Mass cytometric single cell immune profiles of peripheral blood from acute myeloid leukemia patients in complete remission with measurable residual disease.

Measurable residual disease (MRD) is detected in approximately a quarter of AML chemotherapy responders, serving as a predictor for relapse and shorter survival. Immunological control of residual disease is suggested to prevent relapse, but the mechanisms involved are not fully understood. We present a peripheral blood single cell immune profiling by mass cytometry using a 42-antibody panel with particular emphasis on markers of cellular immune response.

A systematic literature review on the significance of deep learning and machine learning in predicting Alzheimer's disease.

Background: Alzheimer's disease (AD) is the most prevalent cause of dementia, characterized by a steady decline in mental, behavioral, and social abilities and impairs a person's capacity for independent functioning. It is a fatal neurodegenerative disease primarily affecting older adults.

Objectives: The purpose of this literature review is to investigate various AD detection techniques, datasets, input modalities, algorithms, libraries, and performance evaluation metrics used to determine which model or strategy may provide superior performance.

Acute Bilateral Pyelonephritis in the Setting of Newly Diagnosed Diabetes Mellitus: A Case Report.

Introduction: Acute pyelonephritis is a bacterial infection that starts in the bladder and ascends to the kidneys, causing inflammation of the renal parenchyma. Women are more likely to get infected compared to men, with diabetics being at higher risk. The pathophysiology of how diabetics are more prone to getting urinary tract infections/pyelonephritis has been studied, particularly the difference between bilateral pyelonephritis and unilateral pyelonephritis.

Real and synthetic Punjabi speech datasets for automatic speech recognition.

Automatic speech recognition (ASR) has been an active area of research. Training with large annotated datasets is the key to the development of robust ASR systems. However, most available datasets are focused on high-resource languages like English, leaving a significant gap for low-resource languages.

Derivation, validation, and prediction of loading-induced mineral apposition rates at endocortical and periosteal bone surfaces based on fluid velocity and pore pressure.

The capacity of bone to optimize its structure in response to mechanical loads has been widely observed. The mechanical load acting on a bone at the macroscopic level influences the bone cells, particularly osteocytes within the lacunae canalicular network (LCN). Osteocytes are responsive to a range of physical signals, including strain, interstitial fluid flow, and pore pressure.

Otolith microchemistry of freshwater indigenous minor carp (Bangana dero) as a biomonitoring tool to trace heavy metals in River Sutlej, Ropar Wetland (Ramsar site), Punjab, India.

The elemental composition of the fish otolith may represent a permanent record of the environmental condition the fish inhabited. Fish otolith grows incrementally from the core to a marginal region that acts as a repository of trace metal signatures. The present study explores the potential application of otolith microchemistry of the benthopelagic indigenous minor carp Bangana dero sampled from the Ropar wetland on River Sutlej, Punjab.

Advances and challenges in thyroid cancer: The interplay of genetic modulators, targeted therapies, and AI-driven approaches.

Thyroid cancer continues to exhibit a rising incidence globally, predominantly affecting women. Despite stable mortality rates, the unique characteristics of thyroid carcinoma warrant a distinct approach. Differentiated thyroid cancer, comprising most cases, is effectively managed through standard treatments such as thyroidectomy and radioiodine therapy.

Pharmacophore derived 3D-QSAR, molecular docking, and simulation studies of quinoxaline derivatives as ALR2 inhibitors.

Aldose Reductase 2 (ALR2), a key enzyme of the polyol pathway, plays a crucial role in the pathogenesis of diabetic complications. Quinoxaline scaffold-based compounds have been identified as potential ALR2 inhibitors for the management of diabetic complications. In the present work, molecular dynamic simulation studies in conjugation with pharmacophore mapping and atom-based 3D-QSAR were performed on a dataset of 99 molecules in comparison with Epalrestat (reference) to mark the desirable structural features of quinoxaline analogs to generate a probable template for designing novel and effective ALR2 inhibitors.

Insight into the liver dysfunction in COVID-19 patients: Molecular mechanisms and possible therapeutic strategies.

As of June 2022, more than 530 million people worldwide have become ill with coronavirus disease 2019 (COVID-19). Although COVID-19 is most commonly associated with respiratory distress (severe acute respiratory syndrome), meta-analysis have indicated that liver dysfunction also occurs in patients with severe symptoms. Current studies revealed distinctive patterning in the receptors on the hepatic cells that helps in viral invasion through the expression of angiotensin-converting enzyme receptors.

Dual aromatase-steroid sulfatase inhibitors (DASI's) for the treatment of breast cancer: a structure guided ligand based designing approach.

Dual aromatase-steroid sulfatase inhibitors (DASIs) lead to significant deprivation of estrogen levels as compared to a single target inhibition and thereby exhibited an additive or synergistic effect in the treatment of hormone-dependent breast cancer (HDBC). Triazole-bearing DASI's having structural features of clinically available aromatase inhibitors are identified as lead structures for optimization as DASI's. To identify the spatial fingerprints of target-specific triazole as DASI's, we have performed molecular docking assisted Gaussian field-based comparative 3D-QSAR studies on a dataset with dual aromatase-STS inhibitory activities.

Targeting mitochondrial bioenergetics as a promising therapeutic strategy in metabolic and neurodegenerative diseases.

Mitochondria are the organelles that generate energy for the cells and act as biosynthetic and bioenergetic factories, vital for normal cell functioning and human health. Mitochondrial bioenergetics is considered an important measure to assess the pathogenesis of various diseases. Dysfunctional mitochondria affect or cause several conditions involving the most energy-intensive organs, including the brain, muscles, heart, and liver.

Molecular dynamics and 3D-QSAR studies on indazole derivatives as HIF-1α inhibitors.

Hypoxia-inducible factor (HIF) is a transcriptional factor which plays a crucial role in tumour metastasis thereby responsible for development of various forms of cancers. Indazole derivatives have been reported in the literature as potent HIF-1α inhibitor interaction with key residues of the HIF-1α active site. Taking into consideration the role HIF-1α in cancer and potency of indazole derivative against HIF-1α; it was considered of interest to correlate structural features of known indazole derivatives with specified HIF-1α inhibitory activity to map pharmacophoric features through Three-dimensional quantitative structural activity relationship (3D-QSAR) and pharmacophore mapping.

Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade.

DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of cells from the human DCOne myeloid leukemic cell line. This results in a vaccine comprising a broad array of endogenous tumor antigens combined with a mature dendritic cell (mDC) costimulatory profile, functioning as a local inflammatory adjuvant when injected into an allogeneic recipient. Intradermal DCP-001 vaccination has been shown to be safe and feasible as a post-remission therapy in acute myeloid leukemia.

Anti-Inflammatory Treatment of COVID-19 Pneumonia With Tofacitinib Alone or in Combination With Dexamethasone is Safe and Possibly Superior to Dexamethasone as a Single Agent in a Predominantly African American Cohort.

Objective: To explore the survival benefit of tofacitinib in addition to dexamethasone in hospitalized patients treated for coronavirus disease 2019 (COVID-19)-related pneumonia.

Patients And Methods: This is a single-center retrospective observational study. All patients who were hospitalized at Delta Regional Medical Center (a regional hospital in the Mississippi Delta) with a COVID-19 diagnosis and discharged between March 1 and September 30, 2020, are included.

Towards the Objective Speech Assessment of Smoking Status based on Voice Features: A Review of the Literature.

Background And Objective: In smoking cessation clinical research and practice, objective validation of self-reported smoking status is crucial for ensuring the reliability of the primary outcome, that is, smoking abstinence. Speech signals convey important information about a speaker, such as age, gender, body size, emotional state, and health state. We investigated (1) if smoking could measurably alter voice features, (2) if smoking cessation could lead to changes in voice, and therefore (3) if the voice-based smoking status assessment has the potential to be used as an objective smoking cessation validation method.

Seven novel genetic variants in a North Indian cohort with classical homocystinuria.

Classical homocystinuria is the most common cause of isolated homocystinuria. The variants of the CBS gene remain unidentified in Indian children with this disorder. Based on the hallmark clinical features, family history, and/or biochemical clues for classical homocystinuria, 16 children below the age of 18 years were evaluated by Sanger sequencing of the coding exons of CBS gene with flanking intronic regions.

A novel allogeneic off-the-shelf dendritic cell vaccine for post-remission treatment of elderly patients with acute myeloid leukemia.

In elderly acute myeloid leukemia (AML) patients post-remission treatment options are associated with high comorbidity rates and poor survival. Dendritic cell (DC)-based immunotherapy is a promising alternative treatment strategy. A novel allogeneic DC vaccine, DCP-001, was developed from an AML-derived cell line that uniquely combines the positive features of allogeneic DC vaccines and expression of multi-leukemia-associated antigens.

Structure and function of renal macrophages and dendritic cells from lupus-prone mice.

Objective: To characterize renal macrophages and dendritic cells (DCs) in 2 murine models of lupus nephritis.

Methods: We used a bead-based enrichment step followed by cell sorting to isolate populations of interest from young mice and nephritic mice. Cell morphology was examined by microscopy.

Hierarchical modeling for rare event detection and cell subset alignment across flow cytometry samples.

Flow cytometry is the prototypical assay for multi-parameter single cell analysis, and is essential in vaccine and biomarker research for the enumeration of antigen-specific lymphocytes that are often found in extremely low frequencies (0.1% or less). Standard analysis of flow cytometry data relies on visual identification of cell subsets by experts, a process that is subjective and often difficult to reproduce.

The development of standard samples with a defined number of antigen-specific T cells to harmonize T cell assays: a proof-of-principle study.

The validation of assays that quantify antigen-specific T cell responses is critically dependent on cell samples that contain clearly defined measurable numbers of antigen-specific T cells. An important requirement is that such cell samples are handled and analyzed in a comparable fashion to peripheral blood mononuclear cells (PBMC). We performed a proof-of-principle study to show that retrovirally TCR-transduced T cells spiked at defined numbers in autologous PBMC can be used as standard samples for HLA/peptide multimer staining.

The simultaneous ex vivo detection of low-frequency antigen-specific CD4+ and CD8+ T-cell responses using overlapping peptide pools.

The ability to measure antigen-specific T cells at the single-cell level by intracellular cytokine staining (ICS) is a promising immunomonitoring tool and is extensively applied in the evaluation of immunotherapy of cancer. The protocols used to detect antigen-specific CD8+ T-cell responses generally work for the detection of antigen-specific T cells in samples that have undergone at least one round of in vitro pre-stimulation. Application of a common protocol but now using long peptides as antigens was not suitable to simultaneously detect antigen-specific CD8+ and CD4+ T cells directly ex vivo in cryopreserved samples.

Design of neo-glycoconjugates that target the mannose receptor and enhance TLR-independent cross-presentation and Th1 polarization.

Cross-presentation is an important mechanism by which DCs present exogenous antigens on MHC-I molecules, and activate CD8(+) T cells, cells that are crucial for the elimination of tumors. We investigated the feasibility of exploiting the capacity of the mannose receptor (MR) to improve both cross-presentation of tumor antigens and Th polarization, processes that are pivotal for the anti-tumor potency of cytotoxic T cells. To this end, we selected two glycan ligands of the MR, 3-sulfo-Lewis(A) and tri-GlcNAc (N-acetylglucosamine), to conjugate to the model antigen OVA and assessed in vitro the effect on antigen presentation and Th differentiation.