tbuckley/cabot-search huggingface dataset:
Mitochondrial DNA Mutation, Diseases, and Nutrient-Regulated Mitophagy
Authors: Xuan Yang, Ruoyu Zhang, Kiichi Nakahira, Zhenglong Gu
Journal: Annual Review of Nutrition (2019)

A wide spectrum of human diseases, including cancer, neurodegenerative diseases, and metabolic disorders, have been shown to be associated with mitochondrial dysfunction through multiple molecular mechanisms. Mitochondria are particularly susceptible to nutrient deficiencies, and nutritional intervention is an essential way to maintain mitochondrial homeostasis. Recent advances in genetic manipulation and next-generation sequencing reveal the crucial roles of mitochondrial DNA (mtDNA) in various pathophysiological conditions. Mitophagy, a term coined to describe autophagy that targets dysfunctional mitochondria, has emerged as an important cellular process to maintain mitochondrial homeostasis and has been shown to be regulated by various nutrients and nutritional stresses. Given the high prevalence of mtDNA mutations in humans and their impact on mitochondrial function, it is important to investigate the mechanisms that regulate mtDNA mutation. Here, we discuss mitochondrial genetics and mtDNA mutations and their implications for human diseases. We also examine the role of mitophagy as a therapeutic target, highlighting how nutrients may eliminate mtDNA mutations through mitophagy.
Association of China’s universal two child policy with changes in births and birth related health factors: national, descriptive comparative study
Authors: Hong-tian Li, Ming Xue, Susan Hellerstein, Yue Cai, Yanqiu Gao, Yali Zhang, Jie Qiao, Jan Blustein, Jian-meng Liu
Journal: BMJ (2019)

Abstract Objective To measure the association of China’s universal two child policy, announced in October 2015, with changes in births and health related birth characteristics. Design National, descriptive before-and-after comparative study. Setting Every county in 28 of 31 provinces of mainland China. Participants Births included in two national databases: 67 786 749 births from county level monthly aggregated data between January 2014 and December 2017; and 31 786 279 deliveries from individual level delivery information records between January 2015 and December 2017. Main outcome measures Monthly mean number of births and mean proportion of multiparous mothers and mothers aged 35 and over, preterm deliveries, and caesarean deliveries. Results The study had two phases: the baseline period (up to and including June 2016, nine months after the policy announcement) and the effective period (from July 2016 to December 2017). The estimated number of additional births attributable to the new policy between July 2016 and December 2017 was 5.40 million (95% confidence interval 4.34 to 6.46). The monthly mean percentage of multiparous mothers and mothers aged 35 and over increased by 9.1 percentage points (95% confidence interval 6.4 to 11.7) and 5.8 percentage points (5.2 to 6.4), respectively. This increase in older mothers, however, was not associated with a concurrent increase in the overall rate of preterm birth. The monthly mean caesarean delivery rate among multiparous mothers increased by 1.2 percentage points (0.8 to 1.6) from 39.7% to 40.9%, and decreased by 3.0 percentage points (−3.5 to −2.5) among nulliparous mothers from 39.6% to 36.6%. Conclusions Since its announcement in October 2015, the universal two child policy has been associated with a rise in births in China and with changes in health related birth characteristics: women giving birth have been more likely to be multiparous, and more likely to be aged 35 and over. No evidence of concurrent worsening outcomes (that is, premature births) was seen.
Can Plant-Based Meat Alternatives Be Part of a Healthy and Sustainable Diet?
Authors: Frank B. Hu, Brett O. Otis, Gina McCarthy
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Association Between Indefinite Dysplasia and Advanced Neoplasia in Patients With Inflammatory Bowel Diseases Undergoing Surveillance
Authors: Remi Mahmoud, Shailja C. Shah, Joana Torres, Daniel Castaneda, Jason Glass, Jordan Elman, Akash Kumar, Jordan Axelrad, Noam Harpaz, Thomas Ullman, Jean-Frédéric Colombel, Bas Oldenburg, Steven H. Itzkowitz
Journal: Clinical Gastroenterology and Hepatology (2019)
Treating murine inflammatory diseases with an anti-erythrocyte antibody
Authors: Andrew R. Crow, Rick Kapur, Sandra Koernig, Ian K. Campbell, Chao-Ching Jen, Patrick J. Mott, Danielle Marjoram, Ramsha Khan, Michael Kim, Jennifer Brasseit, Yoelys Cruz-Leal, Alaa Amash, Simrat Kahlon, Issaka Yougbare, Heyu Ni, Adrian W. Zuercher, Fabian Käsermann, John W. Semple, Alan H. Lazarus
Journal: Science Translational Medicine (2019)

An anti-erythrocyte antibody redirects inflammation in multiple mouse models.
Tumor biology and multidisciplinary strategies of oligometastasis in gastrointestinal cancers
Authors: Yue Zhao, Jiahui Li, Dai Li, Zhefang Wang, Jiangang Zhao, Xiaolin Wu, Qiye Sun, Peter Ping Lin, Patrick Plum, Alexander Damanakis, Florian Gebauer, Menglong Zhou, Zhen Zhang, Hans Schlösser, Karl-Walter Jauch, Peter J. Nelson, Christiane J. Bruns
Journal: Seminars in Cancer Biology (2019)
Pyrotinib or Lapatinib Combined With Capecitabine in HER2–Positive Metastatic Breast Cancer With Prior Taxanes, Anthracyclines, and/or Trastuzumab: A Randomized, Phase II Study
Authors: Fei Ma, Quchang Ouyang, Wei Li, Zefei Jiang, Zhongsheng Tong, Yunjiang Liu, Huiping Li, Shiying Yu, Jifeng Feng, Shusen Wang, Xichun Hu, Jianjun Zou, Xiaoyu Zhu, Binghe Xu
Journal: Journal of Clinical Oncology (2019)

Pyrotinib, an irreversible pan-ErbB inhibitor, showed promising antitumor activity and acceptable tolerability in a phase I trial. We assessed the efficacy and tolerability of pyrotinib versus lapatinib, both in combination with capecitabine, in women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in an open-label, multicenter, randomized phase II study.Chinese patients with HER2-positive relapsed or metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab were assigned (1:1) to receive 400 mg pyrotinib or lapatinib 1,250 mg orally once per day for 21-day cycles in combination with capecitabine (1,000 mg/m2 orally twice per day on days 1 to 14). The primary end point was investigator-assessed overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.Between May 29, 2015, and March 15, 2016, 128 eligible patients were randomly assigned to the pyrotinib (n = 65) or lapatinib (n = 63) treatment groups. The overall response rate was 78.5% (95% CI, 68.5% to 88.5%) with pyrotinib and 57.1% (95% CI, 44.9% to 69.4%) with lapatinib (treatment difference, 21.3%; 95% CI, 4.0% to 38.7%; P = .01). The median progression-free survival was 18.1 months (95% CI, 13.9 months to not reached) with pyrotinib and 7.0 months (95% CI, 5.6 to 9.8 months) with lapatinib (adjusted hazard ratio, 0.36; 95% CI, 0.23 to 0.58; P < .001). The most frequent grade 3 to 4 adverse events were hand-foot syndrome in 16 of 65 patients (24.6%) in the pyrotinib group versus 13 of 63 (20.6%) in the lapatinib group; diarrhea in 10 patients (15.4%) versus three patients (4.8%), respectively; and decreased neutrophil count in six patients (9.2%) versus two patients (3.2%), respectively.In women with HER2-positive metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab, pyrotinib plus capecitabine yielded statistically significant better overall response rate and progression-free survival than lapatinib plus capecitabine in this randomized phase II trial.
An economic analysis of axitinib and sorafenib for second-line treatment of cytokine-refractory patients with advanced renal cell carcinoma in the United States (US).
Authors: Ipek Özer-Stillman, Apoorva Ambavane, Paul Cislo
Journal: Journal of Clinical Oncology (2013)

e15601 Background: Cytokines are a first-line treatment option for a subset of advanced RCC patients in the US. After progression on cytokines, NCCN guidelines recommend targeted agents, such as axitinib and sorafenib. Subgroup analysis of post-cytokine patients in the phase III AXIS trial found that axitinib increased median progression free survival (PFS) compared with sorafenib (12.0 vs. 6.6 months, p&lt;0.0001), while overall survival (OS) showed no difference (29.4 vs. 27.8 months, p=0.144). An economic analysis for this subgroup was conducted from a US healthcare payer perspective. Methods: A cohort partition model with monthly cycles was constructed to estimate direct medical costs and health outcomes, discounted at 3.0% per annum, over cohort lifetime. Patients were apportioned into 3 health states (progression-free, progressed and dead) based on OS and PFS Kaplan-Meier curves for the post-cytokine subgroup in the AXIS trial. Active treatment was applied until progression, followed by best supportive care (BSC) alone thereafter. The wholesale acquisition costs were based from RedBook. Adverse event (AE) management costs were obtained from published studies. AE rates and utility values were informed by the AXIS trial. Administrative claims data from MarketScan Database were analyzed to estimate costs for BSC and routine care of second-line advanced RCC patients. Results: The total per-patient lifetime costs were estimated to be $242,750 for axitinib and $168,880 for sorafenib and most of the cost difference (84%) was due to the higher total medication cost of axitinib. The cost difference was sensitive to dose intensity and length of treatment. The difference in quality-adjusted life-years (QALY) for axitinib versus sorafenib was minor (1.3 versus 1.2) and the incremental cost-effectiveness ratio (ICER) for axitinib compared with sorafenib was $683,209/QALY. Conclusions: For cytokine-refractory advanced RCC patients, axitinib resulted in an ICER &gt; $650,000/QALY versus sorafenib due to high drug costs and lack of OS benefit, indicating that axitinib may not present good value for money as 2 nd line treatment when compared to sorafenib in the US.
Repurposing approved drugs on the pathway to novel therapies
Authors: Catherine H. Schein
Journal: Medicinal Research Reviews (2019)

Abstract The time and cost of developing new drugs have led many groups to limit their search for therapeutics to compounds that have previously been approved for human use. Many “repurposed” drugs, such as derivatives of thalidomide, antibiotics, and antivirals have had clinical success in treatment areas well beyond their original approved use. These include applications in treating antibiotic‐resistant organisms, viruses, cancers and to prevent burn scarring. The major theoretical justification for reusing approved drugs is that they have known modes of action and controllable side effects. Coadministering antibiotics with inhibitors of bacterial toxins or enzymes that mediate multidrug resistance can greatly enhance their activity. Drugs that control host cell pathways, including inflammation, tumor necrosis factor, interferons, and autophagy, can reduce the “cytokine storm” response to injury, control infection, and aid in cancer therapy. An active compound, even if previously approved for human use, will be a poor clinical candidate if it lacks specificity for the new target, has poor solubility or can cause serious side effects. Synergistic combinations can reduce the dosages of the individual components to lower reactivity. Preclinical analysis should take into account that severely ill patients with comorbidities will be more sensitive to side effects than healthy trial subjects. Once an active, approved drug has been identified, collaboration with medicinal chemists can aid in finding derivatives with better physicochemical properties, specificity, and efficacy, to provide novel therapies for cancers, emerging and rare diseases.
A Delicate Balance between Bacterial Iron and Reactive Oxygen Species Supports Optimal C. elegans Development
Authors: Jingyan Zhang, Xuhang Li, Maria Olmedo, Amy D. Holdorf, Ye Shang, Marta Artal-Sanz, L. Safak Yilmaz, Albertha J.M. Walhout
Journal: Cell Host & Microbe (2019)
Efficacy of a Clinical Prediction Rule to Identify Febrile Young Infants at Low Risk for Serious Bacterial Infections
Authors: Sergio Verd, Pia Moll
Journal: JAMA Pediatrics (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Human Papillomavirus–Attributable Cancers — United States, 2012–2016
Authors: Virginia Senkomago, S. Jane Henley, Cheryll C. Thomas, Jacqueline M. Mix, Lauri E. Markowitz, Mona Saraiya
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Human papillomavirus (HPV) causes nearly all cervical cancers and some cancers of the vagina, vulva, penis, anus, and oropharynx (1).* Most HPV infections are asymptomatic and clear spontaneously within 1 to 2 years; however, persistent infection with oncogenic HPV types can lead to development of precancer or cancer (2). In the United States, the 9-valent HPV vaccine (9vHPV) is available to protect against oncogenic HPV types 16, 18, 31, 33, 45, 52, and 58 as well as nononcogenic types 6 and 11 that cause genital warts. CDC analyzed data from the U.S. Cancer Statistics (USCS)† to assess the incidence of HPV-associated cancers and to estimate the annual number of cancers caused by HPV, overall and by state, during 2012-2016 (3,4). An average of 43,999 HPV-associated cancers were reported annually, and an estimated 34,800 (79%) of those cancers were attributable to HPV. Of these 34,800 cancers, an estimated 32,100 (92%) were attributable to the types targeted by 9vHPV, with 19,000 occurring among females and 13,100 among males. The most common were cervical (9,700) and oropharyngeal cancers (12,600). The number of cancers estimated to be attributable to the types targeted by 9vHPV ranged by state from 40 to 3,270 per year. HPV vaccination is an important strategy that could prevent these cancers, but during 2018, only half of adolescents were up to date on HPV vaccination (5). These surveillance data from population-based cancer registries can be used to inform the planning for, and monitor the long-term impact of, HPV vaccination and cancer screening efforts nationally and within states.
Ross Levine: Focus on the critical questions
Authors: Stephanie Houston
Journal: The Journal of Experimental Medicine (2019)

Ross Levine is a physician-scientist at Memorial Sloan Kettering Cancer Center in New York, where his laboratory studies the genetic basis of myeloid malignancies. Work from Ross' laboratory has shown how mutations in the JAK-STAT pathway and epigenetic regulators play a role in myeloproliferative neoplasms, and JAK inhibitors are now successfully used to treat myeloproliferative neoplasms. We spoke to Ross about his journey in science so far.
A plasma proteogenomic signature for fibromuscular dysplasia
Authors: Jeffrey W Olin, Antonio F Di Narzo, Valentina d’Escamard, Daniella Kadian-Dodov, Haoxiang Cheng, Adrien Georges, Annette King, Allison Thomas, Temo Barwari, Katherine C Michelis, Rihab Bouchareb, Emir Bander, Anelechi Anyanwu, Paul Stelzer, Farzan Filsoufi, Sander Florman, Mete Civelek, Stephanie Debette, Xavier Jeunemaitre, Johan L M Björkegren, Manuel Mayr, Nabila Bouatia-Naji, Ke Hao, Jason C Kovacic
Journal: Cardiovascular Research (2019)

Fibromuscular dysplasia (FMD) is a poorly understood disease that predominantly affects women during middle-life, with features that include stenosis, aneurysm, and dissection of medium-large arteries. Recently, plasma proteomics has emerged as an important means to understand cardiovascular diseases. Our objectives were: (i) to characterize plasma proteins and determine if any exhibit differential abundance in FMD subjects vs. matched healthy controls and (ii) to leverage these protein data to conduct systems analyses to provide biologic insights on FMD, and explore if this could be developed into a blood-based FMD test.
Is APOC3 the driver of cardiovascular disease in people with type I diabetes mellitus?
Authors: Henry N. Ginsberg, Gissette Reyes-Soffer
Journal: Journal of Clinical Investigation (2019)

In this issue of the JCI, Kanter et al. make a strong case for implicating apolipoprotein C3 (APOC3) as a central player in atherosclerotic cardiovascular disease that is commonly seen in individuals with type 1 diabetes mellitus (T1DM). Kanter and colleagues suggest that insulin deficiency elevates plasma APOC3 as well as atherogenic triglyceride-rich (TG-rich) lipoproteins (TRLs). Using two mouse models of T1DM, the authors investigated APOC3-mediated inhibition of both TG hydrolysis by lipoprotein lipase and hepatic uptake of remnant lipoproteins. They suggest that poorly catabolized lipoproteins, enriched in both APOC3 and APOE content, are particularly atherogenic. Notably, treating both mouse models with an APOC3 antisense oligonucleotide lowered both plasma APOC3 and TRLs, and prevented atherosclerosis. These impactful mouse studies were supported by the initial finding that APOC3 predicted coronary artery disease events in participants of the prospective Coronary Artery Calcification in Type 1 Diabetes study with normal TG levels.
Reply to Bogaard <i>et al.</i>: Emphysema Is—at the Most—Only a Mild Phenotype in the Sugen/Hypoxia Rat Model of Pulmonary Arterial Hypertension
Authors: Baktybek Kojonazarov, Stefan Hadzic, Hossein Ardeschir Ghofrani, Friedrich Grimminger, Werner Seeger, Norbert Weissmann, Ralph Theo Schermuly
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

critically depends on standardized tracheal inflation pressure and volume, in the absence of a pleural leakage.In summary, based on a search of the literature and on the analysis of our own SuHx rat studies (Table 1 and Figure 1), we cannot confirm the presence of moderate or severe emphysema in the established SuHx rat model of PAH.At most, there may be mild enlargement of intraalveolar spaces depending on rat strain, number of SU5146 doses, and timing of lung harvest.In contrast, there is ample evidence that repetitive SU5416 injections alone (i.e., blockade of VEGFR2 and other kinases), in the absence of hypoxia, can produce an emphysema-like lung phenotype, but the latter mainly occurs in younger rats in which postnatal lung development may still be ongoing (3).Our data provide evidence that the SuHx rat model, when yielding RVSP consistently mm Hg, using adequate controls and standardized lung inflation, is currently one of the best rodent models for studying PAH and pulmonary vascular disease.The SuHx rat model allows the study of the mechanisms of cardiovascular remodeling, vessel loss and RV failure, and lacks a biologically relevant emphysemalike lung phenotype.
Immunoinflammatory responses to febrile lower respiratory infections in infants display uniquely complex/intense transcriptomic profiles
Authors: Anya C. Jones, Denise Anderson, Sally Galbraith, Emmanuelle Fantino, Diana Gutierrez Cardenas, James F. Read, Michael Serralha, Barbara J. Holt, Deborah H. Strickland, Peter D. Sly, Anthony Bosco, Patrick G. Holt
Journal: Journal of Allergy and Clinical Immunology (2019)
Chronic hydroxychloroquine exposure and the risk of Alzheimer’s disease
Authors: Shih-Wei Lai, Yu-Hung Kuo, Kuan-Fu Liao
Journal: Annals of the Rheumatic Diseases (2019)

Hydroxychloroquine is an immunomodulatory agent which is commonly used to treat malaria and autoimmune diseases.1 The association between hydroxychloroquine therapy and subsequent comorbidities has been extensively addressed.1 2 Recently, a cohort study conducted in the UK by Fardet et al published in Annals of the Rheumatic Diseases reported that long-term use of hydroxychloroquine was not associated with the risk of Alzheimer’s disease when compared with non-use of hydroxychloroquine (adjusted HR=0.81, 95% CI=0.58 to 1.12, p=0.20).3 One comment published in Annals of the Rheumatic Diseases reported that due to conflicting results between observational studies regarding the impact of hydroxychloroquine on Alzheimer’s disease, the relationship cannot be determined currently.4

In order to test such an association in a different population, a …