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Biological,pathological,and multifaceted therapeutic functions of exosomes to target cancer

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Oncology Research 2024年第1期32卷 73-94页

作者： VIGNESH BALAJI E DIVYA ramesh MANISHA CHUNGAN SHAJU AKSHARA KUMAR SAMYAK PANDEY RAKSHA NAYAK V.ALKA SRISHTI MUNJAL AMIR SALIMI K.SREEDHARA RANGANATH PAI SHANKAR M.BAKKANNAVAR Department of Pharmacology Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalKarnataka576104India Department of Forensic Medicine and Toxicology Kasturba Medical CollegeManipal Academy of Higher EducationManipalKarnataka576104India School of Health and Community Services Durham CollegeOshawaOntarioL1G2G5Canada Department of Pharmaceutical Regulatory Affairs and Management Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalKarnataka576104India Department of Clinical Psychology Manipal College of Health ProfessionsManipal Academy of Higher EducationManipalKarnataka576104India Department of Speech and Hearing Manipal College of Health ProfessionsManipal Academy of Higher EducationManipalKarnataka576104India Department of Pharmacy Practice Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalKarnataka576104India

Exosomes,small tiny vesicle contains a large number of intracellular particles that employ to cause various diseases and prevent several pathological events as well in the human *** is considered a“double-edged sword”,and depending on its biological source,the action of exosomes varies under physiological ***,the isolation and characterization of the exosomes should be performed accurately and the methodology also will vary depending on the exosome ***,the uptake of exosomes from the recipients’cells is a vital and initial step for all the physiological *** are different mechanisms present in the exosomes’cellular uptake to deliver their cargo to acceptor *** the exosomal uptake takes place,it releases the intracellular particles that leads to activate the physiological *** though exosomes have lavish functions,there are some challenges associated with every step of their preparation to bring potential therapeutic ***,overcoming the pitfalls would give a desired quantity of exosomes with high purity.

关键词： Exosomes Physiology Cancer Therapeutics Challenges

Genomic selection in plant breeding:Key factors shaping two decades of progress

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Molecular Plant 2024年第4期17卷 552-578页

作者： Admas Alemu Johanna Astrand Osval A.Montesinos-López Julio Isidro y Sanchez Javier Fernandez-Gónzalez Wuletaw Tadesse ramesh R.Vetukuri Anders S.Carlsson Alf Ceplitis JoséCrossa Rodomiro Ortiz Aakash Chawade Department of Plant Breeding Swedish University of Agricultural SciencesAlnarpSweden Lantmannen Lantbruk SvalövSweden Facultad de Telematica University de ColimaColimaColima 28040Mexico Centro de Biotecnología y Genómica de Plantas(CBGP UPM-INIA)Universidad Politécnica de Madrid(UPM)-Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria(INIA)Campus de Montegancedo-UPM28223 MadridSpain International Center for Agricultural Research in the Dry Areas(ICARDA) RabatMorocco International Maize and Wheat Improvement Center(CIMMYT) Km 45Carretera México-VeracruzTexcocoMéxico 52640Mexico

Genomic selection,the application of genomic prediction(GP)models to select candidate individuals,has significantly advanced in the past two decades,effectively accelerating genetic gains in plant *** article provides a holistic overview of key factors that have influenced GP in plant breeding during this *** delved into the pivotal roles of training population size and genetic diversity,and their relationship with the breeding population,in determining GP *** emphasis was placed on optimizing training population *** explored its benefits and the associated diminishing returns beyond an optimum *** was done while considering the balance between resource allocation and maximizing prediction accuracy through current optimization *** density and distribution of single-nucleotide polymorphisms,level of linkage disequilibrium,genetic complexity,trait heritability,statistical machine-learning methods,and non-additive effects are the other vital *** wheat,maize,and potato as examples,we summarize the effect of these factors on the accuracy of GP for various *** search for high accuracy in GP—theoretically reaching one when using the Pearson’s correlation as a metric—is an active research area as yet far from optimal for various *** hypothesize that with ultra-high sizes of genotypic and phenotypic datasets,effective training population optimization methods and support from other omics approaches(transcriptomics,metabolomics and proteomics)coupled with deep-learning algorithms could overcome the boundaries of current limitations to achieve the highest possible prediction accuracy,making genomic selection an effective tool in plant breeding.

关键词： genomic selection genetic gain genomic prediction optimization deep learning training population optimization

Novel automated non-invasive detection of ocular surface squamous neoplasia using artificial intelligence

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World Journal of Methodology 2024年第2期14卷 51-64页

作者： Sony Sinha Prasanna Venkatesh ramesh Prateek Nishant Arvind Kumar Morya Ripunjay Prasad Department of Ophthalmology–Vitreo Retina Neuro Ophthalmology and OculoplastyAll India Institute of Medical SciencesPatna 801507India Department of Glaucoma and Research Mahathma Eye Hospital Private LimitedTrichy 620017India Department of Ophthalmology ESIC Medical CollegePatna 801113India Department of Ophthalmology All India Institute of Medical SciencesHyderabad 508126India Department of Ophthalmology RP Eye InstituteDelhi 110001India

Ocular surface squamous neoplasia(OSSN)is a common eye surface tumour,characterized by the growth of abnormal cells on the ocular *** includes invasive squamous cell carcinoma(SCC),in which tumour cells penetrate the basement membrane and infiltrate the stroma,as well as non-invasive conjunctival intraepithelial neoplasia,dysplasia,and SCC in-situ thereby presenting a challenge in early detection and *** identification and precise demarcation of the OSSN border leads to straightforward and curative treatments,such as topical medicines,whereas advanced invasive lesions may need orbital exenteration,which carries a risk of *** intelligence(AI)has emerged as a promising tool in the field of eye care and holds potential for its application in OSSN *** algorithms trained on large datasets can analyze ocular surface images to identify suspicious lesions associated with OSSN,aiding ophthalmologists in early detection and *** can also track and monitor lesion progression over time,providing objective measurements to guide treatment ***,AI can assist in treatment planning by offering personalized recommendations based on patient data and predicting the treatment *** manuscript highlights the role of AI in OSSN,specifically focusing on its contributions in early detection and diagnosis,assessment of lesion progression,treatment planning,telemedicine and remote monitoring,and research and data analysis.

关键词： Conjunctival neoplasm Early detection of cancer Machine learning Deep neural network Precision medicine

Renal resistive index measurements by ultrasound in patients with liver cirrhosis:Magnitude and associations with renal dysfunction

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World Journal of Radiology 2024年第6期16卷 221-231页

作者： Himanshu Surya ramesh Kumar Rajeev Nayan Priyadarshi Sabbu Surya Prakash Sudhir Kumar Department of Gastroenterology All India Institute of Medical SciencesPatna 801507India Department of Radiodiagnosis All India Institute of Medical SciencesPatna 801507India

BACKGROUND The hemodynamic alterations seen in liver cirrhosis lead to renal vasoconstriction,ultimately causing acute kidney injury(AKI).The renal resistive index(RRI)is the most common Doppler ultrasound variable for measuring intrarenal vascular *** To evaluate the association of the RRI with AKI in patients with liver cirrhosis and to identify risk factors for high *** This was a prospective observational study,where RRI was measured using Doppler ultrasound in 200 consecutive hospitalized patients with *** association of RRI with AKI was *** receiver operating characteristic(ROC)curve analysis was utilized to determine discriminatory cut-offs of RRI for various AKI *** analysis was conducted to determine the predictors of high *** The mean patient age was 49.08±11.68 years,with the majority(79.5%)being male;the predominant etiology of cirrhosis was alcohol(39%).The mean RRI for the study cohort was 0.68±0.09,showing a progressive increase with higher Child-Pugh class of ***,AKI was present in 129(64.5%)*** mean RRI was significantly higher in patients with AKI compared to those without it(0.72±0.06 vs 0.60±0.08;P<0.001).A total of 82 patients(41%)had hepatorenal syndrome(HRS)-AKI,29(22.4%)had prerenal AKI(PRA),and 18(13.9%)had acute tubular necrosis(ATN)-*** mean RRI was significantly higher in the ATN-AKI(0.80±0.02)and HRS-AKI(0.73±0.03)groups than in the PRA(0.63±0.07)and non-AKI(0.60±0.07)*** demonstrated excellent discriminatory ability in distinguishing ATN-AKI from non-ATN-AKI(area under ROC curve:93.9%).AKI emerged as an independent predictor of high RRI(adjusted odds ratio[OR]:11.52),and high RRI independently predicted mortality among AKI patients(adjusted OR:3.18).CONCLUSION In cirrhosis patients,RRI exhibited a significant association with AKI,effectively differentiated between AKI phenotypes,and predicted AKI mortality.

关键词： Renal resistive index Cirrhosis Acute kidney injury Hepatorenal syndrome Renal Doppler

Clinical profile and outcomes of hepatocellular carcinoma in primary Budd-Chiari syndrome

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 699-715页

作者： Ankit Agarwal Sagnik Biswas Shekhar Swaroop Arnav Aggarwal Ayush Agarwal Gautam Jain Anshuman Elhence Arun Vaidya Amit Gupte Ravi Mohanka ramesh Kumar Ashwani Kumar Mishra Shivanand Gamanagatti Shashi Bala Paul Subrat Kumar Acharya Akash Shukla Shalimar Department of Gastroenterology and Human Nutrition All India Institute of Medical SciencesNew Delhi 110029DelhiIndia Department of Gastroenterology Seth Gordhandas Sunderdas Medical College and KEM HospitalMumbai 400012MaharashtraIndia Department of Gastroenterology Sir HN Reliance Foundation HospitalMumbai 400004India Department of Liver Transplant and HPB Sir HN Reliance Foundation HospitalMumbai 400004India Department of Gastroenterology All India Institute of Medical SciencesPatna 801507India Professor of Biostatistics National Drug Dependence Treatment Centre(NDDTC)All India Institute of Medical SciencesNew Delhi 110029India Department of Radiodiagnosis All India Institute of Medical SciencesNew Delhi 110029DelhiIndia

BACKGROUND There is scant literature on hepatocellular carcinoma(HCC)in patients with Budd-Chiari syndrome(BCS).AIM To assess the magnitude,clinical characteristics,feasibility,and outcomes of treatment in *** A total of 904 BCS patients from New Delhi,India and 1140 from Mumbai,India were *** prevalence and incidence of HCC were determined,and among patients with BCS-HCC,the viability and outcomes of interventional therapy were *** In the New Delhi cohort of 35 BCS-HCC patients,18 had HCC at index presentation(prevalence 1.99%),and 17 developed HCC over a follow-up of 4601 person-years,[incidence 0.36(0.22-0.57)per 100 person-years].BCS-HCC patients were older when compared to patients with BCS alone(P=0.001)and had a higher proportion of inferior vena cava block,cirrhosis,and long-segment vascular *** median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up(13029 ng/mL vs 500 ng/mL,P=0.01).Of the 35 BCS-HCC,26(74.3%)underwent radiological interventions for BCS,and 22(62.8%)patients underwent treatment for HCC[transarterial chemoembolization in 18(81.8%),oral tyrosine kinase inhibitor in 3(13.6%),and transarterial radioembolization in 1(4.5%)].The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo(P=0.0001).In contrast to the New Delhi cohort,the Mumbai cohort of BCS-HCC patients were predominantly males,presented with a more advanced HCC[Barcelona Clinic Liver Cancer C and D],and 2 patients underwent liver *** HCC is not uncommon in patients with *** interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.

关键词： Budd chiari syndrome Cancer Cirrhosis Thrombosis Liver Varices Transarterial chemoembolization Hepatic venous outflow tract obstruction

Evaluation of Rainfall Tendency for the Twentieth Century over Indira Sagar Region in Central India

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American Journal of Climate Change 2024年第1期13卷 47-68页

作者： Rituraj Shukla Deepak Khare ramesh P. Rudra Priti Tiwari Himanshu Sharma Prasad Daggupati Pradeep Goel School of Engineering University of Guelph Guelph Canada Department of Water Resources Development and Management Indian Institute of Technology Roorkee India Indira Gandhi Agricultural University Raipur India Department of Civil Engineering Institute of Infrastructure Technology Research and Management (IITRAM) Ahmedabad India

The study investigates long-term changes in annual and seasonal rainfall patterns in the Indira Sagar Region of Madhya Pradesh, India, from 1901 to 2010. Agriculture sustainability, food supply, natural resource development, and hydropower system reliability in the region rely heavily on monsoon rainfall. Monthly rainfall data from three stations (East Nimar, Barwani, and West Nimar) were analyzed. Initially, the pre-whitening method was applied to eliminate serial correlation effects from the rainfall data series. Subsequently, statistical trends in annual and seasonal rainfall were assessed using both parametric (student-t test) and non-parametric tests [Mann-Kendall, Sen’s slope estimator, and Cumulative Sum (CUSUM)]. The magnitude of the rainfall trend was determined using Theil-Sen’s slope estimator. Spatial analysis of the Mann-Kendall test on an annual basis revealed a statistically insignificant decreasing trend for Barwani and East Nimar and an increasing trend for West Nimar. On a seasonal basis, the monsoon season contributes a significant percentage (88.33%) to the total annual rainfall. The CUSUM test results indicated a shift change detection in annual rainfall data for Barwani in 1997, while shifts were observed in West and East Nimar stations in 1929. These findings offer valuable insights into regional rainfall behavior, aiding in the planning and management of water resources and ecological systems.

关键词： Precipitation Parametric Non-Parametric Tests Trend Analysis Serial Correlations

Diabetic retinopathy:A review on its pathophysiology and novel treatment modalities

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World Journal of Methodology 2024年第4期14卷 61-76页

作者： Arvind Kumar Morya Prasanna Venkatesh ramesh Prateek Nishant Kirandeep Kaur Bharat Gurnani Aarti Heda Sarika Salodia Head of the Department Department of OphthalmologyAll India Institute of Medical SciencesHyderabad 508126TelanganaIndia Glaucoma Medical Officer Department of Glaucoma and ResearchMahathma Eye Hospital Private LimitedTrichy 620017Tamil NaduIndia Department of Ophthalmology ESIC Medical CollegePatna 801103BiharIndia Department of Pediatric Ophthalmology and Strabismus Gomabai Netralaya and Research CentreNeemuch 458441Madhya PradeshIndia Cornea and Refractive Services Gomabai Netralaya and Research CentreNeemuch 458441Madhya PradeshIndia Department of Ophthalmology National Institute of OphthalmologyPune 411000MaharashtraIndia Global Medical Safety LundbeckSingapore 569933SingaporeSingapore

Diabetes mellitus(DM)is a chronic metabolic non-communicable disease with the ability to cause serious microvascular and macrovascular complications throughout the body,including in the *** retinopathy(DR),present in onethird of patients with diabetes,is a vision-threatening complication caused by uncontrolled diabetes,which greatly affects the retinal blood vessels and the lightsensitive inner retina,eventually leading to *** epidemiological studies elucidate that DR can vary by age of onset,duration,types of diabetes,and *** studies show that the pathogenesis of diabetic retinopathy has spread its roots beyond merely being the result of *** complexity of its etiopathology and diagnosis makes therapeutic intervention *** review throws light on the pathological processes behind DR,the cascade of events that follow it,as well as the available and emerging treatment options.

关键词： Diabetes Diabetic retinopathy Diabetic macular edema Intravitreal injection Laser photocoagulation

Pharmacological adjuvants for diabetic vitrectomy surgery

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World Journal of Methodology 2024年第4期14卷 84-90页

作者： ramesh Venkatesh Chaitra Jayadev Vishma Prabhu Priyanka Gandhi Rupal Kathare Naresh K Yadav Ayushi Choudhary Jay Chhablani Department of Ophthalmology Narayana NethralayaBangalore 560010India Department of Retina Narayana Nethralaya Eye InstituteBangalore 560010India Department of Vitreo Retina Narayana NethralayaRetina ServSuper Specialty Eye Hospital and Post Graduate Institute of OphthalmologyBangalore 560010India Department of Retina University of Pittsburg School of MedicinePittsburgPA 15213United States

Diabetic vitrectomy is a highly intricate surgical procedure performed during the advanced stages of diabetic retinopathy(DR).It is used to treat conditions such as tractional or combined retinal detachment,vitreous hemorrhage,and subhyaloid hemorrhage,which are all severe manifestations of proliferative *** results of the surgery are uncertain and *** surgery has made significant progress since the early stages of *** the past ten years,advancements in intravitreal pharmacotherapy have emerged,offering new possibilities to improve the surgical results for our *** the realm of medical terminology,an"adjunct"refers to a pharmaceutical or substance employed to aid or expedite the primary therapeutic intervention for a particular *** introduction has broadened the range of therapeutic choices that are accessible prior to,during,and following surgical *** review article will specifically analyze the pharmacological adjuncts used in diabetic vitrectomy surgery,with a focus on their role in facilitating or aiding specific steps of the *** implementation of this system of categorization offers benefits to the surgeon by allowing them to foresee potential difficulties that may occur during the surgical procedure and to choose the appropriate pharmacological agent to effectively tackle these challenges,thus enhancing surgical success rates.

关键词： Diabetic retinopathy Vitrectomy Intravitreal injections Anti-vascular endothelial growth factor Adjuvants Outcomes

The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang Amy L.Strong Yuxiao Sun Lei Guo Conan Juan Alec C.Bancroft Ji Hae Choi Chase A.Pagani Aysel A.Fernandes Michael Woodard Juhoon Lee Sowmya ramesh Aaron W.James David Hudson Kevin N.Dalby Lin Xu Robert J.Tower Benjamin Levi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research Center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α*** a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant