Search

Although the conventional usage of Sphaeranthus indicus flowers in medicine exists, there is a lack of research on the precise pharmacological characteristics and comprehensive phytochemical composition of its flowers, resulting in a knowledge gap on their whole therapeutic capabilities. The aim of this work is to identify and describe the phytochemicals found in the flowers of Sphaeranthus indicus and assess specific pharmacological effects, such as antioxidant, antibacterial, anti-inflammatory, thrombolytic, antidepressant, and antidiarrheal characteristics. The investigation revealed that the MESIF (methanol extract of S. indicus flowers) showed substantial antioxidant performance (IC50 = 26.33) accompanied by a moderate phenolic content (93.33 ± 1.76). At 250 and 500 µg/ml, the extract exhibited modest to moderate antibacterial sensitivity against many tested pathogens and significantly reduced inflammation by protein denaturation (41.63 ± 0.11 and 70.52 ± 0.20). Furthermore, MESIF exhibited remarkable thrombolytic activity with a statistically significant (***P [ J Adv Biotechnol Exp Ther 2024; 7(3.000): 642-657]

Objective: The purpose of this study was to ascertain the correlation between COVID-19 infection and jaw osteonecrosis, along with the identification of risk factors that could be associated with the development of the condition. Another aim of our study is to establish whether maxillofacial osteonecrosis is an early or late complication seen in COVID-19 patients. Material and method: This was a retrospective study conducted over a period of two years. Case records of patients with a history of severe COVID and steroid treatment who later developed jaw osteonecrosis were evaluated. Result: 13 patients with an age range from 8 years to 70 years were identified. Osteonecrosis was seen as late as 21 months after COVID-19. The majority of the cases involved maxilla, one case was of bi-jaw involvement, and one case presented with isolated mandibular involvement. 6 patients were diabetic and 11 patients gave a history of provocative dental treatment like extraction. Conclusion: A triad of post-COVID coagulopathy, steroid administration, and a provocative dental treatment may contribute to jaw osteonecrosis which may be seen in patients without pre-existing systemic illness and may present as late as 21 months after COVID-19.

Abstract Background Osteoporosis is a gradually recognized health problem with risks related to disease history and living habits. This study aims to establish the optimal prediction model by comparing the performance of four prediction models that incorporated disease history and living habits in predicting the risk of Osteoporosis in Chongqing adults. Methods We conduct a cross-sectional survey with convenience sampling in this study. We use a questionnaire From January 2019 to December 2019 to collect data on disease history and adults’ living habits who got dual-energy X-ray absorptiometry. We established the prediction models of osteoporosis in three steps. Firstly, we performed feature selection to identify risk factors related to osteoporosis. Secondly, the qualified participants were randomly divided into a training set and a test set in the ratio of 7:3. Then the prediction models of osteoporosis were established based on Artificial Neural Network (ANN), Deep Belief Network (DBN), Support Vector Machine (SVM) and combinatorial heuristic method (Genetic Algorithm - Decision Tree (GA-DT)). Finally, we compared the prediction models’ performance through accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) to select the optimal prediction model. Results The univariate logistic model found that taking calcium tablet (odds ratio [OR] = 0.431), SBP (OR = 1.010), fracture (OR = 1.796), coronary heart disease (OR = 4.299), drinking alcohol (OR = 1.835), physical exercise (OR = 0.747) and other factors were related to the risk of osteoporosis. The AUCs of the training set and test set of the prediction models based on ANN, DBN, SVM and GA-DT were 0.901, 0.762; 0.622, 0.618; 0.698, 0.627; 0.744, 0.724, respectively. After evaluating four prediction models’ performance, we selected a three-layer back propagation neural network (BPNN) with 18, 4, and 1 neuron in the input layer, hidden and output layers respectively, as the optimal prediction model. When the probability was greater than 0.330, osteoporosis would occur. Conclusions Compared with DBN, SVM and GA-DT, the established ANN model had the best prediction ability and can be used to predict the risk of osteoporosis in physical examination of the Chongqing population. The model needs to be further improved through large sample research.

The methanol extract of the leaves of Tabernaemontana pauciflora (METP) was screened to investigate the semi-qualitative phytochemical, in vivo anti-depressant, anxiolytic and in vitro thrombolytic activities. The in vivo antidepressant activity of METP was examined by Force swimming test (FST) and Tail suspension test (TST) whereas anxiolytic activity was examined by using Hole-board test (HBT) and Elevated plus maze test (EPM) on mice model. The in vitro thrombolytic model was used to check the clot lysis effect of METP. Additionally, semi-qualitative phytochemical assay was performed through in vitro test. In the antidepressant activity, METP was exhibited significant value of FST (45.64% & 58.31%) and TST (38.67% & 63.62%) whereas the notable anxiolytic effect was observed in EPM (67.67% & 56.06%) and HBT (84) in dose dependent manner which compared with control and standard. In in vitro thrombolytic assessment of METP exposed 22.66% inhibition of clot. The current results proposed that METP might be effective in neuropharmacological and thrombolytic response due to the presence of alkaloids, tannins and flavonoids, which required further studies to investigate the mechanism. [ J Adv Biotechnol Exp Ther 2021; 4(1.000): 9-16]

Abstract Background Colocasia gigantea, locally named as kochu is well-known due to its various healing power. This research is to investigate the antidiarrheal, antimicrobial and antioxidant possibilities of the methanol soluble extract of Colocasia gigantea. Methods The antidiarrheal investigation was performed by using in vivo castor oil-induced diarrheal method whereas in vitro antimicrobial and antioxidant investigation have been implemented by disc diffusion and DPPH scavenging method respectively. Moreover, in silico studies were followed by molecular docking analysis of several secondary metabolites that were appraised with Schrödinger-Maestro v11.1 and Biovia Discovery Studio. Results The induction of plant extract (200 and 400 mg/kg, b.w, p.o) has minimized the castor oil mediated diarrhea by 16.96% (p

Chronic lymphocytic leukemia (CLL) is characterized by disordered DNA methylation, suggesting these epigenetic changes might play a critical role in disease onset and progression. The methyltransferase DNMT3A is a key regulator of DNA methylation. Although DNMT3A somatic mutations in CLL are rare, we found that low DNMT3A expression is associated with more aggressive disease. A conditional knockout mouse model showed that homozygous depletion of Dnmt3a from B cells results in the development of CLL with 100% penetrance at a median age of onset of 5.3 months, and heterozygous Dnmt3a depletion yields a disease penetrance of 89% with a median onset at 18.5 months, confirming its role as a haploinsufficient tumor suppressor. B1a cells were confirmed as the cell of origin of disease in this model, and Dnmt3a depletion resulted in focal hypomethylation and activation of Notch and Myc signaling. Amplification of chromosome 15 containing the Myc gene was detected in all CLL mice tested, and infiltration of high-Myc-expressing CLL cells in the spleen was observed. Notably, hyperactivation of Notch and Myc signaling was exclusively observed in the Dnmt3a CLL mice, but not in three other CLL mouse models tested (Sf3b1-Atm, Ikzf3, and MDR), and Dnmt3a-depleted CLL were sensitive to pharmacologic inhibition of Notch signaling in vitro and in vivo. Consistent with these findings, human CLL samples with lower DNMT3A expression were more sensitive to Notch inhibition than those with higher DNMT3A expression. Altogether, these results suggest that Dnmt3a depletion induces CLL that is highly dependent on activation of Notch and Myc signaling. SIGNIFICANCE: Loss of DNMT3A expression is a driving event in CLL and is associated with aggressive disease, activation of Notch and Myc signaling, and enhanced sensitivity to Notch inhibition.

Abstract Previous studies have revealed a critical role of methylation deregulation in the onset and progression of chronic lymphocytic leukemia (CLL). In mammalian cells, DNA methylation is dynamically established by the DNA methyltransferase 3 (DNMT3) family of de novo methyltransferases DNMT3A. Although mutations of DNMT3A are rarely observed in CLL, our RNA-sequencing (RNA-seq) analysis of 107 human CLLs show that low DNMT3A expression is associated with more aggressive disease, and supports a driving role of DNMT3A loss in CLL. To test this hypothesis, we generated a conditional knock-out mouse model with B cell-restricted deletion of Dnmt3a. Homozygous Dnmt3a depletion in B cells resulted in the development of CD5+ B cell leukemia mimicking human CLL with 100% penetrance at a median age of onset of 5.3 months, and heterozygous Dnmt3a depletion yielded a disease penetrance of 89% with a median onset at 18.5 months, confirming its role as a haplo-insufficient tumor suppressor. Given the known role of Dnmt3a as a de novo methyltransferase, we first evaluated the impact of Dnmt3a depletion on global DNA methylation in non-leukemic CD5+ B cells isolated from the peritoneal cavity by cell sorting (i.e. B1a cells) using reduced representation bisulfite sequencing (RRBS). We identified a set of differentially methylated regions (DMRs) (difference>0.2), mostly hypomethylated, in Dnmt3afl/fl versus WT B1a cells (473 hypomethylated, 19 hypermethylated). Genes with dysregulated methylation were highly enriched in pathways involved in immune response (e.g., Interferon-α signaling, JAK/STAT3 signaling) and proliferation (Wnt Signaling and Notch signaling). Given the prominent hypomethylation changes observed in Dnmt3a depleted B1a cells, we investigated whether these would lead to altered gene transcript expression. Using RNA-seq, we detected 460 downregulated and 168 upregulated genes in the Dnmt3afl/fl B1a cells compared to WT B1a cells (FDR2). Consistent with the methylation data, differentially expressed genes were likewise enriched for JAK/STAT3 signaling, Wnt Signaling and Notch signaling, supporting a direct influence of dysregulated methylation on downstream signaling cascades. We investigated the changes in methylomes of the CLL cells arising from the Dnmt3afl/fl animals. Compared to WT B1a cells, Dnmt3afl/fl CLL cells generated 1335 hypomethylated and 2369 hypermethylated DMRs in. Focusing on genes that were hypomethylated in CLL compared to WT B1a cells, we found that these were highly enriched for several oncogenic signaling pathways including Notch signaling and Wnt Signaling, consistent with the pre-leukemia findings. RNA-seq analysis identified more upregulated (n=2801) than downregulated (n=1244) genes in CLL cells compared to WT B1a cells (FDR2), supporting a role of Dnmt3a depletion in transcriptional activation. We observed a general upregulation of Notch signaling genes and the downstream Notch targets, implicating Notch activation in this CLL mouse model. Of note, we showed Dnmt3a-depleted CLL cells to be highly sensitive to Notch inhibitor DAPT both in vitro and in a transplantable mouse model. Consistently, primary human CLL cells with low DNMT3A expression were more sensitive to DAPT than those with higher DNMT3A expression (P=0.005, Spearman correlation), despite similar sensitivity to ibrutinib and venetoclax. Together, our results have confirmed the causal role of Dnmt3a downregulation in CLL generation. We provide evidence in support of the interaction between Dnmt3a-dependent methylation changes and hyperactivation of Notch signaling in transcriptional reprogramming and transformation of B1a cells into CLL. Furthermore, we demonstrate differential sensitivity of DNMT3A high and low expressing primary CLLs to Notch inhibition, indicative of consistent dependencies of human and murine CLLs. Thus, the Dnmt3a models provides a unique opportunity for the study of non-mutational Notch activation, and a useful platform for the study of Notch-signaling targeted therapeutics. Disclosures Kipps: Abbott Laboratories: Consultancy, Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding; Pharmacyclics LLC, an Abbvie Company: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Genentech, Inc.: Honoraria, Research Funding, Speakers Bureau; Gilead Sciences, Inc.: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; MedImmune Inc: Research Funding; Moores Cancer Center: Current Employment; Oncternal Therapeutics, Inc.: Current holder of stock options in a privately-held company, Other: Stock or other ownership, Patents & Royalties: Cirmtuzumab was developed by Thomas J. Kipps in the Thomas J. Kipps laboratory and licensed by the University of California to Oncternal Therapeutics, Inc., which provided stock options and research funding to the Thomas J. Kipps laboratory., Research Funding; AbbVie: Consultancy, Honoraria, Other, Speakers Bureau; DAVAOncology: Consultancy, Honoraria, Other; DAVA Pharmaceuticals: Speakers Bureau; Bionest Partner: Other; Celgene: Consultancy, Honoraria, Other, Research Funding; Genetech: Honoraria, Other; Genentech-Roche: Consultancy; Gilead Sciences: Consultancy, Honoraria, Other, Speakers Bureau; Janssen: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Roche: Honoraria, Other; MD Anderson Cancer Center: Research Funding; Velos: Research Funding; CRIM: Research Funding; Indy Hematology Review: Other; TG Therapeutics: Other; Verstem: Other, Speakers Bureau; University of California, San Diego: Current Employment; Pharmacyclics/AbbVie: Honoraria, Research Funding; Breast Cancer Research Foundation: Research Funding; SCOR - The Leukemia and Lymphoma Society: Research Funding; National Cancer Institute/NIH: Honoraria, Research Funding; Genentech/Roche: Honoraria; European Research Initiative on CLL (ERIC): Honoraria. Neuberg: Madrigal Pharmaceuticals: Other: Stock ownership; Pharmacyclics: Research Funding. Letai: Flash Therapeutics: Other: equity holding member of the scientific advisory board; Dialectic Therapeutics: Other: equity holding member of the scientific advisory board; Zentalis Pharmaceuticals: Other: equity holding member of the scientific advisory board. Wu: BioNTech: Current equity holder in publicly-traded company; Pharmacyclics: Research Funding.

Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in pre-neoplastic monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significantly differentially methylated regions in the high-count MBL-to-CLL transition. Patient methylomes showed remarkable stability with natural disease and post-therapy progression. Single CLL cells were consistently aberrantly methylated, indicating a homogeneous transition to the altered epigenetic state, and a distinct expression profile together with MBL cells compared to normal B cells. Our longitudinal analysis reveals the cancer methylome to emerge early, which may provide a platform for subsequent genetically-driven growth dynamics and together with its persistent presence suggests a central role in the normal-to-cancer transition.

Leukemic relapse remains a major barrier to successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aggressive hematologic malignancies. The basis for relapse of advanced lymphoid malignancies remains incompletely understood and may involve escape from the graft-versus-leukemia (GvL) effect. We hypothesized that for patients with chronic lymphocytic leukemia (CLL) treated with allo-HSCT, leukemic cell-intrinsic features influence transplant outcomes by directing the evolutionary trajectories of CLL cells. Integrated genetic, transcriptomic, and epigenetic analyses of CLL cells from 10 patients revealed that the clinical kinetics of post-HSCT relapse are shaped by distinct molecular dynamics. Early relapses after allo-HSCT exhibited notable genetic stability; single CLL cell transcriptional analysis demonstrated a cellular heterogeneity that was static over time. In contrast, CLL cells relapsing late after allo-HSCT displayed notable genetic evolution and evidence of neoantigen depletion, consistent with marked single-cell transcriptional shifts that were unique to each patient. We observed a greater rate of epigenetic change for late relapses not seen in early relapses or relapses after chemotherapy alone, suggesting that the selection pressures of the GvL bottleneck are unlike those imposed by chemotherapy. No selective advantage for human leukocyte antigen (HLA) loss was observed, even when present in pretransplant subpopulations. Gain of stem cell modules was a common signature associated with leukemia relapse regardless of posttransplant relapse kinetics. These data elucidate the biological pathways that underlie GvL resistance and posttransplant relapse.

Infrastructure development in mountainous regions is vital due to rapid population growth and increased tourism. Most of these regions are vulnerable to landslides under rainfall events due to changes in the shear strength of the soil slopes under wetting cycles. Thus, the stability of foundations on slopes must be evaluated under variably saturated conditions. Models for evaluating the bearing capacity of foundations on slopes by accounting for variably saturated and transient conditions are scarce. A comprehensive semi-analytical model in the slip-line framework was developed in this study to investigate the bearing capacity of foundations on slopes under various controlling factors. The proposed model integrated the slip-line theory using a one-dimensional unsaturated transient-flow equation––the Richards equation––to evaluate the stability of foundations on soil slopes under unsaturated transient-flow conditions. Suction stress profiles were estimated using different soil hydraulic models for partly saturated soils to incorporate into the slip-line theory for estimating the bearing capacity of foundations under different field conditions. The developed framework was successfully validated using the existing limited cases under unsaturated steady-state and transient conditions. A parametric study was undertaken to study the influence of soil type, slope angle, rainfall infiltration, and depth of water table. The influence of different unsaturated hydraulic characteristics on the bearing capacity was clearly brought out, for the first time, using the measured soil hydraulic characteristics data. The model performance was satisfactory and is useful for evaluating the bearing capacity of footings resting on slopes under different natural conditions. [ABSTRACT FROM AUTHOR]

In exploring the evolutionary trajectories of both pathogenesis and karyotype dynamics in fungi, we conducted a large-scale comparative genomic analysis spanning the Cryptococcus genus, encompassing both global human fungal pathogens and nonpathogenic species, and related species from the sister genus Kwoniella. Chromosome-level genome assemblies were generated for multiple species, covering virtually all known diversity within these genera. Although Cryptococcus and Kwoniella have comparable genome sizes (about 19.2 and 22.9 Mb) and similar gene content, hinting at preadaptive pathogenic potential, our analysis found evidence of gene gain (via horizontal gene transfer) and gene loss in pathogenic Cryptococcus species, which might represent evolutionary signatures of pathogenic development. Genome analysis also revealed a significant variation in chromosome number and structure between the 2 genera. By combining synteny analysis and experimental centromere validation, we found that most Cryptococcus species have 14 chromosomes, whereas most Kwoniella species have fewer (11, 8, 5, or even as few as 3). Reduced chromosome number in Kwoniella is associated with formation of giant chromosomes (up to 18 Mb) through repeated chromosome fusion events, each marked by a pericentric inversion and centromere loss. While similar chromosome inversion–fusion patterns were observed in all Kwoniella species with fewer than 14 chromosomes, no such pattern was detected in Cryptococcus. Instead, Cryptococcus species with less than 14 chromosomes showed reductions primarily through rearrangements associated with the loss of repeat-rich centromeres. Additionally, Cryptococcus genomes exhibited frequent interchromosomal translocations, including intercentromeric recombination facilitated by transposons shared between centromeres. Overall, our findings advance our understanding of genetic changes possibly associated with pathogenicity in Cryptococcus and provide a foundation to elucidate mechanisms of centromere loss and chromosome fusion driving distinct karyotypes in closely related fungal species, including prominent global human pathogens. Understanding the different evolution of closely related pathogenic and non-pathogenic fungi can help decipher the mechanisms of pathogenesis. In this study, comparative genomics is used to analyze the intricate genomic evolution of Cryptococcus and Kwoniella, highlighting distinct mechanisms that drive their biological diversity and lifestyles. [ABSTRACT FROM AUTHOR]

Author(s): Jiho Choi [1, 2, 3, 4]; Aaron J. Huebner [1, 2, 3, 4]; Kendell Clement [3, 4, 5]; Ryan M. Walsh [1, 2, 3, 4]; Andrej Savol [1]; Kaixuan [...]

Background: Critical thinking is defined as the art of analyzing and evaluating thinking along with a review to correct it. Critical thinking is one of the basic needs of human life for decision-making, selection, and deep understanding of various issues. There is a research gap regarding the possible role of analytical literacy and computer literacy in predicting critical thinking with regard to the gender variable. Aims: This study was conducted to predict critical thinking through computer and analytical literacy with the mediating role of gender in second-year high school students of Gilan province. Methods: Research method was descriptive correlation type and the statistical population included second-year high school students of Gilan province in the first half of the academic year 2019-2020. The statistical sample included 384 people (191 girls and 193 boys) who were randomly selected in person and virtual. Data collection tools included critical thinking questionnaire (Ricketts', 2003) and researcher-made computer and analytical literacy questionnaires. The data were analyzed using hierarchical regression, multivariate regression, and Z-test using SPSS software version 26, and a significance level of 0.05 was considered to test the hypotheses. Results: The results showed that the effect of analytical literacy and computer literacy on students' critical thinking is positive and significant and explains 43% of its changes. Also, multiple relationships between analytical literacy and computer literacy with critical thinking have been stronger in male students than in female students. Conclusion: According to the obtained findings, it seems that Critical thinking in students can be predicted by the variables of analytical literacy and computer literacy according to the role of gender

Purpose: NUSAP1 has been reported to be involved in the progression of several types of cancer. However, its expression and exact role in bladder cancer (BLCA) remains elusive. The aim of this study was to determine the expression and role of NUSAP1 in BLCA. Methods: Tissue microarray, real-time PCR, Western blot and immunohistochemistry assays were carried out to determine NUSAP1 expression in BLCA tissues and cells. The biological roles of NUSAP1 were investigated using CCK-8, EdU labeling, flow cytometry, Transwell, and wound healing assays. Additionally, the effect of NUSAP1 on epithelial-mesenchymal transition (EMT) was investigated by Western blotting and real-time PCR. Results: We found that NUSAP1 was upregulated in BLCA, and its expression was closely related to the poor prognosis of patients. Subsequently, we transfected 5637 and T24 cell lines with NUSAP1 siRNA and an NUSAP1 overexpression plasmid, respectively. NUSAP1 downregulation in 5637 cells inhibited cell proliferation, migration, and invasiveness and enhanced chemosensitivity to gemcitabine, while NUSAP1 overexpression in T24 cells resulted in the inverse effects. Moreover, NUSAP1 regulated EMT via the TGF-β signaling pathway, and when TGF-beta receptor 1 (TGFBR1) was inhibited with the inhibitor SB525334, the invasion and metastasis ability of BLCA cells was significantly suppressed, as well as p-Smad2/3 and vimentin expression. Conclusion: Our above data demonstrate that NUSAP1 contributes to BLCA progression via the TGF-β signaling pathway. [ABSTRACT FROM AUTHOR]

In normal mammalian development cytosine methylation is essential and is directed to specific regions of the genome. Despite notable advances through mapping its genome-wide distribution, studying the direct contribution of DNA methylation to gene and genome regulation has been limited by the lack of tools for its precise manipulation. Thus, combining the targeting capability of the CRISPR-Cas9 system with an epigenetic modifier has attracted interest in the scientific community. In contrast to profiling the genome-wide cleavage of a nuclease competent Cas9, tracing the global activity of a dead Cas9 (dCas9) methyltransferase fusion protein is challenging within a highly methylated genome. Here, we report the generation and use of an engineered, methylation depleted but maintenance competent mouse ES cell line and find surprisingly ubiquitous nuclear activity of dCas9- methyltransferases. Subsequent experiments in human somatic cells refine these observations and point to an important difference between genetic and epigenetic editing tools that require unique experimental considerations. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to provide a model of moral education in elementary school. Method:The research method was mixed with a qualitative-quantitative design. The statistical population of the research in the qualitative section included articles, thesis, documents and books from 1390 to 1398 and in a quantitative part, the teachers of the second elementary school were in Kerman. The study sample was based on purposive sampling method in qualitative part and simple random sampling method in quantitative part. The data collection tools in the qualitative section included articles, thesis, books, and in the quantitative section was a questionnaire. The content analysis method was used to analyze the data in the qualitative part and the second-order confirmatory factor analysis was used in the quantitative part. Finding: Findings showed that 35 basic themes, eleven organizing themes and three comprehensive themes were identified in three areas of cognition, belief and moral behavior, then a questionnaire was designed to validate the model with 35 items. The reliability of the questionnaire was calculated using Cronbachchr('39')s alpha (0.95) and its validity was calculated based on the views of experienced faculty members and using the sigma numbering index of 0/85. The results showed that all themes with high factor load were approved, which indicated the high validity of the model. In the quantitative part, the findings showed that all themes with high factor load were approved, which indicated the high validity of the model. Conclusion:According to the results of this study and focusing on the model of moral education, it is possible to help improve the level of cognition, belief and moral behavior of elementary school students.

This study aimed to identify the dimensions and components of moral education through a social approach, and to develop a conceptual model for elementary education. This mixed methods research has combined elements of quantitative and qualitative approaches. In the qualitative part, the population of the study consisted of websites and databases related to moral education which were purposefully selected and thoroughly examined. The data analysis method included categorization which was continuously and simultaneously carried out with data collection. In the quantitative part, the population of the study comprised elementary school teachers in Kerman (District 2, grades 4-6) who were selected by total population sampling. After an overview of the relevant previous research, a number of moral education components were extracted and presented to a group of experts and specialists.This stage led to the deletion of a number of the extracted components and on the basis of the remaining ones a 71-item questionnaire was designed and administered to the statistical population including 408 elementary school teachers. The validity of the questionnaire was confirmed by the specialists and its reliability was assessed using Cronbachchr('39')s alpha test. The research was followed by exploratory and confirmatory factor analyses and the results showed that the core concept of the study includes 11 components in 2 dimensions of "belief" and "behavior". The components of "belief" are: "respect for social values and social norms", "forbearance", "developing an altruistic spirit", and "dialogue". The components of "behavior" are: "dependence on collective identity and its maintenance", "nurturing the spirit of freedom", "peaceful coexistence", "fulfillment of promises", "adherence to moral codes", "respect for the environment", and "fulfillment of social responsibility". The final model was designed based on the aforementioned dimensions and components. Among manifest variables related to the latent variable of "belief", the highest explained variance was obtained for "respecting values" and "social norms", while the lowest explained variable was gained for "dialogue". Among manifest variables related to the latent variable of "behavior", the highest explained variance was obtained for "dependence on collective identity and its maintenance", whereas the lowest explained variable was gained for "fulfillment of social responsibility".

Despite lakes being a key part of the global water cycle and a crucial water resource, there is limited understanding of whether regional or lake-specific factors control water storage variations in small lakes. Here, we study groups of small, unregulated lakes in North Carolina, Washington, Illinois, and Wisconsin, USA using lake level measurements gathered by citizen scientists and lake surface area measurements from optical satellite imagery. We show the lake level measurements to be highly accurate when compared to automated gauges (mean absolute error = 1.6 cm). We compare variations in lake water storage between pairs of lakes within these four states. On average, water storage variations in lake pairs across all study regions are moderately positively correlated (ρ = 0.49) with substantial spread in the degree of correlation. The distance between lake pairs and the extent to which their changes in volume are correlated show a weak but statistically significant negative relationship. Our results indicate that, on regional scales, distance is not a primary factor governing lake water storage patterns, which suggests that other, perhaps lakes-specific, factors must also play important roles. [ABSTRACT FROM AUTHOR]

Cystadenomas of the seminal vesicles are extremely rare. Here, we report a large seminal vesicle cystadenoma. A 37‐year‐old man presented a 6‐month history of haemospermia, 10 days of Lower Urinary Tract symptoms (LUTSs) and gross haematuria. Transabdominal ultrasonography, computed tomography and magnetic resonance imaging were performed and revealed a large solid‐cystic pelvic mass morphometrically measured 7.0 cm × 11.9 cm × 8.6 cm on the right seminal vesicle, which caused hydronephrosis of the right kidney. The prostate‐specific antigen of the patient was 27.860 ng/dl. Laparoscopic exploration found the capsule of tumour was complete and the tumour came from the right seminal vesicle, in addition, the mass had a certain space with the bladder and prostate, which could be separated. So a nerve‐sparing Laparoscopic Vesiculectomy was performed at last, even though the intraoperative frozen section analysis could not make sure the nature of the tumour either. The postoperative pathology revealed cystadenoma of the seminal vesicle. [ABSTRACT FROM AUTHOR]

Summary CTLA-4 immune checkpoint blockade is clinically effective in a subset of patients with metastatic melanoma. We identify a subcluster of MAGE-A cancer-germline antigens, located within a narrow 75 kb region of chromosome Xq28, that predicts resistance uniquely to blockade of CTLA-4, but not PD-1. We validate this gene expression signature in an independent anti-CTLA-4-treated cohort and show its specificity to the CTLA-4 pathway with two independent anti-PD-1-treated cohorts. Autophagy, a process critical for optimal anti-cancer immunity, has previously been shown to be suppressed by the MAGE-TRIM28 ubiquitin ligase in vitro . We now show that the expression of the key autophagosome component LC3B and other activators of autophagy are negatively associated with MAGE-A protein levels in human melanomas, including samples from patients with resistance to CTLA-4 blockade. Our findings implicate autophagy suppression in resistance to CTLA-4 blockade in melanoma, suggesting exploitation of autophagy induction for potential therapeutic synergy with CTLA-4 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Histoplasmosis is a systemic mycosis caused by  Histoplasma capsulatum  ( H. capsulatum ). Systemic involvement of histoplasmosis usually occurs in immune-compromised patients, patients with AIDS, or those taking immunosuppressive therapy. The present study aims to describe the clinical and laboratory characteristics and treatment outcome of histoplasmosis as the diagnosis is challenging and management protocol differs., Method: This retrospective study was done using a data registry at the medicine department of Dhaka Medical College Hospital. Here, patients received the standard treatment of histoplasmosis. Here, patients received the standard treatment of histoplasmosis, and clinical outcome was assessed at 3 months following starting standard treatment., Result: A total of nine patients were enrolled, six (66.7%) had systemic histoplasmosis. Three were poultry workers, and the most common comorbidity was diabetes 3 (33.3%). Fever 7 (77.7%), weight loss 6 (66.7%), hyperpigmentation 5 (55.5%), cough 4 (44.4%), oral ulceration 4 (44.4%), lymphadenopathy 4 (44.4%), and hypotension 3 (33.3%) were the most common clinical presentations. Seven (77.7%) out of nine patients were cured of histoplasmosis; however, one died before initiating antifungal medications and another one died due to a hypersensitivity reaction to liposomal amphotericin B.  Conclusion: For local histoplasmosis, oral itraconazole is an effective antifungal medication. However, in disseminated Histoplasmosis, liposomal amphotericin B followed by oral itraconazole is still one of the preferable and effective treatment options. Clinicians should be aware of hypersensitivity reactions of liposomal amphotericin B and its management before giving an infusion., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Been Sayeed et al.)

Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in pre-neoplastic monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significantly differentially methylated regions in the high-count MBL-to-CLL transition. Patient methylomes showed remarkable stability with natural disease and post-therapy progression. Single CLL cells were consistently aberrantly methylated, indicating a homogeneous transition to the altered epigenetic state, and a distinct expression profile together with MBL cells compared to normal B cells. Our longitudinal analysis reveals the cancer methylome to emerge early, which may provide a platform for subsequent genetically-driven growth dynamics and together with its persistent presence suggests a central role in the normal-to-cancer transition., Competing Interests: The authors declare no potential conflicts of interest.