tbuckley/cabot-search huggingface dataset:
SCEPTRE improves calibration and sensitivity in single-cell CRISPR screen analysis
Authors: Timothy Barry, Xuran Wang, John A. Morris, Kathryn Roeder, Eugene Katsevich
Journal: Genome biology (2021)

Single-cell CRISPR screens are a promising biotechnology for mapping regulatory elements to target genes at genome-wide scale. However, technical factors like sequencing depth impact not only expression measurement but also perturbation detection, creating a confounding effect. We demonstrate on two single-cell CRISPR screens how these challenges cause calibration issues. We propose SCEPTRE: analysis of single-cell perturbation screens via conditional resampling, which infers associations between perturbations and expression by resampling the former according to a working model for perturbation detection probability in each cell. SCEPTRE demonstrates very good calibration and sensitivity on CRISPR screen data, yielding hundreds of new regulatory relationships supported by orthogonal biological evidence.
Less is more? Antibiotic treatment duration for exacerbations of bronchiectasis
Authors: James D. Chalmers, Holly R. Keir
Journal: European Respiratory Journal (2021)

Exacerbations of bronchiectasis are major drivers of morbidity and mortality [1–3]. Severe exacerbations requiring hospitalisation or intravenous antibiotics are particularly damaging, with a 4-year mortality rate of 25% and a major impact on healthcare resources, being the main contributor to healthcare costs in bronchiectasis [4–6]. Exacerbations are defined by an increase in respiratory symptoms requiring a change in treatment, which is usually an antibiotic [2]. In practice, the most common symptoms are cough, sputum production, sputum purulence, fatigue and breathlessness [2, 7]. In common with much of the bronchiectasis evidence base, we know far too little about what causes bronchiectasis exacerbations and almost nothing about how to treat them. Respiratory viruses, such as influenza and rhinovirus, have been identified in up to 50% of events [8, 9]. While bacteria are frequently isolated, the role of changes in bacterial load or strain at exacerbation is unclear, since bacteria are frequently identified in patients with bronchiectasis when clinically stable [10–12]. The first trial of antibiotic duration in bronchiectasis provides surprising results <https://bit.ly/2TeDmsX>
Longitudinal Content Analysis of the Characteristics and Expected Impact of Low-Value Services Identified in US Choosing Wisely Recommendations
Authors: Ishani Ganguli, Nitya Thakore, Meredith B. Rosenthal, Deborah Korenstein
Journal: JAMA Internal Medicine (2021)

<h3>Importance</h3> The US Choosing Wisely campaign has had substantial reach in mobilizing efforts to reduce low-value care, achieved largely by engaging physician specialty societies in stewardship. While some early recommendations were criticized for avoiding revenue-generating services, there is limited evidence of how the composition of recommendations shifted as more societies contributed. <h3>Objective</h3> To analyze the characteristics and expected impact of Choosing Wisely recommendations. <h3>Design, Setting, and Participants</h3> This qualitative study included content and trend analyses of all 626 Choosing Wisely recommendations by US physician societies as of March 1, 2021. Data were analyzed between March and May 2021. <h3>Main Outcomes and Measures</h3> Primary outcomes were proportions of identified low-value services by characteristics (society type, service type, indication, do vs avoid, and clinical context) and expected impact (effect on the revenue of society members, cost, number of individuals at risk, direct harm potential, and cascade potential). <h3>Results</h3> Low-value services identified in the 626 Choosing Wisely recommendations largely covered imaging (168 [26.8%]) and laboratory studies (156 [24.9%]) in the context of chronic conditions (169 [27.0%]) and healthy patients with risk factors alone (126 [20.1%]). Most of the identified low-value services were revenue neutral for the recommending society (402 [64.2%]) and the plurality were low cost (&lt;$200; 284 [45.4%]); low-cost services represented a growing share of low-value services identified by Choosing Wisely recommendations (1.2 percentage points per year;<i>P</i> = .001). Nearly half (280 [44.7%]) of recommendations identified services with high direct harm potential, and 388 (62.0%) identified those with high potential for cascades (ie, triggering downstream services). <h3>Conclusions and Relevance</h3> The results of this qualitative study suggest that the Choosing Wisely recommendations identified services with a range of expected impacts. Stakeholders could explicitly set priorities for future recommendations, while clinical leaders and payers might target intervention efforts on recommendations with the greatest potential for impact based on spending across populations, direct harms, and cascades.
Multiple Novel Traits without Immediate Benefits Originate in Bacteria Evolving on Single Antibiotics
Authors: Shraddha Karve, Andreas Wagner
Journal: Molecular Biology and Evolution (2021)

Abstract How new traits originate in evolution is a fundamental question of evolutionary biology. When such traits arise, they can either be immediately beneficial in their environment of origin, or they may become beneficial only in a future environment. Compared to immediately beneficial novel traits, novel traits without immediate benefits remain poorly studied. Here we use experimental evolution to study novel traits that are not immediately beneficial but that allow bacteria to survive in new environments. Specifically, we evolved multiple E. coli populations in five antibiotics with different mechanisms of action, and then determined their ability to grow in more than 200 environments that are different from the environment in which they evolved. Our populations evolved viability in multiple environments that contain not just clinically relevant antibiotics, but a broad range of antimicrobial molecules, such as surfactants, organic and inorganic salts, nucleotide analogues and pyridine derivatives. Genome sequencing of multiple evolved clones shows that pleiotropic mutations are important for the origin of these novel traits. Our experiments, which lasted fewer than 250 generations, demonstrate that evolution can readily create an enormous reservoir of latent traits in microbial populations. These traits can facilitate adaptive evolution in a changing world.
113P Health outcomes and budget impact projection of the anti-PD-(L)1 class in cancer care in Portugal
Authors: L. Costa, M.T.A. Alexandre, A.B. Mansinho, A.R. Teixeira Sousa, C.M. Pereira Vieira, E. Bell, O. Swales, R. Hughes, N. Nagda, S. Lucherini, A. Roediger, A. Araújo
Journal: Annals of Oncology (2021)
9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Medical Care in Diabetes—2022</i>
Journal: Diabetes Care (2021)

The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
A Machine Learning Model Based on Tumor and Immune Biomarkers to Predict Undetectable Measurable Residual Disease (MRD) in Transplant-Eligible Multiple Myeloma (MM)
Authors: Camila Guerrero, Noemi Puig, María Teresa Cedena, Ibai Goicoechea, Cristina Pérez Ruiz, Juan José Garcés, Cirino Botta, Maria Jose Calasanz, Norma C. Gutierrez, Maria Luisa Martin-Ramos, Albert Oriol, Rafael Rios, Miguel Hernández, Rafael Martínez, Joan Bargay, Felipe De Arriba, Luis Palomera, Ana Pilar Gonzalez, Adrián Mosquera Orgueira, Marta Sonia Gonzalez, Joaquín Martínez-López, Juan Jose Lahuerta, Laura Rosinol, Joan Bladé Creixenti, Maria-Victoria Mateos, Jesus San-Miguel, Bruno Paiva
Journal: Blood (2021)
Prevalence of intratumoral regulatory T cells expressing neuropilin-1 is associated with poorer outcomes in patients with cancer
Authors: Christopher A. Chuckran, Anthony R. Cillo, Jessica Moskovitz, Abigail Overacre-Delgoffe, Ashwin S. Somasundaram, Feng Shan, Grant C. Magnon, Sheryl R. Kunning, Irina Abecassis, Amer H. Zureikat, James Luketich, Arjun Pennathur, John Sembrat, Mauricio Rojas, Daniel T. Merrick, Sarah E. Taylor, Brian Orr, Francesmary Modugno, Ron Buckanovich, Robert E. Schoen, Seungwon Kim, Umamaheswar Duvvuri, Herbert Zeh, Robert Edwards, John M. Kirkwood, Lan Coffman, Robert L. Ferris, Tullia C. Bruno, Dario A. A. Vignali
Journal: Science Translational Medicine (2021)

Despite the success of immune checkpoint blockade therapy, few strategies sufficiently overcome immunosuppression within the tumor microenvironment (TME). Targeting regulatory T cells (T
Adjuvant radiotherapy may not significantly change outcomes in high-risk cutaneous squamous cell carcinomas with clear surgical margins: A systematic review and meta-analysis
Authors: Yesul Kim, Eric J. Lehrer, Paul J. Wirth, Eiman A. Khesroh, Jerry D. Brewer, Elizabeth M. Billingsley, Nicholas G. Zaorsky, Charlene Lam
Journal: Journal of the American Academy of Dermatology (2021)
<scp>d</scp>‐Amino Acid‐Based Metabolic Labeling Enables a Fast Antibiotic Susceptibility Test of Both Isolated Bacteria and Bronchoalveolar Lavage Fluid
Authors: Juan Gao, Junnan Guo, Jianxiao Chen, Chenling Ding, Jiemin Wang, Qian Huang, Ying Jian, Xianyuan Zhao, Min Li, Yuan Gao, Chaoyong Yang, Wei Wang
Journal: Advanced Healthcare Materials (2021)

The threat of multidrug-resistant bacteria has escalated rapidly, increasing the demand for accurate antibiotic susceptibility tests (ASTs). Traditional bacterial growth yield-based ASTs often take overnight to report, delaying the timely guidance of antibiotic use. Here, a fluorescent d-amino acid (FDAA) labeling-based AST (FaAST) is reported, which can quickly provide accurate minimum inhibitory concentrations (MICs). The FDAA-labeling signals that reflect the bacterial metabolic status underlie the flow cytometry-based strategy for MIC determination. Resistant bacteria show a reluctant decline in FDAA-labeling (inhibited metabolism) after treatment with the corresponding antibiotics, whereas susceptible bacteria demonstrate quick responses to low doses of drugs. The MICs are determined based on the changing trends in labeling. After testing 23 clinical isolates and laboratory strains of the most critical drug-resistant bacteria against a panel of representative antibiotics, FaAST shows a high susceptibility category with an accuracy of 98.13%. Moreover, FaAST can also make quick and accurate diagnosis against bronchoalveolar lavage fluids collected from hospital-acquired pneumonia patients, saving 2-4 days in guiding antibiotic use for this life-threatening infection. Thus, the speed, accuracy, and broad applicability of FaAST will be valuable in informing antibiotic decisions when treating critical infections caused by drug-resistant bacteria.
Preliminary Safety and Efficacy from a Multicenter, Investigator-Initiated Phase II Study in Untreated TP53 Mutant Mantle Cell Lymphoma with Zanubrutinib, Obinutuzumab, and Venetoclax (BOVen)
Authors: Anita Kumar, Jacob D. Soumerai, Jeremy S. Abramson, Connie Lee Batlevi, Puja Chadha, Ahmet Dogan, Lorenzo Falchi, Kelsey Flaherty, Chaya Friedman, Clare Grieve, Caleb Ho, P. Connor Johnson, Ashlee Joseph, Niloufer Khan, Joanna Mi, Rosalba Martignetti, Matthew J. Matasar, Colette Owens, Jade Ruiters, Sidney Sechio, Venkatraman Seshan, Elizabeth Simkins, Omar Abdel-Wahab, Andrew D. Zelenetz
Journal: Blood (2021)
Corrigendum to “Biodegradable thermal imaging-tracked ultralong nanowire-reinforced conductive nanocomposites elastomers with intrinsical efficient antibacterial and anticancer activity for enhanced biomedical application potential” [Biomaterials 201 (2019) 68–76]
Authors: Yannan Li, Na Li, Juan Ge, Yumeng Xue, Wen Niu, Mi Chen, Yaping Du, Peter X. Ma, Bo Lei
Journal: Biomaterials (2021)
Cancer Care Creates Substantial Costs for US Patients
Authors: Bridget M. Kuehn
Journal: JAMA (2021)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Low-Risk Polycythemia Vera Treated with Phlebotomies: Clinical Characteristics, Hematologic Control and Complications in 358 Patients from the Spanish Registry of Polycythemia Vera
Authors: Ana Triguero, Alexandra Pedraza, Manuel Pérez, María Isabel Mata, Beatriz Bellosillo, María Laura Fox, Montserrat Gómez, Regina Garcia-Delgado, Mercedes Gasior Kabat, Francisca Ferrer Marin, Valentín Garcia Gutierrez, Anna Angona, María Teresa Gómez-Casares, Beatriz Cuevas, Clara Martínez, Raul Perez Lopez, Jose Maria Raya Sanchez, Lucia Guerrero, Ilda Maria Murillo, Carlos Castillo, Cristina Sanz, Juan Carlos Hernandez Boluda, Alberto Alvarez-Larran
Journal: Blood (2021)
NEAT1 is essential for metabolic changes that promote breast cancer growth and metastasis
Authors: Mi Kyung Park, Li Zhang, Kyung-Won Min, Jung-Hyun Cho, Chih-Chen Yeh, Hyesu Moon, Daniel Hormaechea-Agulla, Hyejin Mun, Seungbeom Ko, Ji Won Lee, Sonali Jathar, Aubrey S Smith, Yixin Yao, Nguyen Thu Giang, Hong Ha Vu, Victoria C Yan, Mary C Bridges, Antonis Kourtidis, Florian Muller, Jeong Ho Chang, Su Jung Song, Shinichi Nakagawa, Tetsuro Hirose, Je-Hyun Yoon, Min Sup Song
Journal: Cell Metabolism (2021)
Re: Keisuke Shigeta, Kazuhiro Matsumoto, Koichiro Ogihara, et al. Does Neoadjuvant Chemotherapy Have Therapeutic Benefit for Node-positive Upper Tract Urothelial Carcinoma? Results of a Multi-center Cohort Study. Urol Oncol. In press. https://doi.org/10.1016/j.urolonc.2021.07.029
Authors: Fredrik Liedberg, Johan Abrahamsson, Johannes Bobjer
Journal: European Urology (2021)
Microbiota-dependent increase in δ-valerobetaine alters neuronal function and is responsible for age-related cognitive decline
Authors: Omar Mossad, Elisa Nent, Sabrina Woltemate, Shani Folschweiller, Joerg M. Buescher, Daniel Schnepf, Daniel Erny, Peter Staeheli, Marlene Bartos, Antal Szalay, Bärbel Stecher, Marius Vital, Jonas F. Sauer, Tim Lämmermann, Marco Prinz, Thomas Blank
Journal: Nature Aging (2021)
Therapeutic Drug Monitoring for Immune-Mediated Inflammatory Diseases
Authors: Zachary S. Wallace, Jeffrey A. Sparks
Journal: JAMA (2021)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Glutamine promotes antibiotic uptake to kill multidrug-resistant uropathogenic bacteria
Authors: Xian-liang Zhao, Zhuang-gui Chen, Tian-ci Yang, Ming Jiang, Jie Wang, Zhi-xue Cheng, Man-jun Yang, Jia-xin Zhu, Tian-tuo Zhang, Hui Li, Bo Peng, Xuan-xian Peng
Journal: Science Translational Medicine (2021)

Multidrug-resistant Escherichia coli metabolomes are reprogrammed by glutamine to be sensitive to ampicillin in vitro and in vivo.
Efficacy, safety, and biomarker analysis of Camrelizumab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma (CAPTAIN study)
Authors: Yunpeng Yang, Ting Zhou, Xiaozhong Chen, Jingao Li, Jianji Pan, Xiaohui He, Lizhu Lin, Ying-rui Shi, Weineng Feng, Jianping Xiong, Kunyu Yang, Qitao Yu, Qunling Zhang, Desheng Hu, Yan Sun, Guangyuan Hu, Ping Li, Liangfang Shen, Qin Lin, Ben Zhang, Xiao Qu, Jianjun Zou, Li Zhang, Wenfeng Fang, Yuanyuan Zhao
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background This study aimed to evaluate the antitumor activity of camrelizumab, an antiprogrammed cell death-1 antibody, in pretreated recurrent or metastatic nasopharyngeal carcinoma (NPC) and to explore predictive biomarkers. Methods Patients with recurrent (not amenable to locally curative treatment) or metastatic NPC who had failed at least two lines of chemotherapy were eligible to receive camrelizumab (200 mg intravenously every 2 weeks) for 2 years or until disease progression, intolerable adverse events, withdrawal of consents, or investigator decision. The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC). Programmed cell death-ligand 1 (PD-L1) expression was assessed by immunohistochemistry. Other immune-related biomarkers including major histocompatibility complex class I and major histocompatibility complex class II (MHC-II) were assessed by multiplex immunofluorescence staining. Results Between August 14, 2018, and December 30, 2019, a total of 156 patients were enrolled. The IRC-assessed ORR was 28.2% (95% CI 21.3% to 36.0%). The median progression-free survival was 3.7 months (95% CI 2.0 to 4.1) per IRC, and the median overall survival was 17.4 months (95% CI 15.2 to 21.9). The ORRs were 35.2% (95% CI 25.3% to 46.1%) vs 19.4% (95% CI 10.4% to 31.4%) in patients with tumor PD-L1 expression of ≥10% and&lt;10%, respectively. Patients with durable clinical benefit (DCB), which was defined as complete response, partial response or stable disease of ≥18 weeks, had higher density of MHC-II+ cell in stroma than patients without DCB (median 868.1 (IQR 413.4–2854.0) cells/mm 2 vs median 552.4 (IQR 258.4 to 1242.1) cells/mm 2 ). MHC-II+ cell density did not correlate with PD-L1 expression, and a composite of high stromal MHC-II+ cell density and tumor PD-L1 expression further enriched patients who could benefit from camrelizumab. Conclusions Camrelizumab had clinically meaningful antitumor activity in patients with recurrent or metastatic NPC. The composition of both MHC-II+ cell density and PD-L1 expression could result in better patient selection.
LBA2 Updated analysis and patient-reported outcomes (PROs) from CITYSCAPE: A randomised, double-blind, phase II study of the anti-TIGIT antibody tiragolumab + atezolizumab (TA) versus placebo + atezolizumab (PA) as first-line treatment for PD-L1+ NSCLC
Authors: B.C. Cho, D. Rodriguez-Abreu, M. Hussein, M. Cobo, A. Patel, N. Secen, G. Gerstner, D-W. Kim, Y-G. Lee, W-C. Su, E. Huang, N. Patil, M. Huang, Z. Zhang, X. Wen, D. Mendus, T. Hoang, R. Meng, M.L. Johnson
Journal: Annals of Oncology (2021)
Political Issues Surrounding Gender-Affirming Care for Transgender Youth—Reply
Authors: Benjamin C. Park, Rishub K. Das, Brian C. Drolet
Journal: JAMA Pediatrics (2021)

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 Pediatrics 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 Pediatrics journal
Myth and Mumpsimus in Medicine
Journal: JAMA (2021)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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