tbuckley/cabot-search huggingface dataset:
Patient partnership: a roundup from the BMJ patient advisory panel
Authors: Emma Doble, Henry Scowcroft
Journal: BMJ (2021)

The BMJ has long been committed to partnering with patients and the public. In 2014 it launched the patient partnership strategy, incorporating patient perspectives throughout the journal.1 This included embedding patient peer review in research, inviting patient authored content, and asking authors to seek patient input in their articles, as well as documenting their input—also known as co-production.2 While partnering with patients and the public is not a new concept, during the covid-19 pandemic much of that work in healthcare and research was abandoned, leaving patients feeling excluded, ignored, and forgotten.3 At The BMJ we wanted to ensure we continued pushing patient involvement at the journal during the pandemic, despite …
P-222 Dihydropyrimidine dehydrogenase deficiencies and fluoropyrimidine toxicities: A study in the Tunisian Center
Authors: R. Melliti, I. Belaid, M. Nouira, T. Ben Ahmed, I. Chabchoub, M. Hochlef, M. Ben Fredj, F. Ezzairi, N. Ammar, L. Ben Fatma, S. Saguem, S. Ben Ahmed
Journal: Annals of Oncology (2021)
Case 45-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Jeffrey B. Gould, Lawrence J. Minette
Journal: New England Journal of Medicine (1973)

Presentation of CaseAn infant girl, 10 hours of age, was admitted to the hospital because of respiratory distress.The child was born of an uncomplicated fifth pregnancy and delivered by cesarean section. The mother's blood group was A Rh +. At birth there were no spontaneous respirations. The infant was intubated, and ventilatory assistance was given. Her first spontaneous breath was at two minutes, and she was extubated at five minutes. Mild respiratory distress was observed, with flaring of the alae nasi and sternal retraction. An umbilical-artery catheter was passed. A specimen of arterial blood, drawn with the baby . . .
Prognostic Utility of Breast Cancer Index to Stratify Distant Recurrence Risk in Invasive Lobular Carcinoma
Authors: Raquel Nunes, Tal Sella, Kai Treuner, Jennifer M. Atkinson, Jenna Wong, Yi Zhang, Pedro Exman, David Dabbs, Andrea L. Richardson, Catherine A. Schnabel, Dennis C. Sgroi, Steffi Oesterreich, Ashley Cimino-Mathews, Otto Metzger
Journal: Clinical Cancer Research (2021)

The prognostic utility of Breast Cancer Index (BCI) for risk assessment of overall (0-10 years), early (0-5 years), and late (5-10 years) distant recurrence (DR) in hormone receptor-positive (HR+) invasive lobular carcinoma (ILC) was evaluated.BCI gene expression analysis was performed blinded to clinical outcome utilizing tumor specimens from patients with HR+ ILC from a multi-institutional cohort. The primary endpoint was time to DR. Kaplan-Meier analyses of overall, early, and late DR risk were performed, and statistical significance was evaluated by log-rank test and Cox proportional hazards regression. The prognostic contribution of BCI in addition to clinicopathologic factors was evaluated by likelihood ratio analysis.Analysis of 307 patients (99% ER+, 53% T1, 42% N+, 70% grade II) showed significant differences in DR over 10 years based on BCI risk categories. BCI low- and intermediate-risk patients demonstrated similar DR rates of 7.6% and 8.0%, respectively, compared with 27.0% for BCI high-risk patients. BCI was a significant independent prognostic factor for overall 10-year DR [HR = 4.09; 95% confidence interval (CI), 2.00-8.34; P = 0.0001] as well as for both early (HR = 8.19; 95% CI, 1.85-36.30; P = 0.0042) and late (HR = 3.04; 95% CI, 1.32-7.00; P = 0.0224) DR. In multivariate analysis, BCI remained the only statistically significant prognostic factor for DR (HR = 3.49; 95% CI, 1.28-9.54; P = 0.0150).BCI is an independent prognostic factor for ILC and significantly stratified patients for cumulative risk of 10-year, early, and late DR. BCI added prognostic value beyond clinicopathologic characteristics in this distinct subtype of breast cancer.
Decoding distinctive features of plasma extracellular vesicles in amyotrophic lateral sclerosis
Authors: Laura Pasetto, Stefano Callegaro, Alessandro Corbelli, Fabio Fiordaliso, Deborah Ferrara, Laura Brunelli, Giovanna Sestito, Roberta Pastorelli, Elisa Bianchi, Marina Cretich, Marcella Chiari, Cristina Potrich, Cristina Moglia, Massimo Corbo, Gianni Sorarù, Christian Lunetta, Andrea Calvo, Adriano Chiò, Gabriele Mora, Maria Pennuto, Alessandro Quattrone, Francesco Rinaldi, Vito Giuseppe D’Agostino, Manuela Basso, Valentina Bonetto
Journal: Molecular Neurodegeneration (2021)

Amyotrophic lateral sclerosis (ALS) is a multifactorial, multisystem motor neuron disease for which currently there is no effective treatment. There is an urgent need to identify biomarkers to tackle the disease's complexity and help in early diagnosis, prognosis, and therapy. Extracellular vesicles (EVs) are nanostructures released by any cell type into body fluids. Their biophysical and biochemical characteristics vary with the parent cell's physiological and pathological state and make them an attractive source of multidimensional data for patient classification and stratification.We analyzed plasma-derived EVs of ALS patients (n = 106) and controls (n = 96), and SOD1G93A and TDP-43Q331K mouse models of ALS. We purified plasma EVs by nickel-based isolation, characterized their EV size distribution and morphology respectively by nanotracking analysis and transmission electron microscopy, and analyzed EV markers and protein cargos by Western blot and proteomics. We used machine learning techniques to predict diagnosis and prognosis.Our procedure resulted in high-yield isolation of intact and polydisperse plasma EVs, with minimal lipoprotein contamination. EVs in the plasma of ALS patients and the two mouse models of ALS had a distinctive size distribution and lower HSP90 levels compared to the controls. In terms of disease progression, the levels of cyclophilin A with the EV size distribution distinguished fast and slow disease progressors, a possibly new means for patient stratification. Immuno-electron microscopy also suggested that phosphorylated TDP-43 is not an intravesicular cargo of plasma-derived EVs.Our analysis unmasked features in plasma EVs of ALS patients with potential straightforward clinical application. We conceived an innovative mathematical model based on machine learning which, by integrating EV size distribution data with protein cargoes, gave very high prediction rates for disease diagnosis and prognosis.
Limited evolution of the actionable metastatic cancer genome under therapeutic pressure
Authors: Joris van de Haar, Louisa R. Hoes, Paul Roepman, Martijn P. Lolkema, Henk M. W. Verheul, Hans Gelderblom, Adrianus J. de Langen, Egbert F. Smit, Edwin Cuppen, Lodewyk F. A. Wessels, Emile E. Voest
Journal: Nature Medicine (2021)
Patient‐reported neurocognitive symptoms influence instrumental activities of daily living in sickle cell disease
Authors: Jennifer N. Longoria, Norma L. Pugh, Victor Gordeuk, Lewis L. Hsu, Marsha Treadwell, Allison A. King, Robert Gibson, Mariam Kayle, Nancy Crego, Jeffrey Glassberg, Cathy L. Melvin, Jane S. Hankins, Jerlym Porter
Journal: American Journal of Hematology (2021)

Individuals with sickle cell disease (SCD) experience neurocognitive decline, low medication adherence, increased unemployment, and difficulty with instrumental activities of daily living (IADL). The relationship between self-perceived cognitive difficulties and IADLs, including employment, school enrollment, independence, engagement in leisure activities, and medication adherence is unknown. We hypothesized that self-reported difficulties across neurocognitive areas would predict lower IADL skills. Adolescent and adult participants of the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) (n = 2436) completed patient-reported outcome (PRO) measures of attention, executive functioning, processing speed, learning, and comprehension. Cognitive symptoms were analyzed as predictors in multivariable modeling. Outcome variables included 1) an IADL composite that consisted of employment, participation in school, reliance on others, and leisure pursuits, and 2) hydroxyurea adherence. Participants reported cognitive difficulty across areas of attention (55%), executive functioning (51%), processing speed (57%), and reading comprehension (65%). Executive dysfunction (p < 0.001) and sometimes or often experiencing learning difficulties (p < 0.001 and p = 0.04) and poor comprehension (p = 0.000 and p = 0.001), controlled for age (p < 0.001), pain (p < 0.001), and hydroxyurea use (p = 0.001), were associated with poor IADL skills. Executive functioning difficulties (p = 0.021), controlled for age (p = 0.013 for ages 25-34), genotype (p = 0.001), and hemoglobin (p = 0.004), predicted hydroxyurea non-adherence. Analysis of PRO measures indicated that cognitive dysfunction is prevalent in adolescents and adults with SCD. Cognitive dysfunction translated into clinically meaningful outcomes. PRO of cognitive symptoms can be used as an important adjunct clinical tool to monitor symptoms that impact functional skills, including engagement in societal activities and medication adherence.
Chimeric antigen receptor T cells for gamma–delta T cell malignancies
Authors: P. A. Wawrzyniecka, L. Ibrahim, G. Gritti, M. A. Pule, P. M. Maciocia
Journal: Leukemia (2021)

Cancers derived from the malignant transformation of gamma-delta (γδ) T cells carry very poor prognosis.The major pathologies recognised are γδ T acute lymphoblastic leukaemia (γδ T-ALL), and two lymphoma subtypes: hepatosplenic T cell lymphoma (HSTL) and primary cutaneous γδ T cell lymphoma (PCγδ-TCL) [1].γδ T-ALL represents approximately 10% of cases of T-ALL and is associated with high rates of induction failure, relapse and excess mortality [2].HSTL is a rare (approximately 3% of cases of T cell lymphoma [1]) but highly aggressive disorder, which typically presents in males in the 2nd or 3rd decade of life, often in association with immunosuppressive therapy [3].It carries the worst prognosis of all lymphoma subtypes, with a median survival of only 6-8 months [4] and only isolated cases of long-term survival [5].PCγδ-TCL is also rare (approximately 1% of skin lymphomas [1]) and presents with cutaneous involvement, typically associated with visceral and/or bone marrow disease.Again, outcomes are poor, with 75% 1-year mortality in the largest published case series [6].Treatment for γδ malignancies is with cytotoxic chemotherapy, with no tumour-specific therapies currently available.By contrast, in analogous B-cell malignancies, highly effective immunotherapies, including monoclonal antibodies, bispecific T cell engagers and chimeric antigen receptor (CAR)-T cells [7] are available.These therapies have revolutionised the treatment and outcome of advanced B-cell malignancies.CAR-T cells against CD19 in particular have demonstrated the potential to induce longlasting complete remissions even in patients with advanced and refractory cancers [7].For γδ malignancies, the defining immunophenotypic characteristic is expression of the γδ T cell receptor (TCR), present in >95% of cases of HSTL and in all PCγδ-TCL and γδ T-ALL [3].Importantly, in normal tissues expression is limited to γδ T cells, where it functions as the antigen recognition receptor.Here, we developed CAR-T cells targeting the γδ TCR and demonstrate in vitro and in vivo efficacy against γδ T cell malignancies.Our data offers proof-of-concept for γδ TCR-targeting with CAR-T cells as a potential approach to bring highly potent immunotherapy to the treatment of γδ malignancies.Primary αβ T cells were retrovirally transduced to express anti-γδ TCR CAR or control anti-CD19 CAR (Fig. 1a).Following
Alterations in the gut microbiota contribute to cognitive impairment induced by the ketogenic diet and hypoxia
Authors: Christine A. Olson, Alonso J. Iñiguez, Grace E. Yang, Ping Fang, Geoffrey N. Pronovost, Kelly G. Jameson, Tomiko K. Rendon, Jorge Paramo, Jacob T. Barlow, Rustem F. Ismagilov, Elaine Y. Hsiao
Journal: Cell Host & Microbe (2021)
Induction and expansion of human PRRX1+ limb-bud-like mesenchymal cells from pluripotent stem cells
Authors: Daisuke Yamada, Masahiro Nakamura, Tomoka Takao, Shota Takihira, Aki Yoshida, Shunsuke Kawai, Akihiro Miura, Lu Ming, Hiroyuki Yoshitomi, Mai Gozu, Kumi Okamoto, Hironori Hojo, Naoyuki Kusaka, Ryosuke Iwai, Eiji Nakata, Toshifumi Ozaki, Junya Toguchida, Takeshi Takarada
Journal: Nature Biomedical Engineering (2021)
Efficacy and safety of apremilast in patients with mild-to-moderate plaque psoriasis: Results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial
Authors: Linda Stein Gold, Kim Papp, David Pariser, Lawrence Green, Neal Bhatia, Howard Sofen, Lorne Albrecht, Melinda Gooderham, Mindy Chen, Maria Paris, Yao Wang, Kristina Callis Duffin
Journal: Journal of the American Academy of Dermatology (2021)
Abstract 15850: Midlife Fitness and the Development of Chronic Conditions in the Elderly: Findings From the Cooper Center Longitudinal Study
Authors: Benjamin L Willis, Ang Gao, David Leonard, Laura DeFina, William Haskell, Amit Khera, Jarett Berry
Journal: Circulation (2011)

Background: Cardiorespiratory fitness (fitness) is associated with cardiovascular disease (CVD) mortality and all-cause mortality. However, the association between fitness and the development of no...
Scotland intends to set up safe spaces for drug users in defiance of UK government
Authors: Bryan Christie
Journal: BMJ (2021)

The Scottish government is set to override UK opposition and set up safe consumption rooms where illicit drugs can be used under supervision.

It is part of Scotland’s response to rising numbers of drug related deaths that have left it with the highest death rate in the whole of Europe. Some 1339 people died from drug overdoses in 2020—up 5% on 2019 and more than three times the rate in England and Wales.1

There have been plans since 2018 …
Mapping the genetic architecture of human traits to cell types in the kidney identifies mechanisms of disease and potential treatments
Authors: Xin Sheng, Yuting Guan, Ziyuan Ma, Junnan Wu, Hongbo Liu, Chengxiang Qiu, Steven Vitale, Zhen Miao, Matthew J. Seasock, Matthew Palmer, Myung K. Shin, Kevin L. Duffin, Steven S. Pullen, Todd L. Edwards, Jacklyn N. Hellwege, Adriana M. Hung, Mingyao Li, Benjamin F. Voight, Thomas M. Coffman, Christopher D. Brown, Katalin Susztak
Journal: Nature Genetics (2021)
Framing climate change as a human health issue: enough to tip the scale in climate policy?
Authors: Verena Rossa-Roccor, Amanda Giang, Paul Kershaw
Journal: The Lancet Planetary Health (2021)

Almost four decades of climate science have not yet led to transformative policy change at the pace and scale required to confront the climate crisis. Colleagues in the planetary health community attribute much potential to framing climate change as human health issue in order to create greater impact on policy makers. In this Personal View, we discuss the promise and limitations of this approach by drawing on insights from political science and public policy with regards to the complexity of these contentious policy issues. We argue that we, as academics, have a moral obligation to embrace an active role in the knowledge-to-action (KTA) sphere and that we would be well advised to expand our KTA approach to include evidence-based strategies, such as lobbying or civil resistance. As scientists, we can no longer wait to embrace the realpolitik insights of political science to move our evidence into policy action.
Impact of Yondeli (TM) (trabectedin, ET-743) in the natural history of patients (pts) with pretreated advanced soft tissue sarcomas (PASTS): Long term follow-up results.
Authors: A Lecesne, G Demetri, JL Misset, J Blay, I Judson, A Yovine, A Van Oosterom, J Radford, J Verweij, R Maki, E Brain, P Herait, MA Izquierdo, J Gomez, A Nieto, J Saro, J Jimeno
Journal: Clinical Cancer Research (2003)
Parents of brain damaged girl enlist US and Israeli politicians to maintain treatment as legal options run out
Authors: Clare Dyer
Journal: BMJ (2021)

The parents of a two year old girl with serious brain damage have enlisted politicians in the US and Israel to lobby the UK government after exhausting the available legal remedies in their bid to stop doctors withdrawing life sustaining treatment.

Mr Justice MacDonald ruled in the High Court last May that Alta Fixsler, who suffered a severe hypoxic brain injury at birth, has no hope of improvement, that she suffers consistent pain, and that it would be in her best interests to be allowed to die.

She is cared for in a hospital run by Manchester University NHS Foundation Trust, where she is mechanically ventilated with a tracheostomy and fed by a tube. Her parents, Hasidic Jews and Israeli citizens who moved to the UK in 2014, want to take her to a hospital in …
Impacts of Healthy Aging and Gender on Left Atrial Structure, Function and Pulmonary Capillary Wedge Pressure: Speckle Tracking Echocardiography Study
Authors: Yoshizane Takashi, Kawasaki Masanori, Tanaka Ryuhei, Minatoguchi Shingo, Ishiguro Maya, Miwa Hirotaka, Ono Koji, Tanihata Shintaro, Arai Masazumi, Noda Toshiyuki, Minatoguchi Shinya
Journal: Circulation (2016)
Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer
Authors: Dongqiang Zeng, Jiani Wu, Huiyan Luo, Yong Li, Jian Xiao, Jianjun Peng, Zilan Ye, Rui Zhou, Yunfang Yu, Gaofeng Wang, Na Huang, Jianhua Wu, Xiaoxiang Rong, Li Sun, Huiying Sun, Wenjun Qiu, Yichen Xue, Jianping Bin, Yulin Liao, Nailin Li, Min Shi, Kyoung-Mee Kim, Wangjun Liao
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Durable efficacy of immune checkpoint blockade (ICB) occurred in a small number of patients with metastatic gastric cancer (mGC) and the determinant biomarker of response to ICB remains unclear. Methods We developed an open-source TMEscore R package, to quantify the tumor microenvironment (TME) to aid in addressing this dilemma. Two advanced gastric cancer cohorts (RNAseq, N=45 and NanoString, N=48) and other advanced cancer (N=534) treated with ICB were leveraged to investigate the predictive value of TMEscore. Simultaneously, multi-omics data from The Cancer Genome Atlas of Stomach Adenocarcinoma (TCGA-STAD) and Asian Cancer Research Group (ACRG) were interrogated for underlying mechanisms. Results The predictive capacity of TMEscore was corroborated in patient with mGC cohorts treated with pembrolizumab in a prospective phase 2 clinical trial ( NCT02589496 , N=45, area under the curve (AUC)=0.891). Notably, TMEscore, which has a larger AUC than programmed death-ligand 1 combined positive score, tumor mutation burden, microsatellite instability, and Epstein-Barr virus, was also validated in the multicenter advanced gastric cancer cohort using NanoString technology (N=48, AUC=0.877). Exploration of the intrinsic mechanisms of TMEscore with TCGA and ACRG multi-omics data identified TME pertinent mechanisms including mutations, metabolism pathways, and epigenetic features. Conclusions Current study highlighted the promising predictive value of TMEscore for patients with mGC. Exploration of TME in multi-omics gastric cancer data may provide the impetus for precision immunotherapy.
Dialysis and Total Health Care Costs in the United States and Worldwide: The Financial Impact of a Single-Payer Dominant System in the US
Authors: Benjamin M. Pockros, Daniel J. Finch, Daniel E. Weiner
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement In the United States, dialysis provision is an example of a robust, single-payer dominant system with cost containment. When compared with the cost of dialysis in other countries, Medicare dialysis costs in the United States as a function of overall health care expenditures are approximately $60,000 per patient less than expected, likely due to substantial cost containment imposed by Medicare as the dominant payer.
New Vistas for Cell-Surface GlycoRNAs
Authors: Sigrid Nachtergaele, Yamuna Krishnan
Journal: New England Journal of Medicine (2021)

Discoveries in noncoding RNA have shown it to be remarkably diverse in function and form and to have relevance in drug development. A recent study showed that some noncoding RNAs are glycosylated and sialylated and expressed on the surface of the plasma membrane. Moreover, some interact with Siglec-15, an immune suppressor that is up-regulated in human cancer cells and tumor-infiltrating myeloid cells.
CONSCIENTIOUS OBJECTORS.
Journal: JAMA (1899)

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Self-harm among children and adolescents by ethnic group: an observational cohort study of hospital presentations, characteristics, and outcomes from the Multicentre Study of Self-Harm in England
Authors: B Farooq, C Clements, K Hawton, G Geulayov, D Casey, K Waters, J Ness, A Patel, S Kelly, E Townsend, L Appleby, N Kapur
Journal: The Lancet Child & Adolescent Health (2021)