tbuckley/cabot-search huggingface dataset:
Association between Initiation of Pulmonary Rehabilitation and Rehospitalizations in Patients Hospitalized with Chronic Obstructive Pulmonary Disease
Authors: Mihaela S. Stefan, Penelope S. Pekow, Aruna Priya, Richard ZuWallack, Kerry A. Spitzer, Tara C. Lagu, Quinn R. Pack, Victor M. Pinto-Plata, Kathleen M. Mazor, Peter K. Lindenauer
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Although clinical trials have found that pulmonary rehabilitation (PR) can reduce the risk of readmissions after hospitalization for a chronic obstructive pulmonary disease (COPD) exacerbation, less is known about PR’s impact in routine clinical practice. Objectives: To evaluate the association between initiation of PR within 90 days of discharge and rehospitalization(s). Methods: We analyzed a retrospective cohort of Medicare beneficiaries (66 years of age or older) hospitalized for COPD in 2014 who survived at least 30 days after discharge. Measurements and Main Results: We used propensity score matching and estimated the risk of recurrent all-cause rehospitalizations at 1 year using a multistate model to account for the competing risk of death. Of 197,376 total patients hospitalized in 4,446 hospitals, 2,721 patients (1.5%) initiated PR within 90 days of discharge. Overall, 1,534 (56.4%) patients who initiated PR and 125,720 (64.6%) who did not were rehospitalized one or more times within 1 year of discharge. In the propensity-score–matched analysis, PR initiation was associated with a lower risk of readmission in the year after PR initiation (hazard ratio, 0.83; 95% confidence interval, 0.77–0.90). The mean cumulative number of rehospitalizations at 1 year was 0.95 for those who initiated PR within 90 days and 1.15 for those who did not (P < 0.001). Conclusions: After hospitalization for COPD, Medicare beneficiaries who initiated PR within 90 days of discharge experienced fewer rehospitalizations over 1 year. These results support findings from randomized controlled clinical trials and highlight the need to identify effective strategies to increase PR participation.
Temporal Trends, Characteristics, and Citations of Retracted Articles in Cardiovascular Medicine
Authors: Raoul R. Wadhwa, Chandruganesh Rasendran, Zoran B. Popovic, Steven E. Nissen, Milind Y. Desai
Journal: JAMA Network Open (2021)

This systematic review examines temporal trends of retractions in cardiology literature and assesses their effect.
New mental health waiting time targets to be introduced in England
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The NHS has announced plans to introduce five new waiting time targets for mental health services in England in a bid to improve access to care.

The proposed new standards,1 which are subject to a consultation,2 would guarantee that patients across all age groups requiring urgent care will be seen by community mental health crisis teams within 24 hours of referral, with the most urgent patients receiving help within four hours.

Patients referred from emergency departments will be seen face-to-face within one hour by mental health liaison services or children and young people‘s equivalent …
Magnetic Resonance Imaging Detects Progression of Lung Disease and Impact of Newborn Screening in Preschool Children with Cystic Fibrosis
Authors: Mirjam Stahl, Eva Steinke, Simon Y. Graeber, Cornelia Joachim, Christoph Seitz, Hans-Ulrich Kauczor, Monika Eichinger, Susanne Hämmerling, Olaf Sommerburg, Mark O. Wielpütz, Marcus A. Mall
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Previous cross-sectional studies have demonstrated that chest magnetic resonance imaging (MRI) is sensitive to detect early lung disease in infants and preschool children with cystic fibrosis (CF) without radiation exposure. However, the ability of MRI to detect the progression of lung disease and the impact of early diagnosis in preschool children with CF remains unknown. Objectives: To investigate the potential of MRI to detect progression of early lung disease and impact of early diagnosis by CF newborn screening (NBS) in preschool children with CF. Methods: An annual MRI was performed from diagnosis over 4 years in a cohort of 96 preschool children with CF (age, 0-4 yr) who received concurrent diagnoses on the basis of NBS (n = 28) or clinical symptoms (n = 68). MRI scans were evaluated using a dedicated morphofunctional score, and the relationship between longitudinal MRI score and respiratory symptoms, pulmonary exacerbations, upper airway microbiology, and mode of diagnosis was determined. Measurements and Main Results: The MRI global score increased in the total cohort of children with CF during preschool years (P < 0.001) and was associated with cough, pulmonary exacerbations (P < 0.0001), and the detection of Staphylococcus aureus and Haemophilus influenzae (P < 0.05). MRI-defined abnormalities in lung morphology-especially airway wall thickening/bronchiectasis-were lower in children with CF diagnosed by NBS than in children with clinically diagnosed CF throughout the observation period (P < 0.01). Conclusions: MRI detected progression of early lung disease and benefits of early diagnosis by NBS in preschool children with CF. These findings support MRI as a sensitive outcome measure for diagnostic monitoring and early intervention trials in preschool children with CF. Clinical trial registered with www.clinicaltrials.gov (NCT02270476).
Targeting multiple cell death pathways extends the shelf life and preserves the function of human and mouse neutrophils for transfusion
Authors: Yuping Fan, Yan Teng, Fabien Loison, Aiming Pang, Anongnard Kasorn, Xinqi Shao, Cunling Zhang, Qian Ren, Hongbo Yu, Yi Zheng, Jose A. Cancelas, John Manis, Li Chai, Shin-Young Park, Li Zhao, Yuanfu Xu, Sizhou Feng, Leslie E. Silberstein, Fengxia Ma, Hongbo R. Luo
Journal: Science Translational Medicine (2021)

Survival of neutrophils is prolonged, and their function is preserved by simultaneously targeting multiple cell death pathways.
The P2X4 purinergic receptor has emerged as a potent regulator of hematopoietic stem/progenitor cell mobilization and homing—a novel view of P2X4 and P2X7 receptor interaction in orchestrating stem cell trafficking
Authors: Mateusz Adamiak, Kamila Bujko, Arjun Thapa, Valentina Pensato, Katarzyna Brzezniakiewicz-Janus, Janina Ratajczak, Daryl L. Davies, Henning Ulrich, Magda Kucia, Mariusz Z. Ratajczak
Journal: Leukemia (2021)
MO10-1 Safety of immune checkpoint inhibitors in patients with advanced malignancy complicated with rheumatoid arthritis
Authors: Keita Kudo, Saki Nakajima, Shigeya Uejima, Tetsuya Horiuchi, Fumihiko Nakanishi, Takuhide Utunomiya, Mai Kakiuchi, Mami Yamaguchi, Shiro Ohshima
Journal: Annals of Oncology (2021)
Quarterly versus annual ECG screening for atrial fibrillation in older Chinese individuals (AF-CATCH): a prospective, randomised controlled trial
Authors: Wei Zhang, Yi Chen, Chao-Ying Miao, Qi-Fang Huang, Chang-Sheng Sheng, Shuai Shao, Dian Wang, Shao-Kun Xu, Lei Lei, Di Zhang, Yi-Lin Chen, Lei-Xiao Hu, Jia-Hui Xia, Xiao-Fei Ye, Yi-Bang Cheng, Ying Wang, Qian-Hui Guo, Yan Li, Nicole Lowres, Ben Freedman, Ji-Guang Wang
Journal: The Lancet Healthy Longevity (2021)
Development Over Time of the Population-Attributable Risk Fraction for Cannabis Use Disorder in Schizophrenia in Denmark
Authors: Carsten Hjorthøj, Christine Merrild Posselt, Merete Nordentoft
Journal: JAMA Psychiatry (2021)

Cannabis use and potency of cannabis have increased during the past 2 decades. If the association between cannabis use and schizophrenia is causal, this should be reflected in an increase in the proportion of cases of schizophrenia being attributable to cannabis, the population-attributable risk fraction (PARF).To determine whether the PARF for cannabis use disorder in schizophrenia has increased over time.This nationwide, register-based historical prospective cohort study included all people in Denmark born before December 31, 2000, who were alive and 16 years or older at some point from January 1, 1972, to December 31, 2016. Data analysis was performed from August 2020 to April 2021.Diagnosis of cannabis use disorder.Diagnosis of schizophrenia, with estimated PARF of cannabis use disorder in schizophrenia from 1972 to 2016.A total of 7 186 834 individuals were included in the analysis, including 3 595 910 women (50.0%) and 3 590 924 men (50.0%). The adjusted hazard ratio for schizophrenia fluctuated at approximately 4 (with 95% CIs ranging from approximately 3 to 6) throughout most of the study period when people diagnosed with cannabis use disorder were compared with those without cannabis use disorder. The PARF of cannabis use disorder in schizophrenia also fluctuated, but with clear evidence of an increase from 1995 (when the PARF was relatively stable around 2.0%, with a 95% CI of approximately 0.3% to either side) until reaching some stability around 6.0% to 8.0% (with a 95% CI of approximately 0.5% to either side) since 2010.The results from these longitudinal analyses show the proportion of cases of schizophrenia associated with cannabis use disorder has increased 3- to 4-fold during the past 2 decades, which is expected given previously described increases in the use and potency of cannabis. This finding has important ramifications regarding legalization and control of use of cannabis.
Correction to: The CXCL12gamma chemokine immobilized by heparan sulfate on stromal niche cells controls adhesion and mediates drug resistance in multiple myeloma
Authors: Zemin Ren, Hildo Lantermans, Annemieke Kuil, Willem Kraan, Fernando Arenzana-Seisdedos, Marie José Kersten, Marcel Spaargaren, Steven T. Pals
Journal: Journal of Hematology & Oncology (2021)

An amendment to this paper has been published and can be accessed via the original article.
FDA Approval Summary: Osimertinib for Adjuvant Treatment of Surgically Resected Non–Small Cell Lung Cancer, a Collaborative Project Orbis Review
Authors: Abigail L. Koch, Paz J. Vellanki, Nicole Drezner, Xiaoxue Li, Pallavi S. Mishra-Kalyani, Yuan Li Shen, Huiming Xia, Yangbing Li, Jiang Liu, Jeanne Fourie Zirkelbach, Elitza Palazov, Aleksandr Gamarian, Qiuyi Choo, Arūnas Girčys, Ulrich-Peter Rohr, Nataliya Fesenko, Dianne Spillman, Richard Pazdur, Julia A. Beaver, Harpreet Singh
Journal: Clinical Cancer Research (2021)

On December 18, 2020, the FDA approved osimertinib as adjuvant therapy in patients with non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) mutations, as detected by an FDA-approved test. The approval was based on the ADAURA study, in which 682 patients with NSCLC were randomized to receive osimertinib (n = 339) or placebo (n = 343). Disease-free survival (DFS) in the overall population (stage IB-IIIA) was improved for patients who received osimertinib, with an HR of 0.20; 95% confidence interval (CI), 0.15-0.27; P < 0.0001. Median DFS was not reached for the osimertinib arm compared with 27.5 months (95% CI, 22.0-35.0) for patients receiving placebo. Overall survival data were not mature at the time of the approval. This application was reviewed under FDA's Project Orbis, in collaboration with Australia Therapeutic Goods Administration, Brazil ANVISA, Health Canada, Singapore Health Sciences Authority, Switzerland Swissmedic, and the United Kingdom Medicines and Healthcare products Regulatory Agency. This is the first targeted therapy adjuvant approval for NSCLC and has practice-changing implications.
P28-7 Effects of pemetrexed disodium heptahydrate on apoptosis and cell cycle arrest in PC9 cells
Authors: Md Mohiuddin, Hideharu Kimura, Takashi Sone, Hiroki Matsuoka, Keigo Saeki, Nanao Terada, Kazuo Kasahara
Journal: Annals of Oncology (2021)
An Appropriate Use of Accelerated Approval — Aducanumab for Alzheimer’s Disease
Authors: Billy Dunn, Peter Stein, Robert Temple, Patrizia Cavazzoni
Journal: New England Journal of Medicine (2021)

An Appropriate Use of Accelerated Approval The FDA decision to grant accelerated approval to aducanumab for Alzheimer’s disease fits squarely in the accelerated approval pathway, which was created ...
Serum levels of small HDL particles are negatively correlated with death or lung transplantation in an observational study of idiopathic pulmonary fibrosis
Authors: Amisha V. Barochia, Maryann Kaler, Nargues Weir, Elizabeth M. Gordon, Debbie M. Figueroa, Xianglan Yao, Merte Lemma WoldeHanna, Maureen Sampson, Alan T. Remaley, Geraldine Grant, Scott D. Barnett, Steven D. Nathan, Stewart J. Levine
Journal: European Respiratory Journal (2021)

Background Serum lipoproteins, such as high-density lipoproteins (HDL), may influence disease severity in idiopathic pulmonary fibrosis (IPF). Here, we investigated associations between serum lipids and lipoproteins and clinical end-points in IPF. Methods Clinical data and serum lipids were analysed from a discovery cohort (59 IPF subjects, 56 healthy volunteers) and validated using an independent, multicentre cohort (207 IPF subjects) from the Pulmonary Fibrosis Foundation registry. Associations between lipids and clinical end-points (forced vital capacity, 6-min walk distance, gender age physiology (GAP) index, death or lung transplantation) were examined using Pearson's correlation and multivariable analyses. Results Serum concentrations of small HDL particles measured using nuclear magnetic resonance spectroscopy (S-HDLP NMR ) correlated negatively with the GAP index in the discovery cohort of IPF subjects. The negative correlation of S-HDLP NMR with GAP index was confirmed in the validation cohort of IPF subjects. Higher levels of S-HDLP NMR were associated with lower odds of death or its competing outcome, lung transplantation (OR 0.9 for each 1-μmol·L −1 increase in S-HDLP NMR , p&lt;0.05), at 1, 2 and 3 years from study entry in a combined cohort of all IPF subjects. Conclusions Higher serum levels of S-HDLP NMR are negatively correlated with the GAP index, as well as with lower observed mortality or lung transplantation in IPF subjects. These findings support the hypothesis that S-HDLP NMR may modify mortality risk in patients with IPF.
Determining in which pre-arthritis stage HLA-shared epitope alleles and smoking exert their effect on the development of rheumatoid arthritis
Authors: Fenne Wouters, Marc P Maurits, Laurette van Boheemen, Marloes Verstappen, Kulveer Mankia, Xanthe M E Matthijssen, Annemarie L Dorjée, Paul Emery, Rachel Knevel, Dirkjan van Schaardenburg, René E M Toes, Annette H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2021)

Objectives The human leukocyte antigen-shared epitope (HLA-SE) alleles and smoking are the most prominent genetic and environmental risk factors for rheumatoid arthritis (RA). However, at which pre-arthritis stage (asymptomatic/symptomatic) they exert their effect is unknown. We aimed to determine whether HLA-SE and smoking are involved in the onset of autoantibody positivity, symptoms (clinically suspect arthralgia (CSA)) and/or progression to clinical arthritis. Methods We performed meta-analyses on results from the literature on associations of HLA-SE and smoking with anti-citrullinated protein antibodies (ACPAs) in the asymptomatic population. Next, we studied associations of HLA-SE and smoking with autoantibody positivity at CSA onset and with progression to clinical inflammatory arthritis (IA) during follow-up. Associations in ACPA-positive patients with CSA were validated in meta-analyses with other arthralgia cohorts. Analyses were repeated for rheumatoid factor (RF), anti-carbamylated protein antibodies (anti-CarP) and anti-acetylated protein antibodies (AAPA). Results Meta-analyses showed that HLA-SE is not associated with ACPA positivity in the asymptomatic population (OR 1.06 (95% CI:0.69 to 1.64)), whereas smoking was associated (OR 1.37 (95% CI: 1.15 to 1.63)). At CSA onset, both HLA-SE and smoking associated with ACPA positivity (OR 2.08 (95% CI: 1.24 to 3.49), OR 2.41 (95% CI: 1.31 to 4.43)). During follow-up, HLA-SE associated with IA development (HR 1.86 (95% CI: 1.23 to 2.82)), in contrast to smoking. This was confirmed in meta-analyses in ACPA-positive arthralgia (HR 1.52 (95% CI: 1.08 to 2.15)). HLA-SE and smoking were not associated with RF, anti-CarP or AAPA-positivity at CSA onset. Longitudinally, AAPA associated with IA development independent from ACPA and RF (HR 1.79 (95% CI: 1.02 to 3.16)), anti-CarP did not. Conclusions HLA-SE and smoking act at different stages: smoking confers risk for ACPA and symptom development, whereas HLA-SE mediates symptom and IA development. These data enhance the understanding of the timing of the key risk factors in the development of RA.
Circular RNA circIKBKB promotes breast cancer bone metastasis through sustaining NF-κB/bone remodeling factors signaling
Authors: Yingru Xu, Shuxia Zhang, Xinyi Liao, Man Li, Suwen Chen, Xincheng Li, Xingui Wu, Meisongzhu Yang, Miaoling Tang, Yameng Hu, Ziwen Li, Ruyuan Yu, Mudan Huang, Libing Song, Jun Li
Journal: Molecular Cancer (2021)

Breast cancer (BC) has a marked tendency to spread to the bone, resulting in significant skeletal complications and mortality. Recently, circular RNAs (circRNAs) have been reported to contribute to cancer initiation and progression. However, the function and mechanism of circRNAs in BC bone metastasis (BC-BM) remain largely unknown.Bone-metastatic circRNAs were screened using circRNAs deep sequencing and validated using in situ hybridization in BC tissues with or without bone metastasis. The role of circIKBKB in inducing bone pre-metastatic niche formation and bone metastasis was determined using osteoclastogenesis, immunofluorescence and bone resorption pit assays. The mechanism underlying circIKBKB-mediated activation of NF-κB/bone remodeling factors signaling and EIF4A3-induced circIKBKB were investigated using RNA pull-down, luciferase reporter, chromatin isolation by RNA purification and enzyme-linked immunosorbent assays.We identified that a novel circRNA, circIKBKB, was upregulated significantly in bone-metastatic BC tissues. Overexpressing circIKBKB enhanced the capability of BC cells to induce formation of bone pre-metastatic niche dramatically by promoting osteoclastogenesis in vivo and in vitro. Mechanically, circIKBKB activated NF-κB pathway via promoting IKKβ-mediated IκBα phosphorylation, inhibiting IκBα feedback loop and facilitating NF-κB to the promoters of multiple bone remodeling factors. Moreover, EIF4A3, acted acting as a pre-mRNA splicing factor, promoted cyclization of circIKBKB by directly binding to the circIKBKB flanking region. Importantly, treatment with inhibitor eIF4A3-IN-2 reduced circIKBKB expression and inhibited breast cancer bone metastasis effectively.We revealed a plausible mechanism for circIKBKB-mediated NF-κB hyperactivation in bone-metastatic BC, which might represent a potential strategy to treat breast cancer bone metastasis.
Unannotated small RNA clusters associated with circulating extracellular vesicles detect early stage liver cancer
Authors: Johann von Felden, Teresa Garcia-Lezana, Navneet Dogra, Edgar Gonzalez-Kozlova, Mehmet Eren Ahsen, Amanda Craig, Stacey Gifford, Benjamin Wunsch, Joshua T Smith, Sungcheol Kim, Jennifer E L Diaz, Xintong Chen, Ismail Labgaa, Philipp Haber, Reena Olsen, Dan Han, Paula Restrepo, Delia D'Avola, Gabriela Hernandez-Meza, Kimaada Allette, Robert Sebra, Behnam Saberi, Parissa Tabrizian, Amon Asgharpour, Douglas Dieterich, Josep M. Llovet, Carlos Cordon-Cardo, Ash Tewari, Myron Schwartz, Gustavo Stolovitzky, Bojan Losic, Augusto Villanueva
Journal: Gut (2021)

Surveillance tools for early cancer detection are suboptimal, including hepatocellular carcinoma (HCC), and biomarkers are urgently needed. Extracellular vesicles (EVs) have gained increasing scientific interest due to their involvement in tumour initiation and metastasis; however, most extracellular RNA (exRNA) blood-based biomarker studies are limited to annotated genomic regions.
Evaluation of comprehensive geriatric assessment impact in oncological decision-making process.
Authors: Clara Ejarque, Pablo Villace Gallego, Pablo Andreu, Sandra Soriano, Marta Rodríguez, Laura Medina, Teresa Bonfill, Julia Giner Joaquin, Paula Ribera Fernandez, Ismael Macias Declara, Laia Vilà, Enrique Gallardo Diaz, Miguel Angel Seguí-Palmer
Journal: Journal of Clinical Oncology (2021)

e24020 Background: Elderly patients (pts) diagnosed with cancer may present frailty conditions at baseline that could have a direct impact on tolerance and toxicity of oncological treatments (ttm). Comprehensive geriatric assessment (CGA) is considered a useful tool in the approach of these pts. CGA allows assessing functional reserve and potentially treatable comorbidities, leading to pt classification into 3 categories (fit, medium fit, unfit) before ttm decision. We evaluated the implantation of a CGA program in our center and its impact on ttm-decision and ttm-related toxicities. Furthermore, we evaluated survival outcomes. Methods: Retrospective, observational, single-institution analysis between 2017-2020. Pts ≥70 years with a cancer diagnosis and suspected frailty were evaluated by Oncogeriatry division before ttm decision. Pt characteristics at baseline (functional status [st], cognitive st, nutritional st, and comorbidity) were recorded. IBM SPSS Statistics software was used for statistical analysis. Variance analysis was calculated with Kolmogorov-Smirnov. Survival was calculated with Kaplan-Meier. Results: 147 pts were included (median [m] age 83 years). Referred pts presented good functional st (mBarthel Index 95), cognitive st (mMMSE 28, mMiniCog 3), and nutritional st (m abbreviated MNA13), and low comorbidity (mCharlson Index 1). After CGA, 49% pts were classified as fit, 28.6% as medium fit, and 22.4% as unfit. 71.4% pts received cancer-specific ttm (fit 91.6%, medium-fit 78.5%, unfit 18%). The correlation index between the initial ttm proposal and final ttm performed after CGA was 56.4% (76% in fit, 57.1% in medium-fit, and 12% in unfit). 18.4% of pts had ttm-related complications. 74 pts died during follow-up (34.7% fit, 59.5% medium fit, 72.7% unfit). 35.4% of deaths were related to cancer and 10.9% to comorbidity. Only 4 deaths were related to ttm. The median survival was 29 months (mo) in fit, 12.8 mo in medium-fit, and 8.5 mo in unfit pts. Conclusions: The majority of pts had preserved cognitive functions and low comorbidity, and were independent for daily-life activities. After CGA, almost 50% pts had modifications in their initial treatment strategy (higher rates in medium fit and unfit). Most fit pts received standard oncospecific ttm and had higher survival rates compared to unfit pts. These results show the relevance of geriatric approach in elderly cancer pts, which allows a personalized ttm.