tbuckley/cabot-search huggingface dataset:
SAT0708-HPR DEVELOPING AN ALLIED HEALTH CORE OUTCOME SET FOR PAEDIATRIC RHEUMATOLOGY MUSCULOSKELETAL CONDITIONS
Authors: Verna Cuthbert, Victoria Harbottle, Ellie Potts
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Musculoskeletal (MSK) conditions are prevalent within the general population, including children and young people (CYP) with MSK pain. There is evidence that MSK pain in CYP is an antecedent of adult MSK pain. Paediatric Rheumatology Allied Health Professionals (PRAHPs) are well placed to manage these CYP, but there is no current standardisation in treatment, services or outcomes. <h3>Objectives</h3> To develop a core outcome measure set for clinical use by PRAHPs to facilitate national collaboration and standardisation of care. <h3>Methods</h3> A modified Nominal Group technique study was undertaken by an expert* panel of PRAHP's working in 8 Tertiary Paediatric and Adolescent UK centres. Literature search and presentation of findings informed expert panel discussion with particular reference to the following criteria: paediatric population specific, ease of clinical use, cost, general availability to clinicians, reliability, validity, length to administer/perform and previous research use. Expert panel discussion and ranking identified eight domains. A survey was sent to the 12 members of the expert panel asking participants to choose two measures or none, based on criteria above. Consensus was pre-determined as agreement between experts of 60% or more. <h3>Results</h3> Survey response rate was 83% with consensus achieved for 6 outcome measures- see table. Consensus could not be reached for hand function, sleep and goal-setting in part due to the large number of measures and variation in use, lack of paediatric specific measures, length of time taken to administer or costs involved. Psychological measures were not included within the scope of this work, but would be a valuable future addition. <h3>Conclusion</h3> This study informs a pilot outcome measure set for PRAHPs in clinical settings when time, space, money and ease of use are paramount. <h3>Acknowledgement</h3> Members of Expert PRAHP panel and valuable feedback from Dr Kate Armon, Dr Joyce Davidson &amp; Dr Janet McDonagh <h3>Disclosure of Interests</h3> None declared
Site-Specific and Targeted Therapy Based on Molecular Profiling by Next-Generation Sequencing for Cancer of Unknown Primary Site
Authors: Hidetoshi Hayashi, Yuichi Takiguchi, Hironobu Minami, Kohei Akiyoshi, Yoshihiko Segawa, Hiroki Ueda, Yasuo Iwamoto, Chihiro Kondoh, Koji Matsumoto, Shin Takahashi, Hisateru Yasui, Toshiyuki Sawa, Yusuke Onozawa, Yasutaka Chiba, Yosuke Togashi, Yoshihiko Fujita, Kazuko Sakai, Shuta Tomida, Kazuto Nishio, Kazuhiko Nakagawa
Journal: JAMA Oncology (2020)

Although profiling of gene expression and gene alterations by next-generation sequencing (NGS) to predict the primary tumor site and guide molecularly targeted therapy might be expected to improve clinical outcomes for cancer of unknown primary site (CUP), to our knowledge, no clinical trial has previously evaluated this approach.To assess the clinical use of site-specific treatment, including molecularly targeted therapy based on NGS results, for patients with CUP.This phase 2 clinical trial was conducted at 19 institutions in Japan and enrolled 111 previously untreated patients with the unfavorable subset of CUP between March 2015 and January 2018, with 97 patients being included in the efficacy analysis. Eligibility criteria included a diagnosis of unfavorable CUP after mandatory examinations, including pathological evaluation by immunohistochemistry, chest-abdomen-pelvis computed tomography scans, and a positron emission tomography scan.RNA and DNA sequencing for selected genes was performed simultaneously to evaluate gene expression and gene alterations, respectively. A newly established algorithm was applied to predict tumor origin based on these data. Patients received site-specific therapy, including molecularly targeted therapy, according to the predicted site and detected gene alterations.The primary end point was 1-year survival probability. Secondary end points included progression-free survival (PFS), overall survival (OS), objective response rate, safety, efficacy according to predicted site, and frequency of gene alterations.Of 97 participants, 49 (50.5%) were women and the median (range) age was 64 (21-81) years. The cancer types most commonly predicted were lung (21 [21%]), liver (15 [15%]), kidney (15 [15%]), and colorectal (12 [12%]) cancer. The most frequent gene alterations were in TP53 (45 [46.4%]), KRAS (19 [19.6%]), and CDKN2A (18 [18.6%]). The 1-year survival probability, median OS, and median PFS were 53.1% (95% CI, 42.6%-62.5%), 13.7 months (95% CI, 9.3-19.7 months), and 5.2 months (95% CI, 3.3-7.1 months), respectively. Targetable EGFR mutations in tumor specimens were detected in 5 patients with predicted non-small-cell lung cancer (5.2%), 4 of whom were treated with afatinib; 2 of these patients achieved a durable PFS of longer than 6 months.This study's findings suggest that site-specific treatment, including molecularly targeted therapy based on profiling gene expression and gene alterations by NGS, can contribute to treating patients with the unfavorable subset of CUP.UMIN Identifier: UMIN000016794.
Discovery of a Family of Mixed Lineage Kinase Domain-like Proteins in Plants and Their Role in Innate Immune Signaling
Authors: Lisa K. Mahdi, Menghang Huang, Xiaoxiao Zhang, Ryohei Thomas Nakano, Leïla Brulé Kopp, Isabel M.L. Saur, Florence Jacob, Viera Kovacova, Dmitry Lapin, Jane E. Parker, James M. Murphy, Kay Hofmann, Paul Schulze-Lefert, Jijie Chai, Takaki Maekawa
Journal: Cell Host & Microbe (2020)
Complement activation induced by PEG enhances humoral immune responses against antigens encapsulated in PEG-modified liposomes
Authors: Taro Shimizu, Mizuki Awata, Amr S. Abu Lila, Chihiro Yoshioka, Yoshino Kawaguchi, Hidenori Ando, Yu Ishima, Tatsuhiro Ishida
Journal: Journal of Controlled Release (2020)
Catheter-Related Thrombosis in Patients with Lymphoma or Myeloma Undergoing Autologous Stem Cell Transplantation
Authors: Livia Hegerova, Adam Bachan, Qing Cao, Veronika Bachanova, Mark Reding, John Rogosheske, Brian McClune, Aleksandr Lazaryan, Greg M Vercellotti, Huong X Vu
Journal: Blood (2017)
COVID-19 infection in kidney transplant recipients at the epicenter of pandemics
Authors: Yorg Azzi, Michael Parides, Omar Alani, Pablo Loarte-Campos, Rachel Bartash, Stefanie Forest, Adriana Colovai, Maria Ajaimy, Luz Liriano-Ward, Cindy Pynadath, Jay Graham, Marie Le, Stuart Greenstein, Juan Rocca, Milan Kinkhabwala, Enver Akalin
Journal: Kidney International (2020)

We investigated the prevalence and clinical outcomes of COVID-19 in recipients of kidney transplants in the Bronx, New York, one of the epicenters of the pandemic. Between March 16 and June 2, 2020, 132 kidney transplant recipients tested positive by SARS-CoV-2 RT-PCR. From May 3 to July 29, 2020, 912 kidney transplant recipients were screened for SARS-CoV-2 IgG antibodies during routine clinic visits, of which 16.6% tested positive. Fifty-five of the 152 patients had previously tested positive by RT-PCR, while the remaining 97 did not have significant symptoms and had not been previously tested by RT-PCR. The prevalence of SARS-CoV-2 infection was 23.4% in the 975 patients tested by either RT-PCR or SARS-CoV-2 IgG. Older patients and patients with higher serum creatinine levels were more likely diagnosed by RT-PCR compared to SARS-CoV-2 IgG. Sixty-nine RT-PCR positive patients were screened for SARS-CoV-2 IgG antibodies at a median of 44 days post-diagnosis (Inter Quartile Range 31-58) and 80% were positive. Overall mortality was 20.5% but significantly higher (37.8%) in the patients who required hospitalization. Twenty-three percent of the hospitalized patients required kidney replacement therapy and 6.3% lost their allografts. In multivariable analysis, older age, receipt of deceased-donor transplantation, lack of influenza vaccination in the previous year and higher serum interleukine-6 levels were associated with mortality. Thus, 42% of patients with a kidney transplant and with COVID-19 were diagnosed on antibody testing without significant clinical symptoms; 80% of patients with positive RT-PCR developed SARS-CoV-2 IgG and mortality was high among patients requiring hospitalization.
Case 32-2020: A 63-Year-Old Man with Confusion, Fatigue, and Garbled Speech
Authors: Shibani S. Mukerji, Kevin L. Ard, Pamela W. Schaefer, John A. Branda
Journal: New England Journal of Medicine (2020)

A 63-year-old man with a history of primary membranous nephropathy presented with fever, confusion, headache, garbled speech, vision changes, lymphocytic pleocytosis, and an elevated CSF protein level. MRI of the head revealed sulcal hyperintensity on FLAIR images, with associated subtle enhancement on T1-weighted images. A diagnosis was made.
Urine metabolomic phenotyping for detection of adrenocortical carcinoma: still a long way to go – Authors' reply
Authors: Irina Bancos, Angela E Taylor, Vasileios Chortis, Alice J Sitch, Katharina Lang, Alessandro Prete, Lorna C Gilligan, Michael Biehl, Jonathan J Deeks, Wiebke Arlt
Journal: The Lancet Diabetes & Endocrinology (2020)
Early Trastuzumab Interruption and Recurrence-Free Survival in <i>ERBB2</i>-Positive Breast Cancer
Authors: Robert S. Copeland-Halperin, Mohammed Al-Sadawi, Sujata Patil, Jennifer E. Liu, Richard M. Steingart, Chau T. Dang, Anthony F. Yu
Journal: JAMA Oncology (2020)
Magnitude, demographics and dynamics of the effect of the first wave of the COVID-19 pandemic on all-cause mortality in 21 industrialized countries
Authors: Vasilis Kontis, James E. Bennett, Theo Rashid, Robbie M. Parks, Jonathan Pearson-Stuttard, Michel Guillot, Perviz Asaria, Bin Zhou, Marco Battaglini, Gianni Corsetti, Martin McKee, Mariachiara Di Cesare, Colin D. Mathers, Majid Ezzati
Journal: Nature Medicine (2020)

The Coronavirus Disease 2019 (COVID-19) pandemic has changed many social, economic, environmental and healthcare determinants of health. We applied an ensemble of 16 Bayesian models to vital statistics data to estimate the all-cause mortality effect of the pandemic for 21 industrialized countries. From mid-February through May 2020, 206,000 (95% credible interval, 178,100–231,000) more people died in these countries than would have had the pandemic not occurred. The number of excess deaths, excess deaths per 100,000 people and relative increase in deaths were similar between men and women in most countries. England and Wales and Spain experienced the largest effect: ~100 excess deaths per 100,000 people, equivalent to a 37% (30–44%) relative increase in England and Wales and 38% (31–45%) in Spain. Bulgaria, New Zealand, Slovakia, Australia, Czechia, Hungary, Poland, Norway, Denmark and Finland experienced mortality changes that ranged from possible small declines to increases of 5% or less in either sex. The heterogeneous mortality effects of the COVID-19 pandemic reflect differences in how well countries have managed the pandemic and the resilience and preparedness of the health and social care system. Application of Bayesian models to vital statistics data from 21 industrialized countries shows that approximately 206,000 additional people died than if the COVID-19 pandemic had not occured. The heterogeneous distribution of excess deaths across the countries reflects differences in how the pandemic has been managed as well as the resilience of healthcare systems in these nations.
Distributional Reinforcement Learning in the Brain
Authors: Adam S. Lowet, Qiao Zheng, Sara Matias, Jan Drugowitsch, Naoshige Uchida
Journal: Trends in Neurosciences (2020)

Learning about rewards and punishments is critical for survival. Classical studies have demonstrated an impressive correspondence between the firing of dopamine neurons in the mammalian midbrain and the reward prediction errors of reinforcement learning algorithms, which express the difference between actual reward and predicted mean reward. However, it may be advantageous to learn not only the mean but also the complete distribution of potential rewards. Recent advances in machine learning have revealed a biologically plausible set of algorithms for reconstructing this reward distribution from experience. Here, we review the mathematical foundations of these algorithms as well as initial evidence for their neurobiological implementation. We conclude by highlighting outstanding questions regarding the circuit computation and behavioral readout of these distributional codes.
<scp>Heart Failure Association</scp> of the <scp>European Society of Cardiology</scp> update on sodium–glucose co‐transporter 2 inhibitors in heart failure
Authors: Petar M. Seferović, Gabriele Fragasso, Mark Petrie, Wilfried Mullens, Roberto Ferrari, Thomas Thum, Johann Bauersachs, Stefan D. Anker, Robin Ray, Yuksel Çavuşoğlu, Marija Polovina, Marco Metra, Giuseppe Ambrosio, Krishna Prasad, Jelena Seferović, Pardeep S. Jhund, Giuseppe Dattilo, Jelena Čelutkiene, Massimo Piepoli, Brenda Moura, Ovidiu Chioncel, Tuvia Ben Gal, Stephane Heymans, Tiny Jaarsma, Loreena Hill, Yuri Lopatin, Alexander R. Lyon, Piotr Ponikowski, Mitja Lainščak, Ewa Jankowska, Christian Mueller, Francesco Cosentino, Lars H. Lund, Gerasimos S. Filippatos, Frank Ruschitzka, Andrew J.S. Coats, Giuseppe M.C. Rosano
Journal: European Journal of Heart Failure (2020)
6P The importance of biomarker expression in addition to lymph node status in the ESMO risk stratification of endometrial cancer
Authors: S. Vrede, W.J. Van Weelden, N. Visser, L.V.D. Putten, K.V.D. Vijver, J. Bulten, M. Enitec, A.V.D. Wurff, M. Snijders, H. Küsters, C. Reijnen, J. Pijnenborg
Journal: Annals of Oncology (2020)
Impact of Immunohistochemistry-Defined Cell of Origin and MYC Rearrangements on Outcomes in Patients with PET-Defined Stage I/II Diffuse Large B-Cell Lymphoma Treated with R-CHOP ± Radiotherapy: An International Multi-Center Retrospective Study
Authors: Allison Barraclough, Musa Alzahrani, Marianne Schmidt Ettrup, Mark Bishton, Chris Van Vliet, Laurie H. Sehn, Vishakha Sovani, Mitchell Steven Ward, Bradley Augustson, Pedro Farinha, Jorne Lionel Biccler, Joseph M Connors, David W. Scott, Kerry J Savage, Tarec Christoffer El-Galaly, Diego Villa, Chan Yoon Cheah
Journal: Blood (2017)
Abstract 148: The Optimal Duration Of Asa Treatment After Acute Phase Of Kawasaki Disease Based On Inflammatory Markers
Authors: Jae-won Yoo, ji mok kim, Hong Ryang Kil
Journal: Circulation (2015)

Purpose: Outcomes of Kawasaki disease (KD) are determined by the development of cardiovascular complications. Low dose aspirin(ASA) treatment is used as antithrombotic effect after acute phase of KD for 6-8 weeks.There are no standardized inflammatory markers used as guidance for completing low dose ASA treatment. The optimal duration of low dose ASA treatment is not determined. The aim of this study is to decide the duration of low dose ASA treatment based on inflammatory markers. Methods : We enrolled 80 KD children admitted to the Chungnam National University Hospital,South Korea between Sep 2012 and May 2014. We reviewed the medical records for clinical characteristics, duration of fever, cardiovascular complications and laboratory data on admission. Inflammatory markers were measured every 7-14 days at OPD after immunoglobulin(IVIG) and high dose ASA treatment in acute phase. Low dose ASA was stopped when the level of inflammatory markers were down to the normal without any cardiovascular complications. Echocardiograms were performed at admission, discharge and prior to completion of ASA treatment when the inflammatory marker turned to normal. Results : 80 KD patients,(Complete, n=44; Incomplete, n=36). The incidence of cardiovascular complications was similar both two groups. No significant differences in the laboratory studies either complete or incomplete KD. The levels of inflammatory marker were normalize after the acute phase as 13.0±13.6 days for platelets, 13.8± 8.3 days for CRP, 14.4±9.6 days for d-dimer, and 24.1 ± 10.5 days for ESR. The levels of platelets and CRP were first normalized within 2 weeks, and that of ESR was last within 3-4 weeks. The duration of raised CRP levels showed significantly shorter in incomplete group compared to complete groups (p=0.02). No new coronary lesions were developed among patients who didn’t have the coronary lesions at subacute phase. Conclusion: The majority of the inflammatory marker levels were normalized within 2-3 weeks after acute phase of KD. There were no new cardiovascular complications when the duration of low dose ASA treatment was guided by level of the inflammatory markers. So, the optimal duration of low dose ASA treatment can be reduced to 3-4 weeks without development of coronary lesions.
Trb3 controls mesenchymal stem cell lineage fate and enhances bone regeneration by scaffold-mediated local gene delivery
Authors: Jiabing Fan, Chung-Sung Lee, Soyon Kim, Xiao Zhang, Joan Pi-Anfruns, Mian Guo, Chen Chen, Matthew Rahnama, Jiong Li, Benjamin M. Wu, Tara L. Aghaloo, Min Lee
Journal: Biomaterials (2020)
Self-reported Cannabidiol (CBD) Use for Conditions With Proven Therapies
Authors: Eric C. Leas, Erik M. Hendrickson, Alicia L. Nobles, Rory Todd, Davey M. Smith, Mark Dredze, John W. Ayers
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Use of cannabidiol (CBD) has markedly increased in the past 5 years, concurrent with marketing claims that over-the-counter CBD can be used to treat almost any health condition. However, the reasons why individuals use CBD remain unclear. <h3>Objective</h3> To assess whether individuals are using CBD for diagnosable conditions that have evidence-based therapies. <h3>Design, Setting, and Participants</h3> This case series assessed claimed treatment applications reported by CBD users in public testimonials shared on the Reddit forum r/CBD. The r/CBD forum was selected because it includes a large, naturally occurring sample of 104 917 registered individuals who publicly discuss their experiences using CBD. All r/CBD posts were obtained from January 1, 2014, through August 31, 2019. A random sample of posts was drawn (n = 3000) and filtered to include posts in which self-identified CBD users testified why they take CBD (n = 376). <h3>Exposures</h3> Self-reported use of CBD for medicinal purposes. <h3>Main Outcomes and Measures</h3> Cannabidiol testimonials were divided into 11 subcategories corresponding with the condition's medical subspecialty and 2 subcategories corresponding with wellness benefits. Posts were allowed to receive more than 1 label. <h3>Results</h3> Of the 376 posts labeled as testimonials, 90.0% (95% CI, 86.8%-92.8%) of testimonials claimed that CBD treated the individual's diagnosable conditions. Psychiatric conditions (eg, autism or depression) were the most frequently cited subcategory, mentioned in 63.9% (95% CI, 59.0%-69.1%) of testimonials, followed by orthopedic (26.4%; 95% CI, 21.8%-31.1%), sleep (14.6%; 95% CI, 11.3%-18.5%), and neurological (6.9%; 95% CI, 4.4%-9.6%) conditions. Testimonials also claimed that CBD treated gastroenterological conditions (3.9%; 95% CI, 1.9%-6.1%), as well as addiction, cardiological, dermatological, ophthalmological, oral health, and sexual health conditions (&lt;2.0% each). By contrast, just 29.5% (95% CI, 24.8%-34.2%) of testimonies claimed any wellness benefit, with most citing mental wellness (eg, "quieting my mind") (29.5% [95% CI, 24.2%-34.4%]); 1.4% (95% CI, 0.3%-2.8%) claimed a physical wellness benefit (eg, "exercise performance"). <h3>Conclusions and Relevance</h3> The findings of this case series suggest a need for regulation of factors associated with CBD being used to treat diagnosable conditions, engagement of health care professionals with patients on their potential CBD use, and implementation of public health campaigns that encourage the public to seek treatment advice from health care professionals regarding evidence-based therapies.
Characterising neuropsychiatric disorders in patients with COVID-19
Authors: Mark A Oldham, Arjen J C Slooter, Colm Cunningham, Shibley Rahman, Daniel Davis, Emma R L C Vardy, Flavia B Garcez, Karin J Neufeld, Roberta Esteves Vieira de Castro, E Wesley Ely, Alasdair MacLullich
Journal: The Lancet Psychiatry (2020)
Midwives and paramedics can deliver flu and covid vaccines after new laws come into force
Authors: Elisabeth Mahase
Journal: BMJ (2020)

A wider range of healthcare workers—including midwives, paramedics, physiotherapists, and pharmacists—are now allowed to give flu and potentially covid-19 vaccines after the introduction of new laws by the UK government.

The changes to the Human Medicines Regulations 2012, first proposed in August1 and consulted upon last month, came into effect on 16 October.2

The Department of Health and Social Care said that the expanded workforce will have to undergo additional training to ensure patient safety. It added that government planning …
A Hyperactive RelA/p65-Hexokinase 2 Signaling Axis Drives Primary Central Nervous System Lymphoma
Authors: Kensuke Tateishi, Yohei Miyake, Masahito Kawazu, Nobuyoshi Sasaki, Taishi Nakamura, Jo Sasame, Yukie Yoshii, Toshihide Ueno, Akio Miyake, Jun Watanabe, Yuko Matsushita, Norio Shiba, Naoko Udaka, Kentaro Ohki, Alexandria L. Fink, Shilpa S. Tummala, Manabu Natsumeda, Naoki Ikegaya, Mayuko Nishi, Makoto Ohtake, Ryohei Miyazaki, Jun Suenaga, Hidetoshi Murata, Ichio Aoki, Julie J. Miller, Yukihiko Fujii, Akihide Ryo, Shoji Yamanaka, Hiroyuki Mano, Daniel P. Cahill, Hiroaki Wakimoto, Andrew S. Chi, Tracy T. Batchelor, Motoo Nagane, Koichi Ichimura, Tetsuya Yamamoto
Journal: Cancer Research (2020)

Primary central nervous system lymphoma (PCNSL) is an isolated type of lymphoma of the central nervous system and has a dismal prognosis despite intensive chemotherapy. Recent genomic analyses have identified highly recurrent mutations of MYD88 and CD79B in immunocompetent PCNSL, whereas LMP1 activation is commonly observed in Epstein-Barr virus (EBV)-positive PCNSL. However, a lack of clinically representative preclinical models has hampered our understanding of the pathogenic mechanisms by which genetic aberrations drive PCNSL disease phenotypes. Here, we establish a panel of 12 orthotopic, patient-derived xenograft (PDX) models from both immunocompetent and EBV-positive PCNSL and secondary CNSL biopsy specimens. PDXs faithfully retained their phenotypic, metabolic, and genetic features, with 100% concordance of MYD88 and CD79B mutations present in PCNSL in immunocompetent patients. These models revealed a convergent functional dependency upon a deregulated RelA/p65-hexokinase 2 signaling axis, codriven by either mutated MYD88/CD79B or LMP1 with Pin1 overactivation in immunocompetent PCNSL and EBV-positive PCNSL, respectively. Notably, distinct molecular alterations used by immunocompetent and EBV-positive PCNSL converged to deregulate RelA/p65 expression and to drive glycolysis, which is critical for intracerebral tumor progression and FDG-PET imaging characteristics. Genetic and pharmacologic inhibition of this key signaling axis potently suppressed PCNSL growth in vitro and in vivo. These patient-derived models offer a platform for predicting clinical chemotherapeutics efficacy and provide critical insights into PCNSL pathogenic mechanisms, accelerating therapeutic discovery for this aggressive disease. SIGNIFICANCE: A set of clinically relevant CNSL xenografts identifies a hyperactive RelA/p65-hexokinase 2 signaling axis as a driver of progression and potential therapeutic target for treatment and provides a foundational preclinical platform. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/23/5330/F1.large.jpg.
Artemisinin Resistance in Plasmodium falciparum Malaria (vol 361, pg 455, 2009)
Authors: A M Dondorp, F Nosten, P Yi, D Das, A P Phyo, J Tarning, K M Lwin, F Ariey, W Hanpithakong, S J Lee, P Ringwald, K Silamut, M Imwong, K Chotivanich, P Lim, T Herdman, S S An, S Yeung, P Singhasivanon, Day Npj., N Lindegardh, D Socheat, N J White
Journal: New England Journal of Medicine (2009)