tbuckley/cabot-search huggingface dataset:
Perioperative Immunization for Splenectomy and the Surgeon’s Responsibility
Authors: Fabio Casciani, Maxwell T. Trudeau, Charles M. Vollmer
Journal: JAMA Surgery (2020)

Patients who have had splenectomy have a lifelong risk of overwhelming postsplenectomy infection (OPSI), a condition associated with high mortality rates. Surgeons must be aware of the rationale of vaccination in the case of splenectomy, to provide appropriate immunization in the perioperative time.English-language articles published from January 1, 1990, to December 31, 2019, were retrieved from MEDLINE/PubMed, Cochrane Library, and ClinicalTrials.gov databases. Randomized clinical trials as well as systematic reviews and observational studies were considered. Asplenia yields an impairment of both innate and adaptive immunity, thus increasing the risk of severe encapsulated bacterial infections. Current epidemiology of OPSI ranges from 0.1% to 8.5% but is hard to ascertain because of ongoing shifts in patients' baseline conditions and vaccine penetration. Despite the lack of randomized clinical trials, immunization appears to be effective in reducing OPSI incidence. Unfortunately, vaccination coverage is still suboptimal, with a great variability in vaccination rates being reported across institutions and time frames. Notably, current guidelines do not advocate any particular health care qualification responsible for vaccine prescription or administration. Given the dearth of high-level basic science or clinical evidence, the optimal vaccination timing and the need for booster doses are not yet well established. Although almost all guidelines indicate to not administer vaccines within 14 days before and after surgery, most data suggest that immunization might be effective even in the immediate perioperative time, thus placing the surgeon in a primary position for vaccine delivery. Furthermore, revaccination schedules are the target of ongoing debates, since a vaccine-driven hyporesponsiveness has been postulated.In patients who have undergone splenectomy, OPSI might be effectively prevented by proper immunization. Surgeons have the primary responsibility for achieving adequate, initial immunization in the setting of both planned and urgent splenectomy.
Donald Trump, Boris Johnson, and other leaders win Ig Nobel awards for teaching people about life and death
Authors: Janice Hopkins Tanne
Journal: BMJ (2020)

Politicians are better than doctors or scientists at medical education. Leaders such as Donald Trump, Vladimir Putin, Alexander Lukashenko, Boris Johnson, Jair Bolsonaro, Narendra Modi, Andres Manuel Lopez Obrador, Recep Tayyip Erdogan, and Gurbanguly Berdimuhamedow of Turkmenistan have used covid-19 to teach their citizens about life and death. For their efforts they jointly won the 2020 Ig Nobel prize for medical education, although none of them showed up to make an acceptance speech.

The Ig Nobel awards are given for achievements that first make people laugh and then make them think. The 30th awards were virtually handed out on 17 September by real Nobel prize winners at …
CRISPR/Cas9-Mediated Point Mutation in <i>Nkx3.1</i> Prolongs Protein Half-Life and Reverses Effects <i>Nkx3.1</i> Allelic Loss
Authors: Cai Bowen, Maho Shibata, Hailan Zhang, Sarah K. Bergren, Michael M. Shen, Edward P. Gelmann
Journal: Cancer Research (2020)

Abstract NKX3.1 is the most commonly deleted gene in prostate cancer and is a gatekeeper suppressor. NKX3.1 is haploinsufficient, and pathogenic reduction in protein levels may result from genetic loss, decreased transcription, and increased protein degradation caused by inflammation or PTEN loss. NKX3.1 acts by retarding proliferation, activating antioxidants, and enhancing DNA repair. DYRK1B-mediated phosphorylation at serine 185 of NKX3.1 leads to its polyubiquitination and proteasomal degradation. Because NKX3.1 protein levels are reduced, but never entirely lost, in prostate adenocarcinoma, enhancement of NKX3.1 protein levels represents a potential therapeutic strategy. As a proof of principle, we used CRISPR/Cas9-mediated editing to engineer in vivo a point mutation in murine Nkx3.1 to code for a serine to alanine missense at amino acid 186, the target for Dyrk1b phosphorylation. Nkx3.1S186A/−, Nkx3.1+/−, and Nkx3.1+/+ mice were analyzed over one year to determine the levels of Nkx3.1 expression and effects of the mutant protein on the prostate. Allelic loss of Nkx3.1 caused reduced levels of Nkx3.1 protein, increased proliferation, and prostate hyperplasia and dysplasia, whereas Nkx3.1S186A/− mouse prostates had increased levels of Nkx3.1 protein, reduced prostate size, normal histology, reduced proliferation, and increased DNA end labeling. At 2 months of age, when all mice had normal prostate histology, Nkx3.1+/− mice demonstrated indices of metabolic activation, DNA damage response, and stress response. These data suggest that modulation of Nkx3.1 levels alone can exert long-term control over premalignant changes and susceptibility to DNA damage in the prostate. Significance: These findings show that prolonging the half-life of Nkx3.1 reduces proliferation, enhances DNA end-labeling, and protects from DNA damage, ultimately blocking the proneoplastic effects of Nkx3.1 allelic loss.
Early-life respiratory syncytial virus lower respiratory tract infection in a South African birth cohort: epidemiology and effect on lung health
Authors: Heather J Zar, Polite Nduru, Jacob A M Stadler, Diane Gray, Whitney Barnett, Maia Lesosky, Landon Myer, Mark P Nicol
Journal: The Lancet Global Health (2020)

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) in children. Early-life RSV LRTI might affect long-term health but there are few data from low-income and middle-income countries. We investigated the epidemiology and effect of early-life RSV LRTI on lung health in a South African birth cohort.
One Step at a Time — Clinical Evidence That KRAS Is Indeed Druggable
Authors: Patricia M. LoRusso, Judith S. Sebolt-Leopold
Journal: New England Journal of Medicine (2020)

Overall survival among patients with advanced-stage KRASG12C non–small-cell lung cancer (NSCLC) or colorectal cancer is approximately 1 to 2 years; this startling statistic has fueled nearly four decades of research dedicated to the search for a KRAS-targeted drug.1,2 Because RAS has picomolar affinity for guanosine triphosphate (GTP) and intracellular GTP concentrations are exceedingly high, early strategies to find compounds that preferentially bind to the RAS–GTP pocket failed. Other strategies have attempted to interfere with RAS activation by preventing its membrane localization or by inhibiting downstream kinase signaling, but these also failed because of resistance stemming from compensatory signaling. Renewed interest . . .
CANOMAD: a neurological monoclonal gammopathy of clinical significance that benefits from B-cell–targeted therapies
Authors: Marie Le Cann, Françoise Bouhour, Karine Viala, Laurence Simon, Céline Tard, Cédric Rossi, Guillaume Morel, Emmeline Lagrange, Laurent Magy, Alain Créange, Maud Michaud, Jérôme Franques, Andoni Echaniz-Laguna, Jean-Christophe Antoine, Marine Baron, Bertrand Arnulf, Angela Puma, Emilien Delmont, Thierry Maisonobe, Véronique Leblond, Damien Roos-Weil
Journal: Blood (2020)
Novel Cardiovascular Magnetic Resonance Model to Distinguish Immunoglobulin Light Chain From Transthyretin Cardiac Amyloidosis
Authors: Jeremy A. Slivnick, Matthew S. Tong, Haikady N. Nagaraja, Mohamed B. Elamin, Alex Wallner, Aaron O’Brien, Subha V. Raman, Karolina M. Zareba
Journal: JACC. Cardiovascular imaging (2020)
Pharmacologic Suppression of B7-H4 Glycosylation Restores Antitumor Immunity in Immune-Cold Breast Cancers
Authors: Xinxin Song, Zhuan Zhou, Hongchun Li, Yifan Xue, Xinghua Lu, Ivet Bahar, Oliver Kepp, Mien-Chie Hung, Guido Kroemer, Yong Wan
Journal: Cancer Discovery (2020)

Despite widespread utilization of immunotherapy, treating immune-cold tumors has proved to be a challenge. Here, we report that expression of the immune checkpoint molecule B7-H4 is prevalent among immune-cold triple-negative breast cancers (TNBC), where its expression inversely correlates with that of PD-L1. Glycosylation of B7-H4 interferes with its interaction/ubiquitination by AMFR, resulting in B7-H4 stabilization. B7-H4 expression inhibits doxorubicin-induced cell death through the suppression of eIF2α phosphorylation required for calreticulin exposure vis-à-vis the cancer cells. NGI-1, which inhibits B7-H4 glycosylation causing its ubiquitination and subsequent degradation, improves the immunogenic properties of cancer cells treated with doxorubicin, enhancing their phagocytosis by dendritic cells and their capacity to elicit CD8+ IFNγ-producing T-cell responses. In preclinical models of TNBC, a triple combination of NGI-1, camsirubicin (a noncardiotoxic doxorubicin analogue) and PD-L1 blockade was effective in reducing tumor growth. Collectively, our findings uncover a strategy for targeting the immunosuppressive molecule B7-H4. SIGNIFICANCE: This work unravels the regulation of B7-H4 stability by ubiquitination and glycosylation, which affects tumor immunogenicity, particularly regarding immune-cold breast cancers. The inhibition of B7-H4 glycosylation can be favorably combined with immunogenic chemotherapy and PD-L1 blockade to achieve superior immuno-infiltration of cold tumors, as well as improved tumor growth control.See related commentary by Pearce and Läubli, p. 1789.This article is highlighted in the In This Issue feature, p. 1775.
Physicians and Social Determinants of Health—Reply
Authors: Nason Maani, Sandro Galea
Journal: JAMA (2020)

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
Effect of Outpatient Rehabilitation on Functional Mobility After Single Total Knee Arthroplasty
Authors: Chinghui Jean Hsieh, Gerben DeJong, Michele Vita, Alexander Zeymo, Sameer Desale
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Even without evidence, rehabilitation practitioners continue to introduce new interventions to enhance the mobility outcomes for the increasing population with a recent total knee arthroplasty (TKA). <h3>Objective</h3> To compare post-TKA functional mobility outcomes among 3 newly developed physical therapy protocols with a standard-of-care post-TKA rehabilitation protocol. <h3>Design, Setting, and Participants</h3> This randomized clinical trial included 4 study arms implemented in 15 outpatient clinics within a single health system in the Baltimore, Maryland, and Washington, District of Columbia, region from October 2013 to April 2017. Participants included patients who underwent elective unilateral TKA, were aged 40 years and older, and began outpatient physical therapy within 24 days after TKA. A total of 505 patients were screened and 386 participants were enrolled. Patients provided informed consent and were randomly assigned to 1 of 4 groups. Blinding patients and treating therapists was not feasible owing to the nature of the intervention. Analysis was conducted under the modified intent-to-treat principle from October 2017 to May 2019. <h3>Interventions</h3> The control group used a standard recumbent bike for 15 to 20 minutes each session. Interventions used 1 of 3 modalities for 15 to 20 minutes each session: (1) a body weight-adjustable treadmill, (2) a patterned electrical neuromuscular stimulation device, or (3) a combination of the treadmill and electrical neuromuscular stimulation. <h3>Main Outcomes and Measures</h3> Outcomes included the Activity Measure for Post-acute Care basic mobility score, a patient-reported outcome measure, and the 6-minute walk test. Outcomes were measured at baseline, monthly, and on discharge from outpatient therapy. <h3>Results</h3> Data from 363 patients (mean [SD] age, 63.4 [7.9] years; 222 [61.2%] women) were included in the final analysis, including 92 participants randomized to the control group, 91 participants randomized to the treadmill group, 90 participants randomized to the neuromuscular stimulation device group, and 90 participants randomized to the combination intervention group. Activity Measure for Post-acute Care scores at discharge were similar across groups, ranging from 61.1 to 61.3 (<i>P</i> = .99) with at least 9.0 points improvement (<i>P</i> = .80) since baseline. The distances as measured by the 6-minute walking test were not statistically different across groups (range, 382.9-404.5 m;<i>P</i> = .60). <h3>Conclusions and Relevance</h3> This randomized clinical trial found no statistically or clinically significant differences in outcomes across the 4 arms. Because outcomes were similar among arms, clinicians should instead consider relative cost in tailoring TKA rehabilitation. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02426190
Change the Trainee, or Change the Training Environment?—Reply
Authors: William Clifton
Journal: JAMA Surgery (2020)

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 Surgery 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 Surgery journal
Digital Negotiations: Navigating Parental Permission and Adolescent Assent for On-Line Survey Participation
Authors: Holly A. Taylor, Douglas B. Mogul
Journal: The American Journal of Bioethics (2020)

"Digital Negotiations: Navigating Parental Permission and Adolescent Assent for On-Line Survey Participation." The American Journal of Bioethics, 20(10), pp. 84–85
Searching for Goldilocks: How Evolution and Ecology Can Help Uncover More Effective Patient-Specific Chemotherapies
Authors: Derek S. Park, Kimberly A. Luddy, Mark Robertson-Tessi, Cliona O'Farrelly, Robert A. Gatenby, Alexander R.A. Anderson
Journal: Cancer Research (2020)

Deaths from cancer are mostly due to metastatic disease that becomes resistant to therapy. A mainstay treatment for many cancers is chemotherapy, for which the dosing strategy is primarily limited by patient toxicity. While this MTD approach builds upon the intuitively appealing principle that maximum therapeutic benefit is achieved by killing the largest possible number of cancer cells, there is increasing evidence that moderation might allow host-specific features to contribute to success. We believe that a "Goldilocks Window" of submaximal chemotherapy will yield improved overall outcomes. This window combines the complex interplay of cancer cell death, immune activity, emergence of chemoresistance, and metastatic dissemination. These multiple activities driven by chemotherapy have tradeoffs that depend on the specific agents used as well as their dosing levels and schedule. Here we present evidence supporting the idea that MTD may not always be the best approach and offer suggestions toward a more personalized treatment regime that integrates insights into patient-specific eco-evolutionary dynamics.
Abstract 15737: The Association Between Congestion and Outcomes for Patients Treated With Sacubitril-Valsartan Compared to Enalapril in the PIONEER-HF Trial
Authors: Marc D Samsky, Eric J Velazquez, Eugene Braunwald, David A Morrow, Hillary Mulder, Hrishikesh Chakraborty, Carol Duffy, Ricardo Rocha, Andrew P Ambrosy, Adam D Devore
Journal: Circulation (2019)

Background: Congestion remains the most common reason for hospitalization among patients with acute decompensated heart failure (ADHF). How treatment with sacubitril/valsartan (S/V) affects outcome...
SPECT imaging of distribution and retention of a brain-penetrating bispecific amyloid-β antibody in a mouse model of Alzheimer’s disease
Authors: Tobias Gustavsson, Stina Syvänen, Paul O’Callaghan, Dag Sehlin
Journal: Translational Neurodegeneration (2020)

Abstract Background Alzheimer’s disease (AD) immunotherapy with antibodies targeting amyloid-β (Aβ) has been extensively explored in clinical trials. The aim of this study was to study the long-term brain distribution of two radiolabeled monoclonal Aβ antibody variants – RmAb158, the recombinant murine version of BAN2401, which has recently demonstrated amyloid removal and reduced cognitive decline in AD patients, and the bispecific RmAb158-scFv8D3, which has been engineered for enhanced brain uptake via transferrin receptor-mediated transcytosis. Methods A single intravenous injection of iodine-125 ( 125 I)-labeled RmAb158-scFv8D3 or RmAb158 was administered to AD transgenic mice (tg-ArcSwe). In vivo single-photon emission computed tomography was used to investigate brain retention and intrabrain distribution of the antibodies over a period of 4 weeks. Activity in blood and brain tissue was measured ex vivo and autoradiography was performed in combination with Aβ and CD31 immunostaining to investigate the intrabrain distribution of the antibodies and their interactions with Aβ. Results Despite faster blood clearance, [ 125 I]RmAb158-scFv8D3 displayed higher brain exposure than [ 125 I]RmAb158 throughout the study. The brain distribution of [ 125 I]RmAb158-scFv8D3 was more uniform and coincided with parenchymal Aβ pathology, while [ 125 I]RmAb158 displayed a more scattered distribution pattern and accumulated in central parts of the brain at later times. Ex vivo autoradiography indicated greater vascular escape and parenchymal Aβ interactions for [ 125 I]RmAb158-scFv8D3, whereas [ 125 I]RmAb158 displayed retention and Aβ interactions in lateral ventricles. Conclusions The high brain uptake and uniform intrabrain distribution of RmAb158-scFv8D3 highlight the benefits of receptor-mediated transcytosis for antibody-based brain imaging. Moreover, it suggests that the alternative transport route of the bispecific antibody contributes to improved efficacy of brain-directed immunotherapy.
Author Correction: WNT signaling and AHCTF1 promote oncogenic MYC expression through super-enhancer-mediated gene gating
Authors: Barbara A. Scholz, Noriyuki Sumida, Carolina Diettrich Mallet de Lima, Ilyas Chachoua, Mirco Martino, Ilias Tzelepis, Andrej Nikoshkov, Honglei Zhao, Rashid Mehmood, Emmanouil G. Sifakis, Deeksha Bhartiya, Anita Göndör, Rolf Ohlsson
Journal: Nature Genetics (2020)
High-Flow Nasal Cannula as Rescue Therapy in Bronchiolitis—Reply
Authors: Shawn L. Ralston
Journal: JAMA Pediatrics (2020)

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
Genomic Analysis of Germline Variation Associated with Survival of Patients with Colorectal Cancer Treated with Chemotherapy Plus Biologics in CALGB/SWOG 80405 (Alliance)
Authors: Federico Innocenti, Alexander B. Sibley, Sushant A. Patil, Amy S. Etheridge, Chen Jiang, Fang-Shu Ou, Stefanie D. Howell, Sarah J. Plummer, Graham Casey, Monica M. Bertagnolli, Howard L. McLeod, James T. Auman, Charles D. Blanke, Yoichi Furukawa, Alan P. Venook, Michiaki Kubo, Heinz-Josef Lenz, Joel S. Parker, Mark J. Ratain, Kouros Owzar
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Irinotecan/5-fluorouracil (5-FU; FOLFIRI) or oxaliplatin/5-FU (FOLFOX), combined with bevacizumab or cetuximab, are approved, first-line treatments for metastatic colorectal cancer (mCRC). We aimed at identifying germline variants associated with survival in patients with mCRC treated with these regimens in Cancer and Leukemia Group B/SWOG 80405. Experimental Design: Patients with mCRC receiving either FOLFOX or FOLFIRI were randomized to either cetuximab or bevacizumab. DNA from peripheral blood was genotyped for approximately 700,000 SNPs. The association between SNPs and overall survival (OS) was tested in 613 patients of genetically estimated European ancestry using Cox proportional hazards models. Results: The four most significant SNPs associated with OS were three haplotypic SNPs between microsomal glutathione S-transferase 1 (MGST1) and LIM domain only 3 (LMO3, representative HR, 1.56; P = 1.30 × 10−6), and rs11644916 in AXIN1 (HR, 1.39, P = 4.26 × 10−6). AXIN1 is a well-established tumor suppressor gene in colorectal cancer, and rs11644916 (G&amp;gt;A) conferred shorter OS. Median OS for patients with the AA, AG, or GG genotypes was 18.4, 25.6, or 36.4 months, respectively. In 90 patients with stage IV colorectal cancer from The Cancer Genome Atlas (TCGA), rs11649255 in AXIN1 [in almost complete linkage disequilibrium (LD) with rs11644916], was associated with shorter OS (HR, 2.24, P = 0.0096). Using rs11648673 in AXIN1 (in very high LD with rs11644916 and with functional evidence), luciferase activity in three colorectal cancer cell lines was reduced. Conclusions: This is the first large genome-wide association study ever conducted in patients with mCRC treated with first-line standard treatment in a randomized phase III trial. A common SNP in AXIN1 conferred worse OS and the effect was replicated in TCGA. Further studies in colorectal cancer experimental models are required.