tbuckley/cabot-search huggingface dataset:
Pension crisis: 11 medical organisations call on chancellor to find long term solution
Authors: Zosia Kmietowicz
Journal: BMJ (2020)

The BMA, along with the Royal Colleges of General Practitioners, Surgeons, and Physicians and seven other medical organisations, have written to the UK chancellor urging him to use the upcoming budget to provide a long term solution to the pension taxation crisis facing the healthcare profession.

Their letter calls on Rishi Sunak to provide a result that enables all doctors and allied health professionals to do the extra work that patients need without fear of incurring unexpected pension tax …
Quantitation of Bleeding Symptoms in Children with von Willebrand Disease (VWD) or a Platelet Function Disorder: Use of a Standardized Pediatric Bleeding Score.
Authors: T.T. Biss, V.S. Blanchette, M. Bowman, D.S. Clark, M. Silva, D. Lillicrap, P.D. James, Margaret L. Rand
Journal: Blood (2007)
Capturing and monitoring global differences in untreated and treated end-stage kidney disease, kidney replacement therapy modality, and outcomes
Authors: Roberto Pecoits-Filho, Ikechi G. Okpechi, Jo-Ann Donner, David C.H. Harris, Harith M. Aljubori, Aminu K. Bello, Ezequiel Bellorin-Font, Fergus J. Caskey, Allan Collins, Alfonso M. Cueto-Manzano, John Feehally, Bak Leong Goh, Kitty J. Jager, Masaomi Nangaku, Muhibur Rahman, Manisha Sahay, Abdulkarim Saleh, Laura Sola, Rumeyza Turan Kazancioglu, Rachael C. Walker, Robert Walker, Qiang Yao, Xueqing Yu, Ming-Hui Zhao, David W. Johnson
Journal: Kidney International Supplements (2020)
Chronic Cough in America: Descriptive Analyses of Cough Characteristics and Diagnostic History
Authors: Eli Meltzer, Peter Dicpinigaitis, Robert Zeiger, Michael Schatz, John Oppenheimer, Jonathan Bernstein, Nate Way, Eileen Fonseca, Robert Boggs, Vicky Li, Jonathan Schelfhout
Journal: Journal of Allergy and Clinical Immunology (2020)
Final analysis of the CheckMate 025 trial comparing nivolumab (NIVO) versus everolimus (EVE) with &gt;5 years of follow-up in patients with advanced renal cell carcinoma (aRCC).
Authors: Robert J. Motzer, Scott S. Tykodi, Bernard Escudier, Stephane Oudard, Hans J. Hammers, David F. McDermott, Saby George, Daniel Castellano, Toni K. Choueiri, Ajjai Shivaram Alva, Martin Eduardo Richardet, Elizabeth R. Plimack, Sandy Srinivas, Giuseppe Procopio, Frede Donskov, Howard Gurney, Yoshihiko Tomita, M. Brent McHenry, Shruti Shally Saggi, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2020)

617 Background: CheckMate 025 demonstrated superior overall survival (OS) in previously treated patients (pts) with aRCC, with improved safety and tolerability in the NIVO arm compared with EVE. The primary analysis was based on 14-months minimum follow-up. Here, we report an updated, final analysis with an extended minimum follow-up of 64 months. Methods: Previously treated pts with predominantly clear cell aRCC were randomized (1:1) to NIVO 3 mg/kg IV every 2 weeks or EVE 10 mg orally once daily until progression or unacceptable toxicity. The primary endpoint was OS. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and safety. Confirmed ORR and PFS were per investigator (inv) using RECIST v1.1. Results: Overall, 410 vs 411 pts were randomized to NIVO vs EVE, respectively. OS benefit was maintained and PFS favored NIVO vs EVE with long-term follow-up (HR 0.84 (95% CI 0.72–0.99). (Table) ORR was higher (23% vs 4%) with NIVO vs EVE and median duration of response (DOR) was longer (18.2 vs 14.0 months). Ongoing response was observed in 28% vs 18% of pts with NIVO vs EVE. Most pts received subsequent systemic anticancer therapy: 276 pts in the NIVO arm (67%; most commonly EVE [35%] or axitinib [33%]) and 296 pts in the EVE arm (72%; most commonly axitinib [41%] or NIVO [26%]). No new safety signals or treatment-related deaths emerged with long-term follow-up in either arm. More pts in the EVE arm (37%) experienced a grade 3/4 treatment-related AE compared with pts in the NIVO arm (21%). Conclusions: At &gt;5-years minimum follow-up, response rates and survival remain superior with NIVO vs EVE, and 28% of responses to NIVO are ongoing. Long-term follow-up highlights the efficacy and safety of NIVO monotherapy in pts with aRCC. Clinical trial information: NCT01668784. [Table: see text]
Males have a worse prognosis than females in chronic lymphocytic leukemia and this may be related to IgVH gene usage and mutational status.
Authors: Tiffany Hernandez, Matthew Seftel, Alain Demers, Donna Hewitt, Carmen Morales, Elizabeth Berg, Brenda Kuschak, Spencer Gibson, James Johnston
Journal: Cancer Research (2008)

2211  It has been suggested that women have a better prognosis than men in chronic lymphocytic leukemia (CLL) and this could be related to hormonal or cellular differences. To assess the sex differences in CLL we have carried out a population-based study in Manitoba (pop. 1.2 million) in which we have identified all patients diagnosed with CLL or small lymphocytic lymphoma (SLL) from 01/01/1998 to 12/31/2003. Patients were identified through the Manitoba Cancer Registry with ICD codes 9 and 10 for CLL or SLL and by our centralized flow cytometry facility. 636 pts were identified (incidence, 88 pts/million/annum); the median age at diagnosis was 71 yrs with a male:female ratio of 1.3:1. There was a predominance of men to women until the age of 70 yrs and a predominace of females thereafter. The median age at diagnosis was higher for women than for men (73 vs 70 yrs, P=0.04). Moreover, women had a better prognosis than men, with the 5 year relative survival being 90% compared with 70% for men. The difference in survival increased with age being most marked in patients >75 yrs old. To examine the cause for this difference, we evaluated cellular prognostic indicators in males and females. Poor prognostic markers include unmutated IgVH, use of certain IgVH genes, eg. VH1-69 and VH3-21, ZAP-70 positivity, CD38 positivity and del 17p13 (p53 mutation). Of >300 pts followed in the CancerCare Manitoba CLL clinic 101 have to date been studied (66 male, 35 female). Overall, there was a predominance of IgVH mutated cases with the mutated:unmutated ratio being 1.6:1. There was a predominance of mutated cases in female patients with the mutated: unmutated ratio being 2.2:1, compared with 1.4:1 in males. Of the twelve VH1-69 cases, 9 were male and 3 female, and of the five VH3-21 cases, all were male. In addition, there was a predominance of ZAP-70 positivity in males compared to females, but no difference was noted in CD38 status, in vitro sensitivity to chlorambucil or fludarabine (as measured by MTT assay) or in the incidence of del 17p13 (as measured by FISH). To determine whether there was a difference in plasma to explain the sex differences, male or female CLL cells were incubated in male or female plasma and spontaneous or drug-induced apoptosis measured by acridine orange staining. To date, no consistent difference has been observed between male and female plasma.  Thus, the worse prognosis for males with CLL may be related to a bias in IgVH gene usage by men and an increased likelihood of being unmutated. Further patients are being studied to confirm these findings.
Impact of marijuana smoking on lung function in older persons
Authors: Wan C. Tan, Jean Bourbeau, Shawn D. Aaron, Don D. Sin
Journal: European Respiratory Journal (2020)

Most previous epidemiological studies support a significant association between marijuana smoking and chronic respiratory symptoms [1], but the effects on lung function remain unclear. Previous longitudinal cohort studies have focused largely on young adults [1]. The results from these studies have shown that marijuana smoking produced marginal or no effects on lung function, which is expected given that with even heavy cigarette exposure, meaningful changes in forced expiratory volume in 1 s (FEV1) or forced vital capacity (FVC) are hard to discern in young adults. Lung function changes, however, accelerate in older age groups and the impact of respiratory irritants and toxins on lung function becomes much more evident [2]. To our knowledge, our study is the first longitudinal study of marijuana smoking in older individuals in a general population whose median age was 65 years [3]. The results of the present study addressed a major gap in marijuana research by demonstrating that marijuana smoking amplifies the harmful effects of tobacco smoking on the risk of COPD and FEV1 decline over time. Marijuana smoke exposure amplifies the harmful effects of cigarette smoke <http://bit.ly/2rS6mtt>
Online mental health services in China during the COVID-19 outbreak
Authors: Shuai Liu, Lulu Yang, Chenxi Zhang, Yu-Tao Xiang, Zhongchun Liu, Shaohua Hu, Bin Zhang
Journal: The Lancet Psychiatry (2020)

by mental health professionals in medical institutions, universities, and academic societies throughout all 31 provinces, municipalities, and autonomous regions in mainland China, which provide free 24-h services on all days of the week.Online psychological self-help intervention systems, including online cognitive behavioural therapy for depression, anxiety, and insomnia (eg, on WeChat), have also been developed.In addition, several artificial intelligence (AI) programmes have been put in use as interventions for psychological crises during the epidemic.For example, individuals at risk of suicide can be recognised by the AI programme Tree Holes Rescue, 5 by monitoring and analysing messages posted on Weibo, and alerting designated volunteers to act accordingly.In general, online mental health services being used for the COVID-19 epidemic are facilitating the development of Chinese public emergency interventions, and eventually could improve the quality and effectiveness of emergency interventions.
Phase II trial of cytoreductive stereotactic hypofractionated radiotherapy with combination ipilimumab/nivolumab for metastatic kidney cancer (CYTOSHRINK).
Authors: Aly-Khan A. Lalani, Anand Swaminath, Gregory Russell Pond, Anil Kapoor, William Chu, Jonathan L. Bramson, Michael G. Surette, Mark Norman Levine, Sebastien J. Hotte
Journal: Journal of Clinical Oncology (2020)

TPS761 Background: Randomized data from the interferon era demonstrated modest survival benefits of cytoreductive nephrectomy (CN) in patients with advanced renal cell carcinoma (aRCC). Results from SURTIME and CARMENA, conducted in the VEGF-targeted therapy era, have challenged the routine use of upfront CN especially in IMDC intermediate and poor risk patients. Furthermore, the treatment landscape in aRCC now includes first-line combination immunotherapy. Data from the Checkmate-214 trial showed that intermediate/poor risk patients have improved overall survival and objective response rate with ipilimumab and nivolumab (I/N) compared to sunitinib. Stereotactic body radiation therapy (SBRT) provides a convenient method for cytoreduction of the primary kidney lesion and may induce an ‘abscopal effect’, leading to enhanced systemic anti-tumour immune response. We hypothesize that SBRT to the primary kidney mass in aRCC patients will enhance the efficacy of I/N compared to standard of care I/N alone. Methods: This phase II trial randomizes untreated aRCC patients in a 2:1 fashion to I/N plus SBRT (30-40 Gy in 5 fractions) to the primary kidney mass between cycles 1 and 2 (experimental arm, E), versus standard of care I/N alone (standard arm, S). Eligible patients have biopsy-proven aRCC (any histology), IMDC intermediate/poor risk disease, and who decline or are unsuitable for CN. Patients with a primary kidney lesion ≥ 20cm, previous abdominal radiation precluding SBRT, or who have a contraindication to I/N are excluded. The primary objective is to compare the efficacy of I/N plus SBRT versus I/N alone, as determined by the hazard ratio for progression free survival (PFS). Secondary objectives include evaluation of safety, overall survival, objective response rate, and health-related quality of life. Exploratory analyses include blood immune signatures and stool microbiome. Up to 78 patients will be enrolled under the assumption of an improved 12-month PFS from 50% (S) to 75% (E), using a two-sided α=0.1, power=80%, and accounting for loss-to-follow-up and stratification using IMDC criteria 1-2 vs 3-6. Clinical trial information: NCT04090710.
A prospective comparison of MRI-planned versus CT-planned radiotherapy for prostate cancer.
Authors: Daniel R Schmidt, Mandar Bhagwat, Daniel I. Glazer, Ming-Hui Chen, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2020)

312 Background: Chronic rectal toxicity significantly decreases the quality of life for men who receive radiotherapy for prostate cancer. The volume of rectum exposed to 70 Gy or more is a validated metric that predicts the risk of late rectal toxicity. We hypothesized that MRI as compared to CT-based prostate radiotherapy treatment planning can reduce the volume of rectum exceeding 70 Gy. Methods: This prospective study single arm study enrolled 15 men treated with external beam radiation therapy for localized prostate cancer. At the time of treatment planning a 3 Tesla T2-weighted magnetic resonance imaging examination of the prostate was obtained. A radiotherapy plan was designed by a medical physicist using identical constraints for both CT and MRI-based consensus volumes defined by a radiologist and radiation oncologist. The volume of rectum exposed to 70 Gy or more was calculated and compared using the paired Signed Rank Test. Results: The median age was 70 years (range 56-84), median PSA 7.3 ng/mL (range 3.2 – 22.1), and median prostate volume 40 mL (range 25 - 65) by transrectal ultrasound. Sixty percent (n=9) were intermediate risk and 40 percent (n=6) high risk by NCCN guidelines. The majority were either clinical stage T1c (n=7) or T2 (n=6). Two men had extracapsular extension (T3a). None of the participants had seminal vesicle invasion (T3b), rectal or bladder involvement (T4), or lymph node metastasis (N1). All 15 men enrolled on the study completed both a standard radiation planning CT and research MRI examination. For CT-based treatment plans the median volume of rectum receiving 70 Gy or more was 9.3 cubic centimeters (cc) [IQR 7.0 to 10.2] compared with 4.9 cc [IQR 4.1 to 8.7] for MRI-based plans. This resulted in a median volume reduction of 2.1 cc [IQR 0.5 to 5.3, P &lt; .001]. Conclusions: MRI-planned prostate radiotherapy can reduce the volume of rectum receiving radiation doses in excess of tolerance (70 Gy or more) and should be considered in men who are at high risk for late rectal toxicity. Clinical trial information: NCT02470910.
Accelerating the Evolution of Nonhuman Primate Neuroimaging
Authors: Michael Milham, Christopher I. Petkov, Daniel S. Margulies, Charles E. Schroeder, Michele A. Basso, Pascal Belin, Damien A. Fair, Andrew Fox, Sabine Kastner, Rogier B. Mars, Adam Messinger, Colline Poirier, Wim Vanduffel, David C. Van Essen, Ashkan Alvand, Yannick Becker, Suliann Ben Hamed, Austin Benn, Clementine Bodin, Susann Boretius, Bastien Cagna, Olivier Coulon, Sherif Hamdy El-Gohary, Henry Evrard, Stephanie J. Forkel, Patrick Friedrich, Sean Froudist-Walsh, Eduardo A. Garza-Villarreal, Yang Gao, Alessandro Gozzi, Antoine Grigis, Renee Hartig, Takuya Hayashi, Katja Heuer, Henrietta Howells, Dirk Jan Ardesch, Béchir Jarraya, Wendy Jarrett, Hank P. Jedema, Igor Kagan, Clare Kelly, Henry Kennedy, P. Christiaan Klink, Sze Chai Kwok, Robert Leech, Xiaojin Liu, Christopher Madan, Wasana Madushanka, Piotr Majka, Ann-Marie Mallon, Kevin Marche, Adrien Meguerditchian, Ravi S. Menon, Hugo Merchant, Anna Mitchell, Karl-Heinz Nenning, Aki Nikolaidis, Michael Ortiz-Rios, Marco Pagani, Vikas Pareek, Mark Prescott, Emmanuel Procyk, Reza Rajimehr, Ioana-Sabina Rautu, Amir Raz, Anna Wang Roe, Román Rossi-Pool, Lea Roumazeilles, Tomoko Sakai, Jerome Sallet, Pamela García-Saldivar, Chika Sato, Stephen Sawiak, Marike Schiffer, Caspar M. Schwiedrzik, Jakob Seidlitz, Julien Sein, Zhi-ming Shen, Amir Shmuel, Afonso C. Silva, Luciano Simone, Nikoloz Sirmpilatze, Julia Sliwa, Jonathan Smallwood, Jordy Tasserie, Michel Thiebaut de Schotten, Roberto Toro, Regis Trapeau, Lynn Uhrig, Julien Vezoli, Zheng Wang, Sara Wells, Bella Williams, Ting Xu, Augix Guohua Xu, Essa Yacoub, Ming Zhan, Lei Ai, Céline Amiez, Fabien Balezeau, Mark G. Baxter, Erwin L.A. Blezer, Thomas Brochier, Aihua Chen, Paula L. Croxson, Christienne G. Damatac, Stanislas Dehaene, Stefan Everling, Lazar Fleysher, Winrich Freiwald, Timothy D. Griffiths, Carole Guedj, Fadila Hadj-Bouziane, Noam Harel, Bassem Hiba, Benjamin Jung, Bonhwang Koo, Kevin N. Laland, David A. Leopold, Patrik Lindenfors, Martine Meunier, Kelvin Mok, John H. Morrison, Jennifer Nacef, Jamie Nagy, Mark Pinsk, Simon M. Reader, Pieter R. Roelfsema, David A. Rudko, Matthew F.S. Rushworth, Brian E. Russ, Michael Christoph Schmid, Elinor L. Sullivan, Alexander Thiele, Orlin S. Todorov, Doris Tsao, Leslie Ungerleider, Charles R.E. Wilson, Frank Q. Ye, Wilbert Zarco, Yong-di Zhou
Journal: Neuron (2020)
Late dosing of luteinizing hormone-releasing hormone agonists (LHRH) and testosterone (T) levels &gt;20 ng/dL in prostate cancer (PCa).
Authors: Przemyslaw Twardowski, Stuart Atkinson, Deborah Boldt-Houle, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2020)

31 Background: LHRH agonists are the most frequently used drugs for the delivery of androgen deprivation therapy (ADT) for PCa. Evidence suggests achieving and sustaining T levels ≤20 ng/dL with ADT is desirable and correlates with improved disease-specific survival in advanced PCa patients. However, T levels may rise above castration level (50 ng/dL) between injections, especially if a subsequent dose is delayed. Increase in prostate-specific antigen (PSA) level on ADT may represent true disease progression to castration resistant PCa, or may be a result of late ADT dosing and inadequate T suppression. Current study evaluated timeliness of LHRH agonist dosing, subsequent rate of T breakthroughs and frequency of T/PSA testing prior to dosing in PCa patients. Methods: A retrospective review of electronic medical records and associated claims data (1/1/07-6/30/16) of LHRH agonist injections (n=85,030) evaluated the frequency of late dosing (defined as occurring after day 32, 97, 128, 194 for 1-, 3-, 4-, 6-month formulations, respectively), T tests &gt;20 ng/dL and frequency of T/PSA tests prior to dosing. Results: 26.9% of injections were late: 14.4% were ≤1 week late, 3.1% were between 1-2 weeks late and 9.4% were &gt;2 weeks late. 43% of T values exceeded 20 ng/dL for late injections; while only 21% exceeded this level for early/on-time injections. 83% of LHRH injections had a PSA value drawn prior to dosing; however, only 13% had a similarly timed T assessment. Conclusions: Overall, &gt;25% of injections were late. For late injections, the proportion of T tests with T &gt;20 ng/dL was higher compared to when the dosing was early/on-time. Late injections correlated with ineffective T suppression (&gt;20 ng/dL) over 40% of the time. For all injections, T levels were not monitored as frequently as PSA levels. Considering the potential clinical benefits of maintaining effective T suppression throughout the course of ADT, clinicians should ensure treatments are delivered within approved dosing instructions, routinely monitor T levels and consider prescribing treatments with proven efficacy through the dosing interval to maintain T ≤20 ng/dL.
Assessment of inherited DNA repair defects in African-American and Caucasian men with prostate cancer.
Authors: A. Oliver Sartor, Shan Yang, Elisa Marie Ledet, Marcus W. Moses, Piper L.W. Nicolosi
Journal: Journal of Clinical Oncology (2020)

185 Background: Pathogenic inherited DNA repair defects are well described in Caucasian American (CA) men with prostate cancer (PCa) but comparative data with large subsets of African-American (AA) men are limited. Methods: Herein we examine germline pathogenic/likely pathogenic defects (P/LP) in 14 well annotated genes involved in DNA repair pathways in a large Invitae Corporation (San Francisco) lab-derived dataset of men with PCa. Frequency of P/LP alteration were directly compared in AA men and CA men. Reliable data on metastatic rates, family history, and Gleason score are missing. These data are derived from “real-world” experiences using both academic and private practice sites in accordance with physician ordering practices. The number of men assessed for individual genes aberrations varied. The 14 genes were assessed in 148-213 AA men and 1760-2488 CA men. Results: Comparative data using Invitae assays have lower levels of P/LP DNA repair alterations (as a whole) in the assays from AA men as compared to CA men (7.5% vs 13.9%, P=0.008). The P/LP variants in AA men were BRCA2 (6/214, 2.8%), BRCA1 (3/213, 1.4%), PALB2 (2/182, 1.1%), ATM (2/206, 1.0%), RAD51C (1/148, 0.68%), CHEK2 (1/207, 0.48%), and PMS2 (1/212, 0.47%). No AA men in this data set had P/LP mutations in BARD1, BRIP1, MLH1, MSH2, MSH6, NBN, or RAD51D. Lower frequency of P/LP findings in non-BRCA alterations were notably different in AA men as compared to CA men (0.48% vs 3.11%, P=0.03). The frequency of BRCA P/LP variants was not distinct between the AA and CA men. Additional comparisons show that Invitae CA data set is similar to a well cited previously published metastatic PCa data set. Conclusions: Taken together these data from comparable commercial assays indicate that AA men with PCa in this large dataset have lower rates of germline DNA repair P/LP alterations as compared to CA men. These findings are driven by lower rates of P/LP alterations in the non-BRCA genes.
Activation of β-catenin signaling by HTLV-1 transforming protein Tax.
Authors: Mariko Tomita, Naoki Mori
Journal: Cancer Research (2005)

355  Human T-cell leukemia virus type-1 (HTLV-1) is the etiologic agent for adult T-cell leukemia (ATL). HTLV-1 transforms T lymphocytes, and there are increasing evidences that the virus-encoded protein Tax plays a primary role in viral transformation. β-catenin is known to play a critical role as a regulator of cell-cell adhesion and transcriptional regulation. Dysregulation of β-catenin signaling has been implicated in the malignant transformation of cells of epithelial origin. Here we found that β-catenin protein is accumulated in the nucleus of HTLV-1-transformed T-cell lines which express viral genes including Tax but not in that of HTLV-1-infected T-cell lines which do not express significant level of viral genes. β-catenin/Tcf transcriptional activity is significantly higher in Tax-positive HTLV-1-transformed T-cell lines than Tax-negative HTLV-1-infected T-cell lines. Moreover, β-catenin protein is rapidly degraded in Tax-negative HTLV-1-infected T-cell lines but it is stabilized in Tax-positive HTLV-1-transformed T-cell lines. Tax enhances the β-catenin transcriptional activity by stabilizing β-catenin protein in transfected Hela cells. Importantly, a mutant Tax which could not activate CREB pathway could not stabilized β-catenin protein, suggesting that the activation of CREB by Tax may be essential for the stabilization of β-catenin protein. Our results suggested that activation of β-catenin/Tcf pathway by Tax may play an important role in the transformation of T lymphocytes in the early stage of HTLV-1 infection.