tbuckley/cabot-search huggingface dataset:
Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells
Authors: H Dolatshad, A Pellagatti, M Fernandez-Mercado, B H Yip, L Malcovati, M Attwood, B Przychodzen, N Sahgal, A A Kanapin, H Lockstone, L Scifo, P Vandenberghe, E Papaemmanuil, C W J Smith, P J Campbell, S Ogawa, J P Maciejewski, M Cazzola, K I Savage, J Boultwood
Journal: Leukemia (2014)

Abstract The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34 + cells from MDS patients with SF3B1 mutations using RNA sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared with wild-type cases include genes that are involved in MDS pathogenesis ( ASXL1 and CBL ), iron homeostasis and mitochondrial metabolism ( ALAS2, ABCB7 and SLC25A37 ) and RNA splicing/processing ( PRPF8 and HNRNPD ). Many genes regulated by a DNA damage-induced BRCA1–BCLAF1–SF3B1 protein complex showed differential expression/splicing in SF3B1 mutant cases. This is the first study to determine the target genes of SF3B1 mutation in MDS CD34 + cells. Our data indicate that SF3B1 has a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link.
PYELITIS IN THE FEMALE
Authors: J. M. HUNDLEY
Journal: JAMA (1926)

Pyelitis is an inflammation of the mucous membrane of the pelvis and calices of the kidney, whereas with pyelonephritis the process is more advanced; in addition to the changes in the pelvis and calices there is an infection of the parenchyma. Acute pyelitis as a distinct pathologic entity is not common, for it is usually associated with varying degrees of pyelonephritis. Pyelitis is usually secondary to infection in the parenchyma and in many cases this infection in the parenchyma clears up, leaving the pelvis and calices of the kidney involved. The differential diagnosis between simple pyelitis and pyelonephritis is impossible without the use of functional tests. Of course, in simple pyelitis there is no decrease in function, for the parenchyma is not involved, whereas in pyelonephritis there is a reduction in the output of dye. In cases in which the infection in the parenchyma has cleared up and with a
Wartime evacuation and mortality from childhood leukaemia in England and Wales in 1945-9
Authors: L J Kinlen, S M John
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Abstract Objective</b>: To discover whether the wartime government evacuation of children from London and other population centres to rural districts was associated with any increase in childhood leukaemia. <b>Design</b>: Observational study of mortality from leukaemia among the childhood population of England and Wales in relation to the unique population movements during the second world war. The 476 rural districts of England and Wales were ranked according to the ratio of government evacuees (two thirds of them children) to local children in September 1941. The districts were divided into three categories, each with similar numbers of children in 1947 but with different ratios of evacuees to local children (“low,” “intermediate,” “high”). Mortality from childhood leukaemia was examined in these three rural categories in 1945-9. Urban areas were also examined according to their exposure to evacuees. <b>Setting</b>: Local authority areas of England and Wales. <b>Subjects</b>: Children aged under 15. <b>Results</b>: 47% excess of leukaemia at ages 0-14 years occurred in 1945-9 in the rural “high” category for evacuees relative to the “low” category, with a significant trend across the three categories. There were increases in both the 0-4 and 5-14 year age groups, but these were larger in the older age group. Rates 25% lower than average occurred in rural areas with few evacuees. <b>Conclusion</b>: These findings suggest that wartime evacuation increased the incidence of childhood leukaemia in rural areas and that other forms of population mixing may have contributed to the increases in past decades. Overall, they add to the appreciable evidence for an infective basis in childhood leukaemia.
Broadening access to undergraduate medical education
Authors: C Angel, A Johnson
Journal: BMJ (2000)

Based on a presentation from the Millennium Festival of Medicine 

In their statement of principles, the Council of Heads of Medical Schools indicate that the purpose of a medical education is to graduate individuals well fitted to meet the present and future needs of society for medical care.1 They go on to state that this can be achieved, at least in part, if the social, cultural, and ethnic backgrounds of graduates reflect broadly the diversity of the patient population. It seems that this principle is not currently met by medical schools in the United Kingdom. In a study commissioned by the Council of Heads of Medical Schools in 1998, McManus found that certain groups (students from ethnic minorities, sixth form colleges or further education institutions, and lower socioeconomic groups) were disadvantaged when seeking admission to medical school.2 As a result, the council devised an action plan in which medical schools were required to draw up policies relating to equal opportunities as a matter of urgency.

#### Summary points

The social, cultural, and ethnic backgrounds of medical graduates should reflect broadly the diversity of the patient population

The groups of people that are underrepresented in the medical profession tend to be overrepresented in the patient population

In the University of Sheffield Medical School the Compact Scheme and Early Outreach Scheme are aimed at attracting underrepresented groups

These schemes raise awareness of higher education in lower socioeconomic groups and provide support, guidance, and advice to pupils

In general, the groups of people that are underrepresented in the medical profession tend to be overrepresented in the patient population as a result of many factors, including poverty, poor diet and housing, poor educational standards, and occupational factors. Pupils from lower socioeconomic groups are disadvantaged in many ways when applying for entry to medical education. Their …
<i>Chlamydia pneumoniae</i> , Herpes Simplex Virus Type 1, and Cytomegalovirus and Incident Myocardial Infarction and Coronary Heart Disease Death in Older Adults
Authors: David S. Siscovick, Stephen M. Schwartz, Lawrence Corey, J. Thomas Grayston, Rhoda Ashley, San-Ping Wang, Bruce M. Psaty, Russell P. Tracy, Lewis H. Kuller, Richard A. Kronmal
Journal: Circulation (2000)

Whether serological evidence of prior infection with Chlamydia pneumoniae, herpes simplex virus type 1 (HSV-1), and cytomegalovirus (CMV) is associated with myocardial infarction (MI) and coronary heart disease (CHD) death remains a source of controversy.We conducted a nested case-control study among participants in the Cardiovascular Health Study, a cohort study of persons aged >/=65 years. Cases experienced an incident MI and CHD death (n=213). Control subjects were matched to cases by age, sex, clinic, year of enrollment, and month of blood draw (n=405). Serum was analyzed for IgG antibodies to C pneumoniae, HSV-1, and CMV. After adjustment for other risk factors, the risk of MI and CHD death was associated with the presence of IgG antibodies to HSV-1 (odds ratio [OR] 2.0, 95% CI 1.1 to 3.6) but was not associated with the presence of IgG antibodies to either C pneumoniae (OR 1.1, 95% CI 0.7 to 1.8) or CMV (OR 1.2, 95% CI 0.7 to 1.9). Although there was little association with low to moderate C pneumoniae antibody titers (</=1:512), high-titer (1:1024) C pneumoniae antibody was associated with an increased risk (OR 2.2, 95% CI 1.1 to 4.4).Among older adults, the presence of IgG antibodies to HSV-1 was associated with a 2-fold increase in the risk of incident MI and CHD death. For C pneumoniae, only high-titer IgG antibodies were associated with an increased risk of MI and CHD death. The presence of IgG antibodies to CMV was not associated with risk among the elderly.
Hemobilia Secondary to Liver Abscess
Authors: Harold C. Urschel
Journal: JAMA (1963)

A SERIOUS DEGREE of hemobilia (hemorrhage into the biliary tract) is uncommon. It usually results from extrahepatic sources such as rupture of a hepatic artery aneurysm into the bile duct or erosion of a biliary calculus into an adjacent vessel.<sup>1,2</sup>Even less common is hemobilia of hepatic origin which may be caused by trauma to the liver,<sup>3,4</sup>malignant tumors,<sup>5</sup>and many other rather esoteric conditions. This present report concerns a case of hemobilia secondary to a liver abscess which required a major resection of the right lobe of the liver for ultimate control. <h3>Report of a Case</h3> A 75-year-old female was admitted to the Surgical Services of the Massachusetts General Hospital on April 29, 1962, because of persistent and severe hemobilia. Sixteen months prior to admission, cholecystectomy and choledochotomy had been performed in another hospital. Multiple stones were removed from the common bile duct. Postoperative cholangiography showed
Let's be fair about equity and equality
Authors: Imre Loefler
Journal: BMJ (2006)

<h3>Objective</h3> Osteoarthritis (OA) has a strong genetic component but the success of previous genome-wide association studies (GWAS) has been restricted due to insufficient sample sizes and phenotype heterogeneity. Our aim was to examine the effect of clinically relevant endophenotyping according to site of maximal joint space narrowing (maxJSN) and bone remodelling response on GWAS signal detection in hip OA. <h3>Methods</h3> A stratified GWAS meta-analysis was conducted in 2118 radiographically defined hip OA cases and 6500 population-based controls. Signals were followed up by analysing differential expression of proximal genes for bone remodelling endophenotypes in 33 pairs of macroscopically intact and OA-affected cartilage. <h3>Results</h3> We report suggestive evidence (p&lt;5×10<sup>−6</sup>) of association at 6 variants with OA endophenotypes that would have been missed by using presence of hip OA as the disease end point. For example, in the analysis of hip OA cases with superior maxJSN versus cases with non-superior maxJSN we detected association with a variant in the <i>LRCH1</i> gene (rs754106, p=1.49×10<sup>−7</sup>, OR (95% CIs) 0.70 (0.61 to 0.80)). In the comparison of hypertrophic with non-hypertrophic OA the most significant variant was located between <i>STT3B</i> and <i>GADL1</i> (rs6766414, p=3.13×10<sup>−6</sup>, OR (95% CIs) 1.45 (1.24 to 1.69)). Both of these associations were fully attenuated in non-stratified analyses of all hip OA cases versus population controls (p&gt;0.05). <i>STT3B</i> was significantly upregulated in OA-affected versus intact cartilage, particularly in the analysis of hypertrophic and normotrophic compared with atrophic bone remodelling pattern (p=4.2×10<sup>−4</sup>). <h3>Conclusions</h3> Our findings demonstrate that stratification of OA cases into more homogeneous endophenotypes can identify genes of potential functional importance otherwise obscured by disease heterogeneity.
Blood Banking Not What It Used to Be, Experts Say
Authors: Andrew A. Skolnick
Journal: JAMA (1994)

IN THE WORDS of one speaker at the American Association of Blood Banks conference, Transfusion Medicine: Update 1994, held in Seattle, Wash, "Blood banking has changed. We are no longer the blood bankers we used to be." Merlin Sayers, MD, PhD, director, Transfusion Surveillance, Puget Sound Blood Center, Seattle, who provided an update on hepatitis virology, cited his own topic as an example of how different the conference program is compared with the topics that concerned blood bankers 10 or more years ago. Indeed, a major part of the 2-day conference included sessions on tissue banking, extracorporeal membrane oxygenation, transfusion-associated graft-vs-host disease, blood conservation during surgery, and red blood cell substitutes, as well as more traditional areas of interest to blood bankers. Based on reports presented at the update of promising new technologies for reducing or eliminating the need for blood transfusions, even greater changes appear to lie ahead. <h3>Blood</h3>
131I-"Hippuran" Renography in Detection of Unilateral Renal Disease in Patients with Hypertension
Authors: A. Doig, J. R. Lawrence, T. Philip, P. Tothill, K. W. Donald
Journal: BMJ (1963)

ANTISEPTICSMEDICALIJORNSAL take 20 to 30 minutes to kill all the organisms, whereas the same strains were killed in less than five minutes by 1 % chloroxylenol and 1 % lysol.Similar tests with 14 more strains of Ps. pyocyanea showed that 1 % chlor- oxylenol and 0.5% chlorhexidine were as powerful as 1% lysol.
Bat Origins of MERS-CoV Supported by Bat Coronavirus HKU4 Usage of Human Receptor CD26
Authors: Qihui Wang, Jianxun Qi, Yuan Yuan, Yifang Xuan, Pengcheng Han, Yuhua Wan, Wei Ji, Yan Li, Ying Wu, Jianwei Wang, Aikichi Iwamoto, Patrick C.Y. Woo, Kwok-Yung Yuen, Jinghua Yan, Guangwen Lu, George F. Gao
Journal: Cell Host & Microbe (2014)
Ibuprofen Interferes with the Efficacy of Antihypertensive Drugs
Authors: KENNETH L RADACK
Journal: Annals of Internal Medicine (1987)

Study Objective: To assess the effects of Ibuprofen on blood pressure control in patients being treated with antihypertensive drugs. Design: Randomized, blinded, placebo-controlled, parallel trial of Ibuprofen compared with acetaminophen and with placebo in 3-week treatment periods. Setting: A general internal medicine clinic at a university hospital. Patients: Forty-five patients with essential hypertension controlled by treatment with at least two antihypertensive drugs were enrolled. Of these, 41 completed the study; treatment was discontinued in 3 of the 15 patients in the Ibuprofen group due to breakage of the drug capsules, and after randomization in 1 of the 14 patients in the placebo group due to unstable angina. All 15 patients in the acetaminophen group completed the study. Interventions: All previous antihypertensive regimens were continued. During the 3-week treatment, Ibuprofen, 400 mg, was administered orally every 8 hours; acetaminophen, 1 g, orally every 8 hours; or placebo, 2 capsules, orally every 8 hours. Measurements and Main Results: In the Ibuprofen group, the mean increase from baseline after 3 weeks of treatment was significant in the average supine diastolic blood pressure (6.4 mm Hg; 95% confidence interval [Cl], 1.05 to 11.75; p = 0.0239); supine mean arterial pressure (6.6 mm Hg; 95% Cl, 1.25 to 11.95; & p = 0.0205); and sitting mean arterial pressure (5.8 mm Hg; 95% Cl, 1.57 to 10.04; p = 0.0123). The mean increase in blood pressure variables in the Ibuprofen group was significantly different compared with the mean increase in the variables in the placebo group after 3 weeks of treatment: supine systolic blood pressure (7.1 mm Hg compared with -4.5 mm Hg; 95% Cl for the difference in means, 2.5 to 20.6; p = 0.0133); supine diastolic pressure (6.4 mm Hg compared with 0.0; 95% Cl for difference in means, 0.87 to 12.4; p = 0.0250); supine mean arterial pressure (6.6 mm Hg compared with -1.5; 95% Cl for difference in means, 2.0 to 14.2; p= 0.0110); sitting systolic pressure (6.8 mm Hg compared with -3.7; 95% Cl for difference in means, 2.0 to 19.0; p = 0.0169); sitting diastolic pressure (5.3 mm Hg compared with -1.1; 95% Cl for difference in means, 0.76 to 12.1; p = 0.0273); and sitting mean arterial pressure (5.8 mm Hg compared with -2.0; 95% Cl for difference in means, 1.5 to 14.1; p = 0.0169). When compared with the acetaminophen group after 3 weeks of treatment, the Ibuprofen group also showed statistically significant changes in supine diastolic and mean arterial pressures, and sitting diastolic and mean arterial pressures. Conclusions: Ibuprofen can interfere with blood pressure control in certain patients with treated mild-to-moderate hypertension. Further clinical studies are needed to document these findings and determine which patients are most likely to have an ibuprofen-related impairment in blood pressure control.
Phase III Evaluation of Fluoxetine for Treatment of Hot Flashes
Authors: Charles L. Loprinzi, Jeff A. Sloan, Edith A. Perez, Susan K. Quella, Phillip J. Stella, James A. Mailliard, Michele Y. Halyard, Sandhya Pruthi, Paul J. Novotny, Teresa A. Rummans
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Hot flashes can be a prominent problem in women with a history of breast cancer. Given concerns regarding the use of hormonal therapies in such patients, other nonhormonal means for treating hot flashes are required. Based on anecdotal information regarding the efficacy of fluoxetine and other newer antidepressants for treating hot flashes, the present trial was developed. PATIENTS AND METHODS: This trial used a double-blinded, randomized, two-period (4 weeks per period), cross-over methodology to study the efficacy of fluoxetine (20 mg/d) for treating hot flashes in women with a history of breast cancer or a concern regarding the use of estrogen (because of breast cancer risk). Eligible patients had to have reported that they averaged at least 14 hot flashes per week; they could have received tamoxifen or raloxifene as long as they were on a stable dose. The major outcome measure was a bivariate construct representing hot flash frequency and hot flash score, analyzed by a classic sums and differences cross-over analysis. RESULTS: Eighty-one randomized women began protocol therapy. By the end of the first treatment period, hot flash scores (frequency × average severity) decreased 50% in the fluoxetine arm versus 36% in the placebo arm. Cross-over analysis demonstrated a significantly greater marked hot flash score improvement with fluoxetine than placebo (P = .02). The results were not adjusted for potential confounding influences, including age and tamoxifen use. The fluoxetine was well tolerated. CONCLUSION: This dose of fluoxetine resulted in a modest improvement in hot flashes.
Metastatic Adrenal Cortical Carcinoma
Authors: Joseph Jarabak, Kathryn L Rice
Journal: JAMA (1981)

CURRENTLY, there is a disagreement concerning the effectiveness of mitotane (o,p'-DDD) (1,1-dichloro-2-[o-chlorophenyl]-2-[p-chlorophenyl]-ethane) in the therapy for metastatic adrenal cortical carcinoma. Following the initial favorable report,<sup>1</sup>measurable tumor response was observed in two large series in 34 %<sup>2</sup>and 61 %<sup>3</sup>of patients treated with this drug, and overall survival was prolonged when compared with an earlier group of untreated persons whose mean survival was 2.9 months. However, in another series,<sup>4</sup>survival was not improved. The following case is presented to illustrate a long-term remission of adrenocortical carcinoma and the effects that have been associated with the ingestion of more than 13 kg of mitotane. <h3>Report of a Case</h3> A 49-year-old woman was admitted to a hospital in November 1967 with hirsutism and masses in the left breast and abdomen. Roentgenograms disclosed metastases in the ribs and liver and downward displacement of the left kidney. Two 24-hour urine collections
GPs need more training in cancer genetics
Authors: R. Dobson
Journal: BMJ (2001)

General practitioners need more help and education to help them to make risk assessments of patients with a family history of breast or ovarian cancer.

Researchers who questioned a group of GPs found that only 1 in 4 knew the three most important criteria for risk assessment.

In the study, researchers from the department of primary health care at Oxford University sent a questionnaire to 282 GP principals asking them to make decisions on six simulated cases …
Male-to-Female Transmission of HIV-Reply
Authors: Nancy Padian
Journal: JAMA (1987)

In Reply.—  I appreciate Dr Trotter's comments about the protective role of condoms in our sample. Part of his confusion lies in the fact that risk factors may be significantly associated with infection in either a protective or an enhancing fashion, depending on the value of the measure of association. Thus, a relative risk greater than 1 connotes a positive association with infection, whereas a relative risk less than 1 connotes protection. Consequently, it is correct to state that condoms were not significantly associated with protection from infection and that failure to use them was not associated with increased risk. Our current data show that nine of 50 women who used condoms were infected with HIV. A protective association was noted, but was not statistically significant (relative risk, 0.6; 95% confidence interval, 0.3 to 1.3). Even so, as stated in the article, all of the infected women who used condoms
The 'Squeaky Wheel' and Health Care Policy
Authors: Gilbert H. Friedell
Journal: JAMA (1991)

ESTABLISHING public policy for health care is difficult at best. But when policy decisions result primarily from the application of the "squeaky wheel" principle, the difficulty is compounded. Decisions are then more likely to deal with the concerns of a small group of individuals rather than the broader interests of society, with private patient care rather than public health needs, and with short-term expenditures rather than long-term savings. A story on the front page of the<i>New York Times</i>on November 12, 1990, focused my attention clearly on an issue that exemplifies this problem. The story reported, "The Blue Cross and Blue Shield Association has agreed to pay a share of the costs of a clinical study of an experimental treatment for advanced breast cancer." The association would expend at least $10 million during the 3-to 4-year study of 1200 women who will undergo autologous bone marrow transplantation in conjunction