tbuckley/cabot-search huggingface dataset:
Next steps for clinical translation of adenosine pathway inhibition in cancer immunotherapy
Authors: Ryan C. Augustin, Robert D. Leone, Aung Naing, Lawrence Fong, Riyue Bao, Jason J. Luke
Journal: Journal for ImmunoTherapy of Cancer (2022)

Increasing evidence supports targeting the adenosine pathway in immuno-oncology with several clinical programs directed at adenosine A2 receptor (A2AR, A2BR), CD73 and CD39 in development. Through a cyclic-AMP-mediated intracellular cascade, adenosine shifts the cytokine and cellular profile of the tumor microenvironment away from cytotoxic T cell inflammation toward one of immune tolerance. A perpetuating cycle of tumor cell proliferation, tissue injury, dysregulated angiogenesis, and hypoxia promote adenosine accumulation via ATP catabolism. Adenosine receptor (eg, A2AR, A2BR) stimulation of both the innate and adaptive cellular precursors lead to immunosuppressive phenotypic differentiation. Preclinical work in various tumor models with adenosine receptor inhibition has demonstrated restoration of immune cell function and tumor regression. Given the broad activity but known limitations of anti-programmed cell death protein (PD1) therapy and other checkpoint inhibitors, ongoing studies have sought to augment the successful outcomes of anti-PD1 therapy with combinatorial approaches, particularly adenosine signaling blockade. Preliminary data have demonstrated an optimal safety profile and enhanced overall response rates in several early phase clinical trials with A2AR and more recently CD73 inhibitors. However, beneficial outcomes for both monotherapy and combinations have been mostly lower than expected based on preclinical studies, indicating a need for more nuanced patient selection or biomarker integration that might predict and optimize patient outcomes. In the context of known immuno-oncology biomarkers such as tumor mutational burden and interferon-associated gene expression, a comparison of adenosine-related gene signatures associated with clinical response indicates an underlying biology related to immunosuppression, angiogenesis, and T cell inflammation. Importantly, though, adenosine associated gene expression may point to a unique intratumoral phenotype independent from IFN-γ related pathways. Here, we discuss the cellular and molecular mechanisms of adenosine-mediated immunosuppression, preclinical investigation of adenosine signaling blockade, recent response data from clinical trials with A2AR, CD73, CD39 and PD1/L1 inhibitors, and ongoing development of predictive gene signatures to enhance combinatorial immune-based therapies.
Ophthalmology
Authors: M. B. McDonald
Journal: JAMA (1990)

One of the most promising new methods for correcting myopia (nearsightedness), with the potential to correct hyperopia (farsightedness) and astigmatism, is excimer laser photorefractive keratectomy, otherwise known as PRK. The excimer laser is a far-UV laser with a wavelength of 193 nm and has been used in the computer industry for many years to aid in the etching of chips. In 1983, the now classic article by Trokel et al<sup>1</sup>reported the use of this industrial laser to remove tissue from the cornea of the eye in an exquisitely precise manner, without damage (thermal or otherwise) to surrounding structures. The article by Trokel and colleagues clearly delineated the potential of this laser as a powerful tool in refractive surgery. More recently, some research groups have used the excimer laser to sculpt the anterior surface of the cornea,<sup>2-6</sup>while others have used it to make fine linear excisions,<sup>7-9</sup>
Development of a core outcome set for lateral elbow tendinopathy (COS-LET) using best available evidence and an international consensus process
Authors: Marcus Bateman, Jonathan P Evans, Viana Vuvan, Val Jones, Adam C Watts, Joideep Phadnis, Leanne M Bisset, Bill Vicenzino
Journal: British Journal of Sports Medicine (2022)

To develop a core outcome set for lateral elbow tendinopathy (COS-LET) and to provide guidance for outcome evaluation in future studies.We implemented a multi-stage mixed-methods design combining two systematic reviews, domain mapping of outcome measurement instruments to the core domains of tendinopathy, psychometric analysis of instruments, two patient focus groups and a Delphi study incorporating two surveys and an international consensus meeting. Following the OMERACT guidelines, we used a 70% threshold for consensus.38 clinicians/researchers and 9 patients participated. 60 instruments were assessed for inclusion. The only instrument that was recommended for the COS-LET was Patient Rated Tennis Elbow Evaluation (PRTEE) for the disability domain. Interim recommendations were made to use: the PRTEE function subscale for the function domain; PRTEE pain subscale items 1, 4 and 5 for the pain over a specified time domain; pain-free grip strength for the physical function capacity domain; a Numerical Rating Scale measuring pain on gripping for the pain on activity/loading domain; and time off work for the participation in life activities domain. No recommendations could be made for the quality-of-life, patient rating of condition and psychological factors domains.The COS-LET comprises the PRTEE for the disability domain. Interim-use recommendations included PRTEE subscales, time off work, pain-free grip strength and a Numerical Rating Scale measuring pain on gripping. Further work is required to validate these interim measures and develop suitable measures to capture the other domains.
Medical Economics
Journal: JAMA (1935)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Mechanism mapping to advance research on implementation strategies
Authors: Elvin H. Geng, Ana A. Baumann, Byron J. Powell
Journal: PLoS Medicine (2022)

To advance as a science, implementation research must build an evidence base using, in part, experimental designs.But trials of implementation strategies-which are often complex health systems interventions-often do not demonstrate anticipated overall effects [1,2].As a consequence, studies to understand whether a strategy will work are strongest when they can also reveal how they succeed or fail.The trial by Sarkies and colleagues published recently in PLOS Medicine illustrates this need [3].Previous randomized trials and a meta-analysis provided evidence that weekend staffing with allied healthcare professionals (e.g., physical therapists) decreased length of stay in rehabilitation units, but such weekend staffing had no effects in general medical and surgical units [4].Because staffing in real-world practice does not reflect these data [5], Sarkies cluster-randomized 45 healthcare units to receive one of 3 conditions: usual practice (the control); written materials about staffing evidence; or a knowledge broker (KB)-defined in this study as "intermediary agents who build relationships between decision makers and researchers, by sharing expert knowledge and establishing communication channels to convey evidence."The study found that neither written dissemination nor a KB had an effect on staffing nor patient length of stay compared to usual practice.Why? Data about implementation showed that managers assigned to a KB had very limited actual interaction with the KB and attended very few meetings.But additional questions remain.Why was KB attendance poor?Was the knowledge itself or the broker of the knowledge unconvincing?Which contextual enablers were missing?The answers to these questions are crucial for understanding the prospects of KB as a useful implementation strategy.Understanding how strategies fail is no less important than identifying success.One way to dissect how implementation strategies fail is through formal exploration of anticipated mechanisms.Several approaches in implementation science offer methods that can help conceptualize mechanisms systematically.The Intervention Mapping approach asks those planning health promotion activities to conceive of the multilevel, theory-based targets for behavior change that underlie a program and how they interact to produce desired effects [6].The Theory of Change approach encourages programs to make their intentions, activities, steps behind change, and assumptions explicit through a visual diagram [7], drawing from literature review, contextual knowledge, and stakeholder-engaged methods."Mechanism mapping" (a concept from policy analysis) [8] advocates decomposing an effect of interest into its component steps and asking how those steps interact with context.Directed acyclic graphs which have become widely used in epidemiology can be conceived of a tool for representing
Graphene and graphene oxide with anticancer applications: Challenges and future perspectives
Authors: Ali Shafiee, Siavash Iravani, Rajender S. Varma
Journal: MedComm (2022)

Abstract Graphene‐based materials have shown immense pertinence for sensing/imaging, gene/drug delivery, cancer therapy/diagnosis, and tissue engineering/regenerative medicine. Indeed, the large surface area, ease of functionalization, high drug loading capacity, and reactive oxygen species induction potentials have rendered graphene‐ (G‐) and graphene oxide (GO)‐based (nano)structures promising candidates for cancer therapy applications. Various techniques namely liquid‐phase exfoliation, Hummer's method, chemical vapor deposition, chemically reduced GO, mechanical cleavage of graphite, arc discharge of graphite, and thermal fusion have been deployed for the production of G‐based materials. Additionally, important criteria such as biocompatibility, bio‐toxicity, dispersibility, immunological compatibility, and inflammatory reactions of G‐based structures need to be systematically assessed for additional clinical and biomedical appliances. Furthermore, surface properties (e.g., lateral dimension, charge, corona influence, surface structure, and oxygen content), concentration, detection strategies, and cell types are vital for anticancer activities of these structures. Notably, the efficient accumulation of anticancer drugs in tumor targets/tissues, controlled cellular uptake properties, tumor‐targeted drug release behavior, and selective toxicity toward the cells are crucial criteria that need to be met for developing future anticancer G‐based nanosystems. Herein, important challenges and future perspectives of cancer therapy using G‐ and GO‐based nanosystems have been highlighted, and the recent advancements are deliberated.
Erratum
Journal: JNCI Journal of the National Cancer Institute (1970)

In “Report on 151 Childhood Malignancies Observed in Jamaica,” by G. Bras, H. Cole, A. Ashmeade-Dyer, and D. C. Watler, the heading of table 3 should read: “Childhood malignancies in Jamaica (1958–67 inclusive): Annual incidences expressed per 1,000,000.”
Drowning
Authors: Jane F. Desforges, Jerome H. Modell
Journal: New England Journal of Medicine (1993)

Drowning is an unexpected tragedy, in which previously healthy persons are exposed to severe cerebral hypoxia leading to death or, if they survive near-drowning, to brain damage in some cases. If survival with normal brain function is to occur, a thorough understanding of the pathophysiology of drowning and near-drowning and an organized approach to therapy are imperative.CausesFor many years, drowning was considered a "fight for survival"1: a person who could not swim, arms flailing and screaming for help, struggled to remain on the surface of the water and to reach safety. This situation is rarely reported by . . .
The Chemical Neuroanatomy of Sympathetic Ganglia
Authors: E. Lars-Gosta
Journal: Annual Review of Neuroscience (1993)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Classified Advertising
Journal: JAMA (1987)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Outcomes From Opportunistic Salpingectomy for Ovarian Cancer Prevention
Authors: Gillian E. Hanley, Celeste Leigh Pearce, Aline Talhouk, Janice S. Kwon, Sarah J. Finlayson, Jessica N. McAlpine, David G. Huntsman, Dianne Miller
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Opportunistic salpingectomy (OS), which is the removal of fallopian tubes during hysterectomy or instead of tubal ligation without removal of ovaries, is recommended to prevent ovarian cancer, particularly serous ovarian cancer. However, the effectiveness of OS is still undetermined. <h3>Objective</h3> To examine observed vs expected rates of ovarian cancer among individuals who have undergone OS. <h3>Design, Setting, and Participants</h3> This is a population-based, retrospective cohort study of all individuals in British Columbia, Canada, who underwent OS or a control surgery (hysterectomy alone or tubal ligation) between 2008 and 2017, with follow-up until December 31, 2017. Those with any gynecological cancer diagnosed before or within 6 months of their procedure were excluded. Data analysis was performed from April to August 2021. <h3>Exposures</h3> Removal of both fallopian tubes at the time of hysterectomy or instead of tubal ligation while leaving ovaries intact. <h3>Main Outcomes and Measures</h3> An ovarian cancer diagnosis listed in the British Columbia Cancer Registry. Age-specific rates of epithelial and serous ovarian cancer in the control group were combined with the specific follow-up time in the OS group to calculate expected numbers (and 95% CIs) of ovarian cancers in the OS group. These were compared with observed numbers. Age-adjusted expected and observed numbers of breast and colorectal cancers were also examined in the OS group. <h3>Results</h3> There were 25 889 individuals who underwent OS (mean [SD] age, 40.2 [7.1] years; median [IQR] follow-up, 3.2 [1.6-5.1] years) and 32 080 who underwent hysterectomy alone or tubal ligation (mean [SD] age, 38.2 [7.9] years; median [IQR] follow-up, 7.3 [4.6-8.7] years). There were no serous ovarian cancers in the OS group and 5 or fewer epithelial ovarian cancers. The age-adjusted expected number was 5.27 (95% CI, 1.78-19.29) serous cancers and 8.68 (95% CI, 3.36-26.58) epithelial ovarian cancers. Age-adjusted expected vs observed numbers of breast cancers (22.1 expected vs 23 observed) and colorectal cancers (9.35 expected vs 8 observed) were not significantly different. <h3>Conclusions and Relevance</h3> In this cohort study, the OS group had significantly fewer serous and epithelial ovarian cancers than were expected according to the rate at which they arose in the control group. These findings suggest that OS is associated with reduced ovarian cancer risk.
The Diseases of Infants and Children.
Journal: JAMA (1920)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
A human antibody reveals a conserved site on beta-coronavirus spike proteins and confers protection against SARS-CoV-2 infection
Authors: Panpan Zhou, Meng Yuan, Ge Song, Nathan Beutler, Namir Shaabani, Deli Huang, Wan-ting He, Xueyong Zhu, Sean Callaghan, Peter Yong, Fabio Anzanello, Linghang Peng, James Ricketts, Mara Parren, Elijah Garcia, Stephen A. Rawlings, Davey M. Smith, David Nemazee, John R. Teijaro, Thomas F. Rogers, Ian A. Wilson, Dennis R. Burton, Raiees Andrabi
Journal: Science Translational Medicine (2022)

Broadly neutralizing antibodies (bnAbs) to coronaviruses (CoVs) are valuable in their own right as prophylactic and therapeutic reagents to treat diverse CoVs and as templates for rational pan-CoV vaccine design. We recently described a bnAb, CC40.8, from a CoV disease 2019 (COVID-19) convalescent donor that exhibits broad reactivity with human β-CoVs. Here, we showed that CC40.8 targets the conserved S2 stem helix region of the CoV spike fusion machinery. We determined a crystal structure of CC40.8 Fab with a SARS-CoV-2 S2 stem peptide at 1.6-Å resolution and found that the peptide adopted a mainly helical structure. Conserved residues in β-CoVs interacted with CC40.8 antibody, thereby providing a molecular basis for its broad reactivity. CC40.8 exhibited in vivo protective efficacy against SARS-CoV-2 challenge in two animal models. In both models, CC40.8-treated animals exhibited less weight loss and reduced lung viral titers compared to controls. Furthermore, we noted that CC40.8-like bnAbs are relatively rare in human COVID-19 infection, and therefore, their elicitation may require rational structure-based vaccine design strategies. Overall, our study describes a target on β-CoV spike proteins for protective antibodies that may facilitate the development of pan–β-CoV vaccines.
Pushing for change: a qualitative study of the experiences of elite athletes during pregnancy
Authors: Margie H Davenport, Autumn Nesdoly, Lauren Ray, Jane S Thornton, Rshmi Khurana, Tara-Leigh F McHugh
Journal: British Journal of Sports Medicine (2022)

Athletes train and compete at the elite level during their reproductive years, yet sport policies that support pregnant athletes are lacking. The experiences of elite athletes during pregnancy are vastly under-represented, and such voices are needed to support evidence-informed policy. Thus, the purpose of this qualitative study was to describe the experiences of elite female athletes as they navigate pregnancy, and to identify sport policy considerations regarding participation during pregnancy.Twenty athletes (mean age 35±5 years) who, within the last 5 years, had trained or competed at the elite level immediately prior to becoming pregnant were included. Data were generated via one-on-one semistructured interviews that were audio-recorded, transcribed verbatim and analysed through a process of content analysis.The findings of this study are represented by one overarching message: mother versus athlete, and five main themes: (1) pregnancy planning and fertility, (2) pregnancy disclosure and discrimination, (3) training pregnant athletic bodies, (4) safety concerns, and (5) supportive network and equitable funding.In-depth stories shared by participants highlight the many significant decisions athletes must make as they navigate pregnancy alongside elite sport participation. The shared experiences of pregnant athletes highlight clear challenges that should be considered in the development of sport policy and practices that are inclusive and supportive of female athletes.
ART OF PHILADELPHIA MEDICINE
Journal: JAMA (1965)

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