tbuckley/cabot-search huggingface dataset:
<i>HSD3B1</i> Genotype and Clinical Outcomes in Metastatic Castration-Sensitive Prostate Cancer
Authors: Jason W. D. Hearn, Christopher J. Sweeney, Nima Almassi, Chad A. Reichard, Chandana A. Reddy, Hong Li, Brian Hobbs, David F. Jarrard, Yu-Hui Chen, Robert Dreicer, Jorge A. Garcia, Michael A. Carducci, Robert S. DiPaola, Nima Sharifi
Journal: JAMA Oncology (2020)

The adrenal-restrictive HSD3B1(1245A) allele limits extragonadal dihydrotestosterone synthesis, whereas the adrenal-permissive HSD3B1(1245C) allele augments extragonadal dihydrotestosterone synthesis. Retrospective studies have suggested an association between the adrenal-permissive allele, the frequency of which is highest in white men, and early development of castration-resistant prostate cancer (CRPC).To examine the association between the adrenal-permissive HSD3B1(1245C) allele and early development of CRPC using prospective data.The E3805 Chemohormonal Therapy vs Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) was a large, multicenter, phase 3 trial of castration with or without docetaxel treatment in men with newly diagnosed metastatic prostate cancer. From July 28, 2006, through December 31, 2012, 790 patients underwent randomization, of whom 527 had available DNA samples. In this study, the HSD3B1 germline genotype was retrospectively determined in 475 white men treated in E3805 CHAARTED, and clinical outcomes were analyzed by genotype. Data analysis was performed from July 28, 2006, to October 17, 2018.Men were randomized to castration plus docetaxel, 75 mg/m2, every 3 weeks for 6 cycles or castration alone.Two-year freedom from CRPC and 5-year overall survival, with results stratified by disease volume. Patients were combined across study arms according to genotype to assess the overall outcome associated with genotype. Secondary analyses by treatment arm evaluated whether the docetaxel outcome varied with genotype.Of 475 white men with DNA samples, 270 patients (56.8%) inherited the adrenal-permissive genotype (≥1 HSD3B1[1245C] allele). Mean (SD) age was 63 (8.7) years. Freedom from CRPC at 2 years was diminished in men with low-volume disease with the adrenal-permissive vs adrenal-restrictive genotype: 51.0% (95% CI, 40.9%-61.2%) vs 70.5% (95% CI, 60.0%-80.9%) (P = .01). Overall survival at 5 years was also worse in men with low-volume disease with the adrenal-permissive genotype: 57.5% (95% CI, 47.4%-67.7%) vs 70.8% (95% CI, 60.3%-81.3%) (P = .03). Hazard ratios were 1.89 (95% CI, 1.13-3.14; P = .02) for CRPC and 1.74 (95% CI, 1.01-3.00; P = .045) for death. There was no association between genotype and outcomes in men with high-volume disease. There was no interaction between genotype and benefit from docetaxel.Inheritance of the adrenal-permissive HSD3B1 genotype is associated with earlier castration resistance and shorter overall survival in men with low-volume metastatic prostate cancer and may help identify men more likely to benefit from escalated androgen receptor axis inhibition beyond gonadal testosterone suppression.
Lack of Clinical Benefit of Interferon β-1a Among Patients With Severe Acute Respiratory Distress Syndrome
Authors: Manu Shankar-Hari, Carolyn S. Calfee
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 slipped-CAG DNA-binding small molecule induces trinucleotide-repeat contractions in vivo
Authors: Masayuki Nakamori, Gagan B. Panigrahi, Stella Lanni, Terence Gall-Duncan, Hideki Hayakawa, Hana Tanaka, Jennifer Luo, Takahiro Otabe, Jinxing Li, Akihiro Sakata, Marie-Christine Caron, Niraj Joshi, Tanya Prasolava, Karen Chiang, Jean-Yves Masson, Marc S. Wold, Xiaoxiao Wang, Marietta Y. W. T. Lee, John Huddleston, Katherine M. Munson, Scott Davidson, Mehdi Layeghifard, Lisa-Monique Edward, Richard Gallon, Mauro Santibanez-Koref, Asako Murata, Masanori P. Takahashi, Evan E. Eichler, Adam Shlien, Kazuhiko Nakatani, Hideki Mochizuki, Christopher E. Pearson
Journal: Nature Genetics (2020)
Abstract P6-13-02: Subcutaneous trastuzumab for the treatment of HER2+ breast cancer in Canada: A cost-minimization study
Authors: Megan Coombes, Lori Yin, Ingrid Liu, Norman Shek, Flavia Rusu, Som Mukherjee
Journal: Cancer Research (2020)

Abstract Background: There is an urgent need to alleviate the pressure on healthcare resources and decrease treatment burden for patients. Recently, a new fixed dose subcutaneous (SC) formulation of trastuzumab was approved by Health Canada for use in HER2-positive breast cancer (HER2+ BC) patients. Studied in multiple trials and treatment settings, the totality of evidence demonstrated similar safety and efficacy to the IV formulation as well as a strong preference for trastuzumab SC by patients and health care professionals. Objective: To estimate the incremental costs/savings associated with the use of trastuzumab SC for the treatment of HER2+ BC if reimbursed with the same provincial funding criteria as trastuzumab IV in Ontario, Canada. Methods: An Excel-based cost-minimization and budget impact model was developed to determine the economic impact of trastuzumab SC in comparison to trastuzumab IV in Ontario. Direct medical costs in the analysis included drug acquisition, drug preparation, drug administration, central venous access device (CVAD), and systemic therapy suite costs. Results: Early and metastatic HER2+ BC patients treated with trastuzumab SC are expected to generate a net cost savings to the health system compared to treatment with trastuzumab IV. Savings are estimated at $11,943 per eBC patient and $11,943 per mBC patient, representing total savings of $15.8M in Year 1, $19.4M in Year 2, and $23.0M in Year 3. The use of trastuzumab SC in these populations enhances the ability of the payer to manage drug and medical resources, while offering a therapy that is aligned with patient and clinician preferences. Citation Format: Megan Coombes, Lori Yin, Ingrid Liu, Norman Shek, Flavia Rusu, Som Mukherjee. Subcutaneous trastuzumab for the treatment of HER2+ breast cancer in Canada: A cost-minimization study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-13-02.
Abstract P4-09-09: Characteristics of stage 1 to 3 breast cancer patients with amplification of centromere of chromosome 17
Authors: Ioannis Voutsadakis, Vanessa Davies
Journal: Cancer Research (2020)

Abstract Background: Amplification of the centromeric region of chromosome 17 (CEP17) as measured by In Situ Hybridization (ISH) of the CEP17 probe is used clinically as part of the ISH assay for HER2 status determination in breast cancer. The value of amplification of CEP17 beyond its use in the HER2 ISH test and characteristics of cases bearing CEP17 amplification, have not been fully explored. Methods: A retrospective review of charts of patients with stage 1 to 3 breast cancer that had a dual probe HER2/ CEP17 FISH test in our cancer center during an eight-year period was performed. Data on demographic, and cancer-specific characteristics of the included patients were extracted. The group of patients with an amplified CEP17 defined as mean copy number ≥3 per nucleus was compared with the group without amplification. Results: Two hundred and two patients were included in the analysis. Amplification of CEP17 was observed in 36 patients (17.8%). All patients in the amplified group had a concomitant amplification of HER2 (mean copy number ≥3 per nucleus). In the CEP17 non-amplified group 78 of 166 patients (47%) had an amplified HER2 status. More patients in the amplified group had a clinical HER2+ status according to the 3-protein classifier (33.3% versus 11.5% in the non-amplified group) and less patients in the amplified group had a clinical ER+/ HER2- status (63.9% versus 81.8% in the non-amplified group, x2 p=0.0003). Other significant differences between the amplified and CEP17 non-amplified groups were observed in their lymph node (LN) status (55.6% of patients in the amplified group versus 36.8% in the non-amplified group were lymph node positive, p= 0.04) and in the nuclear heterogeneity component of grade (90.9% of patients in the amplified group were nuclear grade 3 versus 66.9% in the non-amplified group, p= 0.02). There were no statistically significant differences between the groups in overall stage, grade, menopause status or histology. Conclusion: Patients with amplification of CEP17 had a co-amplified HER2 and were more commonly HER2+, LN positive and grade 3 in the nuclear component of grade. Citation Format: Ioannis Voutsadakis, Vanessa Davies. Characteristics of stage 1 to 3 breast cancer patients with amplification of centromere of chromosome 17 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-09.
Tuberculosis-induced cartilage fractures leading to collapse of the left main stem bronchus
Authors: Vanina Livi, Marco Ferrari, Daniela Paioli, Filippo Natali, Rocco Trisolini
Journal: Thorax (2020)

A 94-year-old female patient was referred to the emergency department of our hospital for cough productive of purulent sputum and recurrent episodes of haemoptysis. She was a mild, former smoker. Her medical history was notable for a left-sided pleuropulmonary infection treated for months with antibiotics at the age of 2 years, and for recurrent respiratory infections occurring ever since. Chest CT revealed multiple abnormalities of the left lung consisting of a marked volume loss; diffuse bronchiectasis prevailing in the upper lobe, where a large airway consolidation was also evident; and multiple centrilobular nodules of variable sizes (figure 1A,B). Furthermore, a reduction of the lumen of the left main stem bronchus associated with possible fractures of some …
New onset weakness in the face and arm
Authors: Luisa Brites, Marília Rodrigues, Mariana Luis, Mariana Santiago
Journal: BMJ (2020)

A 32 year old woman with a seven year history of discoid lupus erythematosus (a form of cutaneous lupus erythematosus) was admitted with one week of anisocoria (unequal pupil size), left sided facial weakness, and weakness in her left arm. She had areas of hair loss—a long term sign of her discoid lupus erythematosus—but no other symptoms, infections, toxicological habits, or history of thrombotic events or obstetric complications.

Blood tests results are in table 1.

View this table:

Table 1 
Relevant blood test results 



Her anisocoria and weakness of the face and arm prompted further central nervous system investigations:

• Cerebrospinal fluid analysis was normal

• Brain computed tomography scan showed bilateral cortical and subcortical frontal lesions of a potentially ischaemic nature

• Brain magnetic resonance imaging …
ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia
Authors: Denis Claude Roy, Irwin Walker, Johan Maertens, Philippe Lewalle, Eduardo Olavarria, Dominik Selleslag, Sylvie Lachance, Marc Buyse, Kun Wang, Jeroen Rovers, Irene Santi, Halvard Bonig, Andrew Sandler, Jurjen Velthuis, Stephan Mielke
Journal: Leukemia (2020)

Abstract Overcoming graft-versus-host disease (GvHD) without increasing relapse and severe infections is a major challenge after allogeneic hematopoietic stem-cell transplantation (HSCT). ATIR101 is a haploidentical, naïve cell-enriched T-cell product, depleted of recipient-alloreactive T cells to minimize the risk of GvHD and provide graft-versus-infection and -leukemia activity. Safety and efficacy of ATIR101 administered after T-cell-depleted haploidentical HSCT (TCD-haplo + ATIR101) without posttransplant immunosuppressors were evaluated in a Phase 2, multicenter study of 23 patients with acute leukemia and compared with an observational cohort undergoing TCD-haplo alone ( n = 35), matched unrelated donor (MUD; n = 64), mismatched unrelated donor (MMUD; n = 37), and umbilical cord blood (UCB; n = 22) HSCT. The primary endpoint, 6-month non-relapse mortality (NRM), was 13% with TCD-haplo + ATIR101. One year post HSCT, TCD-haplo + ATIR101 resulted in lower NRM versus TCD-haplo alone ( P = 0.008). GvHD-free, relapse-free survival (GRFS) was higher with TCD-haplo + ATIR101 versus MMUD and UCB (both P &lt; 0.03; 1-year rates: 56.5%, 27.0%, and 22.7%, respectively) and was not statistically different from MUD (1 year: 40.6%). ATIR101 grafts with high third-party reactivity were associated with fewer clinically relevant viral infections. Results suggest that haploidentical, selective donor-cell depletion may eliminate requirements for posttransplant immunosuppressors without increasing GvHD risk, with similar GRFS to MUD. Following these results, a randomized Phase 3 trial versus posttransplant cyclophosphamide had been initiated.
Effects of ruxolitinib cream on pruritus and quality of life in atopic dermatitis: Results from a phase 2, randomized, dose-ranging, vehicle- and active-controlled study
Authors: Brian S. Kim, Kang Sun, Kim Papp, May Venturanza, Adnan Nasir, Michael E. Kuligowski
Journal: Journal of the American Academy of Dermatology (2020)

Atopic dermatitis (AD), a chronic, highly pruritic skin disorder, impairs quality of life (QoL). Janus kinase inhibitors suppress inflammatory and pruritus-associated cytokine signaling in AD.To report the effects of ruxolitinib (RUX) cream on itch and QoL in AD.A total of 307 adult patients with an Investigator's Global Assessment (score of 2 or 3) and 3% to 20% affected body surface area were randomly assigned for 8 weeks to receive double-blind treatment with RUX (1.5% twice daily, 1.5% once daily, 0.5% once daily, or 0.15% once daily), vehicle twice daily, or triamcinolone cream (0.1% twice daily for 4 weeks then vehicle for 4 weeks). Itch was measured by using the numerical rating scale, and patient QoL was assessed with Skindex-16.Improvements in itch numerical rating scale and Skindex-16 were observed with RUX cream. Overall, 42.5% of patients who applied 1.5% RUX twice daily experienced minimal clinically important difference in itch within 36 hours of treatment (vehicle, 13.6%; P < .01); near-maximal improvement was observed by week 4. Itch reduction was associated with improved QoL burden (Pearson correlation, 0.67; P < .001). Significant improvements in Skindex-16 overall scores were noted at week 2.Facial AD lesions were not treated.RUX cream provides a clinically meaningful reduction in itch and QoL burden.
Abstract 13416: Post-Dilation in Primary Percutaneous Coronary Stenting of Patients With ST-Elevation Myocardial Infarction: A Cohort Study and Pooled Analysis
Authors: Mohammad Saadat, Naser Saadat, Sanam Ebtehaj, Arash Aghajani Nargesi, Mohammad Alidoosti, Hamidreza Poorhosseini, Alireza Amirzadegan, Reza Lashkari, Seyedeh Hamideh Mortazavi, Mojtaba Salarifar
Journal: Circulation (2018)

Introduction: Benefits of coronary stent post-dilation (PD) in primary PCI is still a matter of debate. We studied patient- and device-oriented outcomes after PD in a cohort of patients with STEMI ...
On Suboptimization — Cadillac Care at the Mecca
Authors: Brendan M. Reilly
Journal: New England Journal of Medicine (2020)

David was happy with his care at the Mecca, though it meant a year of unnecessary tests and worry. But it revealed a problem of suboptimization: what happens when the whole is greater than the sum of its parts and the right hand doesn't know what the left hand is doing.
Pazopanib for treatment of typical solitary fibrous tumours: a multicentre, single-arm, phase 2 trial
Authors: Javier Martin-Broto, Josefina Cruz, Nicolas Penel, Axel Le Cesne, Nadia Hindi, Pablo Luna, David S Moura, Daniel Bernabeu, Enrique de Alava, Jose Antonio Lopez-Guerrero, Joaquin Dopazo, Maria Peña-Chilet, Antonio Gutierrez, Paola Collini, Marie Karanian, Andres Redondo, Antonio Lopez-Pousa, Giovanni Grignani, Juan Diaz-Martin, David Marcilla, Antonio Fernandez-Serra, Cristina Gonzalez-Aguilera, Paolo G Casali, Jean-Yves Blay, Silvia Stacchiotti
Journal: The Lancet Oncology (2020)
Chitosan based bioactive materials in tissue engineering applications-A review
Authors: Md. Minhajul Islam, Md. Shahruzzaman, Shanta Biswas, Md. Nurus Sakib, Taslim Ur Rashid
Journal: Bioactive Materials (2020)

In recent years, there have been increasingly rapid advances of using bioactive materials in tissue engineering applications. Bioactive materials constitute many different structures based upon ceramic, metallic or polymeric materials, and can elicit specific tissue responses. However, most of them are relatively brittle, stiff, and difficult to form into complex shapes. Hence, there has been a growing demand for preparing materials with tailored physical, biological, and mechanical properties, as well as predictable degradation behavior. Chitosan-based materials have been shown to be ideal bioactive materials due to their outstanding properties such as formability into different structures, and fabricability with a wide range of bioactive materials, in addition to their biocompatibility and biodegradability. This review highlights scientific findings concerning the use of innovative chitosan-based bioactive materials in the fields of tissue engineering, with an outlook into their future applications. It also covers latest developments in terms of constituents, fabrication technologies, structural, and bioactive properties of these materials that may represent an effective solution for tissue engineering materials, making them a realistic clinical alternative in the near future.
Near-IR emissive rare-earth nanoparticles for guided surgery
Authors: Zhibei Qu, Jianlei Shen, Qian Li, Feng Xu, Fei Wang, Xueli Zhang, Chunhai Fan
Journal: Theranostics (2020)

Intraoperative image-guided surgery (IGS) has attracted extensive research interests in determination of tumor margins from surrounding normal tissues.Introduction of near infrared (NIR) fluorophores into IGS could significantly improve the in vivo imaging quality thus benefit IGS.Among the reported NIR fluorophores, rare-earth nanoparticles exhibit unparalleled advantages in disease theranostics by taking advantages such as large Stokes shift, sharp emission spectra, and high chemical/photochemical stability.The recent advances in elements doping and morphologies controlling endow the rare-earth nanoparticles with intriguing optical properties, including emission span to NIR-II region and long life-time photoluminescence.Particularly, NIR emissive rare earth nanoparticles hold advantages in reduction of light scattering, photon absorption and autofluorescence, largely improve the performance of nanoparticles in biological and pre-clinical applications.In this review, we systematically compared the benefits of RE nanoparticles with other NIR probes, and summarized the recent advances of NIR emissive RE nanoparticles in bioimaging, photodynamic therapy, drug delivery and NIR fluorescent IGS.The future challenges and promises of NIR emissive RE nanoparticles for IGS were also discussed.
Abstract P2-04-03: The roles of fucosylation in promoting tumorigenic signaling in breast cancer
Authors: Kara Snyder, Hui Ren, Daniel Lester, Bin Fang, John Koomen, Eric Lau. H
Journal: Cancer Research (2020)

Abstract Fucosylation is an important form of protein glycosylation involved in the progression of cancer. Aberrant fucose and fucosylated serum protein/oligosaccharide levels have been previously described in breast cancer (BC). Fucosylation has been reported impact proliferation and key signaling pathways (e.g., ERK1/2, p38 MAPK, and E-selectin) in human breast invasive ductal carcinoma. However, precise roles and functions of fucosylated proteins function in BC remain largely unclear. In our preliminary analyses, we performed immunofluorescent lectin staining of BC tissue microarrays and cell lines grown in vitro and found that fucosylation is increased in BC vs. normal breast tissues. To study the functional contributions of fucosylation to BC biology, we either pharmacologically or genetically suppressed fucosylation in BC cell lines. The treated or modified cell lines were characterized for their ability to grow/proliferate in 2D or 3D, as well as on adhesion to extracellular matrix (ECM). We observed that inhibiting fucosylation blunted BC cell proliferation, particularly in 3D, and attenuated adhesive capacity. To determine the mechanism(s) underlying the biological functions of fucosylation in BC cells, we performed parallel fucosylated and phosphoproteomic mass spectrometric analyses on BC cells that were either pharmacologically or genetically inhibited for fucosylation to identify: (i) all fucosylated proteins in BC cells and (ii) signaling pathways that comprise directly fucosylated proteins and that are significantly altered in activity (phosphorylation). All filtered hits were subject to Ingenuity Pathway Analysis. Thirteen signaling pathways were identified in common amongst both pharmacologically or genetically modulated BC groups. These pathways clustered into the following 3 major functional groups: cell-cell/cell-matrix contact, RNA processing, and endosomal/phagosomal dynamics. The most fucosylated proteins included integrins. We validated the direct fucosylation of integrins and further dissected the molecular and functional contributions of fucosylation to integrin signaling in vitro and in vivo in mouse models of breast cancer. Our data identify new roles for fucosylation in regulating key signal transduction pathways in BC. How integrin signaling and BC cell biology is regulated by fucosylation, as well as potential clinical utility of fucosylated integrins for BC, will be discussed. Citation Format: Kara Snyder, Hui Ren, Daniel Lester, Bin Fang, John Koomen, Eric Lau. H. The roles of fucosylation in promoting tumorigenic signaling in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-04-03.
State Medicaid Coverage for Tobacco Cessation Treatments and Barriers to Accessing Treatments — United States, 2008–2018
Authors: Anne DiGiulio, Zach Jump, Stephen Babb, Anna Schecter, Kisha-Ann S. Williams, Debbie Yembra, Brian S. Armour
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

State Medicaid programs that cover all evidence-based cessation treatments, remove barriers to accessing these treatments, and promote covered treatments to Medicaid enrollees and health care providers could reduce smoking, smoking-related disease, and smoking-attributable federal and state health care expenditures.