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Cancer immunotherapy with envelopedself-amplifying mRNA CARG-2020 thatmodulates IL-12,IL-17 and pD-L1 pathways toprevent tumor recurrence

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Acta pharmaceutica Sinica B 2024年第1期14卷 335-349页

作者： Ju Chen Bhaskara reddy Madina Elham Ahmadi Timur Olegovich Yarovinsky Marie Marthe Krady Eileen Victoria Meehan Isabella China Wang Xiaoyang Ye Elise pitmon Xian-Yong Ma Bijan Almassian Valerian Nakaar Kepeng Wang Department of Immunology School of MedicineUniversity of Connecticut Health CenterFarmingtonCT 06030USA CaroGen Corporation FarmingtonCT 06030USA The Eighth Clinical Medical College of Guangzhou University of Chinese Medicine Foshan Hospital of Traditional Chinese MedicineFoshan 528000China The Loomis Chaffee School WindsorCT 06095USA

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for ***,we describe the application of virus-like vesicles(VLV)for delivery of three immunomodulators alone and in combination,as a promising approach for cancer *** vectors were designed to deliver single chain interleukin(IL)-12,shorthairpin RNA(shRNA)targeting programmed death ligand 1(pD-L1),and a dominant-negative form of IL-17 receptor A(dn-IL17RA)as a single payload or as a combination *** delivery of the VLV vector expressing IL-12 alone,as well as the trivalent vector(designated CARG-2020)eradicated large established ***,only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice,indicating a benefit of the combined *** abscopal effects of CARG-2020 on the non-injected contralateral tumors,as well as protection from the tumor cell re-challenge,suggest immune-mediated mechanism of protection and establishment of immunological ***,CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting *** ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

关键词： Virus-like vesicles Oncolytic virus IL-12 IL-17 pD-L1 T cell exhaustion Combination therapy Cancer immunotherapy

Organ and function preservation in gastrointestinal cancer: Current and future perspectives on endoscopic ablation

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World Journal of Gastrointestinal Endoscopy 2024年第6期16卷 282-291页

作者： Youssef Yousry Soliman Megan Soliman Shravani reddy James Lin Toufic Kachaamy Department of Gastroenterology City of Hope PhoenixGoodyearAZ 85338United States Department of Medicine Medical ConsultingGoodyearAZ 85395United States Department of Gastroenterology University of California IrvineIrvineCA 92697United States Department of Gastroenterology City of Hope National Medical CenterDuarteCA 91010United States

The escalating prevalence of gastrointestinal cancers underscores the urgency for transformative *** treatment costs amount to billions of dollars annually,combined with the risks and comorbidities associated with invasive *** highlights the importance of less invasive alternatives with organ preservation being a central aspect of the treatment *** current standard of care typically involves neoadjuvant systemic therapy followed by surgical *** is a growing interest in organ preservation approaches by way of minimizing extensive surgical *** ablation has proven to be useful in precursor lesions,as well as in palliative cases of unrese-ctable *** recently,there has been an increase in reports on the utility of adjunct endoscopic ablative techniques for downstaging disease as well as contributing to non-surgical complete clinical *** expansive field within endoscopic oncology holds great potential for advancing patient *** addressing challenges,fostering collaboration,and embracing technological advancements,the gastrointestinal cancer treatment paradigm can shift towards a more sustainable and patient-centric future emphasizing organ and function *** editorial examines the evolving landscape of endoscopic ablation strategies,emphasizing their potential to improve patient *** briefly review current applications of endoscopic ablation in the esophagus,stomach,duodenum,pancreas,bile ducts,and colon.

关键词： Gastrointestinal cancer Endoscopic ablation Organ preservation Complete clinical response Neoadjuvant therapy Endoscopic oncology palliative treatment

Xenoesterogens and male infertility:myth or reality?

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Asian Journal of Andrology 2000年第4期2卷 263-269页

作者： Roya Rozati p.p.reddy p.Reddanna Rubina Mujtaba Assisted Conception Services Unit Mahavir Hospital and Research Centre Hyderabad(A. P.) 500 028 IndiaInstitute of Genetics and Hospital for Genetic Diseases Hyderabad IndiaDepartment of Animal Sciences School of Life Sciences University of Hyderabad IndiaAssisted Conception Services Unit Mahavir Hospital and Research Centre Hyderabad(A. P.) 500 028 India

Aim: To evaluate the role of polychlorinated biphenyls (pCBs) as a potential environmental hazard in the deteriora-tion of male fertility. Methods: Fifty-three males were studied. After a thorough case history evaluation and rele-vant clinical and laboratory investigations, pCBs were estimated in the seminal plasma of 21 infertile men with 'Unex-plained Male Factor' and 32 fertile controls. peak retention times of the eluants were compared with those of the com-mercially available standard pCB Mix, and the results confirmed spectrophotometrically. Seminal pCB concentrafonswere compared between i) fertile and infertile men and ii) men from different areas and diets. The relationship betweenpCB concentrations and measures of sperm quality such as the total motile sperm count, was assessed. Results:pCBs were detected in seminal plasma of infertile men but absent from controls. Sperm quantity and quality were sig-nificantly lower in infertile men compared to controls. The highest average pCB concentrations were found in fish-eat-ing urban dwellers, and followed in succession by fish-eating rural dwellers, non fish-eating urban dwellers and nonfish-eating mral dwellers. The total motile sperm counts were inversely proportional to the pCB concentrations and weresignificantly lower than those of the respective controls. Conclusion: pCBs may be instrumental in the deteriorationof sperm quantity and quality, a contaminated fish diet being the main source of exposure.(Asian J Androl 2000 Dec; 2: 263-269 )

关键词： polychlorinated biphenyls xenoestrogens male infertility sperm

prevalence of malignant neoplasms in celiac disease patients-a nationwide United States p.p.lation-based study

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World Journal of Clinical Oncology 2024年第8期15卷 1048-1060页

作者： Maryam Bilal Haider Ali Al Sbihi Sushmitha Nanja reddy peter Green Department of Gastroenterology Northshore University Health SystemEvanstonIL 60201United States Department of Hematology/Oncology University of Miami Miller School of MedicineMiamiFL 33101United States Department of Hematology/Oncology Karmanos Cancer Institute/Wayne State UniversityDetroitMI 48235United States Celiac Disease Center Columbia UniversityNew YorkNY 10032United States

BACKGROUND Celiac disease(CeD)is an autoimmune disorder triggered by the immune response to gluten in genetically predisposed *** research has unveiled a heightened risk of developing specific malignant neoplasms(MN)and various malignancies,including gastrointestinal,lymphomas,skin,and others,in individuals with *** To investigate the prevalence of MN in hospitalized CeD patients in the United *** Using data from the National Inpatient Sample spanning two decades,from January 2000 to December 2019,we identified 529842 CeD patients,of which 78128(14.75%)had *** score matching,based on age,sex,race,and calendar year,was employed to compare CeD patients with the general non-CeD p.p.lation at a 1:1 *** positive associations were observed for several malignancies,including small intestine,lymphoma,nonmelanoma skin,liver,melanoma skin,pancreas myelodysplastic syndrome,biliary,stomach,and other neuroendocrine tumors(excluding small and large intestine malignant carcinoid),leukemia,uterus,and ***,CeD patients exhibited a reduced risk of respiratory and secondary ***,certain malignancies showed null associations with CeD,including head and neck,nervous system,esophagus,colorectal,anus,breast,malignant carcinoids,bone and connective tissues,myeloma,cervix,and ovary *** Our study is unique in highlighting the detailed results of positive,negative,or null associations between different hematologic and solid malignancies and ***,it offers insights into evolving trends in CeD hospital outcomes,shedding light on advancements in its management over the past two *** findings contribute valuable information to the understanding of CeD’s impact on health and healthcare utilization.

关键词： Celiac disease Malignant neoplasm Autoimmune disorder Hospitalized patients Healthcare utilization Gastrointestinal malignancies Lymphomas Epidemiology

Remimazolam in intensive care unit:potential applications and considerations

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World Journal of Critical Care Medicine 2024年第3期13卷 25-31页

作者： praveen reddy Elmati Teja Nagaradona Gowthami Sai Kogilathota Jagirdhar Salim Surani Department of Anesthesiology Saint Clair HospitalDoverNJ 07801United States School of Medicine St George UniversityGranada SW170BDWest Indies Department of Medicine Saint Michaels Medical CenterNewarkNJ 07107United States Department of Medicine&pharmacology Texas A&M UniversityCollege StationTX 77843United States

This manuscript explores the potential use of Remimazolam in the intensive care unit(ICU)and critical care units,considering its pharmacological characteristics,clinical applications,advantages,and comparative effectiveness over current sedatives and *** reviewed existing pubMed and Google Scholar literature to find relevant studies on Remimazolam in *** created search criteria using a combination of free text words,including Remimazolam,critical care,intensive care,sedation,anesthesia,pharmacokinetics,and *** articles published in the English language were analyzed and *** is an ultra-short-acting benzodiazepine derivative promising for sedation and *** is a safer option for hemodynamically unstable,elderly,or liver or kidney *** also has comparable deep sedation properties to propofol in the ***,it reduces post-procedural delirium and patient comfort and reduces the need for additional sedatives in pediatric *** conclusion,Remimazolam is an excellent alternative to current sedatives and anesthetics in the *** cost is comparable to that of current *** research on its long-term safety in the ICU and its broader application and incorporation into routine use is necessary.

关键词： Remimazolam Intensive care Critical care Anesthesia Sedation Mechanical ventilation Benzodiazepine

NLDA non-linear regression model for preserving data privacy in wireless sensor networks

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Digital Communications and Networks 2020年第1期6卷 101-107页

作者： A.L.Sreenivasulu p.Chenna reddy Dept.of CSE JNTU AnantapurAndhra PradeshIndia

Recently,the application of Wireless Sensor Networks(WSNs)has been increasing *** requires privacy preserving data aggregation protocols to secure the data from *** privacy of the sensor data is a challenging *** p.p.r presents a non-linear regression-based data aggregation protocol for preserving privacy of the sensor *** proposed protocol uses non-linear regression functions to represent the sensor data collected from the sensor *** of sending the complete data to the cluster head,the sensor nodes only send the coefficients of the non-linear *** will reduce the communication overhead of the *** data aggregation is performed on the masked coefficients and the sink node is able to retrieve the approximated results over the aggregated *** analysis of experiment results shows that the proposed protocol is able to minimize communication overhead,enhance data aggregation accuracy,and preserve data privacy.

关键词： Sensor nodes Data accuracy Wireless sensor networks Data aggregation privacy preserving

Quantification of Structurally Alert Mutagenic Impurities in Meropenem Trihydrate Drug Substance by Liquid Chromatography with High Resolution Mass Spectrometer (LC-HRMS)

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American Journal of Analytical Chemistry 2024年第3期15卷 119-133页

作者： Anwar Sulaiman K. Ramakrishna reddy Vundavilli Jagadeesh Kumar Hemant Kumar Sharma REVA University Bangalore India Quality Division Aurobindo Pharma Limited Hyderabad India ApL Research Centre-II Analytical Research Department Aurobindo Pharma Limited Hyderabad India

potential mutagenic impurities in Active pharmaceutical Ingredient, Meropenem Trihydrate were assessed and a novel analytical method for their quantification was developed and validated. This Liquid Chromatographic method using High Resolution Mass Spectrometer (LC-HRMS) technique is proved to be suitable for simultaneous quantification of all ten identified impurities with required specificity, sensitivity, resolution, precision, accuracy, and other method characteristics as per ICH Guidelines. The acceptable limit of less than 2.9 μg/g was considered for evaluations, based on drug substance dosage and duration of treatment. The method stands most sensitive with a Limit of Detection of 0.35 μg/g, considering the challenge full acceptance criteria as per current regulatory standards.

关键词： Mutagenic Impurities LC-HRMS Meropenem Trihydrate Method Validation

Oncologic outcomes with and without amniotic membranes in robotic-assisted radical prostatectomy:A propensity score matched analysis

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Asian Journal of Urology 2024年第1期11卷 19-25页

作者： Jonathan Noël Daniel Stirt Marcio Covas Moschovas Sunil reddy Abdel Rahman Jaber Marco Sandri Seetharam Bhat Travis Rogers Subuhee Ahmed Anya Mascarenhas Ela patel Vipul patel Advent Health Global Robotics Institute CelebrationFLUSA University of Central Florida College of Medicine OrlandoFLUSA Big and Open Data Innovation Laboratory University of BresciaItaly SUNY Upstate Medical University SyracuseNYUSA Kansas City University College of Medicine Kansas CityMOUSA Harvard University CambridgeMAUSA

Objective:placement of human placenta derived grafts during robotic-assisted radical prostatectomy(RARp)hastens the return of continence and *** long-term impact on the oncologic outcomes remains to be *** objective was to determine the oncologic outcomes of patients with dehydrated human amnion chorion membrane(dHACM)at RARp compared to a matched ***:In a referral centre,from August 2013 to October 2019,599 patients used dHACM in bilateral nerve-sparing *** excluded patients with less than 12 months follow-up,simple prostatectomy,and unilateral *** with dHACM(amnio group)were 529,and were propensity score matched 1:1 to 2465 patients without dHACM(non-amnio group)and a minimum follow-up of 36 *** the time of RARp,dHACM was placed around the neurovascular bundle in the amnio *** and categorical variables in matched groups was tested by two-sample Kolmogorov-Smirnov test and Fisher's exact test *** measured were biochemical recurrence(BCR),adjuvant and salvage therapy ***:propensity score matching resulted in two groups of 444 *** incidence functions for BCR did not show a difference between the groups(p=0.3).patients in the non-amnio group required salvage therapy more frequently than the amnio group.p.rticularly after partial nerve-sparing RARp(6.3%vs.2.3%,p=0.001).Limitations are the absence of prospective ***:The data suggest that using dHACM does not have a negative impact on BCR in *** of cancer specific and overall survival will require follow-up study to increase our understanding of these grafts’impact on prostate cancer biology.

关键词： prostatectomy prostatecancer Robotic Oncology Outcome Allograft Biomaterial Dehydrated human amnionchorion membrane

prediabetes: An overlooked risk factor for major adverse cardiac and cerebrovascular events in atrial fibrillation patients

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World Journal of Diabetes 2024年第1期15卷 24-33页

作者： Rupak Desai Nishanth Katukuri Sumaja reddy Goguri Azra Kothawala Naga Ruthvika Alle Meena Kumari Bellamkonda Debankur Dey Sharmila Ganesan Minakshi Biswas Kuheli Sarkar pramoda prattipati Shaylika Chauhan Independent Researcher Independent ResearcherAtlantaGA 30079United States Department of Internal Medicine Mayo ClinicRochesterMN 55902United States Department of Medicine Chalmeda Anand Rao Institute of Medical SciencesTelangana 505001India Department of Medicine Jawaharlal Nehru Medical CollegeBelgaum 590010India Department of Medicine Narayana Medical CollegeAndhra PradeshNellore 524003India Department of Medicine Dr Pinnamaneni Siddhartha Institute of Medical Sciences and Research FoundationVijaywada 521286India Department of Medicine Medical College KolkataKolkata 700073India Department of Medicine P.E.S.Institute of Medical Sciences and ResearchAndhra Pradesh 517425India Department of Medicine Shaheed Ziaur Rahman Medical CollegeBogra 5800Bangladesh Department of Medicine College of Medicine and J.N.M HospitalKalyani 741235India Department of Medicine Jawaharlal Nehru Medical College IndiaKarnatakaBelagavi 590010India Department of Internal Medicine Geisinger Health SystemWikes-BarrePA 18702United States

BACKGROUND prediabetes is a well-established risk factor for major adverse cardiac and cerebrovascular events(MACCE).However,the relationship between prediabetes and MACCE in atrial fibrillation(AF)patients has not been extensively ***,this study aimed to establish a link between prediabetes and MACCE in AF *** To investigate a link between prediabetes and MACCE in AF *** We used the National Inpatient Sample(2019)and relevant ICD-10 CM codes to identify hospitalizations with AF and categorized them into groups with and without prediabetes,excluding *** primary outcome was MACCE(all-cause inpatient mortality,cardiac arrest including ventricular fibrillation,and stroke)in AF-related *** Of the 2965875 AF-related hospitalizations for MACCE,47505(1.6%)were among patients with *** prediabetes cohort was relatively younger(median 75 vs 78 years),and often consisted of males(56.3%vs 51.4%),blacks(9.8%vs 7.9%),Hispanics(7.3%vs 4.3%),and Asians(4.7%vs 1.6%)than the non-prediabetic cohort(pprediabetes group had significantly higher rates of hypertension,hyperlipidemia,smoking,obesity,drug abuse,prior myocardial infarction,peripheral vascular disease,and hyperthyroidism(all pprediabetes cohort was often discharged routinely(51.1%vs 41.1%),but more frequently required home health care(23.6%vs 21.0%)and had higher *** adjusting for baseline characteristics or comorbidities,the prediabetes cohort with AF admissions showed a higher rate and significantly higher odds of MACCE compared to the non-prediabetic cohort[18.6%vs 14.7%,odds ratio(OR)1.34,95%confidence interval 1.26-1.42,pp analyses,males had a stronger association(aOR 1.43)compared to females(aOR 1.22),whereas on the race-wise comparison,Hispanics(aOR 1.43)and Asians(aOR 1.36)had a stronger association with MACCE with prediabetes vs whites(aOR 1.33)and blacks(aOR 1.21).CONCLUSION This p.p.lation-

关键词： prediabetes Atrial fibrillation Cardiovascular disease risk Major adverse cardiovascular and cerebrovascular events Stroke Mortality