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REVOLUTIONIZING TUBERCULOSIS REGIMEN DEVELOPMENT. 革新结核病治疗方案的发展。
Transactions of the American Clinical and Climatological Association Pub Date : 2025-01-01
Kelly E Dooley, Radojka Savic
{"title":"REVOLUTIONIZING TUBERCULOSIS REGIMEN DEVELOPMENT.","authors":"Kelly E Dooley, Radojka Savic","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Today's first-line tuberculosis regimen was developed in the 1950s to 1970s, followed by a long period of stagnation. New drugs have progressed to market only recently, with long timelines from target discovery to clinical trial success, alongside costly Phase 3 failures. Currently, the tuberculosis drug development pipeline is robust, containing multiple new chemical entities from diverse drug classes, motivating us to optimize this opportunity to advance compounds effectively and efficiently. In this article, we explore how recent innovations in data integration and computational methods are revolutionizing tuberculosis drug development, accelerating development timelines, and heightening the probability of success. We anticipate that these breakthroughs will lead to approval of novel drugs in unprecedented time frames, marking a significant milestone in the fight against this age-old disease. This progress is timely, as resistance to even recently registered drugs is emerging rapidly. Our hope is that these strategies will also be of value in other medical fields.</p>","PeriodicalId":23186,"journal":{"name":"Transactions of the American Clinical and Climatological Association","volume":"135 ","pages":"269-280"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795574","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}
引用次数: 0
THE GID COMPLEX REGULATES DNA END PROCESSING DURING DNA DOUBLE-STRAND BREAK REPAIR BY NONHOMOLOGOUS END JOINING. 在DNA双链断裂的非同源末端连接修复过程中，gid复合物调节DNA末端加工。
Transactions of the American Clinical and Climatological Association Pub Date : 2025-01-01
Barry P Sleckman, Bo-Ruei Chen
{"title":"THE GID COMPLEX REGULATES DNA END PROCESSING DURING DNA DOUBLE-STRAND BREAK REPAIR BY NONHOMOLOGOUS END JOINING.","authors":"Barry P Sleckman, Bo-Ruei Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Genome instability is a hallmark of cancer, allowing for clonal evolution and improved tumor fitness. The mis-repair of DNA double-strand breaks (DSBs) is a major source of genome instability. DNA DSBs are normally repaired by homologous recombination (HR) and nonhomologous end joining (NHEJ). The nucleolytic resection of broken DNA ends generates single-stranded DNA (ssDNA) overhangs that are required for HR, but inhibitory to NHEJ. DNA end resection must be prevented in nondividing cells where NHEJ is the only active DSB repair pathway. Using a novel whole genome gRNA CRISPR/Cas9 screen, we identified the GID complex as functioning to protect DNA ends from nucleolytic resection. The GID complex contains multiple E3 ubiquitin ligase subunits and regulates the expression and function of pro-resection machinery. Thus, by antagonizing DNA end resection GID may prevent homology-mediated joining leading to aberrant DSB repair and genome instability in normal and cancerous nondividing cells.</p>","PeriodicalId":23186,"journal":{"name":"Transactions of the American Clinical and Climatological Association","volume":"135 ","pages":"281-293"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795580","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}
引用次数: 0
NEUROENDOCRINE TUMORS NEARLY CAUSING EXTINCTION OF A MAMMAL. 神经内分泌肿瘤几乎导致哺乳动物灭绝。
Transactions of the American Clinical and Climatological Association Pub Date : 2025-01-01
Herbert Chen
{"title":"NEUROENDOCRINE TUMORS NEARLY CAUSING EXTINCTION OF A MAMMAL.","authors":"Herbert Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>I have spent most of my career studying neuroendocrine (NE) tumors or cancers (1-5). NE cancers are a diverse group of tumors that develop in multiple organs throughout the body. During a recent trip to Tasmania, I learned that there is currently an epidemic within the animal kingdom of a transmissible NE cancer. The Tasmanian devil (<i>Sarcophilus harrisii</i>) is only found in Tasmania. Devil facial tumor disease (DFTD) is an aggressive, transmissible, and uniformly fatal NE cancer found exclusively in Tasmanian devils. Tumor cells are transmitted between devils through frequent biting during mating and recognized as a rare clonally transmissible cancer. Tasmanian devils were declared an endangered species in 2008. Several interventions are underway to save this species from this deadly transmissible cancer.</p>","PeriodicalId":23186,"journal":{"name":"Transactions of the American Clinical and Climatological Association","volume":"135 ","pages":"34-42"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795609","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}
引用次数: 0
NEURAL CONTROL OF SOMATIC FUNCTION: THE NEW FRONTIER OF PHYSIOLOGY AND PATHOPHYSIOLOGY. 躯体功能的神经控制：生理学和病理生理学的新前沿。
Transactions of the American Clinical and Climatological Association Pub Date : 2024-01-01
Mark L Zeidel
{"title":"NEURAL CONTROL OF SOMATIC FUNCTION: THE NEW FRONTIER OF PHYSIOLOGY AND PATHOPHYSIOLOGY.","authors":"Mark L Zeidel","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":23186,"journal":{"name":"Transactions of the American Clinical and Climatological Association","volume":"134 ","pages":"165-172"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972552","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}
引用次数: 0
WALKING BACKWARDS: REFLECTING ON THE VALUE OF MENTORS. 走回头路：反思导师的价值。
Transactions of the American Clinical and Climatological Association Pub Date : 2024-01-01
Wesley Burks
{"title":"WALKING BACKWARDS: REFLECTING ON THE VALUE OF MENTORS.","authors":"Wesley Burks","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The author, Dr. A. Wesley Burks, reflects on his life's work to improve the lives of his patients.</p>","PeriodicalId":23186,"journal":{"name":"Transactions of the American Clinical and Climatological Association","volume":"134 ","pages":"21-28"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971887","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}
引用次数: 0
ADRENOCORTICAL CARCINOMA: AN ORPHAN MALIGNANCY: FROM THE PATIENT TO THE BENCH AND BACK. 肾上腺皮质癌：一种孤儿恶性肿瘤：从病人到工作台再到病人。
Transactions of the American Clinical and Climatological Association Pub Date : 2024-01-01
Margaret E Wierman, Katja Kiseljak Vassiliades
{"title":"ADRENOCORTICAL CARCINOMA: AN ORPHAN MALIGNANCY: FROM THE PATIENT TO THE BENCH AND BACK.","authors":"Margaret E Wierman, Katja Kiseljak Vassiliades","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Adrenocortical carcinoma (ACC) is an orphan cancer with 35% five-year survival that has been unchanged for last five decades. Patients often present with severe hypercortisolism or with mass effects. The only Food and Drug Administration (FDA)-approved drug for ACC is mitotane, an insecticide derivative, which provides only limited additional months of survival, but with toxicities. Little progress in the field has occurred due to a lack of preclinical models. We recently developed new human ACC <i>in vitro</i> and <i>in vivo</i> research models. We produced the first two new ACC cell lines for the field, CU-ACC1 and CU-ACC2, which we have distributed for global collaborations. In addition, we developed 10 ACC patient-derived xenograft (PDX) and two humanized ACC-PDX models to test new therapeutics and examine the mechanism of mitotane action in combination with immunotherapy. These new preclinical models allow us to identify novel targets and test new therapeutics for our patients with adrenal cancer.</p>","PeriodicalId":23186,"journal":{"name":"Transactions of the American Clinical and Climatological Association","volume":"134 ","pages":"113-122"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971919","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}
引用次数: 0
DEVELOPING A BEDSIDE TEST FOR PREECLAMPSIA: OVERCOMING SISYPHUS. 开发子痫前期床旁检验：克服西西弗斯。
Transactions of the American Clinical and Climatological Association Pub Date : 2024-01-01
Ravi Thadhani
{"title":"DEVELOPING A BEDSIDE TEST FOR PREECLAMPSIA: OVERCOMING SISYPHUS.","authors":"Ravi Thadhani","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":23186,"journal":{"name":"Transactions of the American Clinical and Climatological Association","volume":"134 ","pages":"66-74"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972547","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}
引用次数: 0
PHENOTYPING REPAIR AFTER ACUTE KIDNEY INJURY: PRECISION MEDICINE TO CLINICAL TRIALS. 对急性肾损伤后的修复进行表型分析：从精准医学到临床试验。
Transactions of the American Clinical and Climatological Association Pub Date : 2024-01-01
Chirag R Parikh, Jeanine Hernandez
{"title":"PHENOTYPING REPAIR AFTER ACUTE KIDNEY INJURY: PRECISION MEDICINE TO CLINICAL TRIALS.","authors":"Chirag R Parikh, Jeanine Hernandez","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is common during hospitalization and is associated with long-term risk of readmissions and chronic kidney disease (CKD). Preclinical studies and novel urine biomarkers have demonstrated that subclinical inflammation and repair continue for several months after AKI. We conducted three clinical and translational studies to alleviate long-term sequelae after AKI. First, we assessed repair in deceased donor kidneys which can assist with organ allocation and reduce discard. In an ongoing study, organ procurement organizations are measuring repair biomarkers via lateral flow devices to assess organ quality and adding it to their workflow. Second, we performed research biopsies during AKI to interrogate kidney tissue with novel transcriptomic and proteomic techniques to advance therapeutic development. Third, we initiated pragmatic clinical trials to reduce readmissions after an episode of AKI by providing nurse navigator and pharmacist support to optimize blood pressure, fluid, and medication management.</p>","PeriodicalId":23186,"journal":{"name":"Transactions of the American Clinical and Climatological Association","volume":"134 ","pages":"37-46"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971879","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}
引用次数: 0
OFFICERS AND COUNCIL FALL 2023. 2023 年秋季主席团和理事会。
Transactions of the American Clinical and Climatological Association Pub Date : 2024-01-01
{"title":"OFFICERS AND COUNCIL FALL 2023.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":23186,"journal":{"name":"Transactions of the American Clinical and Climatological Association","volume":"134 ","pages":"iii"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972553","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}
引用次数: 0
SECRETARY-TREASURER'S REPORT. 秘书兼财务主任的报告。
Transactions of the American Clinical and Climatological Association Pub Date : 2024-01-01
{"title":"SECRETARY-TREASURER'S REPORT.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":23186,"journal":{"name":"Transactions of the American Clinical and Climatological Association","volume":"134 ","pages":"lxi-lxvii"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972560","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}
引用次数: 0
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