tbuckley/cabot-search huggingface dataset:
Changes in T-cell subsets and clonal repertoire during chemoimmunotherapy with pembrolizumab and paclitaxel or capecitabine for metastatic triple-negative breast cancer
Authors: Brie Chun, Joanna Pucilowska, ShuChing Chang, Isaac Kim, Benjamin Nikitin, Yoshinobu Koguchi, William L Redmond, Brady Bernard, Venkatesh Rajamanickam, Nathan Polaske, Paul A Fields, Valerie Conrad, Mark Schmidt, Walter J Urba, Alison K Conlin, Heather L McArthur, David B Page
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Chemoimmunotherapy is a standard treatment for triple-negative breast cancer (TNBC), however, the impacts of different chemotherapies on T-cell populations, which could correlate with clinical activity, are not known. Quantifying T-cell populations with flow cytometry and T-cell receptor (TCR) immunosequencing may improve our understanding of how chemoimmunotherapy affects T-cell subsets, and to what extent clonal shifts occur during treatment. TCR immunosequencing of intratumoral T cells may facilitate the identification and monitoring of putatively tumor-reactive T-cell clones within the blood. Methods Blood and tumor biopsies were collected from patients with metastatic TNBC enrolled in a phase Ib clinical trial of first or second-line pembrolizumab with paclitaxel or capecitabine. Using identical biospecimen processing protocols, blood samples from a cohort of patients treated for early-stage breast cancer were obtained for comparison. Treatment-related immunological changes in peripheral blood and intratumoral T cells were characterized using flow cytometry and TCR immunosequencing. Clonal proliferation rates of T cells were compared based on intratumoral enrichment. Results When combined with pembrolizumab, paclitaxel and capecitabine resulted in similar time-dependent lymphodepletions across measured peripheral T-cell subsets. Their effects were more modest than that observed following curative-intent dose-dense anthracycline and cyclophosphamide (ddAC) (average fold-change in CD3 + cells, capecitabine: −0.42, paclitaxel: −0.56, ddAC: −1.21). No differences in T-cell clonality or richness were observed following capecitabine or paclitaxel-based treatments. Regression modeling identified differences in the emergence of novel T-cell clones that were not detected at baseline (odds compared with ddAC, capecitabine: 0.292, paclitaxel: 0.652). Pembrolizumab with paclitaxel or capecitabine expanded T-cell clones within tumors; however, these clones did not always expand within the blood. Proliferation rates within the blood were similar between clones that were enriched and those that were not enriched within tumors. Conclusion Chemoimmunotherapy for metastatic TNBC with pembrolizumab and capecitabine or paclitaxel resulted in similar peripheral T-cell subset lymphodepletion without altering T-cell clonal diversity. Regression modeling methods are applicable in immune monitoring studies, such as this to identify the odds of novel T-cell clones emerging during treatment, and proliferation rates of tumor-enriched T-cell clones.
The dawn of digital public health in Europe: Implications for public health policy and practice
Authors: Brian Li Han Wong, Laura Maaß, Alice Vodden, Robin van Kessel, Sebastiano Sorbello, Stefan Buttigieg, Anna Odone
Journal: The Lancet Regional Health - Europe (2022)

The COVID-19 pandemic has highlighted the importance of digital health technologies and the role of effective surveillance systems. While recent events have accelerated progress towards the expansion of digital public health (DPH), there remains significant untapped potential in harnessing, leveraging, and repurposing digital technologies for public health. There is a particularly growing need for comprehensive action to prepare citizens for DPH, to regulate and effectively evaluate DPH, and adopt DPH strategies as part of health policy and services to optimise health systems improvement. As representatives of the European Public Health Association's (EUPHA) Digital Health Section, we reflect on the current state of DPH, share our understanding at the European level, and determine how the application of DPH has developed during the COVID-19 pandemic. We also discuss the opportunities, challenges, and implications of the increasing digitalisation of public health in Europe.
Selective reduction of astrocyte apoE3 and apoE4 strongly reduces Aβ accumulation and plaque-related pathology in a mouse model of amyloidosis
Authors: Thomas E. Mahan, Chao Wang, Xin Bao, Ankit Choudhury, Jason D. Ulrich, David M. Holtzman
Journal: Molecular Neurodegeneration (2022)

Abstract Background One of the key pathological hallmarks of Alzheimer disease (AD) is the accumulation of the amyloid-β (Aβ) peptide into amyloid plaques. The apolipoprotein E ( APOE ) gene is the strongest genetic risk factor for late-onset AD and has been shown to influence the accumulation of Aβ in the brain in an isoform-dependent manner. ApoE can be produced by different cell types in the brain, with astrocytes being the largest producer of apoE, although reactive microglia also express high levels of apoE. While studies have shown that altering apoE levels in the brain can influence the development of Aβ plaque pathology, it is not fully known how apoE produced by specific cell types, such as astrocytes, contributes to amyloid pathology. Methods We utilized APOE knock-in mice capable of having APOE selectively removed from astrocytes in a tamoxifen-inducible manner and crossed them with the APP/PS1-21 mouse model of amyloidosis. We analyzed the changes to Aβ plaque levels and assessed the impact on cellular responses to Aβ plaques when astrocytic APOE is removed. Results Tamoxifen administration was capable of strongly reducing apoE levels in the brain by markedly reducing astrocyte apoE, while microglial apoE expression remained. Reduction of astrocytic apoE3 and apoE4 led to a large decrease in Aβ plaque deposition and less compact plaques. While overall Iba1 + microglia were unchanged in the cortex after reducing astrocyte apoE, the expression of the disease-associated microglial markers Clec7a and apoE were lower around amyloid plaques, indicating decreased microglial activation. Additionally, astrocyte GFAP levels are unchanged around amyloid plaques, but overall GFAP levels are reduced in the cortex of female apoE4 mice after a reduction in astrocytic apoE. Finally, while the amount of neuritic dystrophy around remaining individual plaques was increased with the removal of astrocytic apoE, the overall amount of cortical amyloid-associated neuritic dystrophy was significantly decreased. Conclusion This study reveals an important role of astrocytic apoE3 and apoE4 on the deposition and accumulation of Aβ plaques as well as on certain Aβ-associated downstream effects.
Partial loss of function mutations in GINS4 lead to natural killer cell deficiency with neutropenia
Authors: Matilde Conte, Angelo Taglialatela, Giuseppe Leuzzi, Ivan Chinn, Sandra Salinas, Cecilia Poli, Liz Veramendi Espinoza, Alberto Ciccia, James Lupski, Juan Aldave Becerra, Emily Mace, Jordan Orange
Journal: Journal of Allergy and Clinical Immunology (2022)
Medizinische Klinik, Munich
Journal: JAMA (1966)

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
Newborn screening as a fully integrated system to stimulate equity in neonatal screening in Europe
Authors: Maurizio Scarpa, James R. Bonham, Carlo Dionisi-Vici, Johan Prevot, Martine Pergent, Isabelle Meyts, Nizar Mahlaoui, Peter C.J.I. Schielen
Journal: The Lancet Regional Health - Europe (2022)
A novel technique for the treatment of impacted pancreatic stones after pancreatoduodenectomy using transanastomotic fluoroscopic-guided electrohydraulic lithotripsy
Authors: Sho Kitagawa, Shori Ishikawa, Shuzo Monden
Journal: Endoscopy (2022)

Nowadays the role of endoscopic intervention is becoming more important in patients with obstructive pancreatitis. Although a recent study reported that 90 % of patients with obstructing pancreatic stones achieved pancreatic ductal clearance using digital single-operator pancreatoscopy (D-SOP) with electrohydraulic lithotripsy (EHL) or laser lithotripsy [1], endoscopic treatment of obstructive pancreatic stones is still challenging in patients with surgically altered anatomy. Here, we report a novel technique for the treatment of impacted pancreatic stones after pancreatoduodenectomy without using D-SOP.
Abstract 258: Adherence to the Transport Recommendations in the Universal Termination of Resuscitation Rule and Survival After Out-of-Hospital Cardiac Arrest
Authors: Masashi Okubo, David J Wallace, Brian E Grunau, Mohamud R Daya, Clifton W Callaway
Journal: Circulation (2020)

Introduction: Survival after out-of-hospital cardiac arrest (OHCA) varies across emergency medical services (EMS) systems. The contribution of EMS practices variation on the outcome disparities is unclear. We evaluated the association between EMS agency variation in adherence to the transport recommendations in the Universal Termination of Resuscitation (TOR) Rule and survival after OHCA. Methods: We conducted a secondary analysis of the Resuscitation Outcomes Consortium Epistry. We included adults (≥ 18 years) with OHCA for whom EMS providers attempted resuscitation from 2011 through 2015. The main exposure was the proportion of patients for whom the Universal TOR Rule recommended transport (i.e., meeting any one of the following criteria, EMS-witnessed arrest; return of spontaneous circulation prior to transport; or shock delivery prior to transport) among those transported to hospitals, at the level of EMS agency. We then categorized EMS agencies into quartiles. Our primary outcome was survival to hospital discharge. We used multilevel modified Poisson regression model, including patient-level and EMS-level covariates with patients nested within EMS agencies. Results: We included 42,584 EMS-treated OHCAs from 112 EMS agencies. The median proportion of patients for whom the TOR rule recommended transport among those transported was 88.2% (interquartile range [IQR] 76.1-96.7) across EMS agencies. Compared with the patients treated at EMS agencies in the quartile of the lowest proportion (the median proportion 66.7%[ IQR 50.9-71.7]), survival to hospital discharge was associated with treatment at EMS agencies in the second quartile (the median proportion 83.0% [IQR 79.8-85.3]) (adjusted risk ratio [aRR] 1.12, 95% confidence interval [CI] 0.96-1.31), the third quartile (the median proportion 93.0% [IQR 89.7-95.6]) (aRR 1.58, 95% CI 1.32-1.87), and the fourth quartile (the median proportion 100% [IQR 98.5-100]) (aRR 1.86, 95% CI 1.59-2.19). Conclusions: In this large cohort study of adult patients with OHCA, treatment at EMS agencies with higher proportion of patients who met transport criteria of the Universal TOR rule among transported patients was associated with survival to hospital discharge.
BOOKS IN REVIEW 1992
Authors: ERIC J. SEIFTER
Journal: JNCI Journal of the National Cancer Institute (1993)

BOOKS IN REVIEW 1992 Get access Breast Diseases, 2nd Edition . Jay R. Harris , Samuel Hellman , I. Craig Henderson , David W. Kinne , eds. Philadelphia ; J. B. Lippincott , 1991 . 928 pp., illus. $149.50. Reviewed by Marshall A. Levine (firstcitation) and Gabriel N. Hortobagyi (second citation) (J Natl Cancer Inst 84: 639–640 , 1992 ). ERIC J. SEIFTER ERIC J. SEIFTER Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 2, 20 January 1993, Page 158, https://doi.org/10.1093/jnci/85.2.158 Published: 20 January 1993
Clinical and Economic Burden of Patients With Severe Asthma Untreated With a Biologic in the United States, Overall and by Blood Eosinophil and Level of Asthma Control
Authors: Karynsa Kilpatrick, Heejoo Jo, Pooja Desai, Jean-Pierre Llanos Ackert, Pallavi Rane, Chris Ambrose, Yen Chung, John Oppenheimer, Stanley Goldstein
Journal: Journal of Allergy and Clinical Immunology (2022)
The Dynamic State of Body Constituents
Journal: JAMA (1942)

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
CDK19 regulates the proliferation of hematopoietic stem cells and acute myeloid leukemia cells by suppressing p53-mediated transcription of p21
Authors: Zihao Zhang, Yukai Lu, Yan Qi, Yang Xu, Song Wang, Fang Chen, Mingqiang Shen, Mo Chen, Naicheng Chen, Lijing Yang, Shilei Chen, Fengchao Wang, Yongping Su, Mengjia Hu, Junping Wang
Journal: Leukemia (2022)
Targeting OXPHOS and the electron transport chain in cancer; Molecular and therapeutic implications
Authors: John Greene, Ashvina Segaran, Simon Lord
Journal: Seminars in Cancer Biology (2022)

Oxidative phosphorylation (OXPHOS) takes place in mitochondria and is the process whereby cells use carbon fuels and oxygen to generate ATP. Formerly OXPHOS was thought to be reduced in tumours and that glycolysis was the critical pathway for generation of ATP but it is now clear that OXPHOS, at least in many tumour types, plays a critical role in delivering the bioenergetic and macromolecular anabolic requirements of cancer cells. There is now great interest in targeting the OXPHOS and the electron transport chain for cancer therapy and in this review article we describe current therapeutic approaches and challenges.
Two clinically distinct cases of infant hemispheric glioma carrying <i>ZCCHC8:ROS1</i> fusion and responding to entrectinib
Authors: Ludmila Papusha, Margarita Zaytseva, Agnesa Panferova, Alexander Druy, Andge Valiakhmetova, Anton Artemov, Ekaterina Salnikova, Alexey Kislyakov, Evgeny Imyanitov, Alexander Karachunsky, Alexey Maschan, Eugene I Hwang, Galina Novichkova, Roger J Packer
Journal: Neuro-Oncology (2022)
Automobile drivers and cerebrovascular insufficiency
Authors: W. J. Foley
Journal: JAMA (1969)

Cerebrovascular insufficiency can cause transient neurologic dysfunction without warning to the patient. As such, this condition can suddenly and seriously impair the ability of a person to drive an automobile. Cerebrovascular insufficiency deserves more attention as a cause of transient driver disability. Physicians have an important role in evaluating driver limitations and should advise patients with cerebrovascular insufficiency not to drive an automobile.
International Comments
Journal: JAMA (1969)

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
EFFECTS OF SMOKING AND SMOKING CESSATION ON ENDOTHELIAL FUNCTION: ONE-YEAR OUTCOMES FROM A RANDOMIZED CLINICAL TRIAL
Authors: Linda K. Gossett, Megan E. Piper, Heather M. Johnson, Susan E. Aeschlimann, Claudia E. Korcarz, Timothy B. Baker, Michael C. Fiore, James H. Stein
Journal: Journal of the American College of Cardiology (2010)
Biodegradable Bismuth‐Based Nano‐Heterojunction for Enhanced Sonodynamic Oncotherapy through Charge Separation Engineering
Authors: Kang Song, Jun Du, Xiang Wang, Lulu Zheng, Ruizhuo Ouyang, Yuhao Li, Yuqing Miao, Dawei Zhang
Journal: Advanced Healthcare Materials (2022)

Sonodynamic therapy is a noninvasive treatment method that generates reactive oxygen species (ROS) triggered by ultrasound, to achieve oxidative damage to tumors. However, methods are required to improve the efficiency of ROS generation and achieve continuous oxidative damage. A ternary heterojunction sonosensitizer composed of Bi@BiO2-x @Bi2 S3 -PEG (BOS) to achieve thermal injury-assisted continuous sonodynamic therapy for tumors is prepared. The oxygen vacancy in BOS can capture hot electrons and promotes the separation of hot carriers on the bismuth surface. The local electric field induced by localized surface plasmon resonance also contributes to the rapid transfer of electrons. Therefore, BOS not only possesses the functions of each component but also exhibits higher catalytic activity to generate ROS. Meanwhile, BOS continuously consumes glutathione, which is conducive to its biodegradation and achieves continuous oxidative stress injury. In addition, the photothermal conversion of BOS under near-infrared irradiation helps to achieve thermal tumor damage and further relieves tumor hypoxia, thus amplifying the sonodynamic therapeutic efficacy. This process not only provides a strategy for thermal damage to amplify the efficacy of sonodynamic therapy, but also expands the application of bismuth-based heterojunction nanomaterials as sonosensitizers in sonodynamic therapy.
<i>NEJM Evidence</i> — A New Journal in the NEJM Group Family
Authors: Chana A. Sacks, C. Corey Hardin, Sharon-Lise Normand, Siri Kadire, Kate Takvorian, Neil Galloway, Rebekah Linga, Patrick Hannon, Jeffrey Drazen, Eric Rubin
Journal: New England Journal of Medicine (2022)
Regular Acetaminophen Use and Blood Pressure in People With Hypertension: The PATH-BP Trial
Authors: Iain M. MacIntyre, Emma J. Turtle, Tariq E. Farrah, Catriona Graham, James W. Dear, David J. Webb, Morag McCallum, Vanessa Melville, Henry Fok, Jame C. McCrae, Ashish Sule, Thomas M. Caparrotta, Nicholas S. Kirkby, Jane A. Mitchell
Journal: Circulation (2022)

Acetaminophen is widely used as first-line therapy for chronic pain because of its perceived safety and the assumption that, unlike nonsteroidal anti-inflammatory drugs, it has little or no effect on blood pressure (BP). Although observational studies suggest that acetaminophen may increase BP, clinical trials are lacking. We, therefore, studied the effects of regular acetaminophen dosing on BP in individuals with hypertension.In this double-blind, placebo-controlled, crossover study, 110 individuals were randomized to receive 1 g acetaminophen 4× daily or matched placebo for 2 weeks followed by a 2-week washout period before crossing over to the alternate treatment. At the beginning and end of each treatment period, 24-hour ambulatory BPs were measured. The primary outcome was a comparison of the change in mean daytime systolic BP from baseline to end of treatment between the placebo and acetaminophen arms.One-hundred three patients completed both arms of the study. Regular acetaminophen, compared with placebo, resulted in a significant increase in mean daytime systolic BP (132.8±10.5 to 136.5±10.1 mm Hg [acetaminophen] vs 133.9±10.3 to 132.5±9.9 mm Hg [placebo]; P<0.0001) with a placebo-corrected increase of 4.7 mm Hg (95% CI, 2.9-6.6) and mean daytime diastolic BP (81.2±8.0 to 82.1±7.8 mm Hg [acetaminophen] vs 81.7±7.9 to 80.9±7.8 mm Hg [placebo]; P=0.005) with a placebo-corrected increase of 1.6 mm Hg (95% CI, 0.5-2.7). Similar findings were seen for 24-hour ambulatory and clinic BPs.Regular daily intake of 4 g acetaminophen increases systolic BP in individuals with hypertension by ≈5 mm Hg when compared with placebo; this increases cardiovascular risk and calls into question the safety of regular acetaminophen use in this situation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01997112. URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2013-003204-40.
Beyond Calais.
Journal: BMJ (1976)

suppress ineffective attempts to cough and to relieve general distress.Tolerance is not a problem, and it is rarely necessary to increase the dose.Such a regimen reduces the need for suction of pharyngeal and tracheal secretions.It is a time when support and companionship are of paramount importance.Though the doctor may feel powerless in the face of death, his continued attendance (indicating that he will stand by the patient no matter what happens) is of inestimable value.After the first bad coughing or choking attack the patient will usually need carefully expressed reassurance that he will not be left to die alone or choke to death on his own secretions.Death generally occurs as a result of varying combinations of aspiration pneumonitis, hypostatic bronchopneumonia, and carbon-dioxide narcosis, and both the family and nurses may need to have the inappropriateness of antibiotic treatment explained.
HuR ablation or inhibition reduces lung inflammation and Th2 cytokine expression in mouse model of allergic asthma and in asthmatic CD4+ T cells
Authors: Fatemeh Fattahi, Jason Ellis, Michael Sylvester, Kristin Bahleda, Samuel Hietanen, Njira Lugogo, Ulus Atasoy
Journal: Journal of Allergy and Clinical Immunology (2022)