tbuckley/cabot-search huggingface dataset:
Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study
Authors: Kim N. Chi, Simon Chowdhury, Anders Bjartell, Byung Ha Chung, Andrea J. Pereira de Santana Gomes, Robert Given, Alvaro Juárez, Axel S. Merseburger, Mustafa Özgüroğlu, Hirotsugu Uemura, Dingwei Ye, Sabine Brookman-May, Suneel D. Mundle, Sharon A. McCarthy, Julie S. Larsen, Weili Sun, Katherine B. Bevans, Ke Zhang, Nibedita Bandyopadhyay, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2021)

The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving ongoing androgen deprivation therapy (ADT). Herein, we report final efficacy and safety results after unblinding and placebo-to-apalutamide crossover.Patients with mCSPC (N = 1,052) were randomly assigned 1:1 to receive apalutamide (240 mg QD) or placebo plus ADT. After unblinding in January 2019, placebo-treated patients were allowed to receive apalutamide. Efficacy end points were updated using the Kaplan-Meier method and Cox proportional-hazards model without formal statistical retesting and adjustment for multiplicity. Change from baseline in Functional Assessment of Cancer Therapy-Prostate total score was assessed.With a median follow-up of 44.0 months, 405 OS events had occurred and 208 placebo-treated patients (39.5%) had crossed over to apalutamide. The median treatment duration was 39.3 (apalutamide), 20.2 (placebo), and 15.4 months (crossover). Compared with placebo, apalutamide plus ADT significantly reduced the risk of death by 35% (median OS not reached v 52.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P < .0001) and by 48% after adjustment for crossover (hazard ratio, 0.52; 95% CI, 0.42 to 0.64; P < .0001). Apalutamide plus ADT delayed second progression-free survival and castration resistance (P < .0001 for both). Health-related quality of life, per total Functional Assessment of Cancer Therapy-Prostate, in both groups was maintained through the study. Safety was consistent with previous reports.The final analysis of TITAN confirmed that, despite crossover, apalutamide plus ADT improved OS, delayed castration resistance, maintained health-related quality of life, and had a consistent safety profile in a broad population of patients with mCSPC.
The impact of cell type and context-dependent regulatory variants on human immune traits
Authors: Zepeng Mu, Wei Wei, Benjamin Fair, Jinlin Miao, Ping Zhu, Yang I. Li
Journal: Genome biology (2021)

Abstract Background The vast majority of trait-associated variants identified using genome-wide association studies (GWAS) are noncoding, and therefore assumed to impact gene regulation. However, the majority of trait-associated loci are unexplained by regulatory quantitative trait loci (QTLs). Results We perform a comprehensive characterization of the putative mechanisms by which GWAS loci impact human immune traits. By harmonizing four major immune QTL studies, we identify 26,271 expression QTLs (eQTLs) and 23,121 splicing QTLs (sQTLs) spanning 18 immune cell types. Our colocalization analyses between QTLs and trait-associated loci from 72 GWAS reveals that genetic effects on RNA expression and splicing in immune cells colocalize with 40.4% of GWAS loci for immune-related traits, in many cases increasing the fraction of colocalized loci by two fold compared to previous studies. Notably, we find that the largest contributors of this increase are splicing QTLs, which colocalize on average with 14% of all GWAS loci that do not colocalize with eQTLs. By contrast, we find that cell type-specific eQTLs, and eQTLs with small effect sizes contribute very few new colocalizations. To investigate the 60% of GWAS loci that remain unexplained, we collect H3K27ac CUT&amp;Tag data from rheumatoid arthritis and healthy controls, and find large-scale differences between immune cells from the different disease contexts, including at regions overlapping unexplained GWAS loci. Conclusion Altogether, our work supports RNA splicing as an important mediator of genetic effects on immune traits, and suggests that we must expand our study of regulatory processes in disease contexts to improve functional interpretation of as yet unexplained GWAS loci.
Tamoxifen: Will Less Equal More in Women with Precancerous Breast Disease?
Authors: Carol J. Fabian
Journal: Clinical Cancer Research (2021)

Abstract Similar risk reduction but fewer side effects would predict more uptake and compliance with low (5 mg) versus full (20 mg) dose tamoxifen. Benefit with low dose is demonstrated for perimenopausal/postmenopausal women with intraepithelial neoplasia and high lesion Ki-67. Longer follow-up needed to determine benefit with low lesion Ki-67. See related article by DeCensi et al., p. 3576
Hyperthermic Intraperitoneal Chemotherapy for Ovarian and Colorectal Cancer
Authors: Ruby M. van Stein, Arend G. J. Aalbers, Gabe S. Sonke, Willemien J. van Driel
Journal: JAMA Oncology (2021)

<h3>Importance</h3> The peritoneal surface is a common site of disease in ovarian and colorectal cancer. Peritoneal metastases carry a poor prognosis, despite maximal therapeutic efforts, including surgical removal of tumor deposits and intravenous chemotherapy. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a single intraoperative procedure that delivers chemotherapy directly into the abdominal cavity, leading to high intracellular drug concentration at the peritoneal surface. This review describes the current knowledge regarding the mechanism of action, safety, and efficacy of HIPEC in the treatment of peritoneal metastases from epithelial ovarian and colorectal cancers and explores current knowledge gaps. <h3>Observations</h3> Toxic effects of HIPEC are limited. Evidence from a randomized trial shows improved recurrence-free and overall survival after HIPEC in patients with ovarian cancer who are ineligible for primary cytoreductive surgery (CRS). The effect of HIPEC for patients with ovarian cancer undergoing primary CRS or CRS for recurrent disease has not yet been determined, and results of ongoing trials must be awaited. A recent study in patients with peritoneal metastases from colorectal cancer did not show a benefit of HIPEC when added to perioperative chemotherapy. <h3>Conclusions and Relevance</h3> Based on available evidence, various international guidelines include the option to add HIPEC to interval CRS for patients with stage III ovarian cancer. The role of HIPEC in colorectal cancer is less well defined. Future studies will need to tailor patient selection, timing, and optimal regimens of HIPEC to improve the effectiveness of this specialized treatment in ovarian, colorectal, and other tumor types.
3D Printing of Strontium Silicate Microcylinder‐Containing Multicellular Biomaterial Inks for Vascularized Skin Regeneration
Authors: Jingge Ma, Chen Qin, Jinfu Wu, Hongjian Zhang, Hui Zhuang, Meng Zhang, Zhaowenbin Zhang, Lingling Ma, Xin Wang, Bing Ma, Jiang Chang, Chengtie Wu
Journal: Advanced Healthcare Materials (2021)

The reconstruction of dermal blood vessels is essential for skin regeneration process. However, the lack of vascular structure, insufficient angiogenesis induction, and ineffective graft-host anastomosis of the existing skin substitutes are major bottle-necks for permanent skin replacement in tissue engineering. In this study, the uniform strontium silicate (SS) microcylinders are successfully synthesized and integrated into the biomaterial ink to serve as stable cell-induced factors for angiogenesis, and then a functional skin substitute based on a vascularization-induced biomimetic multicellular system is prepared via a "cell-writing" bioprinting technology. With an unprecedented combination of vascularized skin-mimicking structure and vascularization-induced function, the SS-containing multicellular system exhibits outstanding angiogenic activity both in vitro and in vivo. As a result, the bioprinted skin substitutes significantly accelerate the healing of both acute and chronic wounds by promoting the graft-host integration and vascularized skin regeneration in three animal models. Therefore, the study provides a referable strategy to fabricate biomimetic multicellular constructs with angiogenesis-induced function for regeneration of vascularized complex and hierarchical tissues.
Sixty seconds on . . . concussion in football
Authors: Gareth Iacobucci
Journal: BMJ (2021)

A large study1 of US high school football (or, should we say, soccer) players has found that teenage girls face almost double the risk of concussion playing the game compared with teenage boys (risk ratio 1.88, 95% confidence interval 1.69 to 2.09, P<0.001). The authors said their findings were relevant to growing concerns about the consequences of sport related concussion (SRC), including the possible increased risk of dementia which is still being investigated.

Notably, the study, …
Abstract 15723: Risk Factors of Fluoropyrimidine Induced Cardiotoxicity Among Cancer Patients: A Systematic Review and Meta-analysis
Authors: Chao Li, Kaniz A Tanni, Surachat Ngorsuraches, Chiahung Chou, Li Chen, Jingjing Qian
Journal: Circulation (2020)

Introduction: Cancer patients are at increased risk of experiencing cardiotoxicity during their fluoropyrimidine-based chemotherapy. However, risk factors for fluoropyrimidine-induced cardiotoxicity (FIC) are not entirely understood. Methods: We searched PubMed, PsycINFO, IPA, CINAHL, Web of Science and ClinicalTrials.gov for studies published between January 1, 1990 and December 31, 2019, examining risk factors for cardiotoxicity induced by 5-fluorouracil, capecitabine or floxuridine. Two reviewers independently assessed publication quality and extracted study-level data into standardized evidence tables. Review Manager 5 software was used to convert data to risk ratios (RRs) and calculate pooled RRs for meta-analyses using a random-effects method. We conducted a Cochran’s Q test and obtained I 2 index to quantify study heterogeneity in each meta-analysis, with prediction interval (PI) to show the expected range of true effects in future similar studies. Results: Of 690 publications identified for abstract and title screening, 22 unique studies were included in the final review, and 20 of them had sufficient data for meta-analyses. Results indicated that patients undergoing capecitabine-based combination therapy had a higher risk of FIC than those with capecitabine monotherapy (pooled RR=1.61, 95% CI=1.01-2.55, I 2 =0%, 95% PI=0.08-31.71). Also, patients with pre-existing cardiac disease (pooled RR=3.01, 95% CI=2.02-4.49, I 2 =42%, 95% PI=1.03-8.78), hypertension (pooled RR=1.52, 95% CI=1.20-1.93, I 2 =0%, 95% PI=1.08-2.13) or smoking habit (pooled RR=2.22, 95% CI=1.03-4.78, I 2 =39%, 95% PI=0.15-32.46) had a significantly higher risk of FIC than their counterparts, while gender and comorbidities including diabetes, hyperlipidemia, and obesity were not significant risk factors of FIC. Conclusions: Cancer patients with pre-existing cardiac disease, hypertension, and smoking behavior had a higher risk of FIC when they are undergoing fluoropyrimidine-based treatments. Further research is needed to develop risk assessment tools for a risk prediction of FIC among cancer patients, which could advance risk stratification strategies and improve patient outcomes during the application of fluoropyrimidine-based treatments.
冠動脈バイパス術中大動脈解離術後遠隔期に大動脈基部置換,弓部置換,僧帽弁輪縫縮術を施行した一例
Authors: 塩満大樹, 松宮護郎, 倉谷徹, 坂口太一, 白川幸俊, 藤田知之, 市川肇, 澤芳樹
Journal: Circulation (2008)
CLINICAL OUTCOME FOLLOWING PERCUTANEOUS CORONARY INTERVENTION IN STABLE CORONARY ARTERY DISEASE BASED ON A NOVEL INDEX: COMPUTATIONAL PRESSURE-FLOW DYNAMICS DERIVED FRACTIONAL FLOW RESERVE
Authors: Lok Yee Jane Lam, Ka Lam Calvin Leung, Kwan Yu Li, Shuk Yin Yu, Mei Zhen Wu, Qing Wen Ren, Pui Fai Wong, Yi Kei Tse, Si Yeung Yu, Hang Long Li, Yundi Feng, Yun Long Huo, Hung-Fat Tse, Kai-Hang Yiu
Journal: Journal of the American College of Cardiology (2021)
THE ETHNIC GAP IN CLINICAL OUTCOMES OF SIGNIFICANT AORTIC STENOSIS IN THE ASIAN POPULATION
Authors: Nicholas Chew, Nicholas Ngiam, Clare Cheong, Gwyneth Kong, Ching Hui Sia, Ivandito Kuntjoro, Ruan Wen, William Kong, Edgar Tay, Tiong Cheng Yeo, Kian Keong Poh
Journal: Journal of the American College of Cardiology (2021)
mRNA modifications in cardiovascular biology and disease: with a focus on m6A modification
Authors: Rajesh Kumari, Prabhat Ranjan, Zainab Gbongbo Suleiman, Sumanta Kumar Goswami, Jing Li, Ram Prasad, Suresh Kumar Verma
Journal: Cardiovascular Research (2021)

Among several known RNA modifications, N6-methyladenosine (m6A) is the most studied RNA epitranscriptomic modification and controls multiple cellular functions during development, differentiation, and disease. Current research advancements have made it possible to examine the regulatory mechanisms associated with RNA methylation and reveal its functional consequences in the pathobiology of many diseases, including heart failure. m6A methylation has been described both on coding (mRNA) and non-coding RNA species including rRNA, tRNA, small nuclear RNA and circular RNAs. The protein components which catalyze the m6A methylation are termed methyltransferase or 'm6A writers'. The family of proteins that recognize this methylation are termed 'm6A readers' and finally the enzymes involved in the removal of a methyl group from RNA are known as demethylases or 'm6A erasers'. At the cellular level, different components of methylation machinery are tightly regulated by many factors to maintain the m6A methylation dynamics. The m6A methylation process impacts different stages of mRNA metabolism and the biogenesis of long non-coding RNA and miRNA. Although, mRNA methylation was initially described in the 1970s, its regulatory roles in various diseases, including cardiovascular diseases are broadly unexplored. Recent investigations suggest the important role of m6A mRNA methylation in both hypertrophic and ischaemic heart diseases. In the present review, we evaluate the significance of m6A methylation in the cardiovascular system, in cardiac homeostasis and disease, all of which may help to improve therapeutic intervention for the treatment of heart failure. RNA methylation in cardiovascular diseases: altered m6A RNA (coding and non-coding RNA) methylation is identified during different cardiovascular diseases. Increased cardiac hypertrophy is observed following METTL3 overexpression. In contrast, reduced FTO level was seen in mice following myocardial infarction. Increased cardiac fibroblasts activation or increased atherosclerotic plaques were also co-related with m6A RNA methylation.
Abstract
Journal: Allergy (2020)

Background : To assess an improved version of SLIT by applying a novel short course oromucosal immunotherapy intervention strategy in an allergic pig model.Method : Newborn piglets sensitized intraperitoneally with the common egg allergen ovalbumin (OVA) were sublingually treated five times using a dose ascending administration schedule with a proprietary mouth patch containing high dose of OVA, formulated with immune tolerogenic particles derived from the probiotic bacterium Lactococcus lactis.Physical symptoms were monitored to determine the allergic response.Immunologic assessment was conducted through use of intradermal testing of the allergenic response to OVA.Cryocuts of mucosal and regional lymphoid tissues were analysed by confocal fluorescence microscopy for uptake and migration of OVA allergen and bacterial particles.Following sublingual patch administrations, the pigs were analysed by intradermal allergy testing and for IgE.Results : OVA-sensitized pigs responded with physical symptoms that mimicked those seen in challenges to food allergens in human beings.Intradermal allergy testing suggested an IgE-mediated response; this was confirmed by a negative passive cutaneous anaphylaxis response of heat-treated sera obtained from OVA-sensitized animals.Treatment with a proprietary mouth patch containing high dose OVA and tolerogenic particles derived from the probiotic bacterium L. lactis resulted in lymph node trafficking of both allergen and particles and a better desensitization compared with patches containing OVA alone as measured by intradermal allergy testing. Conclusion : A new short course SLIT strategy has been successfullyimplemented in a novel porcine model of OVA allergy.Treatment with a mouth patch containing OVA and tolerogenic bacterial particles resulted in lymph node trafficking and better desensitization compared with patch containing OVA alone.Furthermore, it was shown that a few high dose allergen administrations resulted in efficient desensitization suggesting that an improved short course SLIT approach is feasible by applying a more efficient sublingual delivery of allergens and proper stimulation of a privileged tolerogenic environment.
IMPACT OF DIASTOLIC VESSEL RESTRICTION ON CLINICAL SYMPTOMS IN PATIENTS WITH SYMPTOMATIC MYOCARDIAL BRIDGING
Authors: Takehiro Hashikata, Yasuhiro Honda, Hanjay Wang, Vedant Pargaonkar, M Brooke Hollak, Ian S Rogers, Paul Yock, Peter Fitzgerald, Ingela Schnittger, Jack Boyd, Jennifer Tremmel
Journal: Journal of the American College of Cardiology (2021)
Ibrutinib combinations in CLL therapy: scientific rationale and clinical results
Authors: Natalia Timofeeva, Varsha Gandhi
Journal: Blood Cancer Journal (2021)

Abstract Ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia (CLL). This drug irreversibly inhibits Bruton tyrosine kinase (BTK) by covalently binding to the C481 residue in the BTK kinase domain. BTK is a pivotal protein for B cell receptor signaling and tissue homing of CLL cells. Preclinical investigations have established the importance of the B cell receptor pathway in the maintenance and survival of normal and malignant B cells, underscoring the importance of targeting this axis for CLL. Clinical trials demonstrated overall and progression-free survival benefit with ibrutinib in multiple CLL subgroups, including patients with relapsed or refractory disease, patients with 17p deletion, elderly patients, and treatment-naïve patients. Consequently, ibrutinib was approved by the US Food and Drug Administration for newly diagnosed and relapsed disease. Ibrutinib has transformed the treatment of CLL; however, several limitations have been identified, including low complete remission rates, development of resistance, and uncommon substantial toxicities. Further, ibrutinib must be used until disease progression, which imposes a financial burden on patients and society. These limitations were the impetus for the development of ibrutinib combinations. Four strategies have been tested in recent years: combinations of ibrutinib with immunotherapy, chemoimmunotherapy, cell therapy, and other targeted therapy. Here, we review the scientific rationale for and clinical outcome of each strategy. Among these strategies, ibrutinib with targeted agent venetoclax results in high complete response rates and, importantly, high rates of undetectable minimal residual disease. Although we concentrate here on ibrutinib, similar combinations are expected or ongoing with acalabrutinib, tirabrutinib, and zanubrutinib, second-generation BTK inhibitors. Future investigations will focus on the feasibility of discontinuing ibrutinib combinations after a defined time; the therapeutic benefit of adding a third agent to ibrutinib-containing combinations; and profiling of resistant clones that develop after combination treatment. A new standard of care for CLL is expected to emerge from these investigations.
MACHINE LEARNING ISCHEMIA RISK SCORE FROM CORONARY CT ANGIOGRAPHY PREDICTS LESION-SPECIFIC ISCHEMIA AND IMPAIRED MYOCARDIAL BLOOD FLOW: RESULTS FROM THE PACIFIC TRIAL
Authors: Andrew Lin, Pepijn Van Diemen, Manish Motwani, Priscilla McElhinney, Yuka Otaki, Alan Kwan, Donghee Han, Keiichiro Kuronuma, Eyal Klein, Kajetan Grodecki, Benjamin Shou, Sebastien Cadet, Ibrahim Danad, Roel Driessen, Piotr Slomka, Daniel Berman, Damini Dey, Paul Knaapen
Journal: Journal of the American College of Cardiology (2021)
Whither Thou Goest... I Will Go
Journal: JAMA (1992)

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
Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): A multicenter study
Authors: Jitao Wang, Zhiyun Hou, Jianxin Liu, Ye Gu, Yunhong Wu, Zhenhuai Chen, Jiansong Ji, Shiqi Diao, Yuanwang Qiu, Shengqiang Zou, Aiguo Zhang, Nina Zhang, Fengxian Wang, Xue Li, Yan Wang, Xing Liu, Cheng Lv, Shubo Chen, Dengxiang Liu, Xiaolin Ji, Chao Liu, Tao Ren, Jingwei Sun, Zhongwei Zhao, Fazong Wu, Fenxiang Li, Ruixu Wang, Yan Yan, Shiliang Zhang, Guohong Ge, Jiangbo Shao, Shiying Yang, Chuan Liu, Yifei Huang, Dan Xu, Xiaoguo Li, Jingwen Ai, Qing He, Ming-Hua Zheng, Liting Zhang, Qing Xie, Don C. Rockey, Jonathan A. Fallowfield, Wenhong Zhang, Xiaolong Qi
Journal: Journal of Hepatology (2021)
Single-nucleotide-level mapping of DNA regulatory elements that control fetal hemoglobin expression
Authors: Li Cheng, Yichao Li, Qian Qi, Peng Xu, Ruopeng Feng, Lance Palmer, Jingjing Chen, Ruiqiong Wu, Tiffany Yee, Jingjing Zhang, Yu Yao, Akshay Sharma, Ross C. Hardison, Mitchell J. Weiss, Yong Cheng
Journal: Nature Genetics (2021)
Omics sciences for systems biology in Alzheimer’s disease: State-of-the-art of the evidence
Authors: Harald Hampel, Robert Nisticò, Nicholas T. Seyfried, Allan I. Levey, Erica Modeste, Pablo Lemercier, Filippo Baldacci, Nicola Toschi, Francesco Garaci, George Perry, Enzo Emanuele, Pedro L. Valenzuela, Alejandro Lucia, Andrea Urbani, Giulia M. Sancesario, Mark Mapstone, Massimo Corbo, Andrea Vergallo, Simone Lista
Journal: Ageing Research Reviews (2021)
Apolipoprotein-1 risk variants and associated kidney phenotypes in an adult HIV cohort in Nigeria
Authors: Usman J. Wudil, Muktar H. Aliyu, Heather L. Prigmore, Donna J. Ingles, Aima A. Ahonkhai, Baba M. Musa, Hamza Muhammad, Mahmoud U. Sani, Aisha M. Nalado, Aliyu Abdu, Kabiru Abdussalam, Bryan E. Shepherd, Faisal S. Dankishiya, Anna M. Burgner, T. Alp Ikizler, Christina M. Wyatt, Jeffrey B. Kopp, Paul L. Kimmel, Cheryl A. Winkler, C. William Wester
Journal: Kidney International (2021)