tbuckley/cabot-search huggingface dataset:
Ablation of Plasma Prekallikrein Decreases Low-Density Lipoprotein Cholesterol by Stabilizing Low-Density Lipoprotein Receptor and Protects Against Atherosclerosis
Authors: Jin-Kai Wang, Yang Li, Xiao-Lu Zhao, Yuan-Bin Liu, Jing Tan, Yu-Ying Xing, Dilare Adi, Yong-Tao Wang, Zhen-Yan Fu, Yi-Tong Ma, Song-Mei Liu, Yong Liu, Yan Wang, Xiong-Jie Shi, Xiao-Yi Lu, Bao-Liang Song, Jie Luo
Journal: Circulation (2022)

High blood cholesterol accelerates the progression of atherosclerosis, which is an asymptomatic process lasting for decades. Rupture of atherosclerotic plaques induces thrombosis, which results in myocardial infarction or stroke. Lowering cholesterol levels is beneficial for preventing atherosclerotic cardiovascular disease. Low-density lipoprotein (LDL) receptor (LDLR) was used as bait to identify its binding proteins in the plasma, and the coagulation factor prekallikrein (PK; encoded by the KLKB1 gene) was revealed. The correlation between serum PK protein content and lipid levels in young Chinese Han people was then analyzed. To investigate the effects of PK ablation on LDLR and lipid levels in vivo, we genetically deleted Klkb1 in hamsters and heterozygous Ldlr knockout mice and knocked down Klkb1 using adeno-associated virus-mediated shRNA in rats. The additive effect of PK and proprotein convertase subtilisin/kexin 9 inhibition also was evaluated. In addition, we applied the anti-PK neutralizing antibody that blocked the PK and LDLR interaction in mice. Mice lacking both PK and apolipoprotein e (Klkb1-/-Apoe-/-) were generated to assess the role of PK in atherosclerosis. PK directly bound LDLR and induced its lysosomal degradation. The serum PK concentrations positively correlated with LDL cholesterol levels in 198 young Chinese Han adults. Genetic depletion of Klkb1 increased hepatic LDLR and decreased circulating cholesterol in multiple rodent models. Inhibition of proprotein convertase subtilisin/kexin 9 with evolocumab further decreased plasma LDL cholesterol levels in Klkb1-deficient hamsters. The anti-PK neutralizing antibody could similarly lower plasma lipids through upregulating hepatic LDLR. Ablation of Klkb1 slowed the progression of atherosclerosis in mice on Apoe-deficient background. PK regulates circulating cholesterol levels through binding to LDLR and inducing its lysosomal degradation. Ablation of PK stabilizes LDLR, decreases LDL cholesterol, and prevents atherosclerotic plaque development. This study suggests that PK is a promising therapeutic target to treat atherosclerotic cardiovascular disease.
Imported measles. A potential control problem
Authors: J. A. Frank
Journal: JAMA (1981)

From Dec 23, 1978, through Jan 31, 1979, an outbreak of five laboratory-confirmed cases and four clinical cases of measles occurred in a Vietnamese refugee population living in a single housing complex in Albuquerque, NM. The index cases were in two refugee siblings in whom measles was incubating on arrival in the United States. Despite spread through three subsequent generations of disease transmission within the Vietnamese population, there was no additional spread into the general Albuquerque population. Responsible factors included the age distribution of susceptible persons, the social isolation of the refugee population, and the physical structure of the housing complex. There is a need to identify the problem of imported measles in "ethnic islands" in need of vaccination. (<i>JAMA</i>1981;245:264-266)
From the Centers for Disease Control and Prevention. Vaccination coverage of 2-year-old children--United States, 1993
Journal: JAMA (1994)

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
Perspectives in immunotherapy: meeting report from the Immunotherapy Bridge (29-30 November, 2017, Naples, Italy)
Authors: Paolo A. Ascierto, James Brugarolas, Luigi Buonaguro, Lisa H. Butterfield, David Carbone, Bruno Daniele, Robert Ferris, Bernard A. Fox, Jérôme Galon, Cesare Gridelli, Howard L. Kaufman, Christopher A. Klebanoff, Ignacio Melero, Paul Nathan, Chrystal M. Paulos, Marco Ruella, Ryan Sullivan, Hassane Zarour, Igor Puzanov
Journal: Journal for ImmunoTherapy of Cancer (2018)

Immunotherapy represents the third important wave in the history of the systemic treatment of cancer after chemotherapy and targeted therapy and is now established as a potent and effective treatment option across several cancer types. The clinical success of anti-cytotoxic T-lymphocyte-associated antigen (CTLA)-4, first, and anti-programmed death (PD)-1/PD-ligand (L)1 agents in melanoma and other cancers a few years later, has encouraged increasing focus on the development of other immunotherapies (e.g. monoclonal antibodies with other immune targets, adoptive cell transfer, and vaccines), with over 3000 immuno-oncology trials ongoing, involving hundreds of research institutes across the globe. The potential use of these different immunotherapeutic options in various combinations with one another and with other treatment modalities is an area of particular promise. The third Immunotherapy Bridge meeting (29-30 November, 2017, Naples, Italy) focused on recent advances in immunotherapy across various cancer types and is summarised in this report.
RIO DE JANEIRO
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
Response to Comment on Fahrmann et al. Modification of the Association Between Severe Hypoglycemia and Ischemic Heart Disease by Surrogates of Vascular Damage Severity in Type 1 Diabetes During ∼30 Years of Follow-up in the DCCT/EDIC Study. Diabetes Care 2021;44;2132–2139
Authors: Elke R. Fahrmann, Henry K. Driscoll
Journal: Diabetes Care (2022)
The impact of the updated EORTC/MSG criteria on the classification of hematological patients with suspected invasive pulmonary aspergillosis
Authors: Hanne Lamberink, Alex Wagemakers, Kim C.E. Sigaloff, Robin van Houdt, Nick A. de Jonge, Karin van Dijk
Journal: Clinical Microbiology and Infection (2022)

Our aim was to evaluate the effect of the updated European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group 2019 definitions for invasive pulmonary aspergillosis (IPA) on patient classification and the related all-cause 12-week mortality.In this retrospective cohort study from our tertiary care centre, we reclassified patients with haematological malignancy who underwent bronchoalveolar lavage between 2014 and 2019 for suspected IPA using the novel EORTC 2019 criteria. We performed receiver operating characteristic curve analysis to define the optimal cut-off for positive PCR and galactomannan and present survival analyses and their possible association with these diagnostic criteria through post hoc comparisons with log rank and Cox regression.From 323 episodes of suspected IPA in 282 patients, 73 were reclassified: 31 (42.5%) from possible to probable IPA, 5 (6.8%) from EORTC criteria not met to probable IPA, and 37 (50.7%) from EORTC criteria not met to possible IPA. Probable IPA increased therefore 11.1% (64/323, 19.8% to 100/323, 30.9%), mostly due to positive PCR (31/36, 86.1%). There was no difference in mortality between newly defined possible and probable IPA (log rank p = 0.950). Mortality was higher in probable cases with lower cycle thresholds (Ct values) versus higher Ct values (p = 0.004). Receiver operating characteristic curve analysis showed an optimal Ct value cut-off of 36.8 with a sensitivity of 75% (95% CI 64.9%-85.1%) and a specificity of 61.7% (95% CI 53.5-69.9) for 12-week mortality.The new EORTC criteria led to 11.1% more probable IPA diagnoses, mostly due to Aspergillus PCR. Restricting positive PCR to below a certain threshold might improve the discrimination of the new EORTC IPA categories for mortality.
Extended D-dimer cut-offs and machine learning for ruling out pulmonary embolism in individuals undergoing computed tomography pulmonary angiography
Authors: Alessandro N. Franciosi, Nicholas McCarthy, Brian Gaffney, John Duignan, Eamon Sweeney, Niall O'Connell, Karen Murphy, Fionnuala Ní Áinle, Marcus W. Butler, Jonathan D. Dodd, Michael P. Keane, David J. Murphy, Kathleen M. Curran, Cormac McCarthy
Journal: European Respiratory Journal (2022)

<b>Combining novel machine learning algorithms with extended D-dimer cut-offs may improve pulmonary embolism prediction and reduce patient radiation exposure resulting from avoidable scans</b>https://bit.ly/3oUKd7X
A Novel Soluble ACE2 Protein Provides Lung and Kidney Protection in Mice Susceptible to Lethal SARS-CoV-2 Infection
Authors: Luise Hassler, Jan Wysocki, Ian Gelarden, Isha Sharma, Anastasia Tomatsidou, Minghao Ye, Haley Gula, Vlad Nicoleascu, Glenn Randall, Sergii Pshenychnyi, Nigar Khurram, Yashpal Kanwar, Dominique Missiakas, Jack Henkin, Anjana Yeldandi, Daniel Batlle
Journal: Journal of the American Society of Nephrology (2022)

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) uses full-length angiotensin converting enzyme 2 (ACE2) as a main receptor to enter target cells. The goal of this study was to demonstrate the preclinical efficacy of a novel soluble ACE2 protein with increased duration of action and binding capacity in a lethal mouse model of COVID-19.
Medical research: civil liability and compensation for personal injury--a discussion paper. Ciba Foundation Study Group.
Authors: R Cowell, D Marshall, J Prothero, J Quin, T Binns, Charles Wilson
Journal: BMJ (1980)

The Ciba Foundation Study Group has considered the most appropriate means of compensating participants (or their relatives) for injuries received as a consequence of medical research. The group recognises that injury may occur despite the exercise of the highest degree of skill and care by the investigator and that compensation through an action for negligence is therefore not available. At present injured participants have to rely on ex gratia payments. The group considers this unsatisfactory and recommends the establishment of a centrally operated fund with authority to provide compensation on a no-fault basis. These recommendations do not diminish the rights of the participant to bring an action in the event of negligence on the part of the investigator or an action under the law relating to product liability against the manufacturers of defective equipment or drugs.
Optimizing therapeutic outcomes of immune checkpoint blockade by a microbial tryptophan metabolite
Authors: Giorgia Renga, Emilia Nunzi, Marilena Pariano, Matteo Puccetti, Marina Maria Bellet, Giuseppe Pieraccini, Fiorella D’Onofrio, Ilaria Santarelli, Claudia Stincardini, Franco Aversa, Francesca Riuzzi, Cinzia Antognelli, Marco Gargaro, Oxana Bereshchenko, Maurizio Ricci, Stefano Giovagnoli, Luigina Romani, Claudio Costantini
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Despite the great success, the therapeutic benefits of immune checkpoint inhibitors (ICIs) in cancer immunotherapy are limited by either various resistance mechanisms or ICI-associated toxic effects including gastrointestinal toxicity. Thus, novel therapeutic strategies that provide manageable side effects to existing ICIs would enhance and expand their therapeutic efficacy and application. Due to its proven role in cancer development and immune regulation, gut microbiome has gained increasing expectation as a potential armamentarium to optimize immunotherapy with ICI. However, much has to be learned to fully harness gut microbiome for clinical applicability. Here we have assessed whether microbial metabolites working at the interface between microbes and the host immune system may optimize ICI therapy. Methods To this purpose, we have tested indole-3-carboxaldehyde (3-IAld), a microbial tryptophan catabolite known to contribute to epithelial barrier function and immune homeostasis in the gut via the aryl hydrocarbon receptor (AhR), in different murine models of ICI-induced colitis. Epithelial barrier integrity, inflammation and changes in gut microbiome composition and function were analyzed. AhR, indoleamine 2,3-dioxygenase 1, interleukin (IL)-10 and IL-22 knockout mice were used to investigate the mechanism of 3-IAld activity. The function of the microbiome changes induced by 3-IAld was evaluated on fecal microbiome transplantation (FMT). Finally, murine tumor models were used to assess the effect of 3-IAld treatment on the antitumor activity of ICI. Results On administration to mice with ICI-induced colitis, 3-IAld protected mice from intestinal damage via a dual action on both the host and the microbes. Indeed, paralleling the activation of the host AhR/IL-22-dependent pathway, 3-IAld also affected the composition and function of the microbiota such that FMT from 3-IAld-treated mice protected against ICI-induced colitis with the contribution of butyrate-producing bacteria. Importantly, while preventing intestinal damage, 3-IAld did not impair the antitumor activity of ICI. Conclusions This study provides a proof-of-concept demonstration that moving past bacterial phylogeny and focusing on bacterial metabolome may lead to a new class of discrete molecules, and that working at the interface between microbes and the host immune system may optimize ICI therapy.
The Hospitals of London. No. VII
Authors: None Cormack, None Semple
Journal: BMJ (1851)

It has always been a maxim-and a very proper one-with the general hospitals of our metropolis, to do the freatest possible amount of good to the greatest possible number of individuals; and this has led unavoidably to the rejection of certain chronic and other affections, ordinarily looked upon as incurable, from their portals.Consumption having been necessarily included in this list, phthisical patients have long required some institution where medical skill might be sedulously devoted to their relief, and, after this may have failed, where tenderness and care might soothe their passage to the grave.In the hospital at Brompton, these objects are combined-both an hospital and an asylum are offered to the consumptive sufferer; whilst an opportunity is afforded, for the first time in this country, for extended scientific and practical observation upon a disease which annually destroys at least one in every 300 persons.
Targeting Immune Suppression in Cancer
Journal: Cancer Discovery (2016)

Abstract Researchers have figured out a way to switch the immunosuppressive phenotype of tumor-associated macrophages to one that's immunostimulatory. By inhibiting PI3Kγ in these macrophages, they significantly suppressed tumor growth in mice; when anti–PD-1 therapy was added to PI3Kγ inhibition, complete and sustained tumor eradication was observed in many cases.
Neuronal Machinery of Sleep Homeostasis in Drosophila
Authors: Jeffrey M. Donlea, Diogo Pimentel, Gero Miesenböck
Journal: Neuron (2014)

(Neuron 81, 860–872; February 19, 2014) We thank Douglas Armstrong, Hugo Bellen, Ronald Davis, Ulrike Heberlein, Martin Heisenberg, Liqun Luo, Gerald Rubin, and Helen Skaer for fly strains. In a regrettable oversight, some strains were credited to stock centers rather than the original sources. The correct attributions are as follows: cv-cMB03717, cv-cMB01956, cv-cDG20401 (Bellen et al., 2011Bellen H.J. Levis R.W. He Y. Carlson J.W. Evans-Holm M. Bae E. Kim J. Metaxakis A. Savakis C. Schulze K.L. et al.Genetics. 2011; 188: 731-743Crossref PubMed Scopus (264) Google Scholar, Venken et al., 2011Venken K.J.T. Schulze K.L. Haelterman N.A. Pan H. He Y. Evans-Holm M. Carlson J.W. Levis R.W. Spradling A.C. Hoskins R.A. Bellen H.J. Nat. Methods. 2011; 8: 737-743Crossref PubMed Scopus (420) Google Scholar); cv-cC524, UAS–cv-c (Denholm et al., 2005Denholm B. Brown S. Ray R.P. Ruiz-Gómez M. Skaer H. Hombría J.C.-G. Development. 2005; 132: 2389-2400Crossref PubMed Scopus (55) Google Scholar); UAS–cv-cRNAi (Billuart et al., 2001Billuart P. Winter C.G. Maresh A. Zhao X. Luo L. Cell. 2001; 107: 195-207Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar); UAS–CD8-GFP (Lee and Luo, 1999Lee T. Luo L. Neuron. 1999; 22: 451-461Abstract Full Text Full Text PDF PubMed Scopus (1990) Google Scholar); C5–GAL4 (Yang et al., 1995Yang M.Y. Armstrong J.D. Vilinsky I. Strausfeld N.J. Kaiser K. Neuron. 1995; 15: 45-54Abstract Full Text PDF PubMed Scopus (289) Google Scholar); 104y–GAL4 (Rodan et al., 2002Rodan A.R. Kiger Jr., J.A. Heberlein U. J. Neurosci. 2002; 22: 9490-9501PubMed Google Scholar, Sakai and Kitamoto, 2006Sakai T. Kitamoto T. J. Neurobiol. 2006; 66: 821-834Crossref PubMed Scopus (48) Google Scholar); C205-GAL4 (Martin et al., 1999Martin J.R. Raabe T. Heisenberg M. J. Comp. Physiol. (A). 1999; 185: 277-288Crossref PubMed Scopus (155) Google Scholar); 23E10–GAL4 (Jenett et al., 2012Jenett A. Rubin G.M. Ngo T.-T.B. Shepherd D. Murphy C. Dionne H. Pfeiffer B.D. Cavallaro A. Hall D. Jeter J. et al.Cell Rep. 2012; 2: 991-1001Abstract Full Text Full Text PDF PubMed Scopus (824) Google Scholar); tubP–GAL80ts (McGuire et al., 2003McGuire S.E. Le P.T. Osborn A.J. Matsumoto K. Davis R.L. Science. 2003; 302: 1765-1768Crossref PubMed Scopus (952) Google Scholar). The article has been corrected online. Neuronal Machinery of Sleep Homeostasis in DrosophilaDonlea et al.NeuronFebruary 19, 2014In BriefDonlea et al. discover mutant flies with a broken sleep homeostat: after an all-nighter, these flies are unable to correct the accumulated sleep deficit. The mutation affects a Rho-GTPase-activating protein that regulates the electrical excitability of sleep-promoting neurons. Full-Text PDF Open Access
"Superfluous Spectacles."
Authors: Horace M. Starkey
Journal: JAMA (1894)

Chicago, Feb. 9,1894. <h3>To the Editor:</h3> —The editorial in theJournalof February 3, under the above title, is on the whole excellent. I had read Dr. Pooley's article which was the text for the editorial carefully and with much pleasure, and in the main concur in his conclusions. There are some points in the editorial, however, which are not deducible from Dr. Pooley's article, and others which are entirely apart from it, which, it seems to me, are open to criticism. First, you seem to argue, though that is not very clear, that if a patient when out of health has glasses prescribed which he wears with relief and comfort until the general health improves and then voluntarily relinquishes them, that the glasses were of no service. As well might you argue that the tonic or restorative medicine taken when out of health was of no benefit because not
PRELIMINARY REPORT OF THE COMMITTEE ON ORGANIZATION.
Journal: JAMA (1901)

The report of your Committee herewith submitted contains suggestions and recommendations which are made with full appreciation of the responsibility assumed. Your Committee has from the outset keenly realized the magnitude of the task to which it was set, but it has been spurred on by the hope that its work, if wisely and conscientiously performed, might if favorably received by theAssociationresult in lasting benefit to the medical profession of America. Actuated by this motive, the Committee, after full consideration of the problem entrusted to its care, early reached the conclusion that it would be useless at this late day to suggest the adoption of either half-way or compromise measures. Thus its report will be found to contain recommendations that to many who have not studied closely the defects of present-day medical organization may appear radical. In order to frankly lay before you a compact scheme of effective
Targeting HIF-1α abrogates PD-L1–mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues
Authors: Christopher M. Bailey, Yan Liu, Mingyue Liu, Xuexiang Du, Martin Devenport, Pan Zheng, Yang Liu, Yin Wang
Journal: Journal of Clinical Investigation (2022)

A combination of anti–CTLA-4 plus anti–PD-1/PD-L1 is the most effective cancer immunotherapy but causes high incidence of immune-related adverse events (irAEs). Here we report that targeting of HIF-1α suppressed PD-L1 expression on tumor cells and tumor-infiltrating myeloid cells, but unexpectedly induced PD-L1 in normal tissues by an IFN-γ–dependent mechanism. Targeting the HIF-1α/PD-L1 axis in tumor cells reactivated tumor-infiltrating lymphocytes and caused tumor rejection. The HIF-1α inhibitor echinomycin potentiated the cancer immunotherapeutic effects of anti–CTLA-4 therapy, with efficacy comparable to that of anti–CTLA-4 plus anti–PD-1 antibodies. However, while anti–PD-1 exacerbated irAEs triggered by ipilimumab, echinomycin protected mice against irAEs by increasing PD-L1 levels in normal tissues. Our data suggest that targeting HIF-1α fortifies the immune tolerance function of the PD-1/PD-L1 checkpoint in normal tissues but abrogates its immune evasion function in the tumor microenvironment to achieve safer and more effective immunotherapy.
The anti‐FcεRI antibody MAR‐1 depletes basophils and cross‐reacts with myeloid cells through its Fc portion
Authors: William P. M. Worrall, Jasper B. J. Kamphuis, Julien Stackowicz, Aurélie Mougel, Emilie Mauré, Cyprien Pecalvel, Sébastien Brûlé, Pierre Bruhns, Laurent Guilleminault, Laurent L. Reber
Journal: Allergy (2022)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
<i>A Compendium of Insanity.</i>By John B. Chapin, M. D., LL. D. 12mo. 234 pp. W. B. Saunders, Philadelphia, 1898
Authors: W. W. G.
Journal: American Journal of Psychiatry (1898)

i8i in the same degree from mental disease or hysteria after the operation as previous to it.Of the 17 cases cured, 12, to use the phrase employed by the reporters themselves, had suffered from nervous disturbances, so that it is not