tbuckley/cabot-search huggingface dataset:
Determinants of biochemical failure and distant metastases-free survival in high-risk prostate cancer patients treated with external beam radiotherapy.
Authors: Avinash Pilar, Andrew Bayley, Danny Shehata, Zhihui (Amy) Liu, Alejandro Berlin, Charles N. Catton, Vickie Kong, Tara Rosewall, Mary K. Gospodarowicz, Tim Craig, Joelle Helou, Padraig Richard Warde, Peter W. M. Chung
Journal: Journal of Clinical Oncology (2020)

371 Background: Objectives were to1) identify predictors of biochemical failure(BCF) -free survival (FFS) &amp; distant metastases free-survival (DMFS) in high-risk prostate cancer (HRPC) patients treated with external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT); 2) assess the impact of nodal irradiation &amp; escalation of dose to the nodal volumes in HRPC. Methods: Between Feb 2000 &amp; May 2011, 462 patients with HRPC were treated with EBRT +/- ADT. This spanned an era of technical development; prior to 2002 conventional dose radiotherapy was routinely delivered, between 2002-2008, dose escalation to the prostate &amp; pelvic lymph nodes was undertaken in a phase II trial &amp; subsequently all patients were treated with a dose-escalated protocol. The disease characteristics included, a median PSA of 20ng/ml (range: 1-563), T3-T4 in 33% (n=158), &amp; Gleason grade group (GGG) 3-5 in 72% (n=331). The majority (n=405, 88%) received ADT with EBRT &amp; median duration of ADT was 36 months (range: 0-197). Dose escalated EBRT was utilized in 52% (n=241) &amp; nodal irradiation in 69% (n=317); escalation of dose to nodal volumes was performed in 20% (n=93). Results: The median follow-up was 8.7yrs (range: 0.9-18.9). Median nadir PSA was &lt; 0.05ng/ml (range: &lt;0.05-5.78) with median time to nadir (TTN) of 11 months (range: 2-130). Cumulative incidence rates of BCF at 5 and 10-yrs were 23% &amp; 45%; corresponding rates for DM were 6.6% &amp; 14%, respectively. The 5 &amp; 10-yr FFS rates were 75% &amp; 51%; corresponding DMFS rates were 91.5% &amp; 80%, respectively. On multivariate analysis, T stage (p&lt;0.001), GGG (p&lt;0.001), ADT (p=0.002), dose escalation to prostate (P=0.012) &amp; median nadir PSA (p&lt;0.001) were independent predictors of FFS. The GGG (p=0.007), median nadir PSA (p=&lt;0.001) &amp; Nodal RT (p=0.03) were independent predictors of DMFS. PSA of 20 &amp; TTN predicted neither FFS nor DMFS. Conclusions: Nadir PSA level was an independent predictor of FFS &amp; DMFS. Undetectable PSA level was associated with prolonged FFS &amp; DMFS. Dose escalation to prostate resulted in an improved FFS &amp; Nodal irradiation in an improved DMFS. Further studies are required to identify subgroups that may benefit the most from nodal irradiation.
The benefits of playing interactive games on virtual reality headsets during procedures in food allergy clinical trials
Authors: Sarah Alonzi, Khushi Parikh, Sara Varadharajulu, Sharad Chandra, Shu Cao, Zach Texeira, Sayantani Sindher, Kari Nadeau, Sharon Chinthrajah
Journal: Journal of Allergy and Clinical Immunology (2020)
Niraparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and biallelic DNA-repair gene defects (DRD): Correlative measures of tumor response in phase II GALAHAD study.
Authors: Matthew Raymond Smith, Karim Fizazi, Shahneen Kaur Sandhu, William Kevin Kelly, Eleni Efstathiou, Primo Lara, Evan Y. Yu, Daniel J. George, Kim N. Chi, Fred Saad, Jason Summa, Jamie M. Freedman, Gary Mason, Byron M. Espina, Eugene Zhu, Deborah S. Ricci, Linda A. Snyder, Jason S. Simon, Shinta Cheng, Howard I. Scher
Journal: Journal of Clinical Oncology (2020)

118 Background: Niraparib, a highly potent and selective poly (ADP-ribose) polymerase inhibitor (PARPi) received breakthrough designation by US FDA for treatment of pts with BRCA1,2 mutant mCRPC who progressed on taxane and androgen receptor-targeted therapy. Circulating tumor cells (CTC) detection associates with poor outcomes, with declining counts consistent with improved survival [1,2]. Methods: GALAHAD study assessed niraparib (300 mg daily) in pts with mCRPC+DRD (NCT02854436). Patients with non-measurable soft tissue disease by RECIST 1.1 were required to have a baseline CTC count ≥1 cell/7.5 mL blood. CTC response was defined as CTC conversion to &lt;5 for pts with baseline CTC≥5 and CTC drop to 0 post-baseline for pts with ≥1 baseline CTC. Alkaline phosphatase (ALP) was collected at each monthly cycle. Results: For primary efficacy population of pts with BRCA1/2 mutations, the objective response rate (ORR) by RECIST 1.1 criteria was 41.4%. CTC response rates for this population were as high as ORR regardless of measurability (Table). Time to CTC response for each CTC responder will be shown. Radiographic progression-free survival (rPFS) durations were similar for patients with a measurable disease response and patients with CTC conversion. Median duration of treatment for responders of any type was 6.7mo (range: 2–27). DRD status, both BRCA and non- BRCA, for each responder will also be discussed. Trends in disease burden and markers of bone metabolism will also be quantitatively explored including 24% pts who were on treatment for at least one cycle who had ≥25% decreased unfractionated ALP from baseline. Conclusions: Niraparib showed clinical activity with CTC response and decline in ALP levels in mCRPC pts having biallelic BRCA mutations, which further supports its recent breakthrough designation. Clinical trial information: NCT02854436. [Table: see text]
“LTP syndrome patients: Sensitization profile and severity of reactions
Authors: Francisca Gomez Perez, Rosa MuNoz Cano, Joan Bartra, Gador Bogas Herrera, Francisca Palomares, Almudena Testera-Montes, María José Rodriguez, Rocio Casas, Raquel Jurado Escobar, Rafael Núñez, Maria Torres Jaen, Cristobalina Mayorga
Journal: Journal of Allergy and Clinical Immunology (2020)
Onabotulinum Toxin A for Sacral and Intergluteal Cleft Hyperhidrosis
Authors: Mariam B. Totonchy
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
MRI-targeted biopsies in prostate cancer screening and the value of its combination with blood-based risk-prediction: The randomized, diagnostic study STHLM3MRI.
Authors: Tobias Nordström, Andrea Discacciati, Fredrik Jäderling, Stefan Gosta Karlsson, Markus Aly, Henrik Gronberg, Martin Eklund
Journal: Journal of Clinical Oncology (2020)

TPS378 Background: Blood-based biomarkers and magnetic resonance imaging followed by targeted biopsies have been suggested to improve detection of prostate cancer by increasing sensitivity to detect significant disease, decrease over-detection of low-risk cancers and avoid benign biopsies. The STHLM3-MRI projects aims to assess the value of combining blood-based risk prediction with bi-parametric MRI (bpMRI) in the prostate cancer diagnostic chain. Methods: The STHLM3MRI Main Study is a randomized, diagnostic study recruiting ≈10,000 Swedish men aged 50-74 for prostate cancer testing in a screen-by-invitation setting. The study design includes a first paired step (blood-test) followed by a randomized step (biopsy technique). Participants with elevated blood-test levels (PSA≥3ng/ml or Stockholm3 test≥11% risk of GG≥2 cancer) are recommended further work-up and randomized 2:3 to 12-core systematic biopsies (standard arm) or to bpMRI followed by MRI-targeted biopsies and systematic biopsies in men with PI-RADSv2 ≥3 lesions (experimental arm). Endpoints include number of detected prostate cancers, number of performed biopsy procedures and number of performed MRIs. The study is centralized to three biopsy sites, one radiology department and one pathology department. A data safety and monitoring board monitors study progress and participant safety. There are two pre-planned main analyses. First, we will report the first large randomized evidence comparing MRI-targeted biopsies and systematic biopsies for prostate cancer detection in a screen-by-invitation setting. Second, we will report a comparison of a diagnostic strategy including the Stockholm3 blood-test and MRI-targeted biopsies with standard practice using PSA and systematic biopsies. A third analysis will compare the use of the bloodtests PSA and Stockholm3 for risk-stratification of men undergoing MRI-targeted biopsy. 9 Oct 2019 the study had included 47% of planned participants (n = 4,701), aiming to close inclusion by March 2020 with first report during 2020. The study is registered at ClinicalTrials.gov: NCT03377881 and has regional ethical approval (2017-1280/31). Clinical trial information: NCT03377881.
AR-V7 and prediction of benefit with taxane therapy: Final analysis of PROPHECY.
Authors: Andrew J. Armstrong, Jun Luo, Monika Anand, Emmanuel S. Antonarakis, David M. Nanus, Paraskevi Giannakakou, Russell Zelig Szmulewitz, Daniel Costin Danila, Patrick Healy, William R. Berry, Rick Wenstrup, Howard I. Scher, Scott T. Tagawa, Daniel J. George, Susan Halabi
Journal: Journal of Clinical Oncology (2020)

184 Background: We previously found that men with AR-V7 (+) poor risk mCRPC have a low chance of benefit with abiraterone or enzalutamide. The benefits of subsequent taxane chemotherapy based on AR-V7 status may help inform treatment decisions. Methods: We conducted a multicenter prospective study of men with poor risk mCRPC (PROPHECY, NCT02269982) starting Abi or Enza and subsequent taxane chemotherapy. AR-V7 status from CTCs was assessed before abi/enza and again before taxane chemotherapy using the Epic nuclear protein assay or the Johns Hopkins Adnatest assay. The primary endpoint was to test the association of AR-V7 with radiographic/ clinical progression free survival (PFS) and OS with taxane chemotherapy, using the proportional hazards model, adjusting for Cell Search enumeration and clinical risk score. Results: We enrolled 118 men with mCRPC starting Abi/Enza; of these, 51 were evaluable with CTC AR-V7 testing and received subsequent taxane chemotherapy. With 50 PFS events, see table for final results. While AR-V7 positivity was associated with worse outcomes overall, AR-V7 (+) patients had similar PFS, OS, and confirmed &gt;50% PSA declines adjusting for CTC enumeration and clinical prognostic factors. Concordance between the two AR-V7 assays pre-taxane was 0.78 (kappa 0.46). AR-V7 positivity increased at progression on abi/enza, but not following taxane chemotherapy. Conclusions: Men with AR-V7 positive mCRPC have poor outcomes, but may benefit from taxane chemotherapy after progression on abi/enza. AR-V7 may provide a helpful predictive biomarker to guide treatment with a second AR inhibitor or a taxane. Clinical trial information: NCT02269982. [Table: see text]
Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial
Authors: Shukui Qin, Zhenggang Ren, Zhiqiang Meng, Zhendong Chen, Xiaoli Chai, Jianping Xiong, Yuxian Bai, Lin Yang, Hong Zhu, Weijia Fang, Xiaoyan Lin, Xiaoming Chen, Enxiao Li, Linna Wang, Chunxia Chen, Jianjun Zou
Journal: The Lancet Oncology (2020)
A pharmacological chaperone improves memory by reducing Aβ and tau neuropathology in a mouse model with plaques and tangles
Authors: Jian-Guo Li, Jin Chiu, Mercy Ramanjulu, Benjamin E. Blass, Domenico Praticò
Journal: Molecular Neurodegeneration (2020)

The vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex system, an ubiquitous multiprotein assembly responsible for sorting and trafficking protein cargos out of the endosomes. VPS35 can regulate APP metabolism and Aβ formation, and its levels are reduced in Alzheimer's disease (AD) brains. We and others demonstrated that VPS35 genetic manipulation modulates the phenotype of mouse models of AD. However, the translational value of this observation remains to be investigated.Triple transgenic mice were randomized to receive a pharmacological chaperone, which stabilizes the retromer complex, and the effect on their AD-like phenotype assessed.Compared with controls, treated mice had a significant improvement in learning and memory, an elevation of VPS35 levels, and improved synaptic integrity. Additionally, the same animals had a significant decrease in Aβ levels and deposition, reduced tau phosphorylation and less astrocytes activation.Our study demonstrates that the enhancement of retromer function by pharmacological chaperones is a potentially novel and viable therapy against AD.
Re: Frank-Jan H. Drost, Daniel Osses, Daan Nieboer, et al. Prostate Magnetic Resonance Imaging, with or Without Magnetic Resonance Imaging-targeted Biopsy, and Systematic Biopsy for Detecting Prostate Cancer: A Cochrane Systematic Review and Meta-analysis. Eur Urol 2020;77:78–94
Authors: Juan Morote, Anna Celma, Jacques Planas
Journal: European Urology (2020)
Efficacy Trends With Continuous Long-Term Use of Crisaborole in Patients With Mild-to-Moderate Atopic Dermatitis (AD)
Authors: Mark Lebwohl, Adelaide Hebert, Liza Takiya, Lauren Miller, John Werth, Chuanbo Zang, Paul Sanders, Bob Geng
Journal: Journal of Allergy and Clinical Immunology (2020)
Fewer Opioids Prescribed for Pain at Emergency Department Discharge
Authors: Bridget M. Kuehn
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 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
A study of quality of life in people with mycosis fungoides and Sézary syndrome
Authors: K. Molloy, C. Jonak, F.J. Sherida, H. Woei‐A‐Ji, E. Guenova, A.M. Busschots, A. Bervoets, E. Hauben, R. Knobler, S. Porkert, C. Fassnacht, R. Cowan, E. Papadavid, M. Beylot‐Barry, E. Berti, S. Alberti Violetti, T. Estrach, R. Matin, O. Akilov, L. Vakeva, M. Prince, A. Bates, M. Bayne, R. Wachsmuch, U. Wehkamp, M. Marschalko, O. Servitje, D. Turner, S. Weatherhead, M. Wobser, J.A. Sanches, P. McKay, D. Klemke, C. Peng, A. Howles, J. Yoo, F. Evison, J. Scarisbrick
Journal: British Journal of Dermatology (2020)

Mycosis fungoides (MF) is the commonest type of skin lymphoma and is part of a group of conditions known as cutaneous T-cell lymphomas (CTCL). MF can appear as flat/raised, smooth/scaly red lesions known as patches and plaques, making it difficult to tell apart from eczema or psoriasis. Raised “lumps” called tumours can appear and the disease can become more serious. Sézary syndrome (SS) is a leukaemic form of CTCL and has an extensive red, itchy rash over most of the body, the presence of cancerous cells in the blood, and enlarged lymph glands. MF/SS can reduce patient quality of life (QoL) due to symptoms including itch and pain, poor self-esteem secondary to cosmetic disfigurement, and can impair interpersonal relationships. In this article, we examine QoL in patients with MF/SS in a large international research study called PROCLIPI, using a questionnaire called Skindex-29 which asks patients to comment on skin related questions which may affect their life enjoyment. We identified a number of important determinants of worse QoL in MF/SS including: female gender, patients diagnosed with SS and those with more widespread disease. Disease features which were associated with more impaired QoL included alopecia (hair loss) and confluent erythema (red patches and plaques merging together to form larger areas of affected skin). Combining all these factors together, we found that female patients, alopecia and confluent erythema were the most important. Given that females had worse QoL, we examined more closely which items in the Skindex-29 questionnaire differed between males and females. Female patients experienced more burning, stinging, itch and irritation on their skin and greater feelings of depression, shame, embarrassment and annoyance with their diagnosis of MF/SS. Our research study has highlighted important aspects of QoL in MF/SS and emphasizes the urgent need for a more comprehensive QoL questionnaire to address not only the skin related aspects of the disease, but also the effects of cancer and its treatment on patient QoL. This is a summary of the study: Characteristics associated with significantly worse quality of life in mycosis fungoides/Sézary syndrome from the Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study
Does escalation results from phase Ib/II Norse study of erdafitinib (ERDA) + PD-1 inhibitor JNJ-63723283 (Cetrelimab [CET]) in patients (pts) with metastatic or locally advanced urothelial carcinoma (mUC) and selected fibroblast growth factor receptor (FGFR) gene alterations.
Authors: Victor Moreno, Yohann Loriot, Begona Pérez Valderrama, Carmen Beato, Yann-Alexandre Vano, Mark T. Fleming, Ignacio Duran, Salvatore Siena, Jaszianne A. Tolbert, Anne OHagan, Sydney Akapame, Yvonne Y. Lau, Lionnel Geoffrois, Scott T. Tagawa, Begona Mellado, Arlene O. Siefker-Radtke
Journal: Journal of Clinical Oncology (2020)

511 Background: ERDA, an oral pan-FGFR inhibitor, is approved by the US FDA for pts with metastatic urothelial carcinoma (mUC) with susceptible FGFR3/2 gene alterations and progressed after ≥1 line of prior platinum-containing chemotherapy (PCC). 1 CET, an IgG4, binds to anti-programmed cell death proteins (PD-1) and has shown activity in solid tumors. 2 ERDA+CET may demonstrate complementary mechanisms as neoantigen release by ERDA may prime the tumor microenvironment for response. NORSE is a phase 1b/2 study to evaluate ERDA+CET in pts with mUC. Methods: Adult mUC pts with specific FGFR alterations who have progressed after ≥1 prior systemic therapy and no prior FGFR or PD-1/PD(L)-1 inhibitors enrolled in 3 dose levels (DL) of ERDA (DL1: 6 mg, DL2A: 8 mg, DL2: 8 mg with uptitration [UPT] to 9 mg) + CET (IV, 240 mg). Cohorts enrolled until dose limiting toxicity (DLT) or RP2D was identified. Primary endpoints: DLT and adverse events (AEs). Results: Of 15 pts (DL1: 4, DL2A: 3, DL2: 8), 11 continued on treatment at the time of the data cut. 14/15 pts experienced AEs; 3 experienced serious unrelated AEs (urinary tract infection, urosepsis, and large intestinal obstruction) all in DL1, 2 led to death; 10 experienced Grade &gt;3 AEs and 2 experienced AEs of special interest, considered related to ERDA (Table). No DLTs were observed in any cohorts, 8 mg with UPT + CET was established as the RP2D. At data cut-off, investigator-assessed best overall response rate (CR+PR+uCR+uPR) in pts treated with the RP2D was 71% and disease control rate was 100% for RECIST 1.1 evaluable pts (n=7). Conclusions: 8 mg ERDA with UPT+240 mg CET was well tolerated and established as the RP2D. The combination of ERDA+CET is being further explored in the ongoing randomized phase 2 study in first-line cisplatin-ineligible mUC pts (NCT03473743). Clinical trial information: 2017-001980-19. [Table: see text]
Exhaled Mycobacterium tuberculosis output and detection of subclinical disease by face-mask sampling: prospective observational studies
Authors: Caroline M Williams, Mohamad Abdulwhhab, Surinder S Birring, Elsabe De Kock, Natalie J Garton, Eleanor Townsend, Manish Pareek, Alaa Al-Taie, Jingzhe Pan, Rakesh Ganatra, Anton C Stoltz, Pranabashis Haldar, Michael R Barer
Journal: The Lancet Infectious Diseases (2020)

Tuberculosis remains a global health challenge, with early diagnosis key to its reduction. Face-mask sampling detects exhaled Mycobacterium tuberculosis. We aimed to investigate bacillary output from patients with pulmonary tuberculosis and to assess the potential of face-mask sampling as a diagnostic method in active case-finding.
Epigenetics, Development, and Psychopathology
Authors: Kieran J. O'Donnell, Michael J. Meaney
Journal: Annual Review of Clinical Psychology (2020)

Epigenetic mechanisms govern the transcription of the genome. Research with model systems reveals that environmental conditions can directly influence epigenetic mechanisms that are associated with interindividual differences in gene expression in brain and neural function. In this review, we provide a brief overview of epigenetic mechanisms and research with relevant rodent models. We emphasize more recent translational research programs in epigenetics as well as the challenges inherent in the integration of epigenetics into developmental and clinical psychology. Our objectives are to present an update with respect to the translational relevance of epigenetics for the study of psychopathology and to consider the state of current research with respect to its potential importance for clinical research and practice in mental health.
From Silk Spinning to 3D Printing: Polymer Manufacturing using Directed Hierarchical Molecular Assembly
Authors: Xuan Mu, Vincent Fitzpatrick, David L. Kaplan
Journal: Advanced Healthcare Materials (2020)

Silk spinning offers an evolution-based manufacturing strategy for industrial polymer manufacturing, yet remains largely inaccessible as the manufacturing mechanisms in biological and synthetic systems, especially at the molecular level, are fundamentally different. The appealing characteristics of silk spinning include the sustainable sourcing of the protein material, the all-aqueous processing into fibers, and the unique material properties of silks in various formats. Substantial progress has been made to mimic silk spinning in artificial manufacturing processes, despite the gap between natural and artificial systems. This report emphasizes the universal spinning conditions utilized by both spiders and silkworms to generate silk fibers in nature, as a scientific and technical framework for directing molecular assembly into high-performance structures. The preparation of regenerated silk feedstocks and mimicking native spinning conditions in artificial manufacturing are discussed, as is progress and challenges in fiber spinning and 3D printing of silk-composites. Silk spinning is a biomimetic model for advanced and sustainable artificial polymer manufacturing, offering benefits in biomedical applications for tissue scaffolds and implantable devices.