritional recommendations. Ruminant meat is the major dietary conjugated linoleic acid (CLA) source, but it also contains SFA at relatively high proportions, deriving from ruminal biohydrogenation of PUFA. Additionally, lipid metabolism in ruminants may differ from other species. Recent research has aimed to modify the fatty acid profile of meat, and other animal products. This review summarizes dietary strategies based on the n-3 PUFA supplementation of ruminant diets and their effects on meat fatty acid composition. Additionally, the role of n-3 PUFA in adipose tissue (AT) development and in the expression of key genes involved in adipogenesis and lipid metabolism is discussed. It has been demonstrated that linseed supplementation leads to an increase in α-linolenic acid (ALA) and eicosapentaenoic acid (EPA), but not in docosahexaenoic acid (DHA), whilst fish oil and algae increase DHA content. Dietary PUFA can alter AT adiposity and modulate lipid metabolism genes expression, although further research is required to clarify the underlying mechanism.
A Multilevel Model Approach for Investigating Individual Accident Characteristics and Neighborhood Environment Characteristics Affecting Pedestrian-Vehicle Crashes

Walking is the most basic movement of humans and the most fundamental mode of transportation. To promote walking, it is necessary to create a safe environment for pedestrians. However, pedestrian-vehicle crashes still remain relatively high in South Korea. This study employs a multilevel model to examine the differences between the lower-level individual characteristics of pedestrian crashes and the upper-level neighborhood environmental characteristics in Seoul, South Korea. The main results of this study are as follows. The individual characteristics of pedestrian-vehicle crashes are better at explaining pedestrian injury severity than built environment characteristics at the neighborhood level. Older pedestrians and drivers suffer more severe pedestrian injuries. Larger vehicles such as trucks and vans are more likely to result in a high severity of pedestrian injuries. Pedestrian injuries increase during inclement weather and at night. The severity of pedestrian injuries is lower at intersections and crosswalks without traffic signals than at crosswalks and intersections with traffic signals. Finally, school zones and silver zones, which are representative policies for pedestrian safety in South Korea, fail to play a significant role in reducing the severity of pedestrian injuries. The results of this study can guide policymakers and planners when making decisions on how to build neighborhoods that are safer for pedestrians.
Optimisation of baking parameters of chapati with respect to vitamin B1 and B2 retention and quality

Summary Vitamin losses during processing of cereal grains and their food products play an important role in human vitamin intake. Therefore, experiments were conducted to optimise the baking parameters for chapati, a flat unleavened, hot-plate-baked product of Asian diet. In the experiments, whole-wheat flour (100% extraction rate) was used for the preparation of chapaties. Central composite rotatable design with three independent variables (thickness of dough sheet, time as well as temperature of baking) at five levels and nine dependent variables, i.e. vitamin B1 and B2 content, textural properties and overall acceptability scores, were used to conduct the experiments. The ranges for three independent variables were: thickness, 2.5–4.5 mm; time, 2.0–3.0 min; and temperature, 200–240 °C. Thickness of the dough sheet had a significant (P ≤ 0.05) positive effect on vitamin retention, while the temperature had greater negative effect as compared with the time of baking. Based on compromise optimisation, optimum conditions for baking of chapati, especially with respect to vitamin retention were: thickness of dough sheet 3.2 mm, time of baking 2.1 min and baking temperature 216.3 °C.
Withdrawal of inhaled corticosteroids in COPD: a European Respiratory Society guideline

Inhaled corticosteroids (ICS) combined with bronchodilators can reduce the frequency of exacerbations in some patients with chronic obstructive pulmonary disease (COPD). There is evidence, however, that ICS are frequently used in patients where their benefit has not been established. Therefore, there is a need for a personalised approach to the use of ICS in COPD and to consider withdrawal of ICS in patients without a clear indication. This document reports European Respiratory Society recommendations regarding ICS withdrawal in patients with COPD. Comprehensive evidence synthesis was performed to summarise all available evidence relevant to the question: should ICS be withdrawn in patients with COPD? The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence synthesis was discussed and recommendations formulated by a committee with expertise in COPD and guideline methodology. After considering the balance of desirable and undesirable consequences, quality of evidence, and feasibility and acceptability of interventions, the guideline panel made: 1) conditional recommendation for the withdrawal of ICS in patients with COPD without a history of frequent exacerbations, 2) strong recommendation not to withdraw ICS in patients with blood eosinophil counts ≥300 eosinophils·µL−1 and 3) strong recommendation to treat with one or two long-acting bronchodilators if ICS are withdrawn. A conditional recommendation indicates that there was uncertainty about the balance of desirable and undesirable consequences of the intervention, and that well-informed patients may make different choices regarding whether to have or not have the specific intervention. This ERS short guideline summarises the evidence and provides recommendations for ICS withdrawal in patients with COPD https://bit.ly/33R3M5w