Miracle-dz/UniFAR-FTUs huggingface dataset:
Cutaneous Leishmaniasis of Lip and Role of Polymerase Chain Reaction: A Case Report

ABSTRACT The diagnosis of cutaneous leishmaniasis is mostly confirmed by the identification of parasite in a skin smear or biopsy. However, this method may not always be sensitive enough to detect the disease when parasitic load is low. Molecular test such as polymerase chain reactions can be useful in such circumstances. Here, we report a case of cutaneous leishmaniasis diagnosed by a polymerase chain reaction test when both smear and biopsy failed to confirm the diagnosis. A 17-years-old female from mountainous district of Nepal, presented with a crusted plaque over the upper lip for a duration of 6 months. Both skin smear and biopsy from the lesion failed to demonstrate Leishmania parasite but a polymerase chain reaction test was positive for Leishmania donovani. This case emphasizes on the importance of molecular testing such as polymerase chain reaction when commonly performed diagnostics test fails to support confirmation of clinical diagnosis.
Computer-Aided Diagnosis in Multiparametric MRI of the Prostate: An Open-Access Online Tool for Lesion Classification with High Accuracy

Computer-aided diagnosis (CADx) approaches could help to objectify reporting on prostate mpMRI, but their use in many cases is hampered due to common-built algorithms that are not publicly available. The aim of this study was to develop an open-access CADx algorithm with high accuracy for classification of suspicious lesions in mpMRI of the prostate. This retrospective study was approved by the local ethics commission, with waiver of informed consent. A total of 124 patients with 195 reported lesions were included. All patients received mpMRI of the prostate between 2014 and 2017, and transrectal ultrasound (TRUS)-guided and targeted biopsy within a time period of 30 days. Histopathology of the biopsy cores served as a standard of reference. Acquired imaging parameters included the size of the lesion, signal intensity (T2w images), diffusion restriction, prostate volume, and several dynamic parameters along with the clinical parameters patient age and serum PSA level. Inter-reader agreement of the imaging parameters was assessed by calculating intraclass correlation coefficients. The dataset was stratified into a train set and test set (156 and 39 lesions in 100 and 24 patients, respectively). Using the above parameters, a CADx based on an Extreme Gradient Boosting algorithm was developed on the train set, and tested on the test set. Performance optimization was focused on maximizing the area under the Receiver Operating Characteristic curve (ROCAUC). The algorithm was made publicly available on the internet. The CADx reached an ROCAUC of 0.908 during training, and 0.913 during testing (p = 0.93). Additionally, established rule-in and rule-out criteria allowed classifying 35.8% of the malignant and 49.4% of the benign lesions with error rates of <2%. All imaging parameters featured excellent inter-reader agreement. This study presents an open-access CADx for classification of suspicious lesions in mpMRI of the prostate with high accuracy. Applying the provided rule-in and rule-out criteria might facilitate to further stratify the management of patients at risk.
Tick-Borne Encephalitis Virus Adaptation in Different Host Environments and Existence of Quasispecies

A highly virulent strain (Hypr) of tick-borne encephalitis virus (TBEV) was serially subcultured in the mammalian porcine kidney stable (PS) and Ixodes ricinus tick (IRE/CTVM19) cell lines, producing three viral variants. These variants exhibited distinct plaque sizes and virulence in a mouse model. Comparing the full-genome sequences of all variants, several nucleotide changes were identified in different genomic regions. Furthermore, different sequential variants were revealed to co-exist within one sample as quasispecies. Interestingly, the above-mentioned nucleotide changes found within the whole genome sequences of the new variants were present alongside the nucleotide sequence of the parental strain, which was represented as a minority quasispecies. These observations further imply that TBEV exists as a heterogeneous population that contains virus variants pre-adapted to reproduction in different environments, probably enabling virus survival in ticks and mammals.
Large-Scale Analyses Provide No Evidence for Gene-Gene Interactions Influencing Type 2 Diabetes Risk

A growing number of genetic loci have been shown to influence individual predisposition to type 2 diabetes (T2D). Despite longstanding interest in understanding whether nonlinear interactions between these risk variants additionally influence T2D risk, the ability to detect significant gene-gene interaction (GGI) effects has been limited to date. To increase power to detect GGI effects, we combined recent advances in the fine-mapping of causal T2D risk variants with the increased sample size available within UK Biobank (375,736 unrelated European participants, including 16,430 with T2D). In addition to conventional single variant–based analysis, we used a complementary polygenic score–based approach, which included partitioned T2D risk scores that capture biological processes relevant to T2D pathophysiology. Nevertheless, we found no evidence in support of GGI effects influencing T2D risk. The current study was powered to detect interactions between common variants with odds ratios >1.2, so these findings place limits on the contribution of GGIs to the overall heritability of T2D.
Phylogenic, molecular and decay analysis of Phialophora species causing soft rot of wood

Soft rot decay of treated wood in ground contact and loss of service-life remains an important economic issue worldwide. This study determined the identity of unclassified Phialophora strains (204-1, 35-1, TS4M3, 25M3) isolated from wood in-service. Phylogenetic analysis clustered strains into a single clade homologous with Phialocephala dimorphospora. Sequencing of internal transcribed spacer (ITS) rDNA showed minor differences at single bases for strains 35-1 and 25M3. Compatibility occurred between TS4M3, 25M3 and 204-1 but not 35-1, Phialophora lagerbergii or Phialophora botulispora. Birch was more rapidly degraded than pine for all strains, with strain 35-1 least aggressive. Light microscopy showed Type I diffuse soft rot cavity formation reminiscent of P. dimorphospora. Growth rates at 15, 20 and 26°C were similar for TS4M3, 25M3 and 204-1 but always less for 35-1. Strains 35-1 and TS4M3 showed highest Cu-tolerance on CuSO4 and micronized copper incorporated into malt extract agar plates. Results indicate the Phialophora spp. A strains represent P. dimorphospora as suggested by strong homology and decay morphology, although considerable intra-variation exists.
A Monitoring System for Online Fault Detection and Classification in Photovoltaic Plants

Photovoltaic (PV) energy use has been increasing recently, mainly due to new policies all over the world to reduce the application of fossil fuels. PV system efficiency is highly dependent on environmental variables, besides being affected by several kinds of faults, which can lead to a severe energy loss throughout the operation of the system. In this sense, we present a Monitoring System (MS) to measure the electrical and environmental variables to produce instantaneous and historical data, allowing to estimate parameters that ar related to the plant efficiency. Additionally, using the same MS, we propose a recursive linear model to detect faults in the system, while using irradiance and temperature on the PV panel as input signals and power as output. The accuracy of the fault detection for a 5 kW power plant used in the test is 93.09%, considering 16 days and around 143 hours of faults in different conditions. Once a fault is detected by this model, a machine-learning-based method classifies each fault in the following cases: short-circuit, open-circuit, partial shadowing, and degradation. Using the same days and faults applied in the detection module, the accuracy of the classification stage is 95.44% for an Artificial Neural Network (ANN) model. By combining detection and classification, the overall accuracy is 92.64%. Such a result represents an original contribution of this work, since other related works do not present the integration of a fault detection and classification approach with an embedded PV plant monitoring system, allowing for the online identification and classification of different PV faults, besides real-time and historical monitoring of electrical and environmental parameters of the plant.
Quantification of Complete Ammonia Oxidizing (Comammox) Bacteria Clades and Strict Nitrite Oxidizers in Nitrospira Using Newly Designed Primers.

Complete ammonia oxidizing (comammox) bacteria play key roles in environmental nitrogen cycling and all belong to the genus Nitrospira, which was originally believed to include only strict nitrite-oxidizing bacteria (sNOB). Thus, differential estimation of sNOB abundance from comammox Nitrospira has become problematic since both contain nitrite oxidoreductase genes that serve as common targets for sNOB detection. Herein, we developed novel comammox Nitrospira clades A- and B-specific primer sets targeting the α-subunit of ammonia monooxygenase gene (amoA) and a sNOB-specific primer set targeting cyanase gene (cynS) for quantitative PCR (qPCR). The high coverage and specificity of these primers had been checked by metagenome and metatranscriptome datasets. Efficient and specific amplification with these primers were demonstrated using various environmental samples. Using the newly designed primers, we successfully estimated the abundances of comammox Nitrospira and sNOB in samples from two chloramination-treated drinking water systems and found that, in most samples, comammox Nitrospira clade A was the dominant Nitrospira, and also served as the primary ammonia oxidizer. Compared with other ammonia oxidizers, comammox Nitrospira took advantage in process water samples in these two drinking water systems. We also demonstrated sNOB can be readily misrepresented with the previous method, calculated by subtracting the comammox abundance from the total Nitrospira, especially when the comammox Nitrospira proportion is relatively high. The new primer sets were successfully applied for the quantification of comammox Nitrospira and sNOB, which may prove useful in understanding the roles of Nitrospira in nitrification in various ecosystems.Importance Nitrospira is a dominant nitrite-oxidizing bacteria in many artificial and natural environments. The discovery of complete ammonia oxidizers in Nitrospira prevents the use of previously identified primers targeting Nitrospira 16S rRNA gene or nitrite oxidoreductase (nxr) gene for differential determination of strict nitrite-oxidizing bacteria in Nitrospira (sNOB) and comammox Nitrospira We designed three novel primer sets that enabled quantification of comammox Nitrospira clades A and B and sNOB with high coverage, specificity, and accuracy in various environments. With designed primer sets, sNOB and comammox Nitrospira were differentially estimated in drinking water systems, and we found that comammox clade A was overcome sNOB and other ammonia oxidizers in process water samples. Accurate quantification of comammox Nitrospira and sNOB using the newly designed primers will provide essential information for evaluating the contribution of Nitrospira to nitrification in various ecosystems.
Biomedical Holistic Ontology for People with Rare Diseases

This research provides a biomedical ontology to adequately represent the information necessary to manage a person with a disease in the context of a specific patient. A bottom-up approach was used to build the ontology, best ontology practices described in the literature were followed and the minimum information to reference an external ontology term (MIREOT) methodology was used to add external terms of other ontologies when possible. Public data of rare diseases from rare associations were used to build the ontology. In addition, sentiment analysis was performed in the standardized data using the Python library Textblob. A new holistic ontology was built, which models 25 real scenarios of people with rare diseases. We conclude that a comprehensive profile of patients is needed in biomedical ontologies. The generated code is openly available, so this research is partially reproducible. Depending on the knowledge needed, several views of the ontology should be generated. Links to other ontologies should be used more often to model the knowledge more precisely and improve flexibility. The proposed holistic ontology has many benefits, such as a more standardized computation of sentiment analysis between attributes.
A Systematic Review of Inverse Agonism at Adrenoceptor Subtypes

As many, if not most, ligands at G protein-coupled receptor antagonists are inverse agonists, we systematically reviewed inverse agonism at the nine adrenoceptor subtypes. Except for β3-adrenoceptors, inverse agonism has been reported for each of the adrenoceptor subtypes, most often for β2-adrenoceptors, including endogenously expressed receptors in human tissues. As with other receptors, the detection and degree of inverse agonism depend on the cells and tissues under investigation, i.e., they are greatest when the model has a high intrinsic tone/constitutive activity for the response being studied. Accordingly, they may differ between parts of a tissue, for instance, atria vs. ventricles of the heart, and within a cell type, between cellular responses. The basal tone of endogenously expressed receptors is often low, leading to less consistent detection and a lesser extent of observed inverse agonism. Extent inverse agonism depends on specific molecular properties of a compound, but inverse agonism appears to be more common in certain chemical classes. While inverse agonism is a fascinating facet in attempts to mechanistically understand observed drug effects, we are skeptical whether an a priori definition of the extent of inverse agonism in the target product profile of a developmental candidate is a meaningful option in drug discovery and development.
Characterization of the Key Aroma Constituents in Fry Breads by Means of the Sensomics Concept

The key aroma constituents in the volatile fractions isolated FROM two differently processed fry breads by solvent-assisted flavor evaporation were characterized by an aroma extract dilution analysis (AEDA). Twenty-two compounds were identified with flavor dilution (FD) factor ranges of 2–516. Among them, 13 compounds (FD ≥ 16) were quantified by stable isotope dilution assays and analyzed by odor activity values (OAVs). Of these, 11 compounds had OAVs ≥ 1, and the highest concentrations were determined for δ-decalactone and 2,3-butanedione. Two recombination models of the fry breads showed similarity to the corresponding fry breads. Omission tests confirmed that aroma-active constituents, such as δ-decalactone (oily/peach), 2-acetyl-1-pyrroline (roasty/popcorn-like), 3-methylbutanal (malty), methional (baked potato-like), 2,3-butanedione (buttery), phenyl acetaldehyde (flowery), (E,E)-2,4-decadienal (deep-fried), butanoic acid, and 3-methylbutanoic acid, were the key aroma constituents of fry bread. In addition, 3-methoxy-4-vinylphenol (smoky) and 4-hydroxy-2,5-dimethyl-3(2H)-furanone were also identified as important aroma constituents of fry bread.
Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

This research demonstrates the use of fill density as an effective tool for controlling the drug release without changing the formulation composition. The merger of hot-melt extrusion (HME) with fused deposition modeling (FDM)-based 3-dimensional (3-D) printing processes over the last decade has directed pharmaceutical research towards the possibility of printing personalized medication. One key aspect of printing patient-specific dosage forms is controlling the release dynamics based on the patient’s needs. The purpose of this research was to understand the impact of fill density and interrelate it with the release of a poorly water-soluble, weakly acidic, active pharmaceutical ingredient (API) from a hydroxypropyl methylcellulose acetate succinate (HPMC-AS) matrix, both mathematically and experimentally. Amorphous solid dispersions (ASDs) of ibuprofen with three grades of AquaSolveTM HPMC-AS (HG, MG, and LG) were developed using an HME process and evaluated using solid-state characterization techniques. Differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), and polarized light microscopy (PLM) confirmed the amorphous state of the drug in both polymeric filaments and 3D printed tablets. The suitability of the manufactured filaments for FDM processes was investigated using texture analysis (TA) which showed robust mechanical properties of the developed filament compositions. Using FDM, tablets with different fill densities (20–80%) and identical dimensions were printed for each polymer. In vitro pH shift dissolution studies revealed that the fill density has a significant impact (F(11, 24) = 15,271.147, p < 0.0001) and a strong negative correlation (r > −0.99; p < 0.0001) with the release performance, where 20% infill demonstrated the fastest and most complete release, whereas 80% infill depicted a more controlled release. The results obtained from this research can be used to develop a robust formulation strategy to control the drug release from 3D printed dosage forms as a function of fill density.
Genetic Diversity of Historical and Modern Populations of Russian Cattle Breeds Revealed by Microsatellite Analysis

Analysis of ancient and historical DNA has great potential to trace the genetic diversity of local cattle populations during their centuries-long development. Forty-nine specimens representing five cattle breeds (Kholmogor, Yaroslavl, Great Russian, Novgorod, and Holland), dated from the end of the 19th century to the first half of the 20th century, were genotyped for nine polymorphic microsatellite loci. Using a multiple-tube approach, we determined the consensus genotypes of all samples/loci analysed. Amplification errors, including allelic drop-out (ADO) and false alleles (FA), occurred with an average frequency of 2.35% and 0.79%, respectively. A significant effect of allelic length on ADO rate (r2 = 0.620, p = 0.05) was shown. We did not observe significant differences in genetic diversity among historical samples and modern representatives of Kholmogor and Yaroslavl breeds. The unbiased expected heterozygosity values were 0.726–0.774 and 0.708–0.739; the allelic richness values were 2.716–2.893 and 2.661–2.758 for the historical and modern samples, respectively. Analyses of FST and Jost’s D genetic distances, and the results of STRUCTURE clustering, showed the maintenance of a part of historical components in the modern populations of Kholmogor and Yaroslavl cattle. Our study contributes to the conservation of biodiversity in the local Russian genetic resources of cattle.
Genetic structure of reintroduced Rio Grande wild turkeys in Kansas

We investigated genetic structure within and among wintering flocks of Rio Grande wild turkeys (Meleagris gallopavo intermedia) to assess the importance of local individual flocks to managing and conserving genetic diversity of the wild turkey. We documented genetic differences among 4 local flocks of female turkeys reintroduced in south-central Kansas. We estimated that ≥2% (P < 0.001) of the total genetic variation observed is partitioned among the 4 wintering flocks sampled. Analysis of a wintering flock sampled in 1991 and 1992 indicated no change in gene frequencies between years (P = 0.65). Spatial genetic differentiation of Rio Grande turkeys may be the result of breeding tactics and occurrence of family groups on wintering areas. In this study genetic variation appeared to be conserved within flocks of Rio Grande wild turkeys.
Antimicrobial Peptides of Salmonid Fish: From Form to Function

Antimicrobial peptides (AMPs) are small, usually cationic, and amphiphilic molecules that play a crucial role in molecular and cellular host defense against pathogens, tissue damage, and infection. AMPs are present in all metazoans and several have been discovered in teleosts. Some teleosts, such as salmonids, have undergone whole genome duplication events and retained a diverse AMP repertoire. Salmonid AMPs have also been shown to possess diverse and potent antibacterial, antiviral, and antiparasitic activity and are induced by a variety of factors, including dietary components and specific molecules also known as pathogen-associated molecular patterns (PAMPs), which may activate downstream signals to initiate transcription of AMP genes. Moreover, a multitude of cell lines have been established from various salmonid species, making it possible to study host-pathogen interactions in vitro, and several of these cell lines have been shown to express various AMPs. In this review, the structure, function, transcriptional regulation, and immunomodulatory role of salmonid AMPs are highlighted in health and disease. It is important to characterize and understand how salmonid AMPs function as this may lead to a better understanding of host-pathogen interactions with implications for aquaculture and medicine.
Nicorandil prevents the nephrotoxic effect of cyclosporine-A in albino rats through modulation of HIF-1α/VEGF /eNOS signaling.

Despite cyclosporine-A (CsA) is a widely used immunosuppressive drug; its nephrotoxic effect puts a limitation for chronic administration. Herein we tried to investigate its renal effect on endothelial dysfunction targeting the hypoxia-inducible factor (HIF-1α)/vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) pathway and the possible modulation by nicorandil. Eight groups of adult male Wistar rats were included; 1: control, 2: vehicle group (received oil), 3: glibebclamide 5mg/kg/day/orally was administered. 4: group received nicorandil 10mg/kg/day/orally. 5: group received cyclosporine 25mg/kg/day/orally. 6: combined cyclosporine and nicorandil, 7: glibenclamide was added to cyclosporine, and 8: group received both cyclosporine and nicorandil combined with glibenclamid. The treatment continued for 6 weeks. Combined nicorandil with cyclosporine improved renal function deterioration initiated by cyclosporine. Cyclosporine decreased the renal expression levels (P<0.001) of HIF-1α, eNOS, and VEGF inducing endothelial dysfunction and the triggered inflammation, and upregulated the pro-fibrotic marker transforming growth factor (TGF-β). Nicorandil fixed the disturbed HIF-1α/VEGF/eNOS signaling. Nicorandil corrected the renal functions confirmed by improved the histological glomerular tuft retraction that was obvious in the cyclosporine group, without significant influence by glibenclamid. Proper protection from CsA-induced nephrotoxicity was achieved by nicorandil. Nicorandil reversed the disturbed HIF-1α/VEGF/eNOS pathway created by cyclosporine.
Predation and interspecific competition in two Microtus voles

We studied predation and interspecific competition in two Microtus species (M. agrestis and M. epiroticus) using long term trapping and data on predator diet in western Finland. In the study area, Microtus densities fluctuated from ten to 100-fold and predator densities fluctuated more than ten-fold. M. epiroticus suffered more from predation than M. agrestis, probably because densities in M. epiroticus patches were higher than densities in M. agrestis patches making M. epiroticus more profitable prey for patch-searching predators. The proportion of M. epiroticus among all voles declined during the crash phase of the vole cycle, at least partly as a result of predation