tbuckley/cabot-search huggingface dataset:
Development of PCR assays to detect signature circulating tumor DNA methylation markers and KRas mutations for pancreatic ductal adenocarcinoma (PDAC).
Authors: Shiwei Guo, Mingyang Su, Xiaohan Shi, Suizhi Gao, Huan Wang, Yaqi Pan, Chengxiang Gong, Qiye He, Rui Liu, Gang Jin
Journal: Journal of Clinical Oncology (2022)

524 Background: PDAC is a cancer of high mortality. Accurate and cost-effective PCR assays detecting diagnostic and prognostic PDAC markers in blood are desirable for conducting PDAC screening in high-risk populations, evaluating treatments for patients and surveying for post-treatment relapse. Methods: We combined PDAC-diagnosing ctDNA methylation markers with PDAC-driving Kras mutations as targets to develop said PCR tests. Methylation markers were previously validated to classify PDAC plasma at a high accuracy by a targeted methylation sequencing assay. Seven known PDAC driver mutations in KRas exon2 were selected. Taqman-based quantitative methylation-specific PCR (MSP) and ARMS PCR were designed for methylation markers and KRas mutations, respectively, and were validated for technical performances. A step of pre-amplification of input DNA by conventional PCR was included prior to quantitative PCR to improve sensitivity. Over 200 clinical PDAC and control tissue and plasma samples were used to determine their analytical performances in classifying PDAC plasma. Results: All targets were detected at a limit-of-detection of 0.25% or better on standards DNA in PCR. To test clinical plasma samples, methylation markers were first filtered by comparing their levels in PDAC-, para-tumor tissues and whole blood cells. Twenty-four most discriminatory markers for PDAC tissues were selected and used to classify 110 PDAC plasma samples from equal number of normal samples. They were evaluated for their sensitivity at a pre-set specificity of 90%. The 4 best-performing markers were selected to build and cross-validate a general-linear-model (GLM) PDAC classifier, which achieved a sensitivity of 66% at 90% specificity (AUC = 0.829) in cross-validation. Adding status of KRas mutations further improved prediction accuracy by increasing sensitivity to 75% (AUC = 0.89), demonstrating the methylation markers and KRas mutations complement each other in detection PDAC plasma. Conclusions: Our results suggest that a small number of our DNA methylation markers can classify PDAC plasma at a reasonably high accuracy by MSP. Incorporating KRas driver mutations further improved classification accuracy. Together they are promising to be further translated into diagnostics for PDAC early screening, treatment assessment and postoperative surveillance.
Early post-transplant recurrence of oxalate nephropathy in a patient with primary hyperoxaluria type 1, despite pretransplant lumasiran therapy
Authors: Nizar Joher, Anissa Moktefi, Philippe Grimbert, Eléonore Pagot, Narindra Jouan, Khalil El Karoui, Cécile Maud Champy, Marie Matignon, Thomas Stehlé
Journal: Kidney International (2022)
Conventional type 1 dendritic cells protect against age-related adipose tissue dysfunction and obesity
Authors: Elena Hernández-García, Francisco J. Cueto, Emma C. L. Cook, Ana Redondo-Urzainqui, Sara Charro-Zanca, Iñaki Robles-Vera, Ruth Conde-Garrosa, Ivana Nikolić, Guadalupe Sabio, David Sancho, Salvador Iborra
Journal: Cellular and Molecular Immunology (2022)

Abstract Conventional dendritic cells (cDCs) scan and integrate environmental cues in almost every tissue, including exogenous metabolic signals. While cDCs are critical in maintaining immune balance, their role in preserving energy homeostasis is unclear. Here, we showed that Batf3-deficient mice lacking conventional type 1 DCs (cDC1s) had increased body weight and adiposity during aging. This led to impaired energy expenditure and glucose tolerance, insulin resistance, dyslipidemia, and liver steatosis. cDC1 deficiency caused adipose tissue inflammation that was preceded by a paucity of NK1.1 + invariant NKT (iNKT) cells. Accordingly, among antigen-presenting cells, cDC1s exhibited notable induction of IFN-γ production by iNKT cells, which plays a metabolically protective role in lean adipose tissue. Flt3L treatment, which expands the dendritic cell (DC) compartment, mitigated diet-induced obesity and hyperlipidemia in a Batf3-dependent manner. This effect was partially mediated by NK1.1 + cells. These results reveal a new critical role for the cDC1-iNKT cell axis in the regulation of adipose tissue homeostasis.
Shielding behaviour in people with psoriasis or a joint condition during the COVID‐19 pandemic differs by treatment type
Journal: British Journal of Dermatology (2021)

Public health measures such as social/physical distancing were introduced early in the pandemic to limit the spread of COVID‐19. Stricter measures referred to as ‘shielding’ (not leaving home and minimizing all face‐to‐face contact) were recommended in groups of people at higher risk of severe infection. Many people taking drugs that affect the immune system to treat psoriasis or a joint condition (e.g. rheumatoid arthritis) were advised to reduce their risk of developing COVID‐19 by shielding. We wanted to find out what factors influenced how much (or strictly) this advice was followed.
GENERAL PARESIS, A TOXINE DISEASE?
Authors: H. M. Bannister
Journal: American Journal of Psychiatry (1894)

In Doctor Bannister's article, "General Paresis a Toxine Disease," in the April issue, '94, it was stated that Griesinger "makes no mention of syphilis in the etiology of general paralysis." This is not strictly correct, as he does mention the view of Jessen, but only to rather discredit it. It should have read, "gives no credit to syphilis."
Multifunctional inorganic nanomaterials for cancer photoimmunotherapy
Authors: Lu Tang, Aining Zhang, Ziyao Zhang, Qingqing Zhao, Jing Li, Yijun Mei, Yue Yin, Wei Wang
Journal: Cancer Communications (2022)

Abstract Phototherapy and immunotherapy in combination is regarded as the ideal therapeutic modality to treat both primary and metastatic tumors. Immunotherapy uses different immunological approaches to stimulate the immune system to identify tumor cells for targeted elimination. Phototherapy destroys the primary tumors by light irradiation, which induces a series of immune responses through triggering immunogenic cancer cell death. Therefore, when integrating immunotherapy with phototherapy, a novel anti‐cancer strategy called photoimmunotherapy (PIT) is emerging. This synergistic treatment modality can not only enhance the effectiveness of both therapies but also overcome their inherent limitations, opening a new era for the current anti‐cancer therapy. Recently, the advancement of nanomaterials affords a platform for PIT. From all these nanomaterials, inorganic nanomaterials stand out as ideal mediators in PIT due to their unique physiochemical properties. Inorganic nanomaterials can not only serve as carriers to transport immunomodulatory agents in immunotherapy owing to their excellent drug‐loading capacity but also function as photothermal agents or photosensitizers in phototherapy because of their great optical characteristics. In this review, the recent advances of multifunctional inorganic nanomaterial‐mediated drug delivery and their contributions to cancer PIT will be highlighted.
Abstract P224: Association of Nonalcoholic Fatty Liver Disease With Left Ventricular Geometry and Remodeling: the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Lisa B VanWagner, Jane E Wilcox, Hongyan Ning, Cora E Lewis, Sanjiv J Shah, John J Carr, Mary E Rinella, Joao A Lima, Donald M Lloyd-Jones
Journal: Circulation (2017)

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with high cardiovascular mortality, including heart failure (HF). Left ventricular hypertrophy (LVH) increases the risk of future HF. The relationship between NAFLD and LV geometry is unknown. In a large prospective population-based sample of black and white adults free from liver or heart disease, we examined the relationship between NAFLD and markers of LV remodeling. Methods: Participants from the CARDIA study (Y25 exam; age 43-55 years) with concurrent CT quantification of liver fat and tissue Doppler echocardiography were included (n=2,576). Echocardiography was repeated at Y30 follow up (age 47-62 years). LV geometry was classified into normal and abnormal geometry by integrating relative wall thickness and LV mass index. NAFLD was defined as CT liver attenuation ≤ 40 Hounsfield units after excluding other causes of liver fat. Logistic and polytomous regression models were used to test associations. Results: NAFLD prevalence was 9.6%. NAFLD participants were more likely to be male (57.7% vs. 40.0%), white (57.3% vs. 50.2%), and had higher BMI (36.0 vs. 29.9 kg/m 2 ) than non-NAFLD. At Y30 NAFLD participants had higher LV mass, left atrial diameter, and LV relative wall thickness compared to non-NAFLD (p&lt;0.01). Those with NAFLD had higher prevalence of LVH (31.9% vs. 18.2%), concentric remodeling (15.3% vs. 13.1%), concentric hypertrophy (12.9% vs. 7.9%) and eccentric hypertrophy (18.9% vs. 10.1%, p&lt;0.0001). In multivariable analyses NAFLD was independently associated with prevalent LV remodeling (Table). Associations were attenuated after adjustment for HF risk factors. In contrast, NAFLD was associated with incident LVH independent of HF risk factors. Adjustment for BMI attenuated this association. There was no interaction by race or sex. Conclusion: NAFLD is associated with subclinical changes in LV geometry and remodeling, a precursor to HF. The role of NAFLD in LV remodeling as a potential therapeutic target warrants further investigation.
Erratum: Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics
Authors: Joanne T. Brindle, Henrik Antti, Elaine Holmes, George Tranter, Jeremy K. Nicholson, Hugh W.L. Bethell, Sarah Clarke, Peter M. Schofield, Elaine McKilligin, David E. Mosedale, David J. Grainger
Journal: Nature Medicine (2003)
Pulmonary Embolism in Patients with COVID-19
Authors: Scarduelli Cleante, Scarduelli Sara, Borghi Claudio
Journal: Clinical Cardiology and Cardiovascular Interventions (2022)

Infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) and the resulting syndrome, COVID-19, have been associated with inflammation and a prothrombotic state, with increases in fibrin, fibrinogen, fibrin degradation products and D-dimers. In some studies, elevations in these markers have been associated with worse clinical outcomes. Several studies have demonstrated a high prevalence of venous thromboembolism (VTE), and pulmonary embolism (PE), particularly in patients admitted to the intensive care unit (ICU), even in those receiving prophylactic anticoagulation. The high rate of thrombosis in COVID-19 is driven by at least two interrelated processes: a hypercoagulable state responsible for large-vessel thrombosis and thromboembolism and direct vascular and endothelial injury responsible for in situ microvascular thrombosis. The presence of PE and pulmonary thrombosis may explain why hypoxemia is out of proportion to impairment in lung compliance in some patients with COVID-19 pneumonia. Diagnosing PE in patients with COVID-19 pneumonia may be challenging, because the two pathologies share many signs and symptoms. It has been demonstrated that the administration of prophylactic anticoagulation within 24 h of admission in patients with COVID-19 was associated with decreased mortality when compared with no prophylactic anticoagulation. Given the antithrombotic, anti-inflammatory and possibly antiviral properties of heparins, it has been hypothesized that anticoagulation with heparin administered at doses higher than conventionally used for venous thromboprophylaxis may improve outcomes. In non-critically ill patients hospitalized with COVID-19, therapeutic-dose anticoagulants with heparin (most commonly, low-molecular-weight heparin) increased the probability of survival until hospital discharge with a reduced need for ICU-level organ support at 21 days as compared with usual-care thromboprophylaxis. In Critically ill patients with confirmed COVID-19, therapeutic-dose anticoagulation did not increase the probability of survival to hospital discharge or the number of days free of cardiovascular o respiratory organ support and had a 95% probability of being inferior to usual-care pharmacologic thromboprophylaxis. Currently, randomized trials evaluating the use of tissue plasminogen activator and Tenecteplase in patients with COVID-19 ARDS are underway.
The prevalence of common <i>KRAS</i> variants and associated outcomes in patients with metastatic colorectal cancer (mCRC).
Authors: Laura W. Musselwhite, Sally J. Trufan, Kunal C. Kadakia, Jimmy J. Hwang, Mohamed E. Salem
Journal: Journal of Clinical Oncology (2022)

173 Background: KRAS is the most common driver oncogene in mCRC. Comprehensive analysis of KRAS variants prevalence and the relationship between variants and outcomes are lacking. Herein, we aimed to examine the impact of KRAS variants on outcomes in patients (pts) with mCRC. Methods: A retrospective review of pts with mCRC with known KRAS mutation status was performed. Fisher’s exact test was used to analyze the association between KRAS variants. Cox Proportional Hazard modeling was used to study the relationship between KRAS variants and overall survival (OS). Kaplan-Meier method was used to assess OS. Results: A total of 423 pts diagnosed with mCRC from 2014-2020 with available extended KRAS status were evaluated. Median age at diagnosis was 59.8 yrs (22.3-92 range), 57% were male, 22% were Black, and 75% presented with de novo metastatic disease. A majority (56%) of tumors harbored KRAS mutations. The most frequent KRAS variants were G12D 47% (111), G12V 12% (28), G12C 13% (31), G13D 9% (21), and 20% (47) were other variants. In univariate analyses, the presence of a KRAS mutation, Black race, de novo metastatic disease, age, receipt of chemotherapy, and receipt of surgery were associated with OS. Tumor location was not associated with OS. In multivariable analyses, mutation type was a significant predictor of death and the presence of G12D was associated with an increased risk of death compared to G12V and KRAS wildtype. There was no increased risk of death in pairwise comparisons of G12D and G13D or other KRAS variants. Black race, de novo metastatic disease, and no receipt of surgery were additional independent predictors of death (Table). With a median follow-up of 25.7 months (mo.), median OS was 35.5 mo. (95% CI 10.5-50.9) with G12C, Not Reached (NR) (95% CI 21-NR) with G12V, 36.2 mo. (95%CI 14.9-58.5) with G13D, 26.2 mo. (95% CI 21.8-37) with G12D, 39.6 mo. (95% CI 22.4-47.9) for other KRAS mutations, and 59.6 mo. (95%CI 48.2-NA) for KRAS wildtype, respectively (p=0.0003). Conclusions: Our findings highlight differences in unadjusted overall survival when comparing G12D to some other KRAS variants. Codon and amino acid-specific mutations of KRAS should be considered when evaluating prognosis and further study on treatment effects and sequencing is warranted. [Table: see text]
<i>De l'Emploi des Moyens de Contrainte dans le Traitment des Aliénés. Etat de la Question en Angleterre.</i>Par le Dr. Victor Parant. (<i>On the Employment of Restraint in the Treatment of the Insane. State of the question in England.</i>)
Authors: H. M. B.
Journal: American Journal of Psychiatry (1890)
Validation of an Oral Disease Severity Score for use in oral lichen planus
Authors: Martyn Ormond, Helen McParland, Priya Thakrar, Ana Donaldson, Manoharan Andiappan, Richard J. Cook, Michael Escudier, Jon Higham, Esther Hullah, Roddy McMillan, Jennifer Taylor, Pepe J. Shirlaw, Stephen J. Challacombe, Jane F. Setterfield
Journal: British Journal of Dermatology (2022)

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Hemoglobin Munchausen
Authors: Ben Fisher
Journal: JAMA (1974)

<h3>To the Editor.—</h3> The recent article by Lindenbaum (228:498, 1974) concerning factitious symptoms of sickle cell crisis in persons trying to obtain medical attention or drugs should bring forth many anecdotal comments. During the present increased interest in sickle cell diseases, symptoms have been described well on television, in paperbound books with cover pictures of black family groups, and in "family" magazines sold at check-out counters of supermarkets. One of our patients changed his requests for medical attention to this "new diagnosis." A 20-year-old black man was hospitalized for investigation of jaundice and upper abdominal pains. He was found to have a compensated spherocytic hemolytic disorder of extracorpuscular type with negative antibody tests. No hemoglobinopathy was present. Conflicting medical histories were given to us about his jaundice and previous illnesses. It became apparent that he had a psychopathic personality and used considerable amounts of alcohol, narcotics, and other drugs. Spleen
Mysticism Lost
Authors: Stella Neeson
Journal: JAMA (1975)

THE MODERN American physician attracts more criticism than his horse-and-buggy grandfather. The significant contribution of the contemporary clinician to the demise or decline of numerous diseases is taken for granted in this era of moon flights and satellite television. Grandpa, who could do little more than lend his physical presence and concern over the sickbed of a scarlet fever victim, is a<i>folk hero</i>. But his general practitioner grandson who undramatically stops a "beta strep" infection with a quiet course of penicillin is emerging as a 20th century<i>folk villain</i>. Since there are no hard data, I feel free to speculate about why one (very hard-working) professional group has been singled out for such severe criticism. I do not believe that the high cost of medical care is the reason. There has been a corresponding increase in legal fees, and, indeed, in the cost of everything else one needs or
Book Review Text-Book of Urology for Students and Practitioners . By Daniel N. Eisendrath, M.D. Attending Urologist Michael Reese and Chicago Memorial Hospitals; Assistant Professor of Surgery (Genitourinary), Rush Medical College of The University of Chicago, and Harry C. Rolnick, M.D. Associciate Urologist Mt. Sinai Hospital; Adjunct Urologist Michael Reese Hospital; Formerly Associate in Genito-urinary Surgery, Northwestern University Medical School. (942 Pages.) Published by J. B. …
Journal: New England Journal of Medicine (1929)
THE CAUSE OF CANCER
Journal: JAMA (1921)

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2012 ACCF/AHA/HRS Focused Update Incorporated Into the ACCF/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities
Authors: Cynthia M. Tracy, Andrew E. Epstein, Dawood Darbar, John P. DiMarco, Sandra B. Dunbar, N.A. Mark Estes, T. Bruce Ferguson, Stephen C. Hammill, Pamela E. Karasik, Mark S. Link, Joseph E. Marine, Mark H. Schoenfeld, Amit J. Shanker, Michael J. Silka, Lynne Warner Stevenson, William G. Stevenson, Paul D. Varosy
Journal: Journal of the American College of Cardiology (2012)
YELLOW FEVER.
Authors: WOLFRED NELSON
Journal: JAMA (1889)

With your kind permission I shall read a brief paper on yellow fever, a theme at once interesting to all students of medicine, and presumably of marked interest to my<i>confreres</i>in the "Sunny South." In what follows I shall refer to my own experience of this dread disease at Panama on the Pacific, Colon on the Atlantic, both ports of the Isthmus of Panama. My studies and observations on the west coast of Mexico, where in 1885 I traced its epidemics of 1883 and 1884. My experience in the hospitals of Cuba, and finally my visit to Florida, in the fall of 1887, when I deliberately forecast the epidemic that swept Jacksonville in 1888. My letter of warning to the people of Florida was published in the<i>Times-Union</i>, of Jacksonville, November 30, 1887, and was recalled<i>when the disease was upon them</i>. Now, to return to the Isthmus of
A prospective trial to evaluate the performance of the multitarget hepatocellular carcinoma blood test (mt-HBT) for screening at-risk patients: The Altus study.
Authors: Binu John, Kyle Porter, Bassam Dahman, Neehar Parikh, Alvin C. Silva, Ju Dong Yang, Patrick Joseph, Laura E. Strong, Paul J. Limburg
Journal: Journal of Clinical Oncology (2022)

TPS486 Background: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death in the U.S. HCC surveillance is associated with improved early detection and receipt of curative treatment. However, current surveillance strategies suffer from low adherence and suboptimal sensitivity. The multi-target HCC blood test (mt-HBT) is a novel early detection assay that provides a qualitative result based on a multiparametric algorithm that incorporates information from methylation markers ( HOXA1, TSPYL5, and B3GALT6), AFP, and patient sex. Here, we describe the protocol for a prospective, multicenter clinical trial designed to investigate the performance of the mt-HBT in patients at risk for HCC. Methods: ALTernative to U/S (ALTUS) is a longitudinal, multicenter, prospective study with a targeted enrollment of 3,000 participants. The main inclusion and exclusion criteria are described in the table. Participants will receive HCC surveillance imaging (either U/S or CT/MRI) and blood collection for the mt-HBT. Those with positive U/S are anticipated to receive standard-of-care imaging follow-up with a multiphase CT or MRI, and those with a negative U/S will receive a study CT/MRI within 30 days of blood collection. Imaging interpretation is based on the CT/MRI LI-RADS (LR) v2018 categories. The primary endpoints are the overall sensitivity and specificity of the mt-HBT to detect HCC, defined as pathology-confirmed HCC or hepatocellular cholangiocarcinoma (cHCC-CCA), LR-4/5, or LR-TIV/M plus definite/probable HCC or cHCC-CCA. The secondary endpoints are mt-HBT early-stage sensitivity, and performance in a) participants with LR-5 or biopsy-confirmed HCC and b) participants confirmed non-HCC. Participants not diagnosed with a liver malignancy at visit one will continue to receive HCC surveillance, returning for a second visit ̃6 months from first blood collection. Blood will be collected after the second visit for the mt-HBT. Data on treatment will be collected for those diagnosed with HCC. Study participants and providers will be blinded to the mt-HBT results. Participants are currently enrolling across the U.S., with 60 targeted sites and an anticipated 12-month enrollment window. Clinical trial information: NCT05064553. [Table: see text]