tbuckley/cabot-search huggingface dataset:
Popliteal cyst rupture in normal knee joints.
Authors: C Bulpitt, Diana Penfold
Journal: BMJ (1980)

diastolic hypertension may be expected to be one-third to a half of those with a casual elevation of pressure1 2-that is, less than two million.We cannot condone the indiscriminate labelling of persons as hypertensive when they have only a transient anxiety-related rise in blood pressure.These patients, if treated, may experience a marked reduction in blood pressure and such treatment may not be in the best interests of the patients.As Anderson has shown,3 from the Framingham data, cardiovascular events do not increase until the diastolic blood pressure exceeds 90-99 mm Hg.There may be no benefit from reducing lower levels of diastolic pressure.
TCT-383 Ten-Year Clinical Outcomes of Sirolimus- Versus Paclitaxel-Eluting Stents for Patients With Unprotected Left Main Coronary Artery Disease
Authors: Hanbit Park, Junho Hyun, Ju Hyeon Kim, Yeongjin Jeong, Yujin Yang, KyungJin Choe, Sangwoo Park, Sang-Cheol Cho, Euihong Ko, Do-Yoon Kang, Pil Hyung Lee, Jung-Min Ahn, Duk-Woo Park, Seung-Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2019)
P09.57 Clinical trials of VAL-083 in patients with chemoresistant glioblastoma
Authors: J. A. Bacha, A. Steino, R. Schwartz, J. Langlands, S. Kanekal, L. M. Lopez, D. M. Brown
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is the most common CNS tumor. Patients with recurrent GBM have few treatment options and dismal prognosis. O6-methylguanine-DNA-methyltransferase (MGMT) is correlated with resistance to standard of care treatment with temozolomide and poor patient outcomes. Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent with a distinct mechanism-of-action differentiating it from other alkylating agents used in the treatment of GBM and other CNS tumors. VAL-083 readily crosses the blood-brain barrier and accumulates in brain tumor tissue. VAL-083 has demonstrated MGMT-independent cytotoxicity in multiple GBM cell-lines and cancer stem cells and is able to overcome TMZ-resistance in vitro demonstrating a different mechanism of action. In multiple prior NCI-sponsored clinical trials VAL-083 showed promise against CNS tumors. We recently concluded a phase I/II clinical trial studying VAL-083 in recurrent GBM patients failing temozolomide and bevacizumab, and data suggests a potential for VAL-083 to offer clinically meaningful survival benefits in patients who have failed or are unlikely to respond to currently available chemotherapeutic regimens. In the phase I portion of the trial, VAL-083, 40 mg/m2/day x 3 every 21 days was well-tolerated and this dose was selected for study in the phase II expansion phase. We are initiating multiple clinical trials targeting adult patients with chemoresistant GBM due to MGMT expression. Enrollment is anticipated to be initiated in early 2017. These trials include i) a pivotal, randomized Phase 3 study measuring survival outcome compared to “physician’s choice” control, which, if successful, would serve as the basis for a New Drug Application (NDA) submission for VAL-083. The control arm will consist of a limited number of salvage chemotherapies currently utilized in bevacizumab-failed GBM. ii) A single-arm, biomarker-driven, Phase 2 study to determine if treatment of MGMT-unmethylated recurrent GBM with VAL-083 improves overall survival at 9 months, compared to historical control in bevacizumab-naïve patients (clinicaltrials.gov identifier: NCT02717962). iii) A single arm Phase 2 study to confirm the tolerability of DelMar’s dosing regimen in combination with radiotherapy and to explore the activity of VAL-083 in newly diagnosed MGMT-unmethylated GBM patients whose tumors are known to express high MGMT levels. The results of these studies may support a new treatment paradigm in chemotherapeutic regimens for the treatment of GBM. Enrollment updates and study design details will be presented at the meeting.
Lassa fever.
Authors: J E Banatvala
Journal: BMJ (1986)

theory.18 The steady flow of publications on hysteria suggests that the conservationists are on top at the moment, but they may be conserving what is merely a faqade and one of only several manifestations of abnormal illness behaviour.Hysteria should be regarded as a first stage in diagnosis.Doctors should then look carefully for neurological or psychiatric illness and particularly for factors in the patient's social orbit that may be rewarding the sick role.
Temporal changes in the screening, diagnosis and surgical treatment of genitourinary (GU) malignancies during the COVID-19 pandemic.
Authors: Chris Labaki, Andrew Lachlan Schmidt, Ziad Bakouny, Muhieddine Labban, Talal El Zarif, Steven Lee Chang, Bradley Alexander McGregor, Adam S. Kibel, Timothy Rebbeck, Quoc-Dien Trinh, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2022)

281 Background: The COVID-19 pandemic has been associated with a significant disruption in healthcare services including cancer screening and diagnosis. Delays in cancer screening and treatment may lead to increased mortality. We aimed to analyze changes in screening, diagnosis and surgical treatment of common GU malignancies in relation to the COVID-19 pandemic. Methods: We evaluated screening, novel diagnoses, and surgical management modalities of prostate cancer (PCa), urothelial carcinoma (UC) and renal cell carcinoma (RCC) within Massachusetts General Brigham, the largest healthcare system in the Northeastern United States, over four 3-month time periods during the pandemic (March 2020- March 2021). The percentage change in screening, diagnoses and management modalities during pandemic periods as compared to the immediate pre-pandemic period (December 2019-March 2020) was calculated as (N period – N control )/N control . The difference in “predicted” versus “observed” diagnoses in each pandemic period was compared to the average of the four preceding 3-month periods (March 2019-March 2020) to account for seasonal variation. Results: The first pandemic peak (March-June 2020) was associated with a significant decline across screening, diagnosis and treatment, ranging from -15.7 to -64.8%, followed by a progressive recovery, ranging from -5.9 to +25.1% in the latest period (December 2020-March 2021) (Table). Although 725 diagnoses were “missed“ between March and June 2020 as compared to the previous 12 months, 971 diagnoses were “recovered” between June 2020 and March 2021. Conclusions: A substantial disruption in the screening, diagnosis and treatment of GU malignancies was observed early in the pandemic, followed by a progressive rebound and recovery. The highest declines were observed for PSA screening, and the lowest for cystectomy procedures, reflecting triaging of care based on severity during the pandemic.[Table: see text]
Erratum: “Environmental, Dietary, Maternal, and Fetal Predictors of Bulky DNA Adducts in Cord Blood: A European Mother–Child Study (NewGeneris)”
Authors: Marie Pedersen, Michelle A. Mendez, Bernadette Schoket, Roger W. Godschalk, Ana Espinosa, Anette Landström, Cristina M. Villanueva, Domenico F. Merlo, Eleni Fthenou, Esther Gracia-Lavedan, Frederik-J. van Schooten, Gerard Hoek, Gunnar Brunborg, Helle M. Meltzer, Jan Alexander, Jeanette K. Nielsen, Jordi Sunyer, John Wright, Katalin Kovács, Kees de Hoogh, Kristine B. Gutzkow, Laura J. Hardie, Leda Chatzi, Lisbeth E. Knudsen, Lívia Anna, Matthias Ketzel, Margaretha Haugen, Maria Botsivali, Mark J. Nieuwenhuijsen, Marta Cirach, Mireille B. Toledano, Rachel B. Smith, Sarah Fleming, Silvia Agramunt, Soterios A. Kyrtopoulos, Viktória Lukács, Jos C. Kleinjans, Dan Segerbäck, Manolis Kogevinas
Journal: Environmental Health Perspectives (2015)

In the "Results" section of the abstract, "median, 12.1 (n = 179) vs. 6.8 (n = 332) adducts per 108 nucleotides, p < 0.001" should have read "median, 12.1 (n = 179) vs. 6.8 (n = 332) adducts per 10 8 nucleotides, p < 0.001.
Phototherapy.
Authors: J. W. Kime
Journal: JAMA (1899)

Fort Dodge, Iowa, Nov. 10, 1899. <h3>To the Editor:</h3> In theJournalfor October 21 (p. 1049), I note your comments on "Phototherapy." In the June number of the<i>Iowa Medical Journal</i>, I called attention to work done along this line by myself. This was some four months in advance of the publication of Finsen's paper quoted by you. At the time of writing my paper I was limiting treatment to the use of rays concentrated by a twelve-inch condensing lens. The volume of sunlight thus utilized was found to be too small, and I have had constructed a metallic reflector that pours a volume of concentrated sunshine over the entire thorax and abdomen, which is as hot as the patient can bear. The heat rays are excluded as much as possible. This reflector is used in the same manner in which Archimedes is said to have fired the Roman
Clinical Cardiology
Authors: David H. Spodick
Journal: JAMA (1978)

The distinguished editors of this text have assembled topnotch contributors to produce a "working manual of clinical cardiology" aimed at students, house officers, and practicing physicians. They clearly achieve their goal, although certain fundamentals (eg, oxygen transport) may require some sophistication. Most of the 56 sections are self-contained discussions of particular topics, so well done that it was difficult to choose outstanding ones. The editors and two colleagues collaborated on a thoughtful, well-organized précis of differential diagnosis of important clinical findings. Blomqvist's "Principles of Electrocardiography," a minimonograph, authoritatively condenses much traditional and contemporary material. "Cardiac Catheterization" by Hawthorne and Sanders is an excellent state-of-the-art summary. In two succinct chapters, Mitchell, Harris, and Blomqvist discuss physiological and clinical aspects of exercise testing. Goldblatt lucidly covers congenital heart disease in only 50 pages. A book of this scope could not avoid all pitfalls, but the hard-to-find lapses hardly detract from a superb
Biodehalogenation.
Authors: C E Castro
Journal: Environmental Health Perspectives (1977)

Haloorganic biocides are widely employed as soil fumigants to combat the destructive action of plant parasitic nematodes and fungi. These substances are dehalogenated by soil organisms, principally species of Pseudomonas and Flavobacteria, to nontoxic metabolities. The paths of metabolism of a vareity of simply alkyl halides are described with emphasis upon the biodehalogenation step.
A Clinical Discussion on the Caesarean Section: And its Claims as an Operation of Election
Authors: R. Greenhalgh
Journal: BMJ (1867)

Cases of Craniotomy in Extreme Distortion of the Pelvis.CASE I.-I was requested on March 17th, i843, to visit Mary M., aged 26, a very rickety woman.She had been married eighteen months, and had reached the full term of her first pregnancy.She had been in labour thirty-two hours; the membranes had been ruptured twelve hours; the os uteri was dilatable; the head was at the brim of the pelvis, with the scalp somewhat swollen.On examination, the pelvis was found greatly deformed.As the skin was hot, the pulse 98 and feeble, and she com- plained of thirst, the tongue dry and furred, and the pains were be- ginning to flag, the head was at once perforated.I succeeded in about two hours and a half, and with great difficulty, in extracting a male child of average dimensions.Shortly after delivery, she was seized with symptoms of peritonitis, of which complaint she died in thirty-two hours.POST MORTEM EXAMINATION.-Theperitoneum was highly vascu- lar.Lymph and serum were effused in considerable quantities in the abdominal cavity.The uterus and surrounding tissues were matted to- gether by recent adhesions.There was no trace of rupture.The other viscera were healthy.The admeasurements of the pelvis were the fol- lowing.Brim: Conjugate (true) diameter, 21 inches.Transverse diameter, 41 inches.Outlet: Conjugate diameter, 41 inches (coccyx pushed back).Transverse diameter, 31 inches.The cavity of the pelvis was lessened in all its diameters by straightness of the sacrum.CASE II.-Mary M., aged 24, a dwarf, 4 feet 2 inches in height, single, had reached eight and a half months of her first pregnancy on April 3rd, I848, when labour came on.The pains had continued with
EAPH-13. PHASE I STUDY OF INTRAVENTRICULAR INFUSIONS OF AUTOLOGOUS EX VIVO EXPANDED NK CELLS IN CHILDREN WITH RECURRENT/REFRACTORY MALIGNANT POSTERIOR FOSSA TUMORS OF THE CENTRAL NERVOUS SYSTEM
Authors: Soumen Khatua, Vidya Gopalakrishnan, David Sandberg, Leena Ketonen, Jason Johnson, Laurence Cooper, Judy Moyes, Dean Lee, Heather Meador, Michael Rytting, Diane Liu, Wafik Zaky
Journal: Neuro-Oncology (2018)

Prognosis of recurrent/refractory medulloblastoma, ependymoma and atypical teratoid/rhabdoid neoplasms (AT/RT) remains dismal. Preclinical data showing efficacy of activated/propagated NK cells to lyse and kill these tumor cells in culture and in mice have been demonstrated, along with feasibility and safety of infusions of biologic agents into the ventricles. The ongoing phase I trial evaluates for the first time in humans, safety of infusions of autologous NK cells directly into the ventricles of patients with these tumors. Assessment of antitumor activity, and correlative biologic studies are being evaluated to define the immunophenotype and function of expanded NK cells. Patients receive three cycles of NK-cell infusions over 12 weeks through an Ommaya reservoir. To date, 9 patients have been enrolled, 8 patients achieved successful expansion of their NK cells, and 7 patients received up to 27 infusions each of NK cells at doses up to 3x10e7/m2/infusion. Currently this study is enrolling patients in the last cohort. This phase I study has so far demonstrated safety with no dose-limiting toxicity attributable to the infused NK cells. Significant CSF pleocytosis is seen in patients receiving NK cells with the increased dosage, with no evidence of infection. Influx of CD4+ and CD8+ T cells into the CSF in noted. This could suggest a proinflammatory environment induced by higher doses of NK cell infusion. This study also intends to evaluate the migration and persistence of NK cells with novel neuroimaging techniques to correlate efficacy outcome and the pharmacokinetics of NK cells.
Professional Etiquette
Authors: W. Reeves
Journal: BMJ (1842)

the most diligent search wouild frequently fail in pro- curiing the medical writings of maniy of our best au- thors whose works have never beeil collected, but arc scattered through the transactions of various societies.The great beauty of the proposed society is this-that, without trouble on the part of the sub- scriber beyond the simple payment of his guinea, four
Characterization of Blood <scp>Mucosal‐Associated</scp> Invariant T Cells in Patients With Axial Spondyloarthritis and of Resident <scp>Mucosal‐Associated</scp> Invariant T Cells From the Axial Entheses of <scp>Non‐Axial</scp> Spondyloarthritis Control Patients
Authors: Nicolas Rosine, Hannah Rowe, Surya Koturan, Hanane Yahia‐Cherbal, Claire Leloup, Abdulla Watad, Francis Berenbaum, Jeremie Sellam, Maxime Dougados, Vishukumar Aimanianda, Richard Cuthbert, Charlie Bridgewood, Darren Newton, Elisabetta Bianchi, Lars Rogge, Dennis McGonagle, Corinne Miceli‐Richard
Journal: Arthritis & Rheumatology (2022)

Objective The importance of interleukin‐17A (IL‐17A) in the pathogenesis of axial spondyloarthritis (SpA) has been demonstrated by the success of IL‐17A blockade. However, the nature of the cell populations that produce this important proinflammatory cytokine remains poorly defined. We undertook this study to characterize the major IL‐17A–producing blood cell populations in the peripheral blood of patients with axial SpA, with a focus on mucosal‐associated invariant T (MAIT) cells, a population known to be capable of producing IL‐17. Methods We evaluated IL‐17A production from 5 sorted peripheral blood cell populations, namely, MAIT cells, γδ T cells, CD4+ T cells, CD8+ T cells, and neutrophils, before and after stimulation with phorbol myristate acetate, the calcium ionophore A23187, and β‐1,3‐glucan. Expression of IL‐17A transcripts and protein were determined using nCounter and ultra‐sensitive Simoa technology, respectively. MAIT cells from the axial entheses of non‐axial SpA control patients (n = 5) were further characterized using flow cytometric immunophenotyping and quantitative polymerase chain reaction, and the production of IL‐17 was assessed following stimulation. Results On a per‐cell basis, MAIT cells from peripheral blood produced the most IL‐17A compared to CD4+ T cells ( P &lt; 0.01), CD8+ T cells ( P &lt; 0.0001), and γδ T cells ( P &lt; 0.0001). IL‐17A was not produced by neutrophils. Gene expression analysis also revealed significantly higher expression of IL17A and IL23R in MAIT cells. Stimulation of peripheral blood MAIT cells with anti‐CD3/CD28 and IL‐7 and/or IL‐18 induced strong expression of IL17F . MAIT cells were present in the normal, unaffected entheses of control patients who did not have axial SpA and showed elevated AHR , JAK1 , STAT4 , and TGFB1 transcript expression with inducible IL‐17A protein. IL‐18 protein expression was evident in spinal enthesis digests. Conclusion Both peripheral blood MAIT cells and resident MAIT cells in normal axial entheses contribute to the production of IL‐17 and may play important roles in the pathogenesis of axial SpA.
IAGS: Inferring Ancestor Genome Structure under a Wide Range of Evolutionary Scenarios
Authors: Shenghan Gao, Xiaofei Yang, Jianyong Sun, Xixi Zhao, Bo Wang, Kai Ye
Journal: Molecular Biology and Evolution (2022)

Abstract Significant improvements in genome sequencing and assembly technology have led to increasing numbers of high-quality genomes, revealing complex evolutionary scenarios such as multiple whole-genome duplication events, which hinders ancestral genome reconstruction via the currently available computational frameworks. Here, we present the Inferring Ancestor Genome Structure (IAGS) framework, a novel block/endpoint matching optimization strategy with single-cut-or-join distance, to allow ancestral genome reconstruction under both simple (single-copy ancestor) and complex (multicopy ancestor) scenarios. We evaluated IAGS with two simulated data sets and applied it to four different real evolutionary scenarios to demonstrate its performance and general applicability. IAGS is available at https://github.com/xjtu-omics/IAGS.
Deciphering mechanisms of immune escape to inform immunotherapeutic strategies in multiple myeloma
Authors: Muthulekha Swamydas, Elena V. Murphy, James J. Ignatz-Hoover, Ehsan Malek, James J. Driscoll
Journal: Journal of Hematology & Oncology (2022)

Abstract Multiple myeloma is an incurable cancer characterized by the uncontrolled growth of malignant plasma cells nurtured within a permissive bone marrow microenvironment. While patients mount numerous adaptive immune responses directed against their disease, emerging data demonstrate that tumor intrinsic and extrinsic mechanisms allow myeloma cells to subvert host immunosurveillance and resist current therapeutic strategies. Myeloma downregulates antigens recognized by cellular immunity and modulates the bone marrow microenvironment to promote uncontrolled tumor proliferation, apoptotic resistance, and further hamper anti-tumor immunity. Additional resistance often develops after an initial clinical response to small molecules, immune-targeting antibodies, immune checkpoint blockade or cellular immunotherapy. Profound quantitative and qualitative dysfunction of numerous immune effector cell types that confer anti-myeloma immunity further supports myelomagenesis, disease progression and the emergence of drug resistance. Identification of tumor intrinsic and extrinsic resistance mechanisms may direct the design of rationally-designed drug combinations that prevent or overcome drug resistance to improve patient survival. Here, we summarize various mechanisms of immune escape as a means to inform novel strategies that may restore and improve host anti-myeloma immunity.
Association News
Journal: JAMA (1935)

<h3>ANNUAL CONGRESS ON MEDICAL EDUCATION, HOSPITALS AND LICENSURE</h3> Thirty-First Annual Meeting, held in Chicago, Feb. 18 and 19, 1935 (Continued from page 1249) Dr. Merritte W. Ireland, Washington, D. C., in the Chair February 18—Afternoon <h3>TUBERCULOSIS: INSTITUTIONAL AND EDUCATIONAL ASPECTS</h3> Objectives of the Campaign Against Tuberculosis Dr. Kendall Emerson, New York: With the founding of the Trudeau Sanatorium fifty years ago there was planted the seed of a sturdy tree, which has since spread its protecting branches over the lives of thousands of patients, at the same time removing from contact with their susceptible neighbors an equal number of foci each capable of indefinitely spreading the disease. With therapeutic aid in abeyance, with the initial step in handling any infectious disease, segregation, already under way, the first decade of the twentieth century offered the opportunity to gird our loins for a grapple with the leading cause of human mortality. Our
Letter from Westminster
Authors: W. Russell
Journal: BMJ (1981)

A fierce parliamentary campaign against the effect the Govern- ment's decision that overseas students must pay full fees could have on London's 13 postgraduate medical institutions has been launched by MPs from both sides of the House.The prospect is that many of the institutions will have to close if something is not done to alter the impact of the Government's decision to cut their grant on the basis of the number of whole-time registered overseas students.The MPs, who have tabled a Commons motion calling on the Government to think again, will be meeting Dr Gerard Vaughan, the Health Minister, and Dr Rhodes Boyson, the junior Education Minister and a former headmaster, to argue the case for a change of heart.Mr Jack Ashley, Labour MP for Stoke on Trent, warned at a meeting in the Commons of representatives of the institutions affected that they could shortly be watching their death throes if nothing was done."That would be a disaster for the disabled and would certainly kill research as we have known it in the past," he added."It would destroy centres of excellence and must be fought very strongly indeed."By coincidence that same day Lord Annan, Vice-chancellor of London University, was warning the Commons Select Committee on the Social Services about the same subject.He said that the institutes would be losing between 40°o and 65°O of their income as a result of the Government's policy and they could not continue if that happened.If the money was not there they would close.He claimed that, unlike the London School of Economics, they could not simply get the money by taking more students at realistic fees.LSE has, apparently, saved the day by increasing its student numbers.The problem is that in science the costs are too high.The economic cost each year for a student at one of the institutes is anything between 10 000 and /14 000.Lord Annan said it was perfectly reasonable to have a dis- criminatory fee for foreign students, but where he parted company with the Government was over its approach."I think they have overdone it," he said.