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Meaningful analysis of voluminous health information has always been a challenge in most healthcare organizations. Accurate and timely information required by the management to lead a healthcare organization through the challenges found in the industry can be obtained using business intelligence (BI) or business analytics tools. However, these require large capital investments to implement and support the large volumes of data that needs to be analyzed to identify trends. They also require enormous processing power which places pressure on the business resources in addition to the dynamic changes in the digital technology. This paper evaluates the various nuances of business analytics of healthcare hosted on the cloud computing environment. The paper explores BI being offered as Software as a Service (SaaS) solution towards offering meaningful use of information for improving functions in healthcare enterprise. It also attempts to identify the challenges that healthcare enterprises face when making use of a BI SaaS solution.

A free convective flow of an incompressible and electrically conducting fluid through a vertical micro-channel of rectangular geometry was considered. Both plates were porous and heated alternately. A transverse magnetic field was applied across the channel. One channel wall surface was no slip and the other was super-hydrophobic. The purpose of the study is to examine the effects of super-hydrophobicity, magnetism and wall porosity on the main characteristics of the flow. The exact solutions of the formulated differential equations were provided. A few highlights of the results obtained include: (1) the magnetic parameter lowered the skin friction at both surfaces when either of them were heated, (2) the suction/injection parameter raised the fluid temperature when the super-hydrophobic surface (SHS) was heated and brought it down when the no slip surface (NSS) was heated, (3) a critical temperature jump coefficient was observed at which the flow rates in both cases (only SHS heated, and only NSS heated) were equal. A few application areas of the research include micro-fluidics and micro-electronics. [ABSTRACT FROM AUTHOR]

Calcium ions are the second messenger playing as regulators for various cellular activities. Its spatiotemporal control is critical for various brain functions, including neuroplasticity, apoptosis, and cell death. The Endoplasmic Reticulum (ER) plays an important role in determining these spatiotemporal calcium dynamics. Stromal interaction molecule (STIM) - Orai channel on the membrane generates additional calcium flow, whereas other membrane fluxes contribute to cytosolic flux. Due to their anomalous character, we used the Caputo fractional differential operator to mimic these interactions in polar coordinates. Solutions were generated using hybrid integral transform methods to control the analytical approach. Using Green's function yielded a closed-form solution for Mittag-Leffler-type functions. This work emphasizes the significant relationship between calcium and various buffer levels in neurons. The differential transition simulation of a time derivative with space across different parameters indicated a decrease in calcium concentration. Anomalously low buffer levels exhibited the impact of Alzheimer's disease on calcium higher concentration, leading to the death of neurons. Additionally, the research introduces a method involving S100B, BAPTA, and calmodulin buffers to uphold optimal calcium levels within the neuronal cytosol. The applicability of this model with different buffer properties and parameters and memory impacts the calcium concentration with the neurological disorder., Competing Interests: Compliance with ethical standards Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Calcium plays a crucial role as a second messenger in neuronal signal transduction pathways. The influx of calcium ions through various physicochemical gating channels activates neuronal calcium signaling. The Endoplasmic Reticulum (ER) is a significant intracellular structure that sequesters calcium and controls signaling through SERCA, IPR, and leak channel mechanisms. Disruption of calcium dynamics can trigger intrinsic dyshomeostasis, cell damage, and apoptosis. The present study articulates a Caputo fractional time derivative in the polar coordinate dimensions to investigate the role of nonlocal calcium-free ions in the neuron through the Orai channel, and ER fluxes, incorporating various physiological parameters. The solution was obtained through the hybrid integral transform technique for analytical form. The closed form was generated using Green's function in terms of Mainardi and Wright's functions. Our simulation uncovered the calcium concentration bandwidth of interaction with different neuronal parameters. Parameters and calcium ion synergy show normal and Alzheimer's disease-impacted interaction through different illustrations. Our simulation reveals that S100B and BAPTA have significant calcium-controlling behavior., Competing Interests: Compliance with Ethical Standards Conflict of Interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Extensive research has demonstrated that astrocytes actively participate in the regulation of synaptic communication. To examine the dynamic behavior of the model, a neuron-astrocyte model has been solved, and a bifurcation analysis has been performed. This paper uses the equilibrium point, stability theory, and the center manifold theorem to theoretically investigate the dynamical analysis of Ca 2+ oscillations in the cytosol. The connections at tripartite synapses between the cells have been modeled using IP 3 and 2-AG. A mathematical model is used to depict the overall framework of bifurcation and induced Ca 2+ dynamics. The differences in the presence and disappearance of Ca 2+ oscillations are partially explained by two subcritical Hopf bifurcation points, according to the results. Communication between the cells occurs through the oscillations of Ca 2+ concentration. Furthermore, numerical simulations are conducted to confirm the efficacy of the suggested approach. Thus, our findings imply that neuron-astrocyte crosstalk plays a fundamental role in generating a variety of neuronal activities, thereby improving the brain's capacity for information processing., Competing Interests: Compliance with Ethical Standards Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

During the COVID-19 pandemic, Nepal, like other countries, faced emerging SARS-CoV-2 variants. To evaluate the circulating variants, 278 samples collected between September 2021 and March 2022 were sequenced in the country. From these, 229 high-quality genomes were obtained (82.97% Omicron and 17.03% Delta) highlighting the genomic diversity of SARS-CoV-2 in Nepal.

Background: The 4 serotypes of dengue virus (DENV1-4) can each cause potentially deadly dengue disease, and are spreading globally from tropical and subtropical areas to more temperate ones. Nepal provides a microcosm of this global phenomenon, having met each of these grim benchmarks. To better understand DENV transmission dynamics and spread into new areas, we chose to study dengue in Nepal and, in so doing, to build the onsite infrastructure needed to manage future, larger studies., Methods and Results: During the 2022 dengue season, we enrolled 384 patients presenting at a hospital in Kathmandu with dengue-like symptoms; 79% of the study participants had active or recent DENV infection (NS1 antigen and IgM). To identify circulating serotypes, we screened serum from 50 of the NS1 + participants by RT-PCR and identified DENV1, 2, and 3 - with DENV1 and 3 codominant. We also performed whole-genome sequencing of DENV, for the first time in Nepal, using our new on-site capacity. Sequencing analysis demonstrated the DENV1 and 3 genomes clustered with sequences reported from India in 2019, and the DENV2 genome clustered with a sequence reported from China in 2018., Conclusion: These findings highlight DENV's geographic expansion from neighboring countries, identify China and India as the likely origin of the 2022 DENV cases in Nepal, and demonstrate the feasibility of building onsite capacity for more rapid genomic surveillance of circulating DENV. These ongoing efforts promise to protect populations in Nepal and beyond by informing the development and deployment of DENV drugs and vaccines in real time., (© 2024. The Author(s).)

Mathematical neuroscience investigates how calcium distribution in nerve cells affects the neurological system. The interaction of numerous systems is necessary for the operation of several cellular processes in neuron cells, such as calcium, buffer, ER etc. The dynamics of interacting parameters give useful information on neural cell function. This work uses a mathematical model to analyze the dynamic interactions of buffer and ER inside neurons, considering their spatial properties. While buffers bind to calcium ions and lower their concentration, the endoplasmic reticulum (ER) serves as a reservoir, holding a significant number of free calcium ions. The uncertainty of initial values of calcium concentration poses challenges for researchers to develop calcium signaling models. In this article, we examined the exact solution and approximate solution of the mathematical model that was analyzed using the fuzzy undetermined coefficient approach. MATLAB is being used to perform the simulation. Endoplasmic reticulum and buffer have been found to have a substantial impact on calcium signaling. Fuzzy differential equation Provides a useful tool for evaluating complicated processes with imprecise values when ordinary differential equations perform not precisely. They allow for the examination of dynamic processes under fuzzy settings, which contributes to advances research., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This work presents a novel feature extraction method for identifying complex patterns in genomic sequences by employing the Hidden Markov Model (HMM). In this study, we use HMM to identify gene nucleotide patterns that are specific to malignant and non-malignant cells. Crucial genetic components DNA and RNA are involved in many biological processes that impact both healthy and malignant cells. Early patient identification is essential to successful cancer diagnosis and therapy. Varying nucleotide patterns indicate different cellular responses, which are important to understanding the molecular causes of cancer and associated disorders. We present a detailed study of nucleotide patterns in whole raw nucleotide sequences with variations in both protein sequence (CDS) and non-protein sequence (NCDS) in both malignant and non-malignant cells. Nucleotide prediction has been achieved while computational expenses are reduced by using the proposed HMM for feature extraction and selection. The classification models implemented in this work for cancer detection are Gradient-Boosted Decision Trees (GBDT), Random Forests (RF), Decision Trees (DT), and Support Vector Machines (SVM) with kernels. The suggested classification model's accuracy and 10-fold cross-validation have been validated via comprehensive case studies. The results reveal that DT and ensemble learning techniques significantly differentiate between malignant and non-malignant DNA sequences. SVM with suitable kernels improves cancer detection accuracy significantly. Combining feature reduction approaches with nucleotide pattern classifiers based on Hidden Markov models improves performance and ensures reliable cancer detection., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Nucleotide-based molecules called DNA and RNA are essential for several biological processes that affect both normal and cancerous cells. They contain the critical genetic material needed for normal cell growth and functioning. The DNA structure patterns that make up the genetic code affect cells' growth, behavior, and control. Different DNA structure patterns indicate different physiological effects in the cell. Knowledge of these patterns is necessary to identify the molecular origins of cancer and other disorders. Analyzing these patterns can help in the early detection of diseases, which is essential for the effectiveness of cancer research and therapy. The novelty of this study is to examine the patterns of dinucleotide structure in many genomic regions, including the non-coding region sequence (N-CDS), coding region sequence (CDS), and whole raw DNA sequence (W.R. sequence). It provides an in-depth discussion of dinucleotide patterns related to these diverse genetic environments and contains malignant and non-malignant DNA sequences. The Markovian modeling that predicts dinucleotide probabilities also reduces feature complexity and minimizes computational costs compared to the approaches of Kernelized Logistic Regression (KLR) and Support Vector Machine (SVM). This technique is effectively evaluated in essential case studies, as indicated by accuracy metrics and 10-fold cross-validation. The classifier and feature reduction, which are generated by Markovian probability, operate well together and can help predict cancer. Our findings successfully distinguish DNA sequences related to cancer from those diagnostics of non-cancerous diseases by analyzing the W.R. DNA sequence as well as its CDS and N-CDS regions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Platinum resistance is the primary cause of poor survival in ovarian cancer (OC) patients. Targeted therapies and biomarkers of chemoresistance are critical for the treatment of OC patients. Our previous studies identified cell surface CD55, a member of the complement regulatory proteins, drives chemoresistance and maintenance of cancer stem cells (CSCs). CSCs are implicated in tumor recurrence and metastasis in multiple cancers., Methods: Protein localization assays including immunofluorescence and subcellular fractionation were used to identify CD55 at the cell surface and nucleus of cancer cells. Protein half-life determinations were used to compare cell surface and nuclear CD55 stability. CD55 deletion mutants were generated and introduced into cancer cells to identify the nuclear trafficking code, cisplatin sensitivity, and stem cell frequency that were assayed using in vitro and in vivo models. Detection of CD55 binding proteins was analyzed by immunoprecipitation followed by mass spectrometry. Target pathways activated by CD55 were identified by RNA sequencing., Results: CD55 localizes to the nucleus of a subset of OC specimens, ascites from chemoresistant patients, and enriched in chemoresistant OC cells. We determined that nuclear CD55 is glycosylated and derived from the cell surface pool of CD55. Nuclear localization is driven by a trafficking code containing the serine/threonine (S/T) domain of CD55. Nuclear CD55 is necessary for cisplatin resistance, stemness, and cell proliferation in OC cells. CD55 S/T domain is necessary for nuclear entry and inducing chemoresistance to cisplatin in both in vitro and in vivo models. Deletion of the CD55 S/T domain is sufficient to sensitize chemoresistant OC cells to cisplatin. In the nucleus, CD55 binds and attenuates the epigenetic regulator and tumor suppressor ZMYND8 with a parallel increase in H3K27 trimethylation and members of the Polycomb Repressive Complex 2., Conclusions: For the first time, we show CD55 localizes to the nucleus in OC and promotes CSC and chemoresistance. Our studies identify a therapeutic mechanism for treating platinum resistant ovarian cancer by blocking CD55 nuclear entry., (© 2024. The Author(s).)

Free Calcium ions in the cytosol are essential for many physiological and physical functions. The free calcium ions are commonly regarded as a second messenger, are an essential part of brain communication. Numerous physiological activities, such as calcium buffering and calcium ion channel flow, etc. influence the cytosolic calcium concentration. In light of the above, the primary goal of this study is to develop a model of calcium distribution in neuron cells when a Voltage-Gated Calcium Channel and Sodium Calcium Exchanger are present. As we know, decreased buffer levels and increased calcium activity in the Voltage-Gated Calcium Channel and Sodium Calcium Exchanger lead to Alzheimer's disease. Due to these changes, the calcium diffusion in that location becomes disrupted and impacted by Alzheimer's disease. The model has been constructed by considering key factors like buffers and ER fluxes when Voltage-Gated Calcium Channels and Sodium Calcium Exchangers are present. Based on the physiological conditions of the parameters, appropriate boundary conditions have been constructed in the fuzzy environment. This model is considered a fuzzy boundary value problem with the source term and initial boundary conditions are modeled by triangular fuzzy functions. In this, paper we observed the approximate solution of the mathematical model which was investigated by the fuzzy undetermined coefficient method. The solution has been performed through MATLAB and numerical results have been computed using simulation. The observation made that the proper operation of the Voltage-Gated Calcium Channel and Sodium Calcium Exchanger is critical for maintaining the delicate equilibrium of calcium ions, which regulates vital cellular activities. Dysregulation of Voltage-Gated Calcium Channel and Sodium Calcium Exchanger activity has been linked to neurodegenerative illnesses like Alzheimer's disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Influenza (sometimes referred to as "flu") is a contagious viral infection of the airways in the lungs that affects a significant portion of the world's population. Clinical symptoms of influenza virus infections can range widely, from severe pneumonia to moderate or even asymptomatic sickness. If left untreated, influenza can have more severe effects on the heart, brain, and lungs than on the respiratory tract and can necessitate hospitalization. This study was aimed to investigate and characterize all types of influenza cases prevailing in Nepal and to analyze seasonal occurrence of Influenza in Nepal in the year 2019. A cross sectional, retrospective and descriptive study was carried out at National Influenza Center (NIC), National Public Health Laboratory Kathmandu Nepal for the period of one year (Jan-Dec 2019). A total of 3606 throat swab samples from various age groups and sexes were processed at the NIC. The specimens were primarily stored at 4 °C and processed using ABI 7500 RT PCR system for the identification of Influenza virus types and subtypes. Data accessed for research purpose were retrieved from National Influenza Centre (NIC) on 1st Jan 2020. Of the total 3606 patients suspected of having influenza infection, influenza viruses were isolated from 1213 (33.6%) patients with male predominance. The highest number of infection was caused by Influenza A/Pdm09 strain 739 (60.9%) followed by Influenza B 304 (25.1%) and Influenza A/H3 169 (13.9%) and most remarkable finding of this study was the detection of H5N1 in human which is the first ever case of such infection in human from Nepal. Similar to other tropical nations, influenza viruses were detected year-round in various geographical locations of Nepal. The influenza virus type and subtypes that were in circulation in Nepal were comparable to vaccine candidate viruses, which the currently available influenza vaccine may prevent., (© 2024. The Author(s).)

An efficient functionalization of tyrosine residues in phenolic regions is achieved under metal-free conditions. The strategy involves the conversion of a tyrosine residue to 4-amino phenylalanine or 4-amino-3-methoxy phenylalanine in short peptides through a controlled oxidative dearomatization. This transformation is achieved in one pot with good yields and excellent regioselectivity. Consequently, the self-assembly of the peptide compounds has been studied at the nanoscopic level before and after functionalization. The results suggest that the peptide derivatives comprising amide groups promote intermolecular H-bonding interactions and the difference in -OH and -NH 2 functional groups is found to be responsible for the morphological changes. Morphological transitions from 1D nanowires to 2D nanosheets were observed during functional group modification.

PHF6 mutations (PHF6 MT ) are identified in various myeloid neoplasms (MN). However, little is known about the precise function and consequences of PHF6 in MN. Here we show three main findings in our comprehensive genomic and proteomic study. Firstly, we show a different pattern of genes correlating with PHF6 MT in male and female cases. When analyzing male and female cases separately, in only male cases, RUNX1 and U2AF1 are co-mutated with PHF6. In contrast, female cases reveal co-occurrence of ASXL1 mutations and X-chromosome deletions with PHF6 MT . Next, proteomics analysis reveals a direct interaction between PHF6 and RUNX1. Both proteins co-localize in active enhancer regions that define the context of lineage differentiation. Finally, we demonstrate a negative prognostic role of PHF6 MT , especially in association with RUNX1. The negative effects on survival are additive as PHF6 MT cases with RUNX1 mutations have worse outcomes when compared to cases carrying single mutation or wild-type., (© 2024. The Author(s).)

Loss of function TET2 mutation (TET2 MT ) is one of the most frequently observed lesions in clonal hematopoiesis (CH). TET2 a member TET-dioxygenase family of enzymes that along with TET1 and TET3, progressively oxidize 5-methyl cytosine (mC) resulting in regulated demethylation of promoter, enhancer and silencer elements of the genome. This process is critical for efficient transcription that determine cell lineage fate, proliferation and survival and the maintenance of the genomic fidelity with aging of the organism. Partial or complete loss-of-function TET2 mutations create regional and contextual DNA hypermethylation leading to gene silencing or activation that result in skewed myeloid differentiation and clonal expansion. In addition to myeloid skewing, loss of TET2 creates differentiation block and provides proliferative advantage to hematopoietic stem and progenitor cells (HSPCs). TET2 MT is a prototypical lesion in CH, since the mutant clones dominate during stress hematopoiesis and often associates with evolution of myeloid malignancies. TET2 MT clones has unique privilege to create and persist in pro-inflammatory milieu. Despite extensive knowledge regarding biochemical mechanisms underlying distorted myeloid differentiation, and enhanced self-replication of TET2 MT HSPC, the mechanistic link of various pathogenesis associated with TET2 loss in CHIP is less understood. Here we review the recent development in TET2 biology and its probable mechanistic link in CH with aging and inflammation. We also explored the therapeutic strategies of targeting TET2 MT associated CHIP and the utility of targeting TET2 in normal hematopoiesis and somatic cell reprograming. We explore the biochemical mechanisms and candidate therapies that emerged in last decade of research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cytosolic-free calcium ions play an important role in various physical and physiological processes. A vital component of neural signaling is the free calcium ion concentration often known as the second messenger. There are many parameters that effect the cytosolic free calcium concentration like buffer, voltage-gated ion channels, Endoplasmic reticulum, Mitochondria, etc. Mitochondria are small organelles located within the nervous system that are involved in processes within cells such as calcium homeostasis management, energy generation, response to stress, and cell demise pathways. In this work, a mathematical model with fuzzy boundary values has been developed to study the effect of Mitochondria and ER fluxes on free Calcium ions. The intended findings are displayed utilizing the physiological understanding that amyloid beta plaques and tangles of neurofibrillary fibers have been identified as the two main causes of AD. The key conclusion of the work is the investigation of [Formula: see text] for healthy cells and cells affected by Alzheimer's disease, which may aid in the study of such processes for computational scientists and medical practitioners. Also, it has been shown that when a unique solution is found for a specific precise problem, it also successfully deals with any underlying ambiguity within the problem by utilizing a technique based on the principles of linear transformation. Furthermore, the comparison between the analytical approach and the generalized hukuhara derivative approach is shown here, which illustrates the benefits of the analytical approach. The simulation is carried out in MATLAB., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ca 2+ signaling is an essential function of neurons to control synaptic activity, memory formation, fertilization, proliferation, etc. Protein and voltage-dependent calcium channels (VDCCs) maintain an adequate level of calcium concentration ([Ca 2+ ]). An alteration in [Ca 2+ ] leads to the death of the neurons that start the primary symptoms of the disease. The present study deals with cell memory-based mathematical modeling of Ca 2+ that is characterized by the presence of protein and VDCC. We developed a two-dimensional Ca 2+ neuronal model to study the spatiotemporal behavior of the Ca 2+ profile. All principal parameters like buffer concentration, diffusion coefficient, VDCC fluxes, etc. are incorporated in this model. Apposite initial and boundary conditions are applied to the physiology of the problem. We obtained an approximate Ca 2+ profile by the fractional integral transform method. The application of obtained results is performed to provide its implications to estimate the [Ca 2+ ] in neurodegenerative disease. It is observed that the protein and VDCC provide a significant impact in the presence of cell memory. The memory of cells shrinks the Ca 2+ flow from elevation and provides better results to estimated Ca 2+ flow in the disease state., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Viral replication often depends on RNA maturation and degradation processes catalyzed by viral ribonucleases, which are therefore candidate targets for antiviral drugs. Here, we synthesized and studied the antiviral properties of a novel nitrocatechol compound ( 1c ) and other analogs that are structurally related to the catechol derivative dynasore. Interestingly, compound 1c strongly inhibited two DEDD box viral ribonucleases, HIV-1 RNase H and SARS-CoV-2 nsp14 3'-to-5' exoribonuclease (ExoN). While 1c inhibited SARS-CoV-2 ExoN activity, it did not interfere with the mRNA methyltransferase activity of nsp14. In silico molecular docking placed compound 1c in the catalytic pocket of the ExoN domain of nsp14. Finally, 1c inhibited SARS-CoV-2 replication but had no toxicity to human lung adenocarcinoma cells. Given its simple chemical synthesis from easily available starting materials, these results suggest that 1c might be a lead compound for the design of new antiviral compounds that target coronavirus nsp14 ExoN and other viral ribonucleases.

Human infection with the protozoan parasite Trypanosoma cruzi causes Chagas disease for which there are no prophylactic vaccines. Cyclophilin 19 is a secreted cis-trans peptidyl isomerase expressed in all life stages of Trypanosoma cruzi. This protein in the insect stage leads to the inactivation of insect anti-parasitic peptides and parasite transformation whereas in the intracellular amastigotes it participates in generating ROS promoting the growth of parasites. We have generated a parasite mutant with depleted expression of Cyp19 by removal of 2 of 3 genes encoding this protein using double allelic homologous recombination. The mutant parasite line failed to replicate when inoculated into host cells in vitro or in mice indicating that Cyp19 is critical for infectivity. The mutant parasite line also fails to replicate in or cause clinical disease in immuno-deficient mice further validating their lack of virulence. Repeated inoculation of mutant parasites into immuno-competent mice elicits parasite-specific trypanolytic antibodies and a Th-1 biased immune response and challenge of mutant immunized mice with virulent wild-type parasites is 100% effective at preventing death from acute disease. These results suggest that parasite Cyp19 may be candidate for small molecule drug targeting and that the mutant parasite line may warrant further immunization studies for prevention of Chagas disease., (© 2023. The Author(s).)

Calcium signaling is decisive for cellular functions. This calcium random walk stipulates neuronal functions. Calcium concentration could provoke gene transcription, apoptosis, neuronal plasticity, etc. A malformation in calcium could change the neuron's intracellular behavior. Calcium concentration balancing is a complex cellular mechanism. This occurrence can be handled with the Caputo fractional reaction-diffusion equation. In this mathematical modeling, we have included the STIM-Orai mechanism and Endoplasmic Reticulum (ER) flux, Inositol Triphosphate Receptor (IPR), SERCA, plasma membrane flux, voltage-gated calcium entry, and different buffer interactions. A hybrid integral transform and Green's function approach were taken to solve the initial boundary problem. A closed-form solution of a Mittag-Leffler family function plotted using MATLAB software. Different parameters impact changes in the spatiotemporal behavior of the calcium concentration. Specific roles of organelles involved in Alzheimer's disease-affected neurons are computed. Ethylene glycol tetraacetic acid (EGTA), 1,2-bis(o-aminophenoxy)ethane N,N,N,N-tetraacetic acid (BAPTA), and S100B protein effects are also observed. In all simulations, we can say S100B and the STIM-Orai effect cannot be neglected. This model lights up the different approaches for calcium signaling pathway simulation. As a consequence, we determine that a generalized reaction-diffusion approach is a better fit realistic model., (© The Author(s), under exclusive licence to Società Italiana di Fisica and Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In this paper, we construct the SV1V2EIR model to reveal the impact of two-dose vaccination on COVID-19 by using Caputo fractional derivative. The feasibility region of the proposed model and equilibrium points is derived. The basic reproduction number of the model is derived by using the next-generation matrix method. The local and global stability analysis is performed for both the disease-free and endemic equilibrium states. The present model is validated using real data reported for COVID-19 cumulative cases for the Republic of India from 1 January 2022 to 30 April 2022. Next, we conduct the sensitivity analysis to examine the effects of model parameters that affect the basic reproduction number. The Laplace Adomian decomposition method (LADM) is implemented to obtain an approximate solution. Finally, the graphical results are presented to examine the impact of the first dose of vaccine, the second dose of vaccine, disease transmission rate, and Caputo fractional derivatives to support our theoretical results.

Multiple myeloma (MM) is a complex hematologic malignancy characterized by the uncontrolled proliferation of clonal plasma cells in the bone marrow that secrete large amounts of immunoglobulins and other non-functional proteins. Despite decades of progress and several landmark therapeutic advancements, MM remains incurable in most cases. Standard of care frontline therapies have limited durable efficacy, with the majority of patients eventually relapsing, either early or later. Induced drug resistance via up-modulations of signaling cascades that circumvent the effect of drugs and the emergence of genetically heterogeneous sub-clones are the major causes of the relapsed-refractory state of MM. Cytopenias from cumulative treatment toxicity and disease refractoriness limit therapeutic options, hence creating an urgent need for innovative approaches effective against highly heterogeneous myeloma cell populations. Here, we present a comprehensive overview of the current and future treatment paradigm of MM, and highlight the gaps in therapeutic translations of recent advances in targeted therapy and immunotherapy. We also discuss the therapeutic potential of emerging preclinical research in multiple myeloma.

Myeloperoxidase (MPO) gene alterations with variable clinical penetrance have been found in hereditary MPO deficiency, but their leukemia association in patients and carriers has not been established. Germline MPO alterations were found to be significantly enriched in myeloid neoplasms: 28 pathogenic/likely pathogenic variants were identified in 100 patients. The most common alterations were c.2031-2 A > C, R569W, M519fs* and Y173C accounting for about half of the cases. While functional experiments showed that the marrow stem cell pool of Mpo -/- mice was not increased, using competitive repopulation demonstrated that Mpo -/- grafts gained growth advantage over MPO wild type cells. This finding also correlated with increased clonogenic potential after serial replating in the setting of H 2 O 2 -induced oxidative stress. Furthermore, we demonstrated that H 2 O 2 -induced DNA damage and activation of error-prone DNA repair may result in secondary genetic damage potentially predisposing to leukemia leukemic evolution. In conclusion, our study for the first time demonstrates that germline MPO variants may constitute risk alleles for MN evolution., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Radiation therapy damages and depletes total bone marrow (BM) cellularity, compromising safety and limiting effective dosing. Aging also strains total BM and BM hematopoietic stem and progenitor cell (HSPC) renewal and function, resulting in multi-system defects. Interventions that preserve BM and BM HSPC homeostasis thus have potential clinical significance. Here, we report that 50% calorie restriction (CR) for 7-days or fasting for 3-days prior to irradiation improved mouse BM regrowth in the days and weeks post irradiation. Specifically, one week of 50% CR ameliorated loss of total BM cellularity post irradiation compared to ad libitum -fed controls. CR-mediated BM protection was abrogated by dietary sulfur amino acid (i.e., cysteine, methionine) supplementation or pharmacological inhibition of sulfur amino acid metabolizing and hydrogen sulfide (H 2 S) producing enzymes. Up to 2-fold increased proliferative capacity of ex vivo -irradiated BM isolated from food restricted mice relative to control mice indicates cell autonomy of the protective effect. Pretreatment with H 2 S in vitro was sufficient to preserve proliferative capacity by over 50% compared to non-treated cells in ex vivo -irradiated BM and BM HSPCs. The exogenous addition of H 2 S inhibited Ten eleven translocation 2 (TET2) activity in vitro , thus providing a potential mechanism of action. Short-term CR or fasting therefore offers BM radioprotection and promotes regrowth in part via altered sulfur amino acid metabolism and H 2 S generation, with translational implications for radiation treatment and aging.

Although recent work has described the microbiome in solid tumors, microbial content in hematological malignancies is not well-characterized. Here we analyze existing deep DNA sequence data from the blood and bone marrow of 1870 patients with myeloid malignancies, along with healthy controls, for bacterial, fungal, and viral content. After strict quality filtering, we find evidence for dysbiosis in disease cases, and distinct microbial signatures among disease subtypes. We also find that microbial content is associated with host gene mutations and with myeloblast cell percentages. In patients with low-risk myelodysplastic syndrome, we provide evidence that Epstein-Barr virus status refines risk stratification into more precise categories than the current standard. Motivated by these observations, we construct machine-learning classifiers that can discriminate among disease subtypes based solely on bacterial content. Our study highlights the association between the circulating microbiome and patient outcome, and its relationship with disease subtype., (© 2022. The Author(s).)