tbuckley/cabot-search huggingface dataset:
Improvement of early mortality in single‐unit cord blood transplantation for Japanese adults from 1998 to 2017
Authors: Takaaki Konuma, Junya Kanda, Yoshihiro Inamoto, Hiromi Hayashi, Shinichi Kobayashi, Naoyuki Uchida, Yasuhiro Sugio, Masatsugu Tanaka, Hikaru Kobayashi, Yasushi Kouzai, Satoshi Takahashi, Tetsuya Eto, Junichi Mukae, Yoshiko Matsuhashi, Takahiro Fukuda, Minoko Takanashi, Yoshinobu Kanda, Yoshiko Atsuta, Fumihiko Kimura
Journal: American Journal of Hematology (2019)

Abstract The major limitation of cord blood transplantation (CBT) for adults remains the delayed hematopoietic recovery and higher incidence of graft failure, which result in a higher risk of early mortality in CBT. We evaluated early overall survival (OS), non‐relapse mortality (NRM), neutrophil engraftment, acute graft‐vs‐host disease, and cause of early death among 9678 adult patients who received single‐unit CBT in Japan between 1998 and 2017. The probability of OS at 100 days was 64.4%, 71.7%, and 78.9% for the periods 1998 to 2007, 2008 to 2012, and 2013 to 2017, respectively ( P &lt; .001). The cumulative incidences of NRM at 100 days during the same period were 28.3%, 20.8%, and 14.6%, respectively ( P &lt; .001). The cumulative incidences of neutrophil engraftment were also improved during the same period ( P &lt; .001). The most common cause of death within 100 days after CBT was bacterial infection in 1998 to 2007 and primary disease in the latter two time periods. Across the three time periods, the proportions of deaths from bacterial and fungal infection, graft failure, hemorrhage, sinusoidal obstructive syndrome, and organ failure decreased in a stepwise fashion. Landmark analysis of OS and NRM after 100 days showed that OS did not change over time in the multivariate analysis. Our registry‐based data demonstrated a significant improvement of early OS after CBT for adults over the past 20 years. The landmark analysis suggested that improvement of early mortality could lead to an improvement of long‐term OS after CBT.
Harmonization and standardization of panel-based tumour mutational burden (TMB) measurement: Real-world results and recommendations of the QuIP study
Authors: A. Stenzinger, V. Endris, J. Budczies, S. Merkelbach-Bruse, W. Dietmaier, U. Siebolts, J. Maas, D.M. Merino, M. Stewart, J. Allen, H. Glimm, M. Thiemann, D. Aust, M. Hummel, H. Moch, A. Jung, F. Haller, W. Weichert, M. Dietel
Journal: Annals of Oncology (2019)
Revisiting pachyonychia congenita: a case‐cohort study of 815 patients
Authors: L. Samuelov, F.J.D. Smith, C.D. Hansen, E. Sprecher
Journal: British Journal of Dermatology (2019)

Pachyonychia congenita (PC) is a group of autosomal dominant disorders caused by mutations in one of five keratin genes (KRT6A, KRT6B, KRT6C, KRT16, KRT17). The establishment of an international registry containing clinical and molecular data led to the development of a disease classification based on the mutant gene and associated features. To harness the same resource to clarify the prevalence of PC‐associated clinical features, delineate phenotype–genotype correlations and identify prognostic features for disease severity. In total, 815 individuals with confirmed keratin mutations registered in the International Pachyonychia Congenita Research Registry were surveyed for clinical findings associated with PC. Data were analysed using various statistical methods, including the Student's t‐test, χ2‐test and anova tests for differences in means/proportions. Spearman correlation and logistic regression were used for phenotype–genotype correlations. KRT6A mutations were associated with oral leucokeratosis, hoarseness, youngest age or highest number of fingernails/toenails involved, and use of walking aids. KRT17 mutations were most commonly associated with cysts and natal teeth. Using logistic regression, we found that oral leucokeratosis was correlated with earlier toenail involvement, walking aids, nursing difficulties and hoarseness. Cysts were correlated with oral leucokeratosis, natal teeth and ear wax. Natal teeth predicted earlier toenail involvement, walking difficulties and cyst formation. Hoarseness was correlated with an increased number of involved fingernails. Here, we establish phenotype–genotype correlations in the largest cohort of patients with PC described to date and reveal novel and clinically useful predictors of disease course and manifestations. What's already known about this topic? Pachyonychia congenita (PC) is a group of autosomal dominant disorders caused by mutations in one of five keratin genes (KRT6A, KRT6B, KRT6C, KRT16, KRT17). The main clinical features are nail dystrophy, palmoplantar keratoderma, oral leucokeratosis and cysts. The establishment of an international registry containing the clinical and molecular data of patients with PC led to the development of a disease classification based on the mutant gene and associated features. What does this study add? Data were collected via an international registry to clarify the prevalence of PC‐associated clinical features, delineate phenotype–genotype correlations and identify prognostic features for disease severity. This is the largest cohort of patients with PC described to date. The earliest clinical manifestations of PC are nail dystrophy and palmoplantar keratoderma. Diagnosis can be suspected and confirmed in preschool years. Painful plantar keratoderma has the most profound and debilitating effect on quality of life and daily function. Linked Editorial:Steele and O'Toole. Br J Dermatol 2020; 182:521–522. Linked Comment:Mordaunt. Br J Dermatol 2020; 182:537.
Is the glass half full or half empty after PARAGON-HF?
Authors: Alain Cohen-Solal, Damien Logeart
Journal: Cardiovascular Research (2019)

HFpEF • Sacubitril/valsartan • PARAGON • Heart failure Heart failure with preserved ejection fraction (HFpEF) is an increasingly common condition, particularly with the aging of the population, and it remains a public health problem because of its poor prognosis and high rate of rehospitalization. 1,2Various drugs effective in heart failure with reduced ejection fraction (HFrEF) have been evaluated to improve the natural history and prognosis in the disease with disappointing results.Thus, beta-blockers, ACE inhibitors (ACE-I), angiotensin receptors blockers (ARB) and mineralocorticoid receptor antagonists (MRA) have not been shown to be convincingly effective.Sacubitril/valsartan, a leader in a new therapeutic class, angiotensin receptor and neprilysin inhibitors (ARNi), has been shown to be particularly effective in improving the prognosis and quality of life of patients with low LVEF (HFrEF).In the PARADIGM trial, sacubitril/valsartan improved symptoms and reduced total patient mortality by 16% and HF rehospitalization by 21%. 3 It was therefore logical to think that this drug could also be effective in patients with LVEF greater than 40% (HFpEF).Especially as a preliminary study, PARAMOUNT,4 conducted in a population comparable to PARADIGM, but with LVEF > 45%, had shown a beneficial effect on plasma natriuretic peptides which decreased compared to the comparator, valsartan.The PARAGON trial 5 was thus performed on nearly 5000 patients who had stable chronic heart failure (CHF) (NYHA II-III) with a LVEF greater than 45% (this cut-off was decided prior to the ESC 2016 Guidelines that defined HFpEF when LVEF is >50%).Sacubitril/valsartan (97/103 mg) bid was tested vs. valsartan (160 mg bid).The primary endpoint was the association of cardiovascular mortality and total hospitalizations for heart failure.The mean age of participants in the study was 72 years, about 7 years more than in HFrEF trials, with 51% being women.The result appears mixed and can be seen optimistically or pessimistically, as with the expression of a glass being half empty or half full.Indeed, the study was negative with regards to the main combined primary endpoint, with a P-value of 0.059 (HR 0.87).Logically, our analysis should stop there because this difference did not meet the predetermined level of statistical significance, and subsequent analyses should be considered to be only exploratory.One cannot help however to look at the various components of the primary criterion: cardiovascular mortality and total mortality were not significantly affected by sacubitril/valsartan and there was only a trend towards a reduction in hospitalizations for heart failure (HR 0.85, P = 0.056).Sacubitril/valsartan also improved quality of life but resulted in more hypotensions.
Pathologists' agreement on treatment suggestions for melanocytic skin lesions
Authors: Mustufa A. Jafry, Sue Peacock, Andrea C. Radick, Hannah L. Shucard, Lisa M. Reisch, Michael W. Piepkorn, Stevan R. Knezevich, Martin A. Weinstock, Raymond L. Barnhill, David E. Elder, Kathleen F. Kerr, Joann G. Elmore
Journal: Journal of the American Academy of Dermatology (2019)
New Perspectives for Cancer Hazard Evaluation by the Report on Carcinogens: A Case Study Using Read-Across Methods in the Evaluation of Haloacetic Acids Found as Water Disinfection By-Products
Authors: Stanley T. Atwood, Ruth M. Lunn, Sanford C. Garner, Gloria D. Jahnke
Journal: Environmental Health Perspectives (2019)

Due to the large number of chemicals not yet tested for carcinogenicity but to which people are exposed, the limited number of human and animal cancer studies conducted each year, and the frequent need for a timely response, mechanistic data are playing an increasingly important role in carcinogen hazard identification.To provide a targeted approach to identify relevant mechanistic data in our cancer evaluation of haloacetic acids (HAAs), we used several approaches including systematic review, the 10 key characteristics of carcinogens (KCs), and read-across methods. Our objective in this commentary is to discuss the strengths, limitations, and challenges of these approaches in a cancer hazard assessment.A cancer hazard assessment for 13 HAAs found as water disinfection by-products was conducted. Literature searches for mechanistic studies focused on the KCs and individual HAAs. Studies were screened for relevance and categorized by KCs and other relevant data, including chemical properties, toxicokinetics, and biological effects other than KCs. Mechanistic data were organized using the KCs, and strength of evidence was evaluated; this information informed potential modes of action (MOAs) and read-across-like approaches. Three read-across options were considered: evaluating HAAs as a class, as subclass(es), or as individual HAAs (analog approach).Because of data limitations and uncertainties, listing as a class or subclass(es) was ruled out, and an analog approach was used. Two brominated HAAs were identified as target (untested) chemicals based on their metabolism and similarity to source (tested) chemicals. In addition, four HAAs with animal cancer data had sufficient evidence for potential listing in the Report on Carcinogens (RoC). This is the first time that the KCs and other relevant data, in combination with read-across principles, were used to support a recommendation to list chemicals in the RoC that did not have animal cancer data. https://doi.org/10.1289/EHP5672.
PD-L1 Testing for Lung Cancer in 2019: Perspective From the IASLC Pathology Committee
Authors: Sylvie Lantuejoul, Ming Sound-Tsao, Wendy A. Cooper, Nicolas Girard, Fred R. Hirsch, Anja C. Roden, Fernando Lopez-Rios, Deepali Jain, Teh-Ying Chou, Noriko Motoi, Keith M. Kerr, Yasushi Yatabe, Elisabeth Brambilla, John Longshore, Mauro Papotti, Lynette M. Sholl, Erik Thunnissen, Natasha Rekhtman, Alain Borczuk, Lukas Bubendorf, Yuko Minami, Mary Beth Beasley, Johan Botling, Gang Chen, Jin-Haeng Chung, Sanja Dacic, David Hwang, Dongmei Lin, Andre Moreira, Andrew G. Nicholson, Masayuki Noguchi, Giuseppe Pelosi, Claudia Poleri, William Travis, Akihiko Yoshida, Jillian B. Daigneault, Ignacio I. Wistuba, Mari Mino-Kenudson
Journal: Journal of Thoracic Oncology (2019)
Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia
Authors: Gail J. Roboz, Courtney D. DiNardo, Eytan M. Stein, Stéphane de Botton, Alice S. Mims, Gabrielle T. Prince, Jessica K. Altman, Martha L. Arellano, Will Donnellan, Harry P. Erba, Gabriel N. Mannis, Daniel A. Pollyea, Anthony S. Stein, Geoffrey L. Uy, Justin M. Watts, Amir T. Fathi, Hagop M. Kantarjian, Martin S. Tallman, Sung Choe, David Dai, Bin Fan, Hongfang Wang, Vickie Zhang, Katharine E. Yen, Stephanie M. Kapsalis, Denice Hickman, Hua Liu, Samuel V. Agresta, Bin Wu, Eyal C. Attar, Richard M. Stone
Journal: Blood (2019)
BMA is “preparing ground” for industrial action on pensions
Authors: Helen Jaques
Journal: BMJ (2011)

The BMA has confirmed that it is preparing to ballot its members on industrial action because of the stalemate in negotiations with the government over changes to pension schemes. 

After a unanimous vote in favour of a national ballot at the BMA’s annual representatives meeting this summer ( BMJ Careers , 1 Jul, http://careers.bmj.com/careers/advice/view-article.html?id=20003604), the association has announced that it has reached the most advanced discussions for 30 years and is “getting everything in place” to take the next steps towards industrial action. 

“We have ploughed the ground and fertilised it. We haven’t planted seeds yet, because we’re …
Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation
Authors: Zhaogang Yang, Junfeng Shi, Jing Xie, Yifan Wang, Jingyao Sun, Tongzheng Liu, Yarong Zhao, Xiuting Zhao, Xinmei Wang, Yifan Ma, Veysi Malkoc, Chiling Chiang, Weiye Deng, Yuanxin Chen, Yuan Fu, Kwang J. Kwak, Yamin Fan, Chen Kang, Changcheng Yin, June Rhee, Paul Bertani, Jose Otero, Wu Lu, Kyuson Yun, Andrew S. Lee, Wen Jiang, Lesheng Teng, Betty Y. S. Kim, L. James Lee
Journal: Nature Biomedical Engineering (2019)
Optical diagnosis for diminutive colorectal polyps: time to implement?
Authors: Daniel von Renteln
Journal: Endoscopy (2019)

In the current issue of Endoscopy, Hassan et al. present a revised optical diagnosis classification (BASIC) in conjunction with blue-light imaging (BLI) for optical diagnosis of colorectal polyps [1]. Using this methodology, the accuracy of optical diagnosis in distinguishing between adenomatous and hyperplastic colorectal polyps was 90.3 % and superior to that when using white-light imaging.
Diagnosis and Management of Chronic Pancreatitis
Authors: Vikesh K. Singh, Dhiraj Yadav, Pramod K. Garg
Journal: JAMA (2019)

<h3>Importance</h3> Chronic pancreatitis (CP) is a chronic inflammatory and fibrotic disease of the pancreas with a prevalence of 42 to 73 per 100 000 adults in the United States. <h3>Observations</h3> Both genetic and environmental factors are thought to contribute to the pathogenesis of CP. Environmental factors associated with CP include alcohol abuse (odds ratio [OR], 3.1; 95% CI, 1.87-5.14) for 5 or more drinks per day vs abstainers and light drinkers as well as smoking (OR, 4.59; 95% CI, 2.91-7.25) for more than 35 pack-years in a case-control study involving 971 participants. Between 28% to 80% of patients are classified as having "idiopathic CP." Up to 50% of these individuals have mutations of the trypsin inhibitor gene (<i>SPINK1</i>) or the cystic fibrosis transmembrane conductance regulator (<i>CFTR</i>) gene. Approximately 1% of people diagnosed with CP may have hereditary pancreatitis, associated with cationic trypsinogen (<i>PRSS1</i>) gene mutations. Approximately 80% of people with CP present with recurrent or chronic upper abdominal pain. Long-term sequelae include diabetes in 38% to 40% and exocrine insufficiency in 30% to 48%. The diagnosis is based on pancreatic calcifications, ductal dilatation, and atrophy visualized by imaging with computed tomography, magnetic resonance imaging, or both. Endoscopic ultrasound can assist in making the diagnosis in patients with a high index of suspicion such as recurrent episodes of acute pancreatitis when imaging is normal or equivocal. The first line of therapy consists of advice to discontinue use of alcohol and smoking and taking analgesic agents (nonsteroidal anti-inflammatory drugs and weak opioids such as tramadol). A trial of pancreatic enzymes and antioxidants (a combination of multivitamins, selenium, and methionine) can control symptoms in up to 50% of patients. Patients with pancreatic ductal obstruction due to stones, stricture, or both may benefit from ductal drainage via endoscopic retrograde cholangiopancreatography (ERCP) or surgical drainage procedures, such as pancreaticojejunostomy with or without pancreatic head resection, which may provide better pain relief among people who do not respond to endoscopic therapy. <h3>Conclusions and Relevance</h3> Chronic pancreatitis often results in chronic abdominal pain and is most commonly caused by excessive alcohol use, smoking, or genetic mutations. Treatment consists primarily of alcohol and smoking cessation, pain control, replacement of pancreatic insufficiency, or mechanical drainage of obstructed pancreatic ducts for some patients.
Radioisotope Imaging and Therapy for Bone Metastasis in Men With Castration-Resistant Prostate Cancer
Authors: Umang Swami, Jeffrey T. Yap, Neeraj Agarwal
Journal: JAMA Oncology (2019)

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 Oncology 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 Oncology journal
Bile duct stone caused by 25-year placement of metal stent: successful diagnosis and extraction using peroral cholangioscopy
Authors: Yuki Tanisaka, Shomei Ryozawa, Masafumi Mizuide, Akashi Fujita, Tomoya Ogawa
Journal: Endoscopy (2019)

Bile duct stones can form when a foreign body (e. g. metal stent) is placed for a long period. We report the case of a bile duct stone caused by a metal stent that had been in place for 25 years.
Enhancing the therapeutic effect of dendritic cell therapy by oncolytic adenovirus 3 encoding CD40-ligand
Authors: S. Zafar, D.C.A. Quixabeira, O. Hemminki, V. Cervera-Carrascon, J.M. Santos, A. Kanerva, A. Hemminki
Journal: Annals of Oncology (2019)
GCN2 drives macrophage and MDSC function and immunosuppression in the tumor microenvironment
Authors: Marie Jo Halaby, Kebria Hezaveh, Sara Lamorte, M. Teresa Ciudad, Andreas Kloetgen, Bethany L. MacLeod, Mengdi Guo, Ankur Chakravarthy, Tiago Da Silva Medina, Stefano Ugel, Aristotelis Tsirigos, Vincenzo Bronte, David H. Munn, Trevor J. Pugh, Daniel D. De Carvalho, Marcus O. Butler, Pamela S. Ohashi, David G. Brooks, Tracy L. McGaha
Journal: Science Immunology (2019)

GCN2 is a key driver of Mϕ and MDSC polarization in the tumor microenvironment causing T cell exhaustion.
On the implications of object permanence: Microhistorical insights from Piaget's new theory
Authors: Jeremy Trevelyan Burman
Journal: Behavioral and Brain Sciences (2020)

Abstract The authors’ arguments reflect the dominant traditions of American Psychology. In doing so, however, they miss relevant insights omitted during the original importation (translation and popularization) of the foreign sources that informed the theories they built upon. Of particular relevance here are Piaget's last studies. These are presented to unpack the meaning of “object permanence” as a kind of representation.
Early changes in plasma cell-free DNA (cfDNA) as a predictive biomarker of immune checkpoint inhibitors (ICIs) efficacy
Authors: I. Matos Garcia, A. Moreno, C. Arenillas, C. Hierro Carbo, E. Munoz-Cosuelo, J. Martin-Liberal, I. Braña, M. Vieito Villar, A. Azaro, O. Saavedra Santa Gadea, I. Gardeazabal Gonzalez, R. Javier, B. Roger, E. Elez, E. Felip, R. Dienstmann, A. Gros, J. Tabernero, R.D.A. Toledo, E. Garralda
Journal: Annals of Oncology (2019)
Human genetics and neuropathology suggest a link between miR-218 and amyotrophic lateral sclerosis pathophysiology
Authors: Irit Reichenstein, Chen Eitan, Sandra Diaz-Garcia, Guy Haim, Iddo Magen, Aviad Siany, Mariah L. Hoye, Natali Rivkin, Tsviya Olender, Beata Toth, Revital Ravid, Amitai D. Mandelbaum, Eran Yanowski, Jing Liang, Jeffrey K. Rymer, Rivka Levy, Gilad Beck, Elena Ainbinder, Sali M. K. Farhan, Kimberly A. Lennox, Nicole M. Bode, Mark A. Behlke, Thomas Möller, Smita Saxena, Cristiane A. M. Moreno, Giancarlo Costaguta, Kristel R. van Eijk, Hemali Phatnani, Ammar Al-Chalabi, A. Nazli Başak, Leonard H. van den Berg, Orla Hardiman, John E. Landers, Jesus S. Mora, Karen E. Morrison, Pamela J. Shaw, Jan H. Veldink, Samuel L. Pfaff, Ofer Yizhar, Christina Gross, Robert H. Brown, John M. Ravits, Matthew B. Harms, Timothy M. Miller, Eran Hornstein
Journal: Science Translational Medicine (2019)

Genetics, pathology, and molecular studies demonstrate that microRNA-218 is modulated and might play a role in amyotrophic lateral sclerosis.
Evaluating e-Cigarette Lung Disease
Authors: Bridget Kuehn
Journal: JAMA (2019)

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