tbuckley/cabot-search huggingface dataset:
A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy
Authors: Lulin Huang, Houbin Zhang, Ching-Yu Cheng, Feng Wen, Pancy O S Tam, Peiquan Zhao, Haoyu Chen, Zheng Li, Lijia Chen, Zhengfu Tai, Kenji Yamashiro, Shaoping Deng, Xianjun Zhu, Weiqi Chen, Li Cai, Fang Lu, Yuanfeng Li, Chui-Ming G Cheung, Yi Shi, Masahiro Miyake, Yin Lin, Bo Gong, Xiaoqi Liu, Kar-Seng Sim, Jiyun Yang, Keisuke Mori, Xiongzhe Zhang, Peter D Cackett, Motokazu Tsujikawa, Kohji Nishida, Fang Hao, Shi Ma, He Lin, Jing Cheng, Ping Fei, Timothy Y Y Lai, Sibo Tang, Augustinus Laude, Satoshi Inoue, Ian Y Yeo, Yoichi Sakurada, Yu Zhou, Hiroyuki Iijima, Shigeru Honda, Chuntao Lei, Lin Zhang, Hong Zheng, Dan Jiang, Xiong Zhu, Tien-Ying Wong, Chiea-Chuen Khor, Chi-Pui Pang, Nagahisa Yoshimura, Zhenglin Yang
Journal: Nature Genetics (2016)
RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence
Authors: Yinghong Xiao, Igor M. Rouzine, Simone Bianco, Ashley Acevedo, Elizabeth Faul Goldstein, Mikhail Farkov, Leonid Brodsky, Raul Andino
Journal: Cell Host & Microbe (2016)

Mutation and recombination are central processes driving microbial evolution. A high mutation rate fuels adaptation but also generates deleterious mutations. Recombination between two different genomes may resolve this paradox, alleviating effects of clonal interference and purging deleterious mutations. Here we demonstrate that recombination significantly accelerates adaptation and evolution during acute virus infection. We identified a poliovirus recombination determinant within the virus polymerase, mutation of which reduces recombination rates without altering replication fidelity. By generating a panel of variants with distinct mutation rates and recombination ability, we demonstrate that recombination is essential to enrich the population in beneficial mutations and purge it from deleterious mutations. The concerted activities of mutation and recombination are key to virus spread and virulence in infected animals. These findings inform a mathematical model to demonstrate that poliovirus adapts most rapidly at an optimal mutation rate determined by the trade-off between selection and accumulation of detrimental mutations.
Host Immune Response to a Common Cell-Surface Antigen in Human Sarcomas
Authors: William C. Wood, Donald L. Morton
Journal: New England Journal of Medicine (1971)

Cytotoxic antibody was demonstrated in the serums of four patients with sarcoma against their own autologous sarcoma cells in tissue culture. The presence of a common cell-surface antigen in human sarcomas was suggested by the finding that 70 per cent (58 of 83) of serums from patients with different histologic types of sarcomas were cytotoxic to an osteosarcoma cell line, whereas in serums from patients with other types of neoplasms cytotoxic antibody was no more frequent than in normal blood-donor serums. Further cross-reactivity studies revealed the common sarcoma antigen on tissue-culture cells from four different human sarcomas. Immunization of patients with sarcoma with their own irradiated sarcoma cells induced an increased immune response to this common sarcoma antigen, with a rising titer of cytotoxic antibody.
Effects of Affirmative Action in Medical Schools
Authors: Stephen N. Keith, Robert M. Bell, August G. Swanson, Albert P. Williams
Journal: New England Journal of Medicine (1985)

In the early 1970s, affirmative-action programs were introduced to accomplish a number of social goals, including increasing the supply of minority physicians and improving the health care of the poor. To assess the success of such programs, we analyzed data on people who graduated from U.S. medical schools in 1975 to determine how specialty choice, practice locations, patient populations served, and board-certification rates differ between minority and nonminority graduates. A larger proportion of minority graduates (55 per cent vs. 41 per cent, P less than 0.001) chose the primary-care specialties of family practice, general internal medicine, general pediatrics, and obstetrics-gynecology. Significantly more minority physicians (12 per cent vs. 6 per cent, P less than 0.01) practiced in locations designated as health-manpower shortage areas by the federal government and had more Medicaid recipients in their patient populations (31 per cent for blacks, 24 per cent for Hispanics, 14 per cent for whites; P less than 0.001). Physicians from each racial or ethnic group served disproportionately more patients of their own racial or ethnic group (P less than 0.001), but minority physicians did not serve significantly more persons from other racial or ethnic minority groups than did nonminority physicians. Many minority physicians served patient populations much like those of their nonminority colleagues, which indicates that substantial integration of the medical marketplace has taken place. Significantly fewer minority graduates had become board-certified by 1984 (48 per cent vs. 80 per cent, P less than 0.001), and most of this disparity was associated with differences in premedical-school characteristics and in the patient populations they served. Our analysis shows that minority graduates of the medical school class of 1975 are fulfilling many of the objectives of affirmative-action programs.
Favorable Effects of Hyaluronidase on Electrocardiographic Evidence of Necrosis in Patients with Acute Myocardial Infarction
Authors: P. R. Maroko, L.D. Hillis, J. E. Muller, L. Tavazzi, G. R. Heyndrickx, M. Ray, M. Chiariello, A. Distante, J. Askenazi, J. Salerno, J. Carpentier, N. I. Reshetnaya, P. Radvany, P. Libby, D.S. Raabe, E.I. Chazov, P. Bobba, E. Braunwald
Journal: New England Journal of Medicine (1977)

To evaluate hyaluronidase's effect in reducing post-infarction myocardial necrosis, we randomized 91 patients with anterior infarction to control (45) or to hyaluronidase-treatment (46) groups. A 35-lead precordial electrocardiogram was recorded on admission and seven days later. Hyaluronidase was administered intravenously after the first electrocardiogram and every six hours for 48 hours. QRS-complex changes were analyzed to assess the drug's effect. Precordial sites with ST-segment elevation (≥0.15 mV) on the initial electrocardiogram that retained an R wave were considered vulnerable for the development of electrocardiographic signs of necrosis. The sum of R-wave voltages of vulnerable sites fell more in the control group than in the hyaluronidase group (70.9±3.6 per cent [±1 S.E.M.] vs. 54.2±5.0 per cent P<0.01). Q waves appeared in 59.3±4.9 per cent of the vulnerable sites in control versus 46.4±4.9 per cent in hyaluronidase-treated patients (P<0.05). Thus, hyaluronidase reduced the frequency of electrocardiographic signs of myocardial necrosis. (N Engl J Med 296:898–903, 1977)
Normal or Early Development of Puberty despite Gonadal Damage in Children Treated for Acute Lymphoblastic Leukemia
Authors: Charmian Quigley, Christopher Cowell, Mark Jimenez, Henry Burger, Judy Kirk, Mary Bergin, Michael Stevens, Judy Simpson, Martin Silink
Journal: New England Journal of Medicine (1989)

To determine the timing of pubertal development and the frequency of gonadal dysfunction in children who survive acute lymphoblastic leukemia, we assessed pubertal status and the plasma levels of sex steroids, gonadotropin, and inhibin in 45 children (20 girls and 25 boys) who had received combination chemotherapy along with 24 Gy of irradiation to the cranium (modified LSA2L2 protocol). We also reexamined testicular biopsy specimens, obtained at the time of the cessation of chemotherapy, for the presence of germ cells. Germ-cell damage, indicated by marked elevations in the plasma level of follicle-stimulating hormone (P<0.001 for the comparison with normal children), was evident in both sexes and was confirmed in the boys by the absence of germ cells in the testicular biopsy specimens and by the small size of the testes for pubic-hair stage. Only 44 percent of the pubertal girls had measurable plasma inhibin levels, as compared with more than 93 percent of normal pubertal girls. Although plasma sex-steroid levels were normal, the secretion of luteinizing hormone in response to stimulation with gonadotropin-releasing hormone was elevated in the pubertal children (P<0.01 for the comparison with normal controls) — a finding that suggests compensation for decreased gonadal function. Despite clear evidence of gonadal damage, girls had early menarche at a mean age (±SD) of 11.95±0.91 years, as compared with the Australian standard of 12.98±1.11 years (P<0.01). Thus, in girls, puberty was early despite primary gonadal damage. Thirteen of 23 boys reached puberty at a mean age of 12.36±0.73 years. We conclude that treatment for acute lymphoblastic leukemia may lead to primary gonadal damage in both sexes, regardless of the age at treatment, but that the secondary characteristics of puberty develop at a normal age or, in girls, relatively early. (N Engl J Med 1989; 321:143–51.)
Adult T-Cell Leukemia with HTLV-I–Associated Myelopathy after Complete Remission of Acute Myelogenous Leukemia
Authors: Masatoshi Kanno, Shinobu Nakamura, Tamotsu Matsuda
Journal: New England Journal of Medicine (1998)

To the Editor: Human T-cell lymphotropic virus type I (HTLV-I) is the causative agent of adult T-cell leukemia–lymphoma (ATL) and HTLV-I–associated myelopathy–tropical spastic paraparesis (HAM–TSP), a neurologic disorder. The virus is transmitted through sexual contact, breast-feeding, and blood transfusion. We describe a patient with both ATL and HAM–TSP, which developed during a complete remission of acute myelogenous leukemia. A 70-year-old heterosexual man, who had been born and lived in an area of Japan where HTLV-I was not endemic, was admitted to our hospital in June 1985. Acute myelogenous leukemia was diagnosed, and he received numerous blood transfusions for two years . . .
Clonal T-Cell Populations in Lymphomatoid Papulosis
Authors: Lawrence M. Weiss, Gary S. Wood, Martha Trela, Roger A. Warnke, Jeffrey Sklar
Journal: New England Journal of Medicine (1986)

Lymphomatoid papulosis is a chronic, clinically benign skin disorder that, when examined histologically, is seen to include numerous large, atypical lymphoid cells that display antigenic markers of T lymphocytes. To investigate the disparity between the clinical behavior of this disease and its malignant histologic appearance, we analyzed the DNA from skin lesions of six patients for rearrangements of beta and gamma T-cell receptor genes. Lesions from five of these patients showed between one and three clonal rearrangements for at least one T-cell receptor gene. Three separate biopsy specimens from a single patient showed different patterns of rearrangements for the beta gene in each specimen. Our results indicate that lymphomatoid papulosis is a clonal T-cell lymphoproliferative process that may possibly be multiclonal in origin. We conclude that this disease has both biologic and histologic features consistent with a malignant T-cell neoplasm despite its indolent course. (N Engl J Med 1986; 315:475–9.)
PTU-026 Patient experience of CT colonography within the Bowel Cancer Screening Programme
Authors: A Ignjatovic, D Burling, L Kallarackel, J Muckian, B P Saunders, J Patnick
Journal: Gut (2010)

<h3>Introduction</h3> Patients with a positive faecal occult blood test in the BCSP are invited to undergo an alternative radiological colonic investigation if deemed unsuitable for colonoscopy. CTC, a radiological modality of choice at St Mark9s, is less invasive than optical colonoscopy but there are conflicting data regarding relative patient experience. Approximately two thirds of patients having colonoscopy in our centre are sedated with a combination of midazolam and pethidine compared to CTC, which is an unsedated procedure. The aim of this study was to compare patient experience of those undergoing CTC vs colonoscopy within the BCSP. <h3>Methods</h3> We retrospectively reviewed our local screening centre9s database from September 2008 to November 2009 to determine the number of patients who had undergone CTC within the BCSP and had also completed and returned a standard 30-day questionnaire (routinely sent to all patients following their secondary examination within the BCSP). The questionnaire includes four domains assessing experience before, during and after the procedure and also overall level of satisfaction. Completed questionnaires were then compared to an equal number of age and sex matched consecutive patients who had undergone optical colonoscopy during the same time period. Fisher9s exact test was used to compare responses. <h3>Results</h3> 21 (10 male, mean age 67 years, SD 4.7) of 83 patients undergoing CTC completed and returned a questionnaire (response rate of 25%), which is significantly lower than colonoscopy response rate of 72% (756 of 1057 patients) (p&lt;0.0001) for the similar time period. There was no significant difference between patient groups with respect to pre-procedure experience or overall satisfaction. However, CTC patients reported more discomfort than expected (8/21 vs 0/21, p=0.003) and only 4/21 (20%) had no or less discomfort than expected compared to colonoscopy (13/21, 62%, p=0.003). CTC patients were also more often discharged without knowing the result of the procedure (10/21 vs 2/21, p&lt;0.001) and were less likely contacted by screening practioners afterwards (13/21, 68% vs 20/21, 95%, p=0.04). <h3>Conclusion</h3> Discomfort during CTC is higher than patients expected and post examination communication is inferior, also reflected by lower questionnaire response rates. While colonoscopy sedation and use of a questionnaire designed for colonoscopy may be confounders, the authors conclude that centres should re-examine the quantity and quality of patient information provided for CTC by screening practitioners. We also recommend a larger prospective multicentre study to compare experience, using a more detailed and less “technique specific” questionnaire.
The Recurrence of Vasoconstrictor Activity after Limb Sympathectomy in Raynaud's Disease and Allied Vasomotor States
Authors: Charles W. Robertson, Reginald H. Smithwick
Journal: New England Journal of Medicine (1951)

TWO types of study are commonly employed in evaluating the physiologic effectiveness of sympathetic denervation of the extremities: those methods based on the presence or absence of sweating in the area denervated and those based on the presence or absence of vasoconstrictor activity in the denervated area.The present report deals with an evaluation of the vasoconstrictor activity in extremities after a number of different operations on the sympathetic pathways to the extremities and a comparison of these physiologic effects with the clinical results in a group of patients having intact peripheral main-vessel circulation before and after operation. The vasoconstrictor . . .
How Sure Is Sure Enough?
Authors: Stephen G. Pauker, Richard I. Kopelman
Journal: New England Journal of Medicine (1992)

The step-by-step process of clinical problem-solving is the subject of this new Journal feature. Information about a real patient is presented to an expert clinician in stages (boldface type), to simulate the way such information emerges in everyday clinical practice. The clinician responds (regular type) as each piece of information is presented, sharing his or her reasoning extemporaneously with the reader. A commentary on the process by the authors follows. A 40-year-old housewife was admitted to the hospital for sharp left-sided chest pain. In the preceding six days she had had one episode of left-shoulder pain and one episode of . . .
Mitral Regurgitation in Idiopathic Hypertrophic Subaortic Stenosis
Authors: Robert E. Dinsmore, Charles A. Sanders, J. Warren Harthorne
Journal: New England Journal of Medicine (1966)

ALTHOUGH mitral regurgitation is a frequent i. finding in patients with idiopathic hypertrophic subaortic stenosis, the cause of the regurgitation has been poorly understood. This report describes an angiographic abnormality of the mitral valve in patients with this condition and offers a possible explanation for the valvular incompetence.Materials and MethodsEleven patients with hypertrophic subaortic stenosis were studied by catheterization of the left side of the heart. The diagnosis was made in each by ventricular angiography and by recognition of the classic pressure abnormalities that have been summarized elsewhere.1 The latter included the presence of a systolic pressure gradient . . .
Acute Pancreatitis
Authors: David C. Whitcomb
Journal: New England Journal of Medicine (2006)

A 56-year-old woman presents with severe epigastric abdominal pain and vomiting of 14 hours' duration, symptoms that developed shortly after dinner the previous evening. She has no history of alcohol use, takes no medications, and has no family history of pancreatitis. On physical examination, she has a heart rate of 110 beats per minute and moderate epigastric abdominal tenderness without peritoneal signs. The white-cell count is 16,500 per cubic millimeter, and the hematocrit is 49 percent. Amylase, lipase, alanine aminotransferase, and lactate dehydrogenase levels are elevated. Calcium, albumin, triglyceride, and electrolyte values are normal. How should this patient be further evaluated and treated?
Increased arterial wall inflammation in patients with ankylosing spondylitis is reduced by statin therapy
Authors: Fleur M van der Valk, Sophie J Bernelot Moens, Simone L Verweij, Aart C Strang, Aart J Nederveen, Hein J Verberne, Michael T Nurmohamed, Dominique L Baeten, Erik S G Stroes
Journal: Annals of the Rheumatic Diseases (2016)

Ankylosing spondylitis (AS) is a chronic inflammatory disease with involvement of axial and sacroiliac joints. In addition, patients with AS have increased risk of cardiovascular disease (CVD), which might be attributed to enhanced inflammatory activity of the arterial wall. In the present study, we compared the level of carotid arterial wall inflammation in patients with AS with healthy controls using (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography with CT. As arterial wall inflammation is reduced by statin therapy, we subsequently assessed the effect of 3-month statin therapy on arterial wall inflammation in AS.We included 24 patients with AS (age 44±10, 72% males) without a history of CVD and 20 controls matched for age and gender. Patients with AS had lower high-density lipoprotein cholesterol and increased C reactive protein (CRP) compared with controls. The 10-year CVD risk was 2% in both groups. Notwithstanding, patients with AS had a 20% increase in arterial wall (18)F-FDG uptake compared with controls. Three-month atorvastatin 40 mg daily significantly lowered low-density lipoprotein cholesterol (baseline 3.55±1.15 mmol/L, -53%) and CRP (baseline 5.0 (1.5-9.3) mg/L, -58%) with a concomitant decrease of carotid arterial wall inflammation (maximum target-to-background ratio from 1.90±0.30 to 1.67±0.27; p=0.009).Patients with AS and without other CVD risk factors have increased arterial wall inflammation, which decreases upon statin therapy. These subjects are not identified as being at risk in current cardiovascular prevention guidelines. Our data support the need to revise CV disease management in AS, with perhaps a role for early statin therapy.
Fecal Immunochemical Test Program Performance Over 4 Rounds of Annual Screening
Authors: Christopher D. Jensen, Douglas A. Corley, Virginia P. Quinn, Chyke A. Doubeni, Ann G. Zauber, Jeffrey K. Lee, Wei K. Zhao, Amy R. Marks, Joanne E. Schottinger, Nirupa R. Ghai, Alexander T. Lee, Richard Contreras, Carrie N. Klabunde, Charles P. Quesenberry, Theodore R. Levin, Pauline A. Mysliwiec
Journal: Annals of Internal Medicine (2016)

Background: The fecal immunochemical test (FIT) is a common method for colorectal cancer (CRC) screening, yet its acceptability and performance over several rounds of annual testing are largely unknown. Objective: To assess FIT performance characteristics over 4 rounds of annual screening. Design: Retrospective cohort study. Setting: Kaiser Permanente Northern and Southern California. Patients: 323 349 health plan members aged 50 to 70 years on their FIT mailing date in 2007 or 2008 who completed the first round of FIT and were followed for up to 4 screening rounds. Measurements: Screening participation, FIT positivity (≥20 µg of hemoglobin/g), positive predictive values for adenoma and CRC, and FIT sensitivity for detecting CRC obtained from Kaiser Permanente electronic databases and cancer registries. Results: Of the patients invited for screening, 48.2% participated in round 1. Of those who remained eligible, 75.3% to 86.1% participated in subsequent rounds. Median follow-up was 4.0 years, and 32% of round 1 participants crossed over to endoscopy over 4 screening rounds—7.0% due to a positive FIT result. The FIT positivity rate (5.0%) and positive predictive values (adenoma, 51.5%; CRC, 3.4%) were highest in round 1. Overall, programmatic FIT screening detected 80.4% of patients with CRC diagnosed within 1 year of testing, including 84.5% in round 1 and 73.4% to 78.0% in subsequent rounds. Limitation: Screening detection, rather than long-term cancer prevention, was evaluated. Conclusion: Annual FIT screening was associated with high sensitivity for CRC, with high adherence to annual follow-up screening among initial participants. The findings indicate that annual programmatic FIT screening is feasible and effective for population-level CRC screening. Primary Funding Source: National Institutes of Health.
In Vivo Visualization of Prostate-Specific Membrane Antigen in Adenoid Cystic Carcinoma of the Salivary Gland
Authors: Susanne Lütje, Wolfgang Sauerwein, Thomas Lauenstein, Andreas Bockisch, Thorsten D. Poeppel
Journal: Clinical Nuclear Medicine (2016)

As the prostate-specific membrane antigen (PSMA) is overexpressed in the neovasculature of several malignancies, it might serve as a target in oncology. Ga-PSMA PET/CT and PET/MRI were performed in a female who developed pulmonary metastases from an adenoid cystic carcinoma of the right sublingual salivary gland after incomplete resection of the primary tumor and radiotherapy. Uptake of Ga-PSMA in tumors was observed, indicating PSMA expression. Moreover, a new cerebral metastasis was detected. Potentially, Ga-PSMA PET might be used for noninvasive assessment of adenoid cystic carcinoma to evaluate whether patients apply for PSMA-based radiotherapy when no further treatment options are available.
Case 24-1984
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Nelson M. Gantz, Nancy L. Harris
Journal: New England Journal of Medicine (1984)

Presentation of CaseA 52-year-old man was admitted to the hospital because of pancytopenia and a question of enteric fever.Three years earlier a cadaveric renal transplantation was performed at this hospital because of polycystic renal disease. He was maintained on azathioprine and prednisone, did well postoperatively, and returned to his home in Caracas, Venezuela. One month before admission there was the onset of fever, sweats, chills, malaise, and weakness. He passed several loose stools, but during the later weeks of his illness he became constipated. A Widal test was reported to be positive; chloramphenicol, 4 g daily, was administered . . .
Prognosis of Cor Pulmonale
Authors: Paul M. Stevens, Martin Terplan, John H. Knowles
Journal: New England Journal of Medicine (1963)

DURING the past decade many aspects of the pathophysiology of pulmonary heart failure have been extensively studied. However, very little attention has been paid to prognosis, once the peripheral signs of congestive heart failure have appeared.Pulmonary heart failure is a common complication and a major cause of death in obstructive pulmonary diseases.1 As such, its appearance portends a grave outcome.2 However, several patients seen recently have had remarkably long periods of survival after the initial episode of heart failure. A review of all patients admitted in recent years to the Massachusetts General Hospital with a diagnosis of chronic cor . . .