scRNAseq and High-Throughput Spatial Analysis of Tumor and Normal Microenvironment in Solid Tumors Reveal a Possible Origin of Circulating Tumor Hybrid Cells.

Metastatic cancer is a leading cause of death in cancer patients worldwide. While circulating hybrid cells (CHCs) are implicated in metastatic spread, studies documenting their tissue origin remain sparse, with limited candidate approaches using one-two markers. Utilizing high-throughput single-cell and spatial transcriptomics, we identified tumor hybrid cells (THCs) co-expressing epithelial and macrophage markers and expressing a distinct transcriptome.

The prevalence of probable overactive bladder and associated risk factors among medical students in Jordan: a cross-sectional study.

Background: To discuss the impact of overactive bladder (OAB) on medical students. overactive bladder. is a chronic condition that causes sudden and intense urges to urinate, which can have significant physical and psychological effects on patients' lives.

mutations are associated with a response to alvocidib and 5-azacytidine combination in myelodysplastic neoplasms.

Inhibitors of anti-apoptotic BCL-2 family proteins in combination with chemotherapy and hypomethylating agents (HMA) are promising therapeutic approaches in acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). Alvocidib, a cyclin-dependent kinase 9 (CDK9) inhibitor and indirect transcriptional repressor of the anti-apoptotic factor MCL-1, has previously shown clinical activity in AML. Availability of biomarkers for response to the alvocidib + 5-azacytidine (5-AZA) could also extend the rationale of this treatment concept to high-risk MDS.

Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis.

Osteoarthritis (OA) is characterised by an irreversible degeneration of articular cartilage. Here we show that the BMP-antagonist Gremlin 1 (Grem1) marks a bipotent chondrogenic and osteogenic progenitor cell population within the articular surface. Notably, these progenitors are depleted by injury-induced OA and increasing age.

Gene expression in notochord and nuclei pulposi: a study of gene families across the chordate phylum.

The transition from notochord to vertebral column is a crucial milestone in chordate evolution and in prenatal development of all vertebrates. As ossification of the vertebral bodies proceeds, involutions of residual notochord cells into the intervertebral discs form the nuclei pulposi, shock-absorbing structures that confer flexibility to the spine. Numerous studies have outlined the developmental and evolutionary relationship between notochord and nuclei pulposi.

Parkinson's Disease Detection Using Filter Feature Selection and a Genetic Algorithm with Ensemble Learning.

Parkinson's disease (PD) is a neurodegenerative disorder marked by motor and non-motor symptoms that have a severe impact on the quality of life of the affected individuals. This study explores the effect of filter feature selection, followed by ensemble learning methods and genetic selection, on the detection of PD patients from attributes extracted from voice clips from both PD patients and healthy patients. Two distinct datasets were employed in this study.

Circulating cancer giant cells with unique characteristics frequently found in patients with myelodysplastic syndromes (MDS).

Myelodysplastic syndromes (MDS) are incurable diseases characterized by dysplastic hematopoietic cells, cytopenias in the blood and an inherent tendency for transformation to secondary acute myeloid leukemia (AML). Since most therapies fail to prevent rapid clonal evolution and disease resistance, new and non-invasive predictive markers are needed to monitor patients and adapt the therapeutic strategy. By using ISET, a very sensitive approach to isolate cells larger than mature leukocytes from peripheral blood samples, we looked for cellular markers in 99 patients (158 samples) with MDS and 66 healthy individuals (76 samples) used as controls.

Taurine deficiency as a driver of aging.

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys.

Multiplex Base Editing to Protect from CD33-Directed Therapy: Implications for Immune and Gene Therapy.

On-target toxicity to normal cells is a major safety concern with targeted immune and gene therapies. Here, we developed a base editing (BE) approach exploiting a naturally occurring CD33 single nucleotide polymorphism leading to removal of full-length CD33 surface expression on edited cells. CD33 editing in human and nonhuman primate (NHP) hematopoietic stem and progenitor cells (HSPCs) protects from CD33-targeted therapeutics without affecting normal hematopoiesis , thus demonstrating potential for novel immunotherapies with reduced off-leukemia toxicity.

A novel therapeutic bispecific format based on synthetic orthogonal heterodimers enables T cell activity against Acute myeloid leukemia.

Many therapeutic bispecific T-cell engagers (BiTEs) are in clinical trials. A modular and efficient process to create BiTEs would accelerate their development and clinical applicability. In this study, we present the design, production, and functional activity of a novel bispecific format utilizing synthetic orthogonal heterodimers to form a multichain modular design.

Detecting High-Risk Factors and Early Diagnosis of Diabetes Using Machine Learning Methods.

Diabetes is a chronic disease that can cause several forms of chronic damage to the human body, including heart problems, kidney failure, depression, eye damage, and nerve damage. There are several risk factors involved in causing this disease, with some of the most common being obesity, age, insulin resistance, and hypertension. Therefore, early detection of these risk factors is vital in helping patients reverse diabetes from the early stage to live healthy lives.

Deep Ensemble Fake News Detection Model Using Sequential Deep Learning Technique.

Recently, fake news has been widely spread through the Internet due to the increased use of social media for communication. Fake news has become a significant concern due to its harmful impact on individual attitudes and the community's behavior. Researchers and social media service providers have commonly utilized artificial intelligence techniques in the recent few years to rein in fake news propagation.

The Effect of Erector Spinae Plane Block With and Without Addition of Magnesium on Relief of Pain from Post-herpetic Neuralgia.

Background: The best tool for management of postherpetic neuralgia (PHN) is a matter of debate. The use of ultrasound-guided erector spinae plane block (ESPB) in patients with PHN may decrease pain severity and the need for analgesics.

Objectives: The objective of this clinical study was to test the efficacy of ESPB with and without the addition of magnesium sulphate on pain control and analgesic consumption in patients with PHN.

Mutation in SF3B1 gene promotes formation of polyploid giant cells in Leukemia cells.

Giant cells with polyploidy, termed polyploid giant cells, have been observed during normal growth, development, and pathologic states, such as solid cancer progression and resistance to therapy. Functional studies of polyploidal giant cancer cells (PGCC) provided evidence that they arise when normal diploid cells are stressed, show stem cell-like properties, and give rise to tumors. In the present study, we report in K562 leukemia cell line that introduction of the hotspot K700E mutation in the gene SF3B1 using CRISPR/Cas9 method results in an increased frequency of multinucleated polyploid giant cells resistant to chemotherapeutic agent and serum starvation stress.

Subversion of Serotonin Receptor Signaling in Osteoblasts by Kynurenine Drives Acute Myeloid Leukemia.

Unlabelled: Remodeling of the microenvironment by tumor cells can activate pathways that favor cancer growth. Molecular delineation and targeting of such malignant-cell nonautonomous pathways may help overcome resistance to targeted therapies. Herein we leverage genetic mouse models, patient-derived xenografts, and patient samples to show that acute myeloid leukemia (AML) exploits peripheral serotonin signaling to remodel the endosteal niche to its advantage.

SF3B1 mutant-induced missplicing of MAP3K7 causes anemia in myelodysplastic syndromes.

SF3B1 is the most frequently mutated RNA splicing factor in cancer, including in ∼25% of myelodysplastic syndromes (MDS) patients. SF3B1-mutated MDS, which is strongly associated with ringed sideroblast morphology, is characterized by ineffective erythropoiesis, leading to severe, often fatal anemia. However, functional evidence linking mutations to the anemia described in MDS patients harboring this genetic aberration is weak, and the underlying mechanism is completely unknown.

Golden Standard and Golden Proportion of Maxillary Anterior Teeth Among Saudi Population in Makkah.

Background: Maxillary anterior teeth are important in achieving optimum aesthetics, Different methods are used to calculate their dimension: as golden standard (GS) to measure Width/Height (W/H) of anterior teeth and Golden Proportion (GP) to measure their perceived widths. Researchers had reported on GS and GP in different populations.

Objectives: The aim of the present study is to evaluate the occurrence of GS and GP of maxillary anterior teeth among the Saudi population in Makkah.

Challenges and Solutions to Bringing Chimeric Antigen Receptor T-Cell Therapy to Myeloid Malignancies.

Myeloid malignancies including myelodysplastic syndromes and acute myeloid leukemia are a group of clonal hematopoietic stem progenitor cell disorders mainly effecting the elderly. Chemotherapeutic approaches improved the outcome in majority of the patients, but it is generally associated with severe toxicities and relapse and does not benefit all the patients. With the success of adoptive cell therapies including chimeric antigen receptor T-cell therapy in treating certain B-cell malignancies, these therapeutic approaches are also being tested for myeloid malignancies, but the preclinical and limited clinical trial data suggest there are significant challenges.

Rewriting the rules for care of MDS and AML patients in the time of COVID-19.

The care of patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) has been radically altered by COVID-19, especially in New York City, the epicenter of the pandemic. Here we summarize how telemedicine, virtual visits, delayed transfusions, and chemotherapy, preferably selecting self-administered medications and visits by home healthcare workers, are employed to minimize exposure of our high-risk population of patients to the virus. The unique challenges of transplants during the pandemic and the consequences of an abrupt halt in all non-essential research activities are described.

Inversion Algorithm of Fiber Bragg Grating for Nanofluid Flooding Monitoring.

In the current study, we developed an adaptive algorithm that can predict oil mobilization in a porous medium on the basis of optical data. Associated mechanisms based on tuning the electromagnetic response of magnetic and dielectric nanoparticles are also discussed. This technique is a promising method in rational magnetophoresis toward fluid mobility via fiber Bragg grating (FBG).

Disease-Causing Mutations in SF3B1 Alter Splicing by Disrupting Interaction with SUGP1.

SF3B1, which encodes an essential spliceosomal protein, is frequently mutated in myelodysplastic syndromes (MDS) and many cancers. However, the defect of mutant SF3B1 is unknown. Here, we analyzed RNA sequencing data from MDS patients and confirmed that SF3B1 mutants use aberrant 3' splice sites.

Gene-edited stem cells enable CD33-directed immune therapy for myeloid malignancies.

Antigen-directed immunotherapies for acute myeloid leukemia (AML), such as chimeric antigen receptor T cells (CAR-Ts) or antibody-drug conjugates (ADCs), are associated with severe toxicities due to the lack of unique targetable antigens that can distinguish leukemic cells from normal myeloid cells or myeloid progenitors. Here, we present an approach to treat AML by targeting the lineage-specific myeloid antigen CD33. Our approach combines CD33-targeted CAR-T cells, or the ADC Gemtuzumab Ozogamicin with the transplantation of hematopoietic stem cells that have been engineered to ablate CD33 expression using genomic engineering methods.

Severely impaired terminal erythroid differentiation as an independent prognostic marker in myelodysplastic syndromes.

Anemia is the defining feature in most patients with myelodysplastic syndromes (MDS), yet defects in erythropoiesis have not been well characterized. We examined freshly obtained bone marrow (BM) samples for stage-specific abnormalities during terminal erythroid differentiation (TED) from 221 samples (MDS, n = 205 from 113 unique patients; normal, n = 16) by measuring the surface expression of glycophorin A, band 3, and integrin α-4. Clinical and biologic associations were sought with presence or absence of TED and the specific stage of erythroid arrest.

Survey and evaluation of mutations in the human KLF1 transcription unit.

Erythroid Krüppel-like Factor (EKLF/KLF1) is an erythroid-enriched transcription factor that plays a global role in all aspects of erythropoiesis, including cell cycle control and differentiation. We queried whether its mutation might play a role in red cell malignancies by genomic sequencing of the KLF1 transcription unit in cell lines, erythroid neoplasms, dysplastic disorders, and leukemia. In addition, we queried published databases from a number of varied sources.