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Background: Cutaneous leishmaniasis (CL) is a vector-borne parasitic diseases of public health importance that is prevalent in the West Bank but not in the Gaza Strip. The disease caused by parasitic protozoans from the genus Leishmania and it is transmitted by infected phlebotomine sand flies. The aim of our study is to investigate the eco-epidemiological parameters and spatiotemporal projections of CL in Palestine over a 30-years period from 1990 through 2020 and to explore future projections until 2060., Methodology/principal Findings: This long-term descriptive epidemiological study includes investigation of demographic characteristics of reported patients by the Palestinian Ministry of Health (PMoH). Moreover, we explored spatiotemporal distribution of CL including future projection based on climate change scenarios. The number of CL patients reported during this period was 5855 cases, and the average annual incidence rate (AAIR) was 18.5 cases/105 population. The male to female ratio was 1.25:1. Patients-age ranged from 2 months to 89 years (mean = 22.5, std 18.67, and the median was 18 years). More than 65% of the cases came from three governates in the West Bank; Jenin 29% (1617 cases), Jericho 25% (1403), and Tubas 12% (658) with no cases reported in the Gaza Strip. Seasonal occurrence of CL starts to increase in December and peaked during March and April of the following year. Current distribution of CL indicate that Jericho, Tubas, Jenin and Nablus have the most suitable climatic settings for the sandfly vectors. Future projections until 2060 suggest an increasing incidence from northwest of Jenin down to the southwest of Ramallah, disappearance of the foci in Jericho and Tubas throughout the Jordan Vally, and possible emergence of new foci in Gaza Strip., Conclusions/significance: The future projection of CL in Palestine until 2060 show a tendency of increasing incidence in the north western parts of the West Bank, disappearance from Jericho and Tubas throughout the Jordan Vally, and emergence of new CL endemic foci in the Gaza Strip. These results should be considered to implement effective control and surveillance systems to counteract spatial expansion of CL vectors., Competing Interests: The authors have declared that no competing interests exist.

Parkinson's disease (PD) is a disabling neurodegenerative disorder in which multiple cell types, including dopaminergic and cholinergic neurons, are affected. The mechanisms of neurodegeneration in PD are not fully understood, limiting the development of therapies directed at disease-relevant molecular targets. C. elegans is a genetically tractable model system that can be used to disentangle disease mechanisms in complex diseases such as PD. Such mechanisms can be studied combining high-throughput molecular profiling technologies such as transcriptomics and metabolomics. However, the integrative analysis of multi-omics data in order to unravel disease mechanisms is a challenging task without advanced bioinformatics training. Galaxy, a widely-used resource for enabling bioinformatics analysis by the broad scientific community, has poor representation of multi-omics integration pipelines. We present the integrative analysis of gene expression and metabolite levels of a C. elegans PD model using GAIT-GM, a new Galaxy tool for multi-omics data analysis. Using GAIT-GM, we discovered an association between branched-chain amino acid metabolism and cholinergic neurons in the C. elegans PD model. An independent follow-up experiment uncovered cholinergic neurodegeneration in the C. elegans model that is consistent with cholinergic cell loss observed in PD. GAIT-GM is an easy to use Galaxy-based tool for generating novel testable hypotheses of disease mechanisms involving gene-metabolite relationships., (© 2022. The Author(s).)

This study aims to establish a link between disturbances in the night sleep habitus, quality of sleep, and daytime sleepiness in adolescents with Internet addiction and different types of content consumed., Methods: This is a cross-sectional observational study of a school sample in three large cities in Central Siberia. 4615 schoolchildren of 12-18 years old were examined. The Russian-language versions of the Chen Internet Addiction Scale, the Game Addiction Scale for Adolescents, and the Social Media Disorder Scale were used to identify Internet addiction. Questions from the Pittsburgh Sleep Quality Index questionnaire were used to assess nighttime sleep. Daytime sleepiness was assessed using the Pediatric Daytime Sleepiness Scale questionnaire., Results: Adolescents with Internet addiction go to bed and wake up late; they are characterized by a decrease in the duration of nighttime sleep, an increase in sleep onset latency, and frequent nighttime awakenings, as well as more pronounced daytime sleepiness. Among the sleep parameters studied, the indicators of daytime sleepiness and night awakening scales have the highest effect size in Internet-addicted adolescents, regardless of the media consumed., Conclusion: Internet-addicted adolescents are characterized by significant disturbances in the quality of nighttime sleep and excessive daytime sleepiness, which requires appropriate psychological correction.

Background: Visceral leishmaniasis (VL) is re-emerging in Armenia since 1999 with 167 cases recorded until 2019. The objectives of this study were (i) to determine for the first time the genetic diversity and population structure of the causative agent of VL in Armenia; (ii) to compare these genotypes with those from most endemic regions worldwide; (iii) to monitor the diversity of vectors in Armenia; (iv) to predict the distribution of the vectors and VL in time and space by ecological niche modeling., Methodology/principal Findings: Human samples from different parts of Armenia previously identified by ITS-1-RFLP as L. infantum were studied by Multilocus Microsatellite Typing (MLMT). These data were combined with previously typed L. infantum strains from the main global endemic regions for population structure analysis. Within the 23 Armenian L. infantum strains 22 different genotypes were identified. The combined analysis revealed that all strains belong to the worldwide predominating MON1-population, however most closely related to a subpopulation from Southeastern Europe, Maghreb, Middle East and Central Asia. The three observed Armenian clusters grouped within this subpopulation with strains from Greece/Turkey, and from Central Asia, respectively. Ecological niche modeling based on VL cases and collected proven vectors (P. balcanicus, P. kandelakii) identified Yerevan and districts Lori, Tavush, Syunik, Armavir, Ararat bordering Georgia, Turkey, Iran and Azerbaijan as most suitable for the vectors and with the highest risk for VL transmission. Due to climate change the suitable habitat for VL transmission will expand in future all over Armenia., Conclusions: Genetic diversity and population structure of the causative agent of VL in Armenia were addressed for the first time. Further genotyping studies should be performed with samples from infected humans, animals and sand flies from all active foci including the neighboring countries to understand transmission cycles, re-emergence, spread, and epidemiology of VL in Armenia and the entire Transcaucasus enabling epidemiological monitoring., Competing Interests: The authors have declared that no competing interests exist.

Machine learning (ML) can aid in novel discoveries in the field of viral gene therapy. Specifically, big data gathered through next-generation sequencing (NGS) of complex capsid libraries is an especially prominent source of lost potential in data analysis and prediction. Furthermore, adeno-associated virus (AAV)-based capsid libraries are becoming increasingly popular as a tool to select candidates for gene therapy vectors. These higher complexity AAV capsid libraries have previously been created and selected in vivo ; however, in silico analysis using ML computer algorithms may augment smarter and more robust libraries for selection. In this study, data of AAV capsid libraries gathered before and after viral assembly are used to train ML algorithms. We found that two ML computer algorithms, artificial neural networks (ANNs), and support vector machines (SVMs), can be trained to predict whether unknown capsid variants may assemble into viable virus-like structures. Using the most accurate models constructed, hypothetical mutation patterns in library construction were simulated to suggest the importance of N495, G546, and I554 in AAV2-derived capsids. Finally, two comparative libraries were generated using ML-derived data to biologically validate these findings and demonstrate the predictive power of ML in vector design., Competing Interests: The authors declare no competing interests., (© 2020 The Authors.)

Background: Metabolomics has the promise to transform the area of personalized medicine with the rapid development of high throughput technology for untargeted analysis of metabolites. Open access, easy to use, analytic tools that are broadly accessible to the biological community need to be developed. While technology used in metabolomics varies, most metabolomics studies have a set of features identified. Galaxy is an open access platform that enables scientists at all levels to interact with big data. Galaxy promotes reproducibility by saving histories and enabling the sharing workflows among scientists., Results: SECIMTools (SouthEast Center for Integrated Metabolomics) is a set of Python applications that are available both as standalone tools and wrapped for use in Galaxy. The suite includes a comprehensive set of quality control metrics (retention time window evaluation and various peak evaluation tools), visualization techniques (hierarchical cluster heatmap, principal component analysis, modular modularity clustering), basic statistical analysis methods (partial least squares - discriminant analysis, analysis of variance, t-test, Kruskal-Wallis non-parametric test), advanced classification methods (random forest, support vector machines), and advanced variable selection tools (least absolute shrinkage and selection operator LASSO and Elastic Net)., Conclusions: SECIMTools leverages the Galaxy platform and enables integrated workflows for metabolomics data analysis made from building blocks designed for easy use and interpretability. Standard data formats and a set of utilities allow arbitrary linkages between tools to encourage novel workflow designs. The Galaxy framework enables future data integration for metabolomics studies with other omics data.

The major drawback of the Baculovirus/Sf9 system for recombinant adeno-associated viral (rAAV) manufacturing is that most of the Bac-derived rAAV vector serotypes, with few exceptions, demonstrate altered capsid compositions and lower biological potencies. Here, we describe a new insect cell-based production platform utilizing attenuated Kozak sequence and a leaky ribosome scanning to achieve a serotype-specific modulation of AAV capsid proteins stoichiometry. By way of example, rAAV5 and rAAV9 were produced and comprehensively characterized side by side with HEK293-derived vectors. A mass spectrometry analysis documented a 3-fold increase in both viral protein (VP)1 and VP2 capsid protein content compared with human cell-derived vectors. Furthermore, we conducted an extensive analysis of encapsidated single-stranded viral DNA using next-generation sequencing and show a 6-fold reduction in collaterally packaged contaminating DNA for rAAV5 produced in insect cells. Consequently, the re-designed rAAVs demonstrated significantly higher biological potencies, even in a comparison with HEK293-manufactured rAAVs mediating, in the case of rAAV5, 4-fold higher transduction of brain tissues in mice. Thus, the described system yields rAAV vectors of superior infectivity and higher genetic identity providing a scalable platform for good manufacturing practice (GMP)-grade vector production., (Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Cutaneous leishmaniasis (CL) is a major public health problem in Libya. In this paper, we describe the eco-epidemiological parameters of CL during the armed conflict period from January 2011 till December 2012. Current spatiotemporal distributions of CL cases were explored and projected to the future using a correlative modelling approach. In addition the present results were compared with our previous data obtained for the time period 1995-2008., Methodology/principal Findings: We investigated 312 CL patients who presented to the Dermatology Department at the Tripoli Central Hospital and came from 81 endemic areas distributed in 10 districts. The patients presented with typical localized lesions which appeared commonly on the face, arms and legs. Molecular identification of parasites by a PCR-RFLP approach targeting the ITS1 region of the rDNA was successful for 81 patients with two causative species identified: L. major and L. tropica comprised 59 (72.8%) and 22 (27.2%) cases, respectively. Around 77.3% of L. tropica CL and 57.7% of L. major CL caused single lesions. Five CL patients among our data set were seropositive for HIV. L. tropica was found mainly in three districts, Murqub (27.3%), Jabal al Gharbi (27.3%) and Misrata (13.7%) while L. major was found in two districts, in Jabal al Gharbi (61%) and Jafara (20.3%). Seasonal occurrence of CL cases showed that most cases (74.2%) admitted to the hospital between November and March, L. major cases from November till January (69.4%), and L. tropica cases mainly in January and February (41%). Two risk factors were identified for the two species; the presence of previously infected household members, and the presence of rodents and sandflies in patient's neighborhoods. Spatiotemporal projections using correlative distribution models based on current case data and climatic conditions showed that coastal regions have a higher level of risk due to more favourable conditions for the transmitting vectors., Conclusion: Future projection of CL until 2060 showed a trend of increasing incidence of CL in the north-western part of Libya, a spread along the coastal region and a possible emergence of new endemics in the north-eastern districts of Libya. These results should be considered for control programs to prevent the emergence of new endemic areas taking also into consideration changes in socio-economical factors such as migration, conflicts, urbanization, land use and access to health care.

Unlabelled: In sub-Saharan Africa, cryptococcal meningitis (CM) continues to be a predominant cause of AIDS-related mortality. Understanding virulence and improving clinical treatments remain important. To characterize the role of the fungal strain genotype in clinical disease, we analyzed 140 Cryptococcus isolates from 111 Ugandans with AIDS and CM. Isolates consisted of 107 nonredundant Cryptococcus neoformans var. grubii strains and 8 C. neoformans var. grubii/neoformans hybrid strains. Multilocus sequence typing (MLST) was used to characterize genotypes, yielding 15 sequence types and 4 clonal clusters. The largest clonal cluster consisted of 74 isolates. The results of Burst and phylogenetic analysis suggested that the C. neoformans var. grubii strains could be separated into three nonredundant evolutionary groups (Burst group 1 to group 3). Patient mortality was differentially associated with the different evolutionary groups (P = 0.04), with the highest mortality observed among Burst group 1, Burst group 2, and hybrid strains. Compared to Burst group 3 strains, Burst group 1 strains were associated with higher mortality (P = 0.02), exhibited increased capsule shedding (P = 0.02), and elicited a more pronounced Th(2) response during ex vivo cytokine release assays with strain-specific capsule stimulation (P = 0.02). The results of these analyses suggest that cryptococcal strain variation can be an important determinant of human immune responses and mortality., Importance: Cryptococcus neoformans is a common life-threatening human fungal pathogen that is responsible for an estimated 1 million cases of meningitis in HIV-infected patients annually. Virulence factors that are important in human disease have been identified, yet the impacts of the fungal strain genotype on virulence and outcomes of human infection remain poorly understood. Using an analysis of strain variation based on in vitro assays and clinical data from Ugandans living with AIDS and cryptococcal infection, we report that strain genotype predicts the type of immune response and mortality risk. These studies suggest that knowledge of the strain genotype during human infections could be used to predict disease outcomes and lead to improved treatment approaches aimed at targeting the specific combination of pathogen virulence and host response.

During examination of kidney function under cisplastin chemotherapy in oncologic patients the nephrotoxicity of the drug have been shown during 24 hours after administration. We found that in 24 hours after injection ofcisplastin in the dose 50 mg/m2 of the surface of the body, the excretion of creatinine, sodium, potassium, osmotic active compounds and chlorides is increased more than two times, indicating for disorder in osmolality, volume and ionic regulation of kidney function. The determined peculiarities are consequences of kidney injuries, which are confirmed by an increase in erythrocyte- and leucocyteuria. We showed that alterations in homeostatic kidney function is due to damage of renal tubules. Our study necessitates a need for renal protection during the whole period of cisplastin chemotherapy.

Purpose: The aim of this work was to study the combined effect of sodium and acetate ions on the radiation yield of 8-hydroxyguanine (8-OHG), one of the major DNA base lesions induced by free radicals., Materials and Methods: Aqueous solutions of DNA and 2'-deoxyguanosine 5'-monophosphate (dGMP) with various concentrations of sodium acetate and sodium perchlorate were γ-irradiated, enzymatically digested and analyzed by high-performance liquid chromatography (HPLC) methods., Results: It was found that both salts decrease the 8-OHG radiation yield in the concentration range studied for both DNA and dGMP, except in the case of dGMP wherein an increase in yield occurs in the concentration range from 0.1-1 mM. The dependence of the 8-hydroxy-2'-deoxyguanosine radiation yield on the concentration of both sodium acetate and sodium perchlorate have different shapes and have steeper slopes for the DNA compared with the dGMP solutions., Conclusions: The observed decrease in the radiation yield of 8-OHG with increasing concentrations of sodium acetate is consistent with the hypothesis that sodium acetate produces two concentration-dependent effects in the DNA solutions: (1) A conformational change in the DNA caused by Na(+) counterions; and (2) free radical reactions related to the radiolysis of acetate ion.

Unlabelled: Mucosa-associated lymphoid tissue (MALT) conception has been extensively developing for last 20 years., The Aim: The aim of this work was to elaborate clinico-morphological and immunohistochemical criteria of gastric MALT-lymphomas and to differentiate them from another with similar histology., Materials and Methods: Between 1983 and 2007, 704 patients with diagnosis of extranodal lymphoma were observed in Russian Cancer Research Center. The work included biopsy and postoperation samples from 115 patients with primary gastric lymphoma, who were observed in Russian Cancer Research Center since 1995. On presented material with primary lymphomas were elaborated morphological criteria of MALT-lymphoma diagnosis for gastrobiopsy, based on histological, immunohistochemical and genetic examination. Also were devised differential diagnostic criteria of MALT-lymphoma., Results: Follow morphological signs were estimated: cell composition, atypia of neoplastic elements, presence of plasmocellular differentiation of lymphoid cells, expression of plasmocytary infiltration, lymphoepithelial lesion and reactive lymphoid follicles with or without colonization, presence of blasts. So, in 35.2% cases part of neoplastic elements had the aspect of monocytoid B-lymphocytes. In the most of observations were revealed plasmatic cells. More often they were under integumentary epithelium as massive layer (46.47%), more rare they were scattered in superficial sections of lamina propria among cells of leukocyte row (39.43%). Lymphoepithelial lesions (LELs) are aggregates from three and more marginal zone cells, destroyed epithelium of glands, were revealed in half of cases. In 17.14% cases were ("blast") LELs, generated by large blasts. For reactive process T-lymphocytes predominate over B-lymhpocytes in the lymphocellular infiltrate, or T-lymphocytes and B-lymhpocytes are in equal ratio. The next important sign is coexpression T-cell marker CD43 on neoplastic B-cells. Cases of MALT-lymphoma with t(11; 18) are resistant to the antihelicobacter therapy., Conclusion: The most informative morphological, immunohistochemical features were ascertained as in diagnosis, as in differentiation with another neoplasms with similar morphology and reactive lymphoid infiltrates.

Unlabelled: BACKGROUND; Many investigators account that a stomach is the most often localization of gastrointestinal lymphomas. But endoscopic semiotics and diagnostic of those lesions is elaborated insufficiently., Purpose: The purpose of our investigation was working out of non-Hodgkin's gastric lymphoma endoscopic criteria., Materials and Methods: We examinated 250 patients with gastric lymphoma, from those primary and secondary lesions were in 160 (64%) cases and 90 (36%) cases, respectively. All patients was performed standard videoendoscopy, which included magnified endoscopy with NBI (Narrow Band Imaging), followed by chromoendoscopy with indigocarmine (0.4% solution) and EUS. Diagnosis of lymphoma was confirmed by morphology and immunohistochemistry., Results: According to our observations gastroenterological pathology duration to diagnosis of tumor was very variable: diagnosis was established during first 3 months in 30.6% cases (49 patients), during 6 month in 18.1% cases (29 patients), from 6 to 12 months in 15.6% cases (25 patients). Separately should was noted, that almost in one third cases primary gastric lymphoma was diagnosed after one year. Macroscopic form of gastric tumor was represented by follow variants: exophytic--22 cases (8.8%), infiltrative--54 cases (21.6%), ulcerous--37 cases (14.8%), infiltrative-ulcerous--71 cases (28.4%), similar to gastritis--36 cases (14.4%), mixed--30 cases (12%). The second endpoint of our work was detection of macroscopic features depending on morphological variant of lymphoma. Analysis of represented data demonstrated prevalence similar to gastritis form (33.4%) for MALT-lymphoma, infiltrative-ulcerous form as for diffuse large-cell B-cell lymphoma of MALT-type, as for diffuse large-cell B-cell lymphoma--45.0% and 41.1%, respectively. Infiltrative form was more often in group of patients with follicular lymphoma--31.8%, and ulcerous form predominated for Burkett's lymphoma--60.0%. CONCLUSION; Were established the most informative endoscopic criteria for diagnosis non-Hodgkin's gastric lymphoma.

Ionizing radiation-induced formation of genomic DNA damage can be modulated by nearby chemical species such as heavy metal ions, which can lead to non-linear dose response. To investigate this phenomenon, we studied cell survival and formation of 8-hydroxyguanine (8-OHG) base modifications and double strand breaks (DSB) caused by combined action of cadmium (Cd) and gamma radiation in cultured medaka fish (Oryzias latipes) fibroblast cells. Our data show that the introduction of Cd leads to a significant decrease in the fraction of surviving cells and to increased sensitivity of cells to ionizing radiation (IR). Cd also appears to cause non-linear increases in radiation-induced yields of 8-OHG and DSB as dose-yield plots of these lesions exhibit non-linear S-shaped curves with a sharp increase in the yields of lesions in the 10-20 microM range of Cd concentrations. The combined action of ionizing radiation and Cd leads to increased DNA damage formation compared to the effects of the individual stressors. These results are consistent with a hypothesis that the presence of Cd modulates the efficiency of DNA repair systems thus causing increases in radiation-induced DNA damage formation and decreases in cell survival.

Patients with carcinoma of the stomach were studied for dependence of development of post-surgical complications on the Helicobacter pylori involvement of the gastric mucosa. As many as 100 percent of patients with carcinoma of the stomach were found out to have H. pylori. Patients with posttreatment inflammatory complications presented with high and moderate levels of H. pylori. A complex was inaugurated of preventive treatment for H. pylori involvement, with tetraciclini, vicalini, and metronidasoli. Incidence rate of postoperative complications was 5.7%, with no fatalities being recordable. In the oncological patient, treatment of the H. pylori involvement in the preoperative period makes for lowering of the initial level of endotoxicosis, which fact is conducive to decrease in the frequency of postoperative inflammatory complications.

The indexes of ultrasound wave absorption in the blood serum of patients with gastric cancer were studied using ultrasound spectroscopy method. The coefficient of absorption (CA) changes were registered 1-2 days before the first clinical signs occurrence. While inflammatory complications presence CA had lowered, the daily gradient of lowering had raised.