tbuckley/cabot-search huggingface dataset:
Clinical Validation of a Multitarget Fecal Immunochemical Test for Colorectal Cancer Screening
Authors: Willemijn de Klaver, Pieter H.A. Wisse, Francine van Wifferen, Linda J.W. Bosch, Connie R. Jimenez, René W.M. van der Hulst, Remond J.A. Fijneman, Ernst J. Kuipers, Marjolein J.E. Greuter, Beatriz Carvalho, Manon C.W. Spaander, Evelien Dekker, Veerle M.H. Coupé, Meike de Wit, Gerrit A. Meijer
Journal: Annals of Internal Medicine (2021)

The fecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening, yet it leaves room for improvement.To develop a multitarget FIT (mtFIT) with better diagnostic performance than FIT.Diagnostic test accuracy study.Colonoscopy-controlled series.Persons (n = 1284) from a screening (n = 1038) and referral (n = 246) population were classified by their most advanced lesion (CRC [n = 47], advanced adenoma [n = 135], advanced serrated polyp [n = 30], nonadvanced adenoma [n = 250], and nonadvanced serrated polyp [n = 53]), along with control participants (n = 769).Antibody-based assays were developed and applied to leftover FIT material. Classification and regression tree (CART) analysis was applied to biomarker concentrations to identify the optimal combination for detecting advanced neoplasia. Performance of this combination, the mtFIT, was cross-validated using a leave-one-out approach and compared with FIT at equal specificity.The CART analysis showed a combination of hemoglobin, calprotectin, and serpin family F member 2-the mtFIT-to have a cross-validated sensitivity for advanced neoplasia of 42.9% (95% CI, 36.2% to 49.9%) versus 37.3% (CI, 30.7% to 44.2%) for FIT (P = 0.025), with equal specificity of 96.6%. In particular, cross-validated sensitivity for advanced adenomas increased from 28.1% (CI, 20.8% to 36.5%) to 37.8% (CI, 29.6% to 46.5%) (P = 0.006). On the basis of these results, early health technology assessment indicated that mtFIT-based screening could be cost-effective compared with FIT.Study population is enriched with persons from a referral population.Compared with FIT, the mtFIT showed better diagnostic accuracy in detecting advanced neoplasia because of an increased detection of advanced adenomas. Moreover, early health technology assessment indicated that these results provide a sound basis to pursue further development of mtFIT as a future test for population-based CRC screening. A prospective screening trial is in preparation.Stand Up to Cancer/Dutch Cancer Society, Dutch Digestive Foundation, and HealthHolland.
Abstract 9550: Regional Variation in Emergency Department Visits for Acute Myocardial Infarction - Nationwide Emergency Department Sample, 2008
Authors: Amy L Valderrama, Julie C Will, Paula W Yoon
Journal: Circulation (2011)

Background: For the majority of patients with acute myocardial infarction (AMI), the emergency department (ED) is the entry point into the healthcare system. Although previous studies have described regional differences in treatment for AMI, few studies have examined regional variations in ED visits for AMI. Objective: This study sought to describe variations in AMI visits to EDs by Census Bureau-designated regions of the U.S. in 2008 and to examine characteristics of those visits. Methods: ED data from the 2008 Nationwide Emergency Department Sample (NEDS) were analyzed. The NEDS is a stratified random probability sample of hospital-based EDs from community, non-rehabilitation hospitals in the U.S. SUDAAN was used to account for the complex sampling scheme. Only adults (aged ≥ 18 years) were included in the analysis. Visits for AMI were defined as the primary diagnosis listed as International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 410.xx, excluding cases for which the fifth digit was 2 which indicates further evaluation of a recent MI. Rates of AMI ED visits per population were calculated by region using U.S. Census estimates for 2008. Results: In 2008, adults made an estimated 98,515,683 ED visits. Of those, 537,167 (0.6%) had a primary diagnosis of AMI; 84% were admitted to the presenting hospital and 11% were transferred to another short-term hospital. Approximately 1% died in the ED. Men accounted for 59.6% of AMI ED visits. Persons aged ≥ 75 years accounted for 37.4% of AMI visits. More than half of visits (57.2%) were made by Medicare beneficiaries. The majority of visits were made to EDs in urban areas (79.4%). ED visit rates per 10,000 population for each region were: Northeast, 23.9 (95% confidence interval [CI]: 20.6-27.1); Midwest, 24.8 (95% CI: 22.1-27.4); South, 25.7 (95% CI: 23.1-28.2); West 17.9 (15.8-20.0). Women in the West had the lowest rate of AMI visits (13.8 per 10,000) compared to women and men in the other regions. Rates increased by age group for all regions. Conclusions: ED visits for AMI vary significantly by geographic region. The lowest rate of AMI visits per population was noted in the West. Further study is needed to identify the factors that cause these regional variations in ED visits.
Psoriasis-related treatment exposure and hospitalization or in-hospital mortality due to COVID-19 during the first and second wave of the pandemic: cohort study of 1 326 312 patients in France
Authors: L. Penso, R. Dray-Spira, A. Weill, M. Zureik, E. Sbidian
Journal: British Journal of Dermatology (2021)

Summary Background Data on treatment exposures for psoriasis and poor COVID-19 outcomes are limited. Objectives To assess the risk of hospitalization or in-hospital mortality due to COVID-19 by treatment exposure in patients with psoriasis. Methods All adults with psoriasis registered in the French national health-insurance (Système National des Données de Santé, SNDS) database between 2008 and 2019 were eligible. Two study periods were considered: 15 February to 30 June 2020 and 1 October 2020 to 31 January 2021, the first and second waves of the COVID-19 pandemic in France, respectively. Patients were classified according to their baseline treatment: biologics, nonbiologics, topicals or no treatment. The primary endpoint was hospitalization for COVID-19 using Cox models with inverse probability of treatment weighting. The secondary endpoint was in-hospital mortality due to COVID-19. Results We identified 1 326 312 patients with psoriasis (mean age 59 years; males, 48%). During the first study period, 3871 patients were hospitalized for COVID-19 and 759 (20%) died; during the second period 3603 were hospitalized for COVID-19 and 686 (19%) died. In the propensity score-weighted Cox models, risk of hospitalization for COVID-19 was associated with exposure to topicals or nonbiologics [hazard ratio (95% confidence interval): 1·11 (1·04–1·20) and 1·27 (1·09–1·48), respectively] during the first period, and with all exposure types, during the second period. None of the exposure types was associated with in-hospital mortality due to COVID-19. Conclusions Systemic treatments for psoriasis (including biologics) were not associated with increased risk of in-hospital mortality due to COVID-19. These results support maintaining systemic treatment for psoriasis during the pandemic.
Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces viral shedding after SARS-CoV-2 D614G challenge in preclinical models
Authors: Neeltje van Doremalen, Jyothi N. Purushotham, Jonathan E. Schulz, Myndi G. Holbrook, Trenton Bushmaker, Aaron Carmody, Julia R. Port, Claude K. Yinda, Atsushi Okumura, Greg Saturday, Fatima Amanat, Florian Krammer, Patrick W. Hanley, Brian J. Smith, Jamie Lovaglio, Sarah L. Anzick, Kent Barbian, Craig Martens, Sarah C. Gilbert, Teresa Lambe, Vincent J. Munster
Journal: Science Translational Medicine (2021)

ChAdOx1 nCoV-19/AZD1222 is an approved adenovirus-based vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently being deployed globally. Previous studies in rhesus macaques revealed that intramuscular vaccination with ChAdOx1 nCoV-19/AZD1222 provided protection against pneumonia but did not reduce shedding of SARS-CoV-2 from the upper respiratory tract. Here, we investigated whether intranasally administered ChAdOx1 nCoV-19 reduces detection of virus in nasal swabs after challenging vaccinated macaques and hamsters with SARS-CoV-2 carrying a D614G mutation in the spike protein. Viral loads in swabs obtained from intranasally vaccinated hamsters were decreased compared to control hamsters, and no viral RNA or infectious virus was found in lung tissue after a direct challenge or after direct contact with infected hamsters. Intranasal vaccination of rhesus macaques resulted in reduced virus concentrations in nasal swabs and a reduction in viral loads in bronchoalveolar lavage and lower respiratory tract tissue. Intranasal vaccination with ChAdOx1 nCoV-19/AZD1222 reduced virus concentrations in nasal swabs in two different SARS-CoV-2 animal models, warranting further investigation as a potential vaccination route for COVID-19 vaccines.
MO8-1 Examination of the usefulness of MeAIB PET for head and neck cancer
Authors: Ayana Komurasaki, Chio Okuyama, Koji Ushiro, Kiyohiro Fujino, Hideaki Ogita, Masahiro Matsumoto, Shyougo Miyabe, Jyuichi Ito
Journal: Annals of Oncology (2021)
Correction: EGFR Exon 20 Insertion Mutations Display Sensitivity to Hsp90 Inhibition in Preclinical Models and Lung Adenocarcinomas
Authors: Susan E. Jorge, Antonio R. Lucena-Araujo, Hiroyuki Yasuda, Zofia Piotrowska, Geoffrey R. Oxnard, Deepa Rangachari, Mark S. Huberman, Lecia V. Sequist, Susumu S. Kobayashi, Daniel B. Costa
Journal: Clinical Cancer Research (2020)
Dysregulation of MYD88 Regulatory Isoforms in Waldenstrom's Macroglobulinemia
Authors: Amanda Kofides, Maria Demos, Nickolas Tsakmaklis, Lian Xu, Xia Liu, Guang Yang, Manit Munshi, Jiaji Chen, Christopher Patterson, Maria Luisa Guerrera, Jorge J. Castillo, Steven P Treon, Zachary Hunter
Journal: Blood (2017)
Combating information chaos: a case for collaborative clinical guidelines in a pandemic
Authors: C. Lee Cohen, Katherine H. Walker, Mina Hsiang, Paul D. Sonenthal, Elisabeth D. Riviello, Shada A. Rouhani, Michael S. Lipnick, Louis T. Merriam, Edy Y. Kim
Journal: Cell Reports Medicine (2021)

The speed and scale of new information during the COVID-19 pandemic required a new approach toward developing best practices and evidence-based clinical guidance. To address this need, we produced COVIDProtocols.org, a collaborative, evidence-based, digital platform for the development and dissemination of COVID-19 clinical guidelines that has been used by over 500,000 people from 196 countries. We use a Collaborative Writing Application (CWA) to facilitate an expedited expert review process and a web platform that deploys content directly from the CWA to minimize any delays. Over 200 contributors have volunteered to create open creative-commons content that spans over 30 specialties and medical disciplines. Multiple local and national governments, hospitals, and clinics have used the site as a key resource for their own clinical guideline development. COVIDprotocols.org represents a model for efficiently launching open-access clinical guidelines during crisis situations to share expertise and combat misinformation.
Anticoagulation after Ablation for Atrial Fibrillation
Authors: Siri R. Kadire, Sana M. Al-Khatib, Hugh Calkins
Journal: New England Journal of Medicine (2021)

This interactive feature about management of atrial fibrillation offers a case vignette accompanied by two essays supporting different approaches to the use of anticoagulants after ablation for atrial fibrillation.
ATP-triggered mitochondrial cascade reactions for cancer therapy with nanoscale zeolitic imidazole framework-90
Authors: Wei Pan, Bingjie Cui, Kaiye Wang, Mingwan Shi, Fei Lu, Na Li, Bo Tang
Journal: Theranostics (2021)

Goals: Chemotherapy, the most conventional modality for cancer therapy, usually brings serious side effects because of the low cancer-therapeutic specificity and bioavailability. It is of great significance for cancer treatment to develop new effective strategies to regulate biochemical reactions in organelles, enhance the specificity of chemotherapeutic drugs and reduce their side effects. Methods: We report herein a zeolitic imidazole framework-90 (ZIF-90) based nanoplatform, which was used to initiate a series of mitochondrial cascade reactions using ATP as a molecular switch for cancer therapy. The thioketal linked camptothecin (camptothecin prodrug, TK-CPT) and 2-Methoxyestradiol (2-ME) were encapsulated into the pores of ZIF-90 nanoparticles using a simple one-pot method, and the nanoplatform was finally coated with a layer of homologous cell membrane. Results: Mitochondrial ATP can efficiently degrade ZIF-90 and then release the loaded 2-ME and CPT prodrugs. 2-ME can inhibit the activity of superoxide dismutase (SOD), which induces the up-regulation of reactive oxygen species (ROS) in situ. The thioketal linkers in CPT prodrug can respond to ROS, thereby achieving subsequent release of parent CPT drug. This cascade of reactions can lead to prolonged high oxidative stress and cause continuous cancer cell apoptosis, due to the increased ROS level and the liberation of CPT. Conclusion: We constructed an ATP-triggered strategy using nanoscale ZIF-90 to initiate mitochondrial cascade reactions for cancer therapy. The ZIF-90 based nanoplatform exhibited low cytotoxicity, good mitochondria-targeting ability, and excellent therapeutic effect. In vivo experiments demonstrated that the growth of tumor can be efficiently inhibited in a mouse model. This ATP-triggered strategy to induce mitochondrial biochemical reactions offers more possibilities for developing organelle-targeted therapeutic platforms.
SARS-CoV-2 Human Challenge Studies — Establishing the Model during an Evolving Pandemic
Authors: Garth Rapeport, Emma Smith, Anthony Gilbert, Andrew Catchpole, Helen McShane, Christopher Chiu
Journal: New England Journal of Medicine (2021)

SARS-CoV-2 Human Challenge Studies While commentators have made theoretical arguments for and against SARS-CoV-2 challenge studies, a consortium of academics, industry collaborators, and the Britis...
GATA4-driven miR-206-3p signatures control orofacial bone development by regulating osteogenic and osteoclastic activity
Authors: Shuyu Guo, Jiawen Gu, Junqing Ma, Rongyao Xu, Qingheng Wu, Li Meng, Haojie Liu, Lu Li, Yan Xu
Journal: Theranostics (2021)

Growth disorders in the orofacial bone development process may lead to orofacial deformities.The balance between bone matrix formation by mesenchymal lineage osteoblasts and bone resorption by osteoclasts is vital for orofacial bone development.Although the mechanisms of orofacial mesenchymal stem cells (OMSCs) in orofacial bone development have been studied intensively, the communication between OMSCs and osteoclasts remains largely unclear.Methods: We used a neural crest cell-specific knockout mouse model to investigate orofacial bone development in GATA-binding protein 4 (GATA4) morphants.We investigated the underlying mechanisms of OMSCs-derived exosomes (OMExos) on osteoclastogenesis and bone resorption activity in vitro.miRNAs were extracted from OMExos, and differences in miRNA abundances were determined using an Affymetrix miRNA array.Luciferase reporter assays were used to validate the binding between GATA4 and miR-206-3p in OMSCs and to confirm the putative binding of miR-206-3p and its target genes in OMSCs and osteoclasts.The regulatory mechanism of the GATA4-miR-206-3p axis in OMSC osteogenic differentiation and osteoclastogenesis was examined in vitro and in vivo.Results: Wnt1-Cre;Gata4 fl/fl mice (cKO) not only presented inhibited bone formation but also showed active bone resorption.Osteoclasts cocultured in vitro with cKO OMSCs presented an increased capacity for osteoclastogenesis, which was exosome-dependent.Affymetrix miRNA array analysis showed that miR-206-3p was downregulated in exosomes from shGATA4 OMSCs.Moreover, the transcriptional activity of miR-206-3p was directly regulated by GATA4 in OMSCs.We further demonstrated that miR-206-3p played a key role in the regulation of orofacial bone development by directly targeting bone morphogenetic protein-3 (Bmp3) and nuclear factor of activated T -cells, cytoplasmic 1 (NFATc1).OMExos and agomiR-206-3p enhanced bone mass in Wnt1-cre;Gata4 fl/fl mice by augmenting trabecular bone structure and decreasing osteoclast numbers.Conclusion: Our findings confirm that miR-206-3p is an important downstream factor of GATA4 that regulates the functions of OMSCs and osteoclasts.These results demonstrate the efficiency of OMExos and microRNA agomirs in promoting bone regeneration, which provide an ideal therapeutic tool for orofacial bone deformities in the future.
Efficacy of chemoprophylaxis and immunoprophylaxis in leprosy prevention: a systematic review and network meta-analysis of randomized controlled trials
Authors: Gehad Mohamed Tawfik, Marwa Biala, Yomna Mahmoud Yousef, Ranjit Tiwari, Monica Dobs, Caroline Ibrahim Lotfy, Doha Ahmed Farrag, Anh Tran Hue, Rie Roselyne Yotsu, Nguyen Tien Huy
Journal: Clinical Microbiology and Infection (2021)
Neuroblastoma Formation Requires Unconventional CD4 T Cells and Arginase-1–Dependent Myeloid Cells
Authors: Lee-Ann Van de Velde, E. Kaitlynn Allen, Jeremy Chase Crawford, Taylor L. Wilson, Clifford S. Guy, Marion Russier, Leonie Zeitler, Armita Bahrami, David Finkelstein, Stephane Pelletier, Stacey Schultz-Cherry, Paul G. Thomas, Peter J. Murray
Journal: Cancer Research (2021)

Immune cells regulate tumor growth by mirroring their function as tissue repair organizers in normal tissues. To understand the different facets of immune-tumor collaboration through genetics, spatial transcriptomics, and immunologic manipulation with noninvasive, longitudinal imaging, we generated a penetrant double oncogene-driven autochthonous model of neuroblastoma. Spatial transcriptomic analysis showed that CD4+ and myeloid populations colocalized within the tumor parenchyma, while CD8+ T cells and B cells were peripherally dispersed. Depletion of CD4+ T cells or CCR2+ macrophages, but not B cells, CD8+ T cells, or natural killer (NK) cells, prevented tumor formation. Tumor CD4+ T cells displayed unconventional phenotypes and were clonotypically diverse and antigen independent. Within the myeloid fraction, tumor growth required myeloid cells expressing arginase-1. Overall, these results demonstrate how arginine-metabolizing myeloid cells conspire with pathogenic CD4+ T cells to create permissive conditions for tumor formation, suggesting that these protumorigenic pathways could be disabled by targeting myeloid arginine metabolism. SIGNIFICANCE: A new model of human neuroblastoma provides ways to track tumor formation and expansion in living animals, allowing identification of CD4+ T-cell and macrophage functions required for oncogenesis.
SARS-CoV-2 and pancreas: a potential pathological interaction?
Authors: Shirin Geravandi, Azam Mahmoudi-aznaveh, Zahra Azizi, Kathrin Maedler, Amin Ardestani
Journal: Trends in Endocrinology and Metabolism (2021)

The widespread extrapulmonary complications of coronavirus disease 2019 (COVID-19) have gained momentum; the pancreas is another major target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we take a closer look into potential pathological interactions. We provide an overview of the current knowledge and understanding of SARS-CoV-2 infection of the pancreas with a special focus on pancreatic islets and propose direct, indirect, and systemic mechanisms for pancreas injury as result of the COVID-19–diabetes fatal bidirectional relationship.
Guideline Update on Indications for Transcatheter Aortic Valve Implantation Based on the 2020 American College of Cardiology/American Heart Association Guidelines for Management of Valvular Heart Disease
Authors: Thoralf M. Sundt, Hani Jneid
Journal: JAMA Cardiology (2021)

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Primary Care Spending in the Veterans Health Administration in 2014 and 2018
Authors: Ashok Reddy, Karin M. Nelson, Edwin S. Wong
Journal: JAMA Network Open (2021)

obtained outside the VHA range from $8.2 billion in 2014 to $14.9 billion in 2018. 6Approximately 30% is spent on outpatient services, but specific data for primary care spending are unknown. 6Our results suggest opportunities to increase investment in primary care to improve care for veterans.
Randomized Phase II Trial Evaluating Two Sequential Treatments in First Line of Metastatic Pancreatic Cancer: Results of the PANOPTIMOX-PRODIGE 35 Trial
Authors: Laetitia Dahan, Nicolas Williet, Karine Le Malicot, Jean-Marc Phelip, Jérôme Desrame, Olivier Bouché, Caroline Petorin, David Malka, Christine Rebischung, Thomas Aparicio, Cédric Lecaille, Yves Rinaldi, Anthony Turpin, Anne-Laure Bignon, Jean-Baptiste Bachet, Jean-François Seitz, Come Lepage, Eric François
Journal: Journal of Clinical Oncology (2021)

Metastatic pancreatic cancer (mPC) still harbors a dismal prognosis. Our previous trial (PRODIGE 4-ACCORD 11) demonstrated the superiority of 6-month chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) over gemcitabine for overall survival. The high limiting oxaliplatin-related neurotoxicity supports the evaluation of an oxaliplatin stop-and-go strategy and a sequential strategy in mPC.In this phase II study, patients were randomly assigned to receive either 6 months of FOLFIRINOX (arm A), 4 months of FOLFIRINOX followed by leucovorin plus fluorouracil maintenance treatment for controlled patients (arm B), or a sequential treatment alternating gemcitabine and fluorouracil, leucovorin, and irinotecan every 2 months (arm C). The primary end point was progression-free survival at 6 months.Between January 2015 and November 2016, 276 patients (mean age: 63 years; range: 40-76 years) were enrolled (A: 91, B: 92, and C: 90). Grade 3 or 4 neurotoxicity occurred in 10.2% of patients in arm A and 19.8% in arm B. The median ratio of received dose/targeted dose of oxaliplatin was 83% in arm A and 92% in arm B. The 6-month progression-free survival was 47.1% in A, 42.9% in B, and 34.1% in C. The median overall survival was 10.1 months in arm A, 11.2 in arm B, and 7.3 in arm C. Median survival without deterioration in quality-of-life scores was higher in the maintenance arm (11.4 months) than in arms A and C (7.2 and 7.5 months, respectively).Maintenance with leucovorin plus fluorouracil appears to be feasible and effective in patients with mPC controlled after 4 months of induction chemotherapy with FOLFIRINOX. Severe neurotoxicity was higher in the maintenance therapy arm, probably because of the higher cumulative dose of oxaliplatin.