Medical research archives最新文献

{"title":"Invited Expert Opinion- Bioinformatic and Limitation Directives to Help Adopt Genetic Addiction Risk Screening and Identify Preaddictive Reward Dysregulation: Required Analytic Evidence to Induce Dopamine Homeostatsis.","authors":"Kenneth Blum, Mark S Gold, Jean Lud Cadet, Marjorie C Gondre-Lewis, Thomas McLaughlin, Eric R Braverman, Igor Elman, B Paul Carney, Rene Cortese, Tomilowo Abijo, Debasis Bagchi, John Giordano, Catherine A Dennen, David Baron, Panayotis K Thanos, Diwanshu Soni, Milan T Makale, Miles Makale, Kevin T Murphy, Nicole Jafari, Keerthy Sunder, Foojan Zeine, Mauro Ceccanti, Abdalla Bowirrat, Rajendra D Badgaiyan","doi":"10.18103/mra.v11i8.4211","DOIUrl":"10.18103/mra.v11i8.4211","url":null,"abstract":"","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"11 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized Immunotherapy of Patients: Defining by Single-cell RNA-seq with Artificial Intelligence.","authors":"Biaoru Li","doi":"10.18103/mra.v11i8.4293","DOIUrl":"10.18103/mra.v11i8.4293","url":null,"abstract":"<p><p>Immunotherapy, including immune cell therapy and targeted therapy, is gradually developed through the ongoing discovery of molecular compounds or immune cells. Choosing the best one or the best combination of target compounds and immune-cell therapy is a challenge for clinical scientists and clinicians. We have found variable efficacy individually after tumor-infiltrating lymphocyte (TIL) therapy, and now TILs have been discovered in a group of heterogeneous immune cells. To select the best immunotherapy for each patient, we started to study TIL genomics, including single-cell mRNA differential display from TIL published in 2007 and single-cell RNA-seq from TIL published in 2013, set up TIL quantitative network in 2015, researched machine-learning model for immune therapy in 2022. These manual reports single-cell RNA-seq data combined with machine learning to evaluate the optimal compounds and immune cells for individual patients. The machine-learning model, one of artificial intelligence, can estimate targeting genomic variance from single-cell RNA-seq so that they can cover thirteen kinds of immune cell therapies and ongoing FDA-approved targeted therapies such as PD1 inhibitors, PDL1 inhibitors, and CTLA4 inhibitors, as well as other different treatments such as HDACI or DNMT1 inhibitors, FDA-approved drugs. Moreover, also cover Phase-1, Phase-2, Phase-3, and Phase-4 of clinical trials, such as TIL, CAR T-cells, TCR T-cells. Single-cell RNA-seq with an Artificial intelligence estimation system is much better than our published models from microarrays or just cell therapy. The medical goal is to address three issues in clinical immunotherapy: the increase of efficacy; the decrease of adverse effects and the decrease of the cost in clinical applications.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"11 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitous Colonic Ileal Metaplasia Consistent with the Diagnosis of Crohn's Colitis among Indeterminate Colitis Cohorts.","authors":"William A Breaux, Maya A Bragg, Amosy E M'Koma","doi":"10.18103/mra.v11i8.4188","DOIUrl":"10.18103/mra.v11i8.4188","url":null,"abstract":"<p><strong>Background: </strong>Inadequate differentiated diagnostic features of predominantly colonic inflammatory bowel diseases i.e., ulcerative colitis and Crohn's colitis, may lead to inexact diagnosis of \"indeterminate colitis\". About 15% of indeterminate colitis patients are diagnosed at colonoscopy, in colonic biopsies, and/or at colectomy. Managing outcomes of indeterminate colitis, given its unpredictable clinical presentation, depends on future diagnosis of colitis, Crohn's colitis or ulcerative colitis.</p><p><strong>Objective: </strong>Overview the diagnostic efficacy of ectopic colonic ileal metaplasia and human α-defens 5 (DEFA5 alias HD5) for accurate delineation of indeterminate colitis into authentic Crohn's colitis and/ or ulcerative colitis.</p><p><strong>Design: </strong>We describe a targeted protein for potentially differentiating indeterminate colitis into an accurate clinical subtype diagnosis of inflammatory bowel diseases i.e., ulcerative colitis and Crohn's colitis.</p><p><strong>Patients: </strong>Twenty-one patients with the clinically inexact diagnosis of indeterminate colitis were followed, reassessed and data analyzed.</p><p><strong>Main outcome measures: </strong>We observed that (i) some patients had their original diagnosis changed from indeterminate colitis to either ulcerative colitis or Crohn's colitis; and (ii) human α-defensin 5 is aberrantly overexpressed in Crohn's colitis.</p><p><strong>Results: </strong>Fifteen of the twenty-one (71.4%) patients with indeterminate colitis had their inconclusive diagnosis changed; nine patients changed to ulcerative colitis and six to Crohn's colitis. In human colon surgical samples, Human α-defensin-5 was significantly upregulated in Crohn's colitis. In addition, Human α-defensin 5 processing enzyme, matrix metalloptotease-7 was inversely expressed compared to Human α- Defensin 5.</p><p><strong>Limitation: </strong>Due to the sequence homology of the α-defensin class of proteins, preceding efforts to raise antibodies (Abs) against DEFA5 have limitations to produce adequate specificity. The Abs used in previous assays recognizes the α-defensins, active α-defensins 5 and inactive pro- α-defensins 5. Monoclonal antibodies (mAbs) to determine specificity and sensitivity of α-defensins 5, which is diagnostic of CC disease, and NOT other α-defensins is the limitation to overcome.</p><p><strong>Conclusion: </strong>It is feasible to differentiate ulcerative colitis from Crohn's colitis among patients with inexact diagnosis of indeterminate colitis using Human α-defensin 5 as a molecular biosignature delineator.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"11 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antigen Presenting Cell-Mediated HIV-1 <i>Trans</i> Infection in the Establishment and Maintenance of the Viral Reservoir.","authors":"Abigail Gerberick, Charles R Rinaldo, Nicolas Sluis-Cremer","doi":"10.18103/mra.v11i7.1.4064","DOIUrl":"10.18103/mra.v11i7.1.4064","url":null,"abstract":"<p><p>Despite potent antiretroviral therapy, an HIV-1 reservoir persists that represents a major barrier to a cure. Understanding the mechanisms by which the HIV-1 reservoir is established and maintained is critical for the discovery of effective treatments to significantly reduce or eliminate the viral reservoir. In addition to <i>cis</i> infection, in which HIV-1 directly infects target CD4⁺ T cells, cell-to-cell transmission, or <i>trans</i> infection, can also occur. HIV-1 <i>trans</i> infection is significantly more efficient than <i>cis</i> infection, mostly due to the occurrence of multiple infections per cell during transfer. Additionally, <i>trans</i> infection is efficient even in the presence of ART and/or neutralizing antibodies. Cell-to-cell transmission is mediated by CD4⁺ T cells and professional antigen presenting cells (APC). Here we focus on APC, i.e., myeloid dendritic cells, B lymphocytes, and monocytes/macrophages, that bind, internalize, and transfer HIV-1 to target CD4⁺ T cells via various proposed mechanisms. We assess the potential impact of <i>trans</i> infection on the establishment and maintenance of the HIV-1 reservoir including its role in disease progression. We consider the natural interactions between APC and CD4⁺ T cells <i>in vivo</i> that HIV-1 may hijack, allowing for the highly efficient <i>trans</i> infection of CD4⁺ T cells, maintaining the viral reservoirs in tissue despite undetectable plasma viral loads in peripheral blood. We propose that these modes of viral pathogenesis need to be addressed in potential cure strategies to ensure eradication of the viral reservoir.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83641049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correspondence of Yolk Sac and Embryonic Genotypes in F0 Mouse CRISPants.","authors":"Kayla T B Fuselier,&nbsp;Claudia Kruger,&nbsp;J Michael Salbaum,&nbsp;Claudia Kappen","doi":"10.18103/mra.v11i6.3989","DOIUrl":"10.18103/mra.v11i6.3989","url":null,"abstract":"<p><p>CRISPR-mediated genome editing <i>in vivo</i> can be accompanied by prolonged stability of the Cas9 protein in mouse embryos. Then, genome edited variant alleles will be induced as long as Cas9 protein is active, and unmodified wildtype target loci are available. The corollary is that CRISPR-modified alleles that arise after the first zygotic cell division potentially could be distributed asymmetrically to the cell lineages that are specified early during morula and blastocyst development. This has practical implications for the investigation of F0 generation individuals, as cells in embryonic and extraembryonic tissues, such as the visceral yolk sac, might end up inheriting different genotypes. We here investigated the hypothetically possible scenarios by genotyping individual F0 CRISPants and their associated visceral yolk sacs in parallel. In all cases, we found that embryonic genotype was accurately reflected by yolk sac genotyping, with the two tissues indicating genetic congruence, even when the conceptus was a mosaic of cells with distinct allele configurations. Nevertheless, low abundance of a variant allele may represent a private mutation occurring only in the yolk sac, and in those rare cases, additional genotyping to determine the mutational status of the embryo proper is warranted.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"11 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DISPOSITION OF ADOLESCENTS TOWARD RECEIVING COVID-19 VACCINATIONS IN VILLAVICENCIO: MYTHS AND BELIEFS","authors":"C. Balaguera, M. Osorio, M. Echavarría, M. Garzón","doi":"10.1101/2023.01.10.23284415","DOIUrl":"https://doi.org/10.1101/2023.01.10.23284415","url":null,"abstract":"Global efforts regarding the COVID-19 pandemic have been focused on preventive activities, such as vaccination, since the disease is expected to become endemic. Adolescents were among the last population groups to be included in the vaccination program in Colombia, and adequate coverage has not yet been achieved in this group and in infants. It is important to understand their motivations to improve the willingness of this population to be vaccinated. A cross-sectional study was designed via an online survey in adolescents aged 14-19 years in Villavicencio Meta after validation of the survey and informed consent. The following options were provided for the question on vaccine disposition: willing, undecided, and unwilling. We described the disposition toward receiving COVID-19 vaccine using graphs and absolute and relative frequencies based on age group. A multinomial regression model was used to assess the relationship between our predictor variables and vaccine disposition in adolescents. In this study, 288 adolescents were surveyed. The risk variables for unwillingness to be vaccinated were being male (odds ratio [OR] 2.18, 95% confidence interval [CI] 0.8-5.7, p = 0.62), belonging to low social stratum (OR 2.29, 95% CI 0.9-5.88, p = 0.19), having a monthly family income of less than 1 million Colombian pesos (250 USD) (OR 2.01, 95% CI 0.8-5.16, p = 0.19), and having basic education (OR 2.59, 95% CI 0.33-20.14, p = 0.18). Unproven myths and beliefs exert a profound influence on adolescents, which results in an unwillingness to be vaccinated. Hence, innovative public health strategies should be designed to improve the disposition to be vaccinated in this population group.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78289204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Current Status of Ultrasonography and Fine-Needle Aspiration Citology for the Management of the Axilla in Breast Cancer","authors":"G. de León, Andrés Dell´Acqua, A. Cristiani","doi":"10.18103/mra.v11i5.3851","DOIUrl":"https://doi.org/10.18103/mra.v11i5.3851","url":null,"abstract":"Objetive: to analyze whether ultrasonography with fine-needle aspiration cytology of an axillary suspicious node, in patients with breast cancer, could help to differentiate between patients with low involvement of the axilla (up to 2 nodes with macrometastasis) of those with high involvement of the axilla (more than 2 lymph nodes with macrometastasis). Material and methods: A total of 115 consecutive patients with breast cancer (up to 5 cm in diameter), with clinically negative axilla and pathologically positive axilla. All patients underwent preoperative axillary ultrasound and ultrasound-guided fine-needle aspiration cytology was performed in patients with suspicious nodes. In all patients with positive cytology, lymphadenectomy was performed. In all patients with negative ultrasound and cytology, sentinel lymph node biopsy was performed, and when it was positive, lymphadenectomy was performed. The number of pathological lymph nodes was evaluated after lymphadenectomy. Results: A total of 61 patients had positive axillary ultrasound and cytology. In 42 of them (69%), there were more than 2 pathological lymph nodes. There were 54 patients with negative axillary ultrasound and cytology. In 49 of them (90%), there were only 1 or 2 pathological lymph nodes. Axillary ultrasound and fine-needle aspiration cytology were able to identify 42 of the 47 patients (89%) with more than 2 pathological lymph nodes. Conclusion: ultrasound and ultrasound-guided fine-needle aspiration citology was able to identify, in a preoperative stage, those patients with high axillary involvement (more than 2 lymph nodes with macrometastasis). The latter are the patients who would benefit from lymphadenectomy of the axilla, ignoring the sentinel lymph node biopsy stage.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73659774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of a β-mannanase enzyme in diets with a reduced net energy content in post-weaning piglets resulted in equal performance and an additional economic benefit","authors":"F. Vangroenweghe, Sarah Goethals, Delphine Zele, Anne Bruijn","doi":"10.18103/mra.v11i6.3954","DOIUrl":"https://doi.org/10.18103/mra.v11i6.3954","url":null,"abstract":"β-Mannans are strongly anti-nutritive polysaccharide fibers found in most vegetable feed ingredients. The estimated content of soluble β-mannans in common swine diets range from 0.15 to 0.40%. In vitro studies have demonstrated that as little as 0.05% soluble β-mannan content in feed can elicit a strong innate immune response. Hemicell HT (Elanco Animal Health) is a β-mannanase enzyme for animal feed that breaks down β-mannans, thereby preventing economic losses from the wasteful immune response to β-mannans. The present study aimed to compare pig performance on a control diet and a reformulated diet with a lower energy content – 45 kcal/kg NE reduction – and the inclusion of a β-mannanase enzyme. A six-week feeding trial was conducted on a commercial post-weaning facility with DanBred x Belgian Piétrain pigs starting at 21 days of age. Standard three-phase control diets were compared to reformulated diets with an energy reduction of 45 kcal NE/kg and inclusion of a β-mannanase enzyme (Hemicell HT; Elanco) at 300 g/tonne. Standard production data were collected. The data were analyzed using JMP 15.0 statistical program. Overall, performance data did not differ significantly between trial groups in both Phase 1 and Phase 2, and overall, during the entire post-weaning period. Mortality was only numerically, but not significantly higher in the Control as compared to the Hemicell HT group. Hemicell HT had an overall benefit of € 1.69 per piglet and € 15.18 per tonne of feed due to the 45 kcal/kg NE reduction. The current trial demonstrated that the inclusion of Hemicell HT in reformulated diets with a lower energy content (45 kcal NE/kg) was able to retain production performance in post-weaned piglets with an economic benefit.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74071905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infections May Cause Arterial Inflammation, Atherosclerosis, Myocarditis and Cardiovascular Disease","authors":"U. Ravnskov, A. Alabdulgader, K. Mccully","doi":"10.18103/mra.v11i5.3866","DOIUrl":"https://doi.org/10.18103/mra.v11i5.3866","url":null,"abstract":"Effective prevention and treatment of atherosclerosis and cardiovascular disease (CVD), the commonest cause of death in most countries, is still lacking. For many years we have studied the cholesterol hypothesis and found that there are many contradictions to this hypothesis. For instance, no trial has shown exposure response; the lipid values are not associated with degree of atherosclerosis, and people with high LDL-C live just as long or longer than people with low LDL-C. These facts together with the observation that inflammation is a common finding in atherosclerotic arteries have probably contributed to the hypothesis that CVD may be caused by inflammation. However, several trials with anti-inflammatory drugs have shown that such treatment increases the risk of CVD. Therefore, a relevant hypothesis is whether it is infections which cause the inflammation and whether CVD may be caused by infections because many human observations and animal experiments are in accordance with this idea. As cholesterol-lowering treatment is ineffective and may cause serious side effects, we believe that future research should elucidate the importance of infections in the etiology of CVD. A relevant method would be to perform a blood culture on all patients with an acute AMI and if it is positive, to treat the patient with an appropriate antibiotic.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74169690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Avcs-Sonr Pilot Study: N-Terminal Pro-Brain Natriuretic Peptide Inversely Correlates with Sonr Signal in Patients with Dilated Cardiomyopathy and Reduced Left Ventricular Ejection Fraction","authors":"J. Guerrero, Joaquín Fernández de la, Concha Castañeda, A. Piñero, F. Javier, G. Md, N. Castellano, J. Ferrer, I. Lozano, Javier Moreno, A. Madrid","doi":"10.18103/mra.v11i7.2.4169","DOIUrl":"https://doi.org/10.18103/mra.v11i7.2.4169","url":null,"abstract":"Background. Chronic heart failure is a very important public health problem, and brain natriuretic peptide monitoring may help in its management but faces important logistical problems. A readily available surrogate of brain natriuretic peptide would be of value in this field. We hypothesized that SonR measurements might be this brain natriuretic peptide surrogate. Methods. Patients with chronic heart failure, left ventricular ejection fraction ≤ 30% and implanted with a cardiac resynchronization therapy defibrillator able to provide SonR values underwent monthly assessment of brain natriuretic peptide levels for 1 year. The relationship between brain natriuretic peptide levels and paired SonR values was evaluated. Results. An inverse and highly significant relationship between brain natriuretic peptide levels and paired SonR values was obtained. Conclusions. We found an inverse and significant relationship between SonR values and brain natriuretic peptide levels. This finding might lead to the use of SonR values to monitor treatment and preclude hospital admissions in patients with chronic heart failure.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75665630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}