tbuckley/cabot-search huggingface dataset:
Effect of dose and duration of reduction in dietary sodium on blood pressure levels: systematic review and meta-analysis of randomised trials
Authors: Liping Huang, Kathy Trieu, Sohei Yoshimura, Bruce Neal, Mark Woodward, Norm R C Campbell, Qiang Li, Daniel T Lackland, Alexander A Leung, Cheryl A M Anderson, Graham A MacGregor, Feng J He
Journal: BMJ (2020)

Abstract Objective To examine the dose-response relation between reduction in dietary sodium and blood pressure change and to explore the impact of intervention duration. Design Systematic review and meta-analysis following PRISMA guidelines. Data sources Ovid MEDLINE(R), EMBASE, and Cochrane Central Register of Controlled Trials (Wiley) and reference lists of relevant articles up to 21 January 2019. Inclusion criteria Randomised trials comparing different levels of sodium intake undertaken among adult populations with estimates of intake made using 24 hour urinary sodium excretion. Data extraction and analysis Two of three reviewers screened the records independently for eligibility. One reviewer extracted all data and the other two reviewed the data for accuracy. Reviewers performed random effects meta-analyses, subgroup analyses, and meta-regression. Results 133 studies with 12 197 participants were included. The mean reductions (reduced sodium v usual sodium) of 24 hour urinary sodium, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were 130 mmol (95% confidence interval 115 to 145, P&lt;0.001), 4.26 mm Hg (3.62 to 4.89, P&lt;0.001), and 2.07 mm Hg (1.67 to 2.48, P&lt;0.001), respectively. Each 50 mmol reduction in 24 hour sodium excretion was associated with a 1.10 mm Hg (0.66 to 1.54; P&lt;0.001) reduction in SBP and a 0.33 mm Hg (0.04 to 0.63; P=0.03) reduction in DBP. Reductions in blood pressure were observed in diverse population subsets examined, including hypertensive and non-hypertensive individuals. For the same reduction in 24 hour urinary sodium there was greater SBP reduction in older people, non-white populations, and those with higher baseline SBP levels. In trials of less than 15 days’ duration, each 50 mmol reduction in 24 hour urinary sodium excretion was associated with a 1.05 mm Hg (0.40 to 1.70; P=0.002) SBP fall, less than half the effect observed in studies of longer duration (2.13 mm Hg; 0.85 to 3.40; P=0.002). Otherwise, there was no association between trial duration and SBP reduction. Conclusions The magnitude of blood pressure lowering achieved with sodium reduction showed a dose-response relation and was greater for older populations, non-white populations, and those with higher blood pressure. Short term studies underestimate the effect of sodium reduction on blood pressure. Systematic review registration PROSPERO CRD42019140812.
Association of Dietary Patterns With Testicular Function in Young Danish Men
Authors: Feiby L. Nassan, Tina K. Jensen, Lærke Priskorn, Thorhallur I. Halldorsson, Jorge E. Chavarro, Niels Jørgensen
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Diet may play a role in testicular function, but data on how adherence to different diet patterns influences human testicular function are scarce. <h3>Objective</h3> To determine whether adherence to specific dietary patterns is associated with testicular function in young men. <h3>Design, Setting, and Participants</h3> This cross-sectional study included 2935 young Danish men unselected regarding fertility status who were enrolled from April 1, 2008, through May 31, 2017. Data were analyzed from July 1, 2017, to January 30, 2019. <h3>Exposures</h3> Dietary patterns identified with principal component analysis based on responses to a validated food frequency questionnaire. <h3>Main Outcomes and Measures</h3> Standard semen quality assessment; serum concentrations of testosterone, free testosterone, estradiol, inhibin B, follicle-stimulating hormone, luteinizing hormone, and sex hormone–binding globulin; and testicular volume measured with ultrasonography. <h3>Results</h3> Among the 2935 participants included in the analysis, median age was 19 (interquartile range, 19-20) years and 2290 (78.0%) had normal body mass index. The 4 dietary patterns identified included Western, prudent, open-sandwich (a traditional Danish eating pattern), and vegetarianlike. The greatest adherence to the prudent pattern was associated with the highest total sperm count (median, 167 [95% CI, 146-183] million), followed by adherence to vegetarianlike (median, 151 [95% CI, 134-168] million) and open-sandwich (median, 146 [95% CI, 131-163] million) patterns. Adherence to the Western pattern was associated with the lowest total sperm count (median, 122 [95% CI, 109-138] million), which was significantly lower than sperm count in the other 3 diet patterns. After adjusting for confounders, the median total sperm count for men in the highest quintile of adherence to the Western pattern was 26 million lower (95% CI, –42 to –9 million) than for men in the lowest quintile of adherence to this pattern. Conversely, the median total sperm count of men in the highest quintile of adherence to the prudent pattern was 43 million (95% CI, 23-63 million) higher than that of men in the lowest quintile. Men with the highest adherence to the Western pattern had a lower median ratio of inhibin B to follicle-stimulating hormone (–12 [95% CI, –20 to –3]) and higher median ratio of free testosterone to luteinizing hormone (10 [95% CI, 2-19]) compared with men with lowest adherence to this pattern. <h3>Conclusions and Relevance</h3> In this cross-sectional study, adherence to generally healthy diet patterns was associated with better semen quality, with potentially more favorable fertility potential among adult men.
Safety and efficacy of neoadjuvant chemotherapy (NAC) with accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (aMVAC) in patients (pts) with muscle invasive bladder cancer (MIBC) as a function of age.
Authors: Matthew R. Zibelman, Bianca Lewis, Eric A. Ross, Fern Anari, Pooja Ghatalia, Elizabeth R. Plimack, Daniel M. Geynisman
Journal: Journal of Clinical Oncology (2020)

506 Background: NAC improves survival in pts with MIBC eligible to receive cisplatin-based chemotherapy. Prospective data supports the use of aMVAC, however concerns about toxicity limits usage compared to gemcitabine and cisplatin, especially in the elderly. We investigated the safety and efficacy of aMVAC as a function of age. Methods: We conducted a retrospective analysis of pts with MIBC at Fox Chase Cancer Center who received NAC with aMVAC from 2008-2017. Pts were excluded for non-urothelial histology, non-muscle-invasive or primary upper tract disease, or if final pathology was not available. Clinicopathologic variables were extracted from charts and pts were grouped into 3 cohorts by age ( &lt; 65, 65-74, ≥75). Associations between age group (gp) and categorical/continuous factors were evaluated using Fisher’s exact/Wilcoxon rank sum tests. Results: A total of 90 pts ( &lt; 65: 40; 65-74: 28; ≥75: 22) were evaluable for safety and 84 for efficacy. The majority of pts were male (72%), PS 0 ( &lt; 65: 85%; 65-74: 85%; ≥75: 68%) and Caucasian (90%). Baseline clinical staging was cT2 in 50%, cT3 in 27% and &gt; cT3 in 14%, with 9% lacking clinical staging. Mean number of aMVAC cycles delivered was numerically similar between age gps, though statistically different (3.1 v 2.8 v 2.6; p = 0.01). There were no statistically significant differences in dose reductions, treatment interruptions, or time to surgery (10.7 v 10.7 v 10.1 wks, p = 0.91) by age. Grade ≥3 AEs were most frequent in the youngest age gp (14.4% v 2.2% v 8.9%, p = 0.018). Split-dose cisplatin was increasingly used in advanced age (2.5% v 17.9% v 31.8%, p = 0.003). Although glomerular filtration rate (GFR) at baseline inversely correlated with age (105 v 93 v 63 ml/min, p &lt; 0.0001), there was no difference in % GFR decline at 90 days or 1 year. The downstaging rate to &lt; pT2N0 disease was similar in all age gps (41.0% v 29.6% v 38.9%; p = 0.41). At median follow-up of 20 months, recurrence rates were 30.0% v 25.9% v 28.6% (p = 0.95). Conclusions: NAC with aMVAC yields similar safety and efficacy outcomes regardless of age, thus age should not be a factor in determining treatment eligibility.
What Does It Mean to Be a Physician?
Authors: Thomas L. Schwenk
Journal: JAMA (2020)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
A gene-expression-based signature predicts survival in adults with T-cell lymphoblastic lymphoma: a multicenter study
Authors: Xiao-Peng Tian, Dan Xie, Wei-Juan Huang, Shu-Yun Ma, Liang Wang, Yan-Hui Liu, Xi Zhang, Hui-Qiang Huang, Tong-Yu Lin, Hui-Lan Rao, Mei Li, Fang Liu, Fen Zhang, Li-Ye Zhong, Li Liang, Xiao-Liang Lan, Juan Li, Bing Liao, Zhi-Hua Li, Qiong-Lan Tang, Qiong Liang, Chun-Kui Shao, Qiong-Li Zhai, Run-Fen Cheng, Qi Sun, Kun Ru, Xia Gu, Xi-Na Lin, Kun Yi, Yue-Rong Shuang, Xiao-Dong Chen, Wei Dong, Wei Sang, Cai Sun, Hui Liu, Zhi-Gang Zhu, Jun Rao, Qiao-Nan Guo, Ying Zhou, Xiang-Ling Meng, Yong Zhu, Chang-Lu Hu, Yi-Rong Jiang, Ying Zhang, Hong-Yi Gao, Wen-Jun He, Zhong-Jun Xia, Xue-Yi Pan, Hai Lan, Guo-Wei Li, Lu Liu, Hui-Zheng Bao, Li-Yan Song, Tie-Bang Kang, Qing-Qing Cai
Journal: Leukemia (2020)
Outpatient Preoperative Penicillin Allergy Testing in Cardiac Surgery Patients
Authors: Jessica Plager, Christian Mancini, Erica Shenoy, Serguei Melnitchouk, Laura Collier, Aleena Banerji, Nivedita Chaudhary, Sharmitha Yerneni, Kimberly Blumenthal
Journal: Journal of Allergy and Clinical Immunology (2020)
Treatment and disease‐related complications in multiple myeloma: Implications for survivorship
Authors: Rajshekhar Chakraborty, Navneet S. Majhail
Journal: American Journal of Hematology (2020)

New treatments have transformed multiple myeloma into a chronic disease. Hence, optimal management of treatment and disease-related complications remains a critical component of survivorship care. Survivorship care model in cancers requiring a fixed-duration therapy may not be applicable to myeloma, since patients are exposed to multiple lines of continuous therapy along the disease trajectory. The two most common therapy-related causes of death, which require special consideration, are infection and second cancers. Identifying patients at a high risk of toxicities will facilitate individualized treatment selection and designing clinical trials for protective strategies targeting those patients. For example, prophylactic antibiotic or immunoglobulin replacement can be tested for primary prevention of infections in high-risk patients. Long-term follow up of ongoing trials and epidemiologic data will help identify the nature and trajectory of rare toxicities with a long latency, such as secondary cancers. Patients who are frail, have persistent renal insufficiency, and refractory to multiple lines of therapy need special attention regarding treatment toxicity and quality of life. In this review, we discuss the incidence, risk-factors, and management of treatment and disease-related complications in myeloma, discuss knowledge gaps and research priorities in this area, and propose a survivorship care model to improve health-care delivery to a growing pool of myeloma survivors.
Early-onset colorectal cancer: initial clues and current views
Authors: Lorne J. Hofseth, James R. Hebert, Anindya Chanda, Hexin Chen, Bryan L. Love, Maria M. Pena, E. Angela Murphy, Mathew Sajish, Amit Sheth, Phillip J. Buckhaults, Franklin G. Berger
Journal: Nature Reviews Gastroenterology & Hepatology (2020)
Beneficence, Interests, and Wellbeing in Medicine: What It Means to Provide Benefit to Patients
Authors: Johan Christiaan Bester
Journal: The American Journal of Bioethics (2020)

Beneficence is a foundational ethical principle in medicine. To provide benefit to a patient is to promote and protect the patient's wellbeing, to promote the patient's interests. But there are different conceptions of wellbeing, emphasizing different values. These conceptions of wellbeing are contrary to one another and give rise to dissimilar ideas of what it means to benefit a patient. This makes the concept of beneficence ambiguous: is a benefit related to the patient's goals and wishes, or is it a matter of objective criteria that constitute wellbeing? This paper suggests a unified conception of wellbeing for use in medicine to determine what counts as a benefit. Two components of wellbeing are identified: (1) objective functioning/health and (2) the patient's view of her own good. The paper explores how to apply, balance, and weigh these components in clinical situations to determine what counts as a benefit to a patient.
Human Adventitial Fibroblast Phenotype Depends on the Progression of Changes in Substrate Stiffness
Authors: Rebecca A. Scott, Karyn G. Robinson, Kristi L. Kiick, Robert E. Akins
Journal: Advanced Healthcare Materials (2020)

Abstract Adventitial fibroblasts (AFs) are major contributors to vascular remodeling and maladaptive cascades associated with arterial disease, where AFs both contribute to and respond to alterations in their surrounding matrix. The relationships between matrix modulus and human aortic AF (AoAF) function are investigated using poly(ethylene glycol)‐based hydrogels designed with matrix metalloproteinase (MMP)‐sensitive and integrin‐binding peptides. Initial equilibrium shear storage moduli for the substrates examined are 0.33, 1.42, and 2.90 kPa; after 42 days of culture, all hydrogels exhibit similar storage moduli (0.3–0.7 kPa) regardless of initial modulus, with encapsulated AoAFs spreading and proliferating. In 10 and 7.5 wt% hydrogels, modulus decreases monotonically throughout culture; however, in 5 wt% hydrogels, modulus increases after an initial 7 days of culture, accompanied by an increase in myofibroblast transdifferentiation and expression of collagen I and III through day 28. Thereafter, significant reductions in both collagens occur, with increased MMP‐9 and decreased tissue inhibitor of metalloproteinase‐1/‐2 production. Releasing cytoskeletal tension or inhibiting cellular protein secretion in 5 wt% hydrogels block the stiffening of the polymer matrix. Results indicate that encapsulated AoAFs initiate cell‐mediated matrix remodeling and demonstrate the utility of dynamic 3D systems to elucidate the complex interactions between cell behavior and substrate properties.
Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340
Authors: Xiangyu Jian, Han He, Jiehong Zhu, Qi Zhang, Zhongxin Zheng, Xiangjing Liang, Liuyan Chen, Meiling Yang, Kaiyue Peng, Zhaowen Zhang, Tengfei Liu, Yaping Ye, Hongli Jiao, Shuyang Wang, Weijie Zhou, Yanqing Ding, Tingting Li
Journal: Molecular Cancer (2020)

Abstract Background Accumulating evidence indicates that circular RNAs (circRNAs) act as microRNA (miRNA) sponges to directly inhibit specific miRNAs and alter their ability to regulate gene expression at the post-transcriptional level; this mechanism is believed to occur in various cancers. However, the expression level, precise function and mechanism of circ_001680 in colorectal carcinoma (CRC) are largely unknown. Methods qRT-PCR was used to detect the expression of circ_001680 and miR-340 in human CRC tissues and their matched normal tissues. Bioinformatics analyses and dual-fluorescence reporter assays were used to evaluate whether circ_001680 could bind to miR-340. Circ_001680 overexpression and knockdown cell lines were constructed to investigate the proliferation and migration abilities in vivo and in vitro through function-based experiments, including CCK8, plate clone formation, transwell, and wounding healing assays. The relationships among circ_001680, miR-340 and BMI1 were investigated by bioinformatics analyses, dual-fluorescence reporter system, FISH, RIP and RNA pull down assays. Sphere forming assays and flow cytometry analyses were used to assess the effect of circ_001680 on the stemness characteristics of CRC cells. Results Circ_001680 was more highly expressed in of CRC tissue than in matched adjacent normal tissues from the same patients. Circ_001680 was observed to enhance the proliferation and migration capacity of CRC cells. Furthermore, dual-fluorescence reporter assays confirmed that circ_001680 affects the expression of BMI1 by targeting miR-340. More importantly, we also found that circ_001680 could promote the cancer stem cell (CSC) population in CRC and induce irinotecan therapeutic resistance by regulating the miR-340 target gene BMI1. Conclusions Our results demonstrated that circ_001680 is a part of a novel strategy to induce chemotherapy resistance in CRC through BMI1 upregulation. Moreover, circ_001680 may be a promising diagnostic and prognostic marker to determine the success of irinotecan-based chemotherapy.
Spectrum of EGFR aberrations and potential clinical implications: insights from integrative pan‐cancer analysis
Authors: Haijing Liu, Bo Zhang, Zhifu Sun
Journal: Cancer Communications (2020)

Abstract Background Human epidermal growth factor receptor ( EGFR ) is an oncogenic gene and one of top targets of precision therapy in lung cancer with EGFR mutations. Although there are many reports for some individual cancers, comprehensive profiling of EGFR mutations, overexpression, amplification, DNA methylation, and their clinical associations across many different cancers simultaneously was not available. This study aimed to fill the gap and provide insights to the alteration spectrum of EGFR and its therapeutic and prognostic implications. Methods The Cancer Genome Atlas (TCGA) datasets for 32 cancer types involving 11,314 patients were analyzed for alterations (mutations and amplification/deletion), abnormal expression and DNA methylation in EGFR gene. Mutation frequency, genomic location distribution, functional impact, and clinical targeted therapy implication were compared among different cancer types, and their associations with patient survival were analyzed. Results EGFR alteration frequency, mutation sites across functional domains, amplification, overexpression, and DNA methylation patterns differed greatly among different cancer types. The overall mutation frequency in all cancers combined was relatively low. Targetable mutations, mainly in lung cancer, were primarily found in the Pkinase_Tyr domain. Glioblastoma multiforme had the highest rate of alterations, but it was dominated by gene amplification and most mutations were in the Furin‐like domain where targeted therapy was less effective. Low‐grade glioma often had gene amplification and increased EGFR expression which was associated with poor outcome. Colon and pancreatic adenocarcinoma had very few EGFR mutations; however, high EGFR expression was significantly associated with short patient survival. Squamous cell carcinoma regardless of their sites (the head and neck, lung, or esophagus) exhibited similar characteristics with an alteration frequency of about 5.0%, was dominated by gene amplification, and had increased EGFR expression generally associated with short patient survival. DNA methylation was highly associated with EGFR expression and patient outcomes in some cancers. Conclusions EGFR aberration type, frequency, distribution in functional domains, and expression vary from cancer to cancer. While mutations in the Pkinase_Tyr domain are more important for treatment selection, increased expression from amplification or deregulation affects more tumor types and leads to worse outcome, which calls for new treatment strategies for these EGFR‐ driven tumors.
Evaluation of Triple-Negative Breast Cancer Early Detection via Mammography Screening and Outcomes in African American and White American Patients
Authors: Yalei Chen, Laura Susick, Melissa Davis, Jessica Bensenhaver, S. David Nathanson, Jessica Burns, Lisa A. Newman
Journal: JAMA Surgery (2020)

Population-based breast cancer mortality is 40% higher among African American women compared with white American women, 1 a disparity partly explained by 2-fold higher incidence of biologically aggressive triple-negative breast cancer (TNBC) in African American women. 2 Screening mammography improves breast cancer survival through early detection, but TNBC is more challenging to detect mammographically compared with non-TNBC. 3-6The value of screening mammography in reducing disparities through early detection of the disproportionately high TNBC burden observed in African American women is therefore uncertain.
Fraction genome altered (FGA) to regulate both cell autonomous and non-cell autonomous functions in prostate cancer and its effect on prostate cancer aggressiveness.
Authors: Goutam Chakraborty, Arnab Ghosh, Subhiksha Nandakumar, Joshua Armenia, Ying Zhang Mazzu, Mohammad Omar Atiq, Gwo-Shu Mary Lee, Lorelei A. Mucci, Taha Merghoub, Jedd D. Wolchok, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2020)

347 Background: Our ability to distinguish lethal from non-lethal forms of prostate cancer (PC) is limited. Given prostate tumors’ genetic heterogeneity, is it unlikely that a single somatic variant is prognostic. Herein we investigated fraction of genome altered (FGA; percentage of copy number altered chromosome regions out of measured regions; cBioportal) and tumor mutational count (TMC; number of mutational events per case) harbored by the primary tumor as two tumor-specific factors posited to influence disease aggressiveness or responsiveness to certain therapeutic agents. Methods: We used the TCGA data (n= 490 primary PC) and MSKCC-IMPACT (n=717, Zehir et al 2017) PC datasets to analyze the correlation between FGA and TMC in PC. GSEA was performed with transcriptomes used to identify signaling pathways associated with these two measures. We then categorized 490 primary PC patients from TCGA dataset into 4 groups based on FGA and TMC levels (based on the median values) to assess associations with outcomes. Results: Primary PC patients who harbor FGA high TMC low exhibited shorter disease-free survival (High Risk). We observed attenuation of the androgen signaling pathway and induction of cell proliferation pathways associated with this aggressive form of disease. We used results from CIBERSORT algorithm and deep learning methods of TCGA data and observed that quantities of tumor infiltrating lymphocytes was higher in the FGA high TMC low group (p=0.038). However, we also observed significantly reduced immune effector signaling-pathway signaling in this high-risk FGA high TMC low group suggesting the presence of immune-suppressive networks in primary disease associated with a high risk of progression. Conclusions: A greater understanding of molecular features of aggressive primary PC (FGA/TMC) will be important in developing management strategies. Based on our preliminary analyses, we hypothesize that patients whose primary PC harbors FGA high TMC low have a higher likelihood of aggressive disease due to their impact on PC cell proliferation and dedifferentiation (cell autonomous), and subdued immune responses (non-cell-autonomous).