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Exportin 1 governs the immunosuppressive functions of myeloid-derived suppressor cells in tumors through ERk1/2 nuclear export

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Cellular & Molecular Immunology 2024年第8期21卷 873-891页

作者： Saeed Daneshmandi Qi Yan Jee Eun Choi Eriko katsuta Cameron R.MacDonald Mounika Goruganthu Nathan Roberts Elizabeth A.Repasky prashant k.singh kristopher Attwood Jianmin Wang Yosef Landesman Philip L.McCarthy Hemn Mohammadpour Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNYUSA Department of Cell Stress Biology Roswell Park Comprehensive Cancer CenterBuffaloNYUSA Department of Oncology Yokohama City UniversityGraduate School of MedicineYokohamaJapan Department of Cancer Genetics&Genomics Roswell Park Comprehensive Cancer CenterBuffaloNYUSA Department of Biostatistics&Bioinformatics Roswell Park Comprehensive Cancer CenterBuffaloNYUSA karyopharm Therapeutics NewtonMAUSA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNYUSA

Myeloid-derived suppressor cells(MDSCs)are a main driver of immunosuppression in *** the mechanisms that determine the development and immunosuppressive function of these cells could provide new therapeutic targets to improve antitumor ***,using preclinical murine models,we discovered that exportin 1(XPO1)expression is upregulated in tumor MDSCs and that this upregulation is induced by IL-6-induced STAT3 activation during MDSC ***1 blockade transforms MDSCs into T-cell-activating neutrophil-like cells,enhancing the antitumor immune response and restraining tumor ***,XPO1 inhibition leads to the nuclear entrapment of ERk1/2,resulting in the prevention of ERk1/2 phosphorylation following the IL-6-mediated activation of the MAPk signaling ***,XPO1 blockade in human MDSCs induces the formation of neutrophil-like cells with immunostimulatory ***,our findings revealed a critical role for XPO1 in MDSC differentiation and suppressive functions;exploiting these new discoveries revealed new targets for reprogramming immunosuppressive MDSCs to improve cancer therapeutic responses.

关键词： MDSCs Tumor Exportin 1 MAPk pathway

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Bianchi type V universe with bulk viscous matter and time varying gravitational and cosmological constants

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Research in Astronomy and Astrophysics 2012年第11期12卷 1457-1466页

作者： prashant singh Baghel Jagdish Prasad singh Department of Mathematical Sciences A. P. S. University

We consider spatially homogeneous and anisotropic Bianchi type V space- time with a bulk viscous fluid source, and time varying gravitational constant G and cosmological term A. The coefficient of bulk viscosity ζ is assumed to be a simple linear function of the Hubble parameter H （i.e. ζ = ζ0 ＋ ζ1H, where ζ0 and ζ1 are constants）. The Einstein field equations are solved explicitly by using a law of varia- tion for the Hubble parameter, which yields a constant value of the deceleration pa- rameter. Physical and kinematical parameters of the models are discussed. The models are found to be compatible with the results of astronomical observations.

关键词： bulk viscosity -- Bianchi V -- relativity: equation of state -- cosmology:cosmological parameters -- miscellaneous

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Who to screen and how to screen for celiac disease

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World Journal of Gastroenterology 2022年第32期28卷 4493-4507页

作者： prashant singh Achintya Dinesh singh Vineet Ahuja Govind k Makharia Department of Gastroenterology University of MichiganAnn ArborMI 48109United States Department of Medicine Cleveland ClinicClevelandOH 44195United States Department of Gastroenterology and Human Nutrition All India Institute of Medical SciencesNew Delhi 110029India

Celiac disease(CeD)is a chronic gluten-induced enteropathy with plethoric *** typical manifestations of CeD such as chronic diarrhea and malabsorption are widely recognized,however,many patients have atypical manifestations like iron deficiency anemia,idiopathic short stature,hypertransaminesemia or infertility,*** patients often present to the primary care physicians and/or non-gastrointestinal ***,due to a lack of awareness among the healthcare professionals about the various atypical manifestations,many patients are not screened for *** this review,we have summarized the available literature about the prevalence of CeD in various gastrointestinal(chronic diarrhea)and non-gastrointestinal conditions(iron deficiency anemia,short stature,cryptogenic hypertransaminesemia,cryptogenic cirrhosis or idiopathic ataxia etc.)where the diagnosis of CeD should be *** addition,we also discuss special scenarios where screening for CeD should be considered even in absence of symptoms such as patients with type 1 diabetes,Down’s syndrome,and first-degree relatives of patients with ***,we discuss the diagnostic performance and limitations of various screening tests for CeD such as IgA anti-tissue transglutaminase antibodies,antiendomysial antibodies and anti-deamidated gliadin *** on the current recommendations,we propose a diagnostic algorithm for patients with suspected CeD.

关键词： Screening Diagnosis Serology High-risk group Small intestine Enteropathy

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Sibling composition and child immunization in India and Pakistan,1990-2007

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World Journal of Pediatrics 2014年第2期10卷 145-150页

作者： prashant kumar singh Sulabha Parsuraman International Institute for Population Sciences(IIPS) Govandi Station RoadDeonarMumbai 400088India Department of Population Policies and Programmes International Institute for Population Sciences(IIPS)Govandi Station RoadDeonarMumbai 400088India

Background:This study aimed to assess trends in gender differentials in child immunization beyond the conventional male-female dichotomy,by considering gender,surviving siblings,birth order and different compositions of older siblings in tandem,during 1990-2007 in India and ***:Using different rounds of Demographic and Health Survey datasets,we adopted the World Health Organization guidelines for appraising full immunization among *** composition of surviving older siblings was ***-Armitage and the Chisquare tests were used to test linear and nonlinear trends,***:Although child immunization has increased during the period of 1990-2007 in both India and Pakistan,results showed that more than 50%of the eligible children did not receive the recommended *** results also showed that boys and girls with no older surviving siblings and those with only surviving siblings of the opposite sex appeared to have fully immunized proportionally compared with the children with other sibling ***:The findings confirmed that girls and boys were not always treated equally,and that there was a clear pattern of selective neglect in child immunization in both countries during the period of 1990-2007.

关键词： gender immunization India Pakistan sibling composition

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Charged current quasi-elastic scattering of vμoff^12C

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Chinese Physics C 2018年第12期42卷 25-31页

作者： Deepika Grover kapil Saraswat prashant Shukla Venktesh singh Department of Physics Institute of ScienceBanaras Hindu UniversityVaranasi 221005India Nuclear Physics Division Bhabha Atomic Research CentreMumbai 400085India Homi Bhabha National Institute Anushakti NagarMumbai 400094India

In this work, we study charged current quasi-elastic scattering （QES） of vμ off nucleon and nucleus using a formalism based on the Llewellyn Smith （LS） model. Parameterizations by Galster et al. are used for electric and magnetic Sach＇s form factors of the nucleons. We use the Fermi gas model along with the Pauli suppression condition to take into account the nuclear effects in the anti-neutrino-nucleus QES. We calculate vμ-p and vμ-^12C charged current quasi-elastic scattering differential and total cross sections for different values of axial mass MA, and compare the results with data from the GGM, SkAT, BNL, NOMAD, MINERVA and MiniBooNE experiments. The present theoretical approach gives a good description of differential cross section data. The calculations with axial mass MA =0.979 and 1.05 GeV are compatible with data from most of the experiments.

关键词： cross section quasi-elastic scattering axial mass form factors

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Cellular and molecular insights into microbiota-mitochondriainterplay, therapeutic biomarkers and interventional approachesin COVID-19: A review

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BIOCELL 2023年第10期47卷 2141-2149页

作者： VIBHAV VARSHNEY prashant singh kUSHWAH NEETU AGRAWAL AHSAS GOYAL GOVIND singh Institute of Pharmaceutical Research GLA UniversityMathuraIndia Department of Pharmaceutical Sciences Maharshi Dayanand UniversityRohtakIndia

The persistent global pandemic,COVID-19,stems from the pathogenic influence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),yielding an unprecedented worldwide *** reference to a WHO report,the count of COVID-19 cases had exceeded 754 million by February 03,***,emerging research has spotlighted the intricate interplay of gut microbiota and mitochondrial entities,acting as potent immunomodulatory factors at the cellular and molecular *** interconnection operates through a series of dynamic ***-CoV-2 infection perturbs the delicate equilibrium of gut microbiota,leading to dysbiosis—a signature *** imbalance is intrinsically linked to exacerbated COVID-19 ***,this microbial dysbiosis triggers aberrant immune responses,marked by cytokine storms,while also inducing mitochondrial *** activities crucial to energy production and immunoregulation are *** dual perturbation of microbiota and mitochondria contributes to disease *** review provides a comprehensive overview of these interconnected mechanisms,illuminating how microbiota-mitochondria interplay serves as both a diagnostic biomarker and a promising therapeutic target in the realm of COVID-19.

关键词： Microbiota Mitochondria SARS-CoV-2 COVID-19 Dysbiosis

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Typhoid fever presenting as neuropsychiatric oddities:A case report

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Asian Pacific Journal of Tropical Medicine 2024年第6期17卷 281-284页

作者： prashant Badole Jivtesh singh Preetam N Wasnik Rohini Rokkam Department of General Medicine All India Institute of Medical SciencesRaipur 492099India

Rationale:Salmonella is a common etiological agent behind the tropical fever syndrome in the Indian *** prevalence in India remains high due to a lack of proper sanitation services in large parts of the *** neuropsychiatric manifestations is rare and the understanding on their pathophysiology is still *** concerns:A 19-year-old male,presented with a 10-day history of altered mental status,high-grade fever and violent behaviour.2 Days prior to admission,he developed decreased responsiveness and a muttering delirium with ***:Coma vigil secondary to ***:Intravenous ceftriaxone and ***:The resolution of the coma vigil and the associated Salmonella infection were observed;however,the patient developed residual ***:The atypical presentation of a globally obtunded state followed by mutism in typhoid coma in this case should be brought to the attention of clinicians ***,the enduring speech limitations and potential psychiatric consequences may be linked to the prolonged duration of the infection.

关键词： Salmonella Salmonellosis Coma vigil Typhoid fever

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Sodium-glucose Cotransporter-2 Inhibitors induced euglycemic diabetic ketoacidosis:A meta summary of case reports

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World Journal of Diabetes 2023年第8期14卷 1314-1322页

作者： Deven Juneja prashant Nasa Ravi Jain Omender singh Institute of Critical Care Medicine Max Super Speciality HospitalSaketNew Delhi 110017India Department of Critical Care Medicine NMC Specialty HospitalDubai 7832United Arab Emirates Department of Internal Medicine College of Medicine and Health SciencesAl Ain 15551Abu DhabiUnited Arab Emirates Department of Critical Care Medicine Mahatma Gandhi Medical College and HospitalJaipur 302022RajasthanIndia

BACkGROUND Sodium-glucose cotransporter-2 inhibitors(SGLT2i)are commonly prescribed to manage patients with diabetes *** agents may rarely lead to the development of euglycemic diabetic ketoacidosis(EDkA),which may complicate the disease course of these *** To analyze the demographic profile,predisposing factors,symptomology,clinical interventions and outcomes of patients presenting with EDkA secondary to SGLT2i use by reviewing the published case reports and *** We performed a systematic search of PubMed,Science Direct,Google Scholar and Reference Citation Analysis databases using the terms“canagliflozin”OR“empagliflozin”OR“dapagliflozin”OR“SGLT2 inhibitors”OR“Sodium-glucose cotransporter-2”AND“euglycemia”OR“euglycemic diabetic ketoacidosis”OR“metabolic acidosis”.The inclusion criteria were:(1)Case reports or case series with individual patient details;and(2)Reported EDkA secondary to ***,the data were filtered from the literature published in the English language and on adults(>18 years).We excluded:(1)Conference abstracts;and(2)Case reports or series which did not have individual biochemical *** the case reports and case series were *** data extracted included patient demographics,clinical symptomatology,clinical interventions,intensive care unit course,need for organ support and *** Overall,108 case reports and 17 cases series with 169 unique patients that met all the inclusion criteria were *** majority of patients were females(54.4%,n=92),and the commonly reported symptoms were gastrointestinal(nausea/vomiting 65.1%,abdominal pain 37.3%)and respiratory(breathlessness 30.8%).One hundred and forty-nine(88.2%)patients had underlying type II diabetes,and the most commonly involved SGLT-2 inhibitor reported was empagliflozin(46.8%).A triggering factor was reported in most patients(78.7%),the commonest being acute severe infection(37.9%),which included patients with sepsis,coronavirus

关键词： Canagliflozin Empagliflozin Euglycemia Diabetes mellitus Diabetic ketoacidosis Sodium-glucose cotransporter-2 inhibitors Sodium-glucose cotransporter-2

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Comparative efficacy of hyperbaric bupivacaine vs hyperbaric ropivacaine in spinal anesthesia for cesarean section:A metaanalysis

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World Journal of Methodology 2025年第2期15卷 154-165页

作者： Rishi Anand Deb Sanjay Nag Roushan Patel prashant Sharma Vamsi krishna Uppalapati Umesh kumar singh Department of Anaesthesiology Tata Main HospitalJamshedpur 831001JhārkhandIndia

BACkGROUND Intrathecal bupivacaine is the traditional anesthetic drug used in spinal anesthesia for caesarean sections(CSs),but ropivacaine has emerged as a potential *** meta-analysis compares the efficacy and safety of intrathecal hyper-baric bupivacaine vs hyperbaric ropivacaine for cesarean *** To systematically evaluate and compare the efficacy and safety of intrathecal hyperbaric bupivacaine and hyperbaric ropivacaine for spinal anesthesia in *** A thorough search of electronic databases was carried out to find pertinent randomized controlled trials(RCTs)comparing intrathecal hyperbaric ropi-vacaine and hyperbaric bupivacaine during ***,Cochrane database,Google Scholar,and Scopus were searched,and papers from January 2000 to January 2024 were deemed eligible and filtered using predetermined inclusion and exclusion *** were assessed for methodological quality,and data were extracted for time to adequate anesthesia(sensory and motor blockade),duration of sensory and motor block,hemodynamic changes and side effect *** standardized mean difference with 95%CI was used for continuous *** variables were assessed using the Mantel-Haenszel test and the random effect model to compute the odds *** Total 8 RCTs were selected from a pool of 119 search results for *** meta-analysis evaluated pooled effect sizes and assessed heterogeneity among the *** primary objective was to compare key outcomes to identify any significant variances in efficacy and safety profiles between two local *** analysis revealed that the difference in the onset of sensory blockade between the two local anesthetics was statistically insignificant(P=0.1586).However,the onset of motor blockade appeared to be faster with bupivacaine(P=0.03589).Additionally,the regression of sensory and motor blockade occurred earlier in the ropivacaine ***,the duration of the first analgesic

关键词： Ropivacaine Bupivacaine Anesthesia Spinal Cesarean section Meta-analysis

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Bayesian optimization with active learning of design constraints using an entropy-based approach

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npj Computational Materials 2023年第1期9卷 1866-1879页

作者： Danial khatamsaz Brent Vela prashant singh Duane D.Johnson Douglas Allaire Raymundo Arróyave J.Mike Walker’66 Department of Mechanical Engineering Texas A&M UniversityCollege StationTX 77843USA Department of Materials Science and Engineering Texas A&M UniversityCollege StationTX 77843USA Ames Laboratory U.S.Department of EnergyIowa State UniversityAmesIA 50011USA Department of Materials Science&Engineering Iowa State UniversityAmesIA 50011USA Department of Industrial and Systems Engineering Texas A&M UniversityCollege StationTX 77843USA

The design of alloys for use in gas turbine engine blades is a complex task that involves balancing multiple objectives and *** alloys must be ductile at room temperature and retain their yield strength at high temperatures,as well as possess low density,high thermal conductivity,narrow solidification range,high solidus temperature,and a small linear thermal expansion *** Integrated Computational Materials Engineering(ICME)methods are not sufficient for exploring combinatorially-vast alloy design spaces,optimizing for multiple objectives,nor ensuring that multiple constraints are *** this work,we propose an approach for solving a constrained multi-objective materials design problem over a large composition space,specifically focusing on the Mo-Nb-Ti-V-W system as a representative Multi-Principal Element Alloy(MPEA)for potential use in next-generation gas turbine *** approach is able to learn and adapt to unknown constraints in the design space,making decisions about the best course of action at each stage of the *** a result,we identify 21 Pareto-optimal alloys that satisfy all *** proposed framework is significantly more efficient and faster than a brute force approach.

关键词： alloys solidification alloy

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