tbuckley/cabot-search huggingface dataset:
Breast Cancer Screening, Incidence, and Mortality Across US Counties
Authors: Charles Harding, Francesco Pompei, Dmitriy Burmistrov, H. Gilbert Welch, Rediet Abebe, Richard Wilson
Journal: JAMA Internal Medicine (2015)

Screening mammography rates vary considerably by location in the United States, providing a natural opportunity to investigate the associations of screening with breast cancer incidence and mortality, which are subjects of debate.To examine the associations between rates of modern screening mammography and the incidence of breast cancer, mortality from breast cancer, and tumor size.An ecological study of 16 million women 40 years or older who resided in 547 counties reporting to the Surveillance, Epidemiology, and End Results cancer registries during the year 2000. Of these women, 53,207 were diagnosed with breast cancer that year and followed up for the next 10 years. The study covered the period January 1, 2000, to December 31, 2010, and the analysis was performed between April 2013 and March 2015.Extent of screening in each county, assessed as the percentage of included women who received a screening mammogram in the prior 2 years.Breast cancer incidence in 2000 and incidence-based breast cancer mortality during the 10-year follow-up. Incidence and mortality were calculated for each county and age adjusted to the US population.Across US counties, there was a positive correlation between the extent of screening and breast cancer incidence (weighted r = 0.54; P < .001) but not with breast cancer mortality (weighted r = 0.00; P = .98). An absolute increase of 10 percentage points in the extent of screening was accompanied by 16% more breast cancer diagnoses (relative rate [RR], 1.16; 95% CI, 1.13-1.19) but no significant change in breast cancer deaths (RR, 1.01; 95% CI, 0.96-1.06). In an analysis stratified by tumor size, we found that more screening was strongly associated with an increased incidence of small breast cancers (≤2 cm) but not with a decreased incidence of larger breast cancers (>2 cm). An increase of 10 percentage points in screening was associated with a 25% increase in the incidence of small breast cancers (RR, 1.25; 95% CI, 1.18-1.32) and a 7% increase in the incidence of larger breast cancers (RR, 1.07; 95% CI, 1.02-1.12).When analyzed at the county level, the clearest result of mammography screening is the diagnosis of additional small cancers. Furthermore, there is no concomitant decline in the detection of larger cancers, which might explain the absence of any significant difference in the overall rate of death from the disease. Together, these findings suggest widespread overdiagnosis.
β-Blockade and Operative Mortality in Noncardiac Surgery
Authors: Mark L. Friedell, Charles W. Van Way, Ron W. Freyberg, Peter L. Almenoff
Journal: JAMA Surgery (2015)

<h3>Importance</h3> The use of perioperative pharmacologic β-blockade in patients at low risk of myocardial ischemic events undergoing noncardiac surgery (NCS) is controversial because of the risk of stroke and hypotension. Published studies have not found a consistent benefit in this cohort. <h3>Objective</h3> To determine the effect of perioperative β-blockade on patients undergoing NCS, particularly those with no risk factors. <h3>Design, Setting, and Participants</h3> This is a retrospective observational analysis of patients undergoing surgery in Veterans Affairs hospitals from October 1, 2008, through September 31, 2013. <h3>Methods</h3> β-Blocker use was determined if a dose was ordered at any time between 8 hours before surgery and 24 hours postoperatively. Data from the Veterans Affairs electronic database included demographics, diagnosis and procedural codes, medications, perioperative laboratory values, and date of death. A 4-point cardiac risk score was calculated by assigning 1 point each for renal failure, coronary artery disease, diabetes mellitus, and surgery in a major body cavity. Previously validated linear regression models for all hospitalized acute care medical or surgical patients were used to calculate predicted mortality and then to calculate odds ratios (ORs). <h3>Main Outcomes and Measures</h3> The end point was 30-day surgical mortality. <h3>Results</h3> There were 326 489 patients in this cohort: 314 114 underwent NCS and 12 375 underwent cardiac surgery. β-Blockade lowered the OR for mortality significantly in patients with 3 to 4 cardiac risk factors undergoing NCS (OR, 0.63; 95% CI, 0.43-0.93). It had no effect on patients with 1 to 2 risk factors. However, β-blockade resulted in a significantly higher chance of death in patients (OR, 1.19; 95% CI, 1.06-1.35) with no risk factors undergoing NCS. <h3>Conclusions and Relevance</h3> In this large series, β-blockade appears to be beneficial perioperatively in patients with high cardiac risk undergoing NCS. However, the use of β-blockers in patients with no cardiac risk factors undergoing NCS increased risk of death in this patient cohort.
Amyl nitrite inhalation, a “volatile” anemia
Authors: Lauriane Filliatre, Julien Broseus, Serge Pissard, Chadia Mekki, Pierre Feugier, Julien Perrin
Journal: American Journal of Hematology (2015)

A 41 year-old Caucasian man was referred to hematology consultation due to iterative episodes (for several weeks) of regenerative anemia associated with asthenia, dyspnea, and diarrhea, but without bacteriological documentation. There was no family or personal medical history, except a bipolar disorder treated with valproic acid. At examination, there was no jaundice, no hepatosplenomegaly, and no lymphadenopathy. The first line of biological data pointed to hemolytic regenerative anemia (Hb = 119 g/L, MCV = 111 fL, reticulocytes 216 G/L), with normal leucocyte and platelet counts (5.5 G/L and 216 G/L, respectively), a low haptoglobin level of 0.08 g/L (normal 0.3–2 g/L), and an increased LDH level at 306 UI/L (normal < 248 UI/L). Further examination of a blood film revealed isolated red blood cell (RBC) abnormalities with moderate anisopoikilocytosis, characterized by hemighosts, bite cells, and spherocytes (Image 1A). A direct Coombs test was negative. RBC enzymes (particularly G6PD) and an EMA (Eosin-5‘-Maleimide) test for hereditary spherocytosis were both normal. Primary analyses of hemoglobin with HPLC revealed small amounts (1.5%) of an unknown fraction (Image 1B); the presence of this fraction was confirmed with isoelectric focusing. An isopropanol test was positive and Heinz bodies were observed upon incubation with brilliant cresyl blue. Taken together, these data suggested unstable hemoglobin. Unexpectedly, after genotyping, we found no evidence of variant α-, β-globin chains or altered cytB5 reductase. During follow-up, the patient experienced four similar episodes. These puzzling results led to re-questioning, and the patient admitted that these episodes corresponded to prior consumption of “poppers.” After stopping consumption, all biological abnormalities disappeared (Images 1C–1D). Amyl nitrites, commonly known as “poppers,” have been used as a recreational drug for about 50 years, due to their effects on mood and sexual intercourse. Many adverse effects (particularly hematological) have been associated with these compounds. In fact, volatile nitrites are powerful oxidants that can cause methemoglobin formation and the dissociation of heme and globin chains, which results in hemichromes and Heinz body formation 1. Individuals with a G6PD deficiency are particularly at risk of developing these events with exposure 2. However, some cases were reported without any intrinsic RBC defects 3. In conclusion, clinicians should keep in mind that unexplained hemolytic anemia may be related to festive consumption of amyl nitrites, in rare cases. Blood films (May Grunwald Giemsa) and hemoglobin study with HPLC. (A) Blood film during volatile nitrite exposure shows anomalous RBCs: a: bite cells; b: hemighosts; c: spherocytes. (B) HPLC during exposure to volatile nitrites reveals the presence of an undetermined fraction (encircled). (C) Blood film and (D) HPLC results show normal findings after the patient ceased consumption of volatile nitrites.
Demand for prostate specific antigen testing in primary care
Authors: K. Hopcroft
Journal: BMJ (2002)

<h3>Objective</h3> This study investigated the relationship between the number of different medications dispensed (NDMD) to senior drivers and the risk of injurious road traffic crashes (RTCs). <h3>Design</h3> A matched case-control study with data from various population-based national registers was conducted. Cases were drivers aged 50–80 years involved in a crash in Sweden between 2005 and 2009. Only the first non-alcohol-related RTC was studied. Controls were residents with a valid license who did not crash. Four controls were matched by sex, age (year and month of birth), and place of residence. Exposure to NDMD prior to the crash date was assessed using four time periods: 1–8, 1–15, 1–30 and 1–90 days. Conditional logistic regression was used and analyses adjusted for civil status, occupation and dispensation of medications affecting the cardiovascular or nervous systems (C/N). <h3>Results</h3> ORs (95% CI) increased progressively with the NDMD. For 1–8 days the OR ranged from 1.15 (1.10 to 1.20) for 1–2 medications to 1.27 (1.13 to 1.42) for five or more medications. The magnitude of the effect declined gradually with longer exposure periods, but remained when five or more medications were used. Adjusting for C/N medications resulted in slightly higher effects; for 1–8 days it ranged from 1.16 (1.10 to 1.23) for 1–2 medications to 1.35 (1.17 to 1.56) for five or more, with similar trends by exposure period. The highest effects were seen for single crashes and for drivers aged 66–80 years. <h3>Conclusions</h3> The NDMD was linked to the likelihood of a senior driver being involved in an injurious RTC. The strength of the association steadily increased with increased NDMD, especially when medications were taken closer to the index date, or when more than five medications were dispensed.
IL-4 polymorphisms in intrinsic and extrinsic asthma in a Greek population
Authors: Eirini Kontakioti, Dionysios Spyratos, Kalliopi Domvri, Michail Daniilidis, Lazaros Sichletidis, Konstantinos Zarogoulidis, Despina Papakosta
Journal: European Respiratory Journal (2013)

Objective. The aim of the study was to investigate the IL-4 and IL-4Receptor polymorphisms in asthmatic patients and their association with asthma and asthma severity in a Greece.  Materials and methods. Thirty patients with extrinsic asthma, mean age 35.2±14.51 years (Group A) and 22 patients with intrinsic asthma, mean age 47.1±16.3 years (Group B) were included in the study. All patients were recruited from the Asthma Clinic of Pulmonary Department, Aristotle University of Thessaloniki. 21 healthy control subjects, mean age 36.6±10.5 years were also included (Group C). All patients were subjected to skin prick tests, spirometry, methacholine challenge, determination of total serum IgE and exhaled FeNO. For the immunogenetic study DNA was extracted from the patients’ peripheral blood samples. Determination of IL4-1098(T/G), IL4-590(C/T), IL4-33(C/Τ), IL4RPOS-1902, polymorphisms were performed by PCR (C:cytocine, T:thymine, G:Guanine και A:Adenine).  Results. Analysis of IL4 -1098 polymorphisms showed an increased frequency of guanine in Group A (p=0.036) when compared to Group C, whereas for IL4 –590, CC genotype showed an increased frequency in Group C and C/T in Group A (p=0.003), Regarding asthma severity, severe asthma when compared with mild asthma, was associated with the IL-4TTT/GCC diplotype (p=0.033).  Conclusions. This is the first study to investigate interleukin gene polymorphisms in a Greek asthmatic population and one of the very few studies on intrinsic asthma. IL-4 polymorphisms showed significant differences between patients with extrinsic and intrinsic asthma and also compared to controls. The above findings could be associated with risk of asthma development and asthma severity.
SYMMETRICAL BILATERAL GRANULAR ATROPHY OF THE CEREBRAL CORTEX OF VASCULAR ORIGIN
Authors: ANDREW J. AKELAITIS
Journal: American Journal of Psychiatry (1942)

A case of symmetrical, bilateral granular atrophy of the cerebral cortex is described. Topographically, the atrophy is limited mainly to those areas lying at the juncture of the vascular supply of the anterior, middle and posterior cerebral arteries. The primary involvement of the gray matter differentiates this form of atrophy from Binswanger's chronic subcortical encephalopathy. In the granular type of atrophy of the cerebral cortex those pial arteries supplying the cortex are mainly involved while in Binswanger's encephalopathy, the arteries supplying the medullary layer are primarily affected.
Does the addition of chemotherapy (CT) to preoperative radiotherapy (preopRT) increase the pathological response in patients with resected rectal cancer : Report of the 22921 EORTC phase III trial
Authors: J.-F. Bosset, G. Calais, L. Mineur, P. Maingon, L. Radosevic-Jelic, A. Daban, E. Bardet, A. Beny, L. Collette, A. Briffaux
Journal: Journal of Clinical Oncology (2004)

3504 Background: This trial evaluates the addition of CT to preop RT, and the value of postop CT for improving survival in T3-T4 resectable rectal cancer. Eligibility : age < 80 y and WHO PS < 2. Arm 1: preopRT 45 Gy in 5 weeks (w). Arm 2 : preopRT + two 5 day CT courses ( 5-FU 350 mg/m2/d; LV : 20 mg/m2/d ), the 1st and 5th w of RT. Arm 3 : preopRT + four postop CT courses. Arm 4 : preopRT-CT + postop CT. We analyzed the pathological response. Methods: 1011 pts entered the trial : group 1-no preop CT (arms 1+3) : 505 pts; group 2- preop CT (arms 2+4) : 506 pts. Patients/tumour (T) : median age 63.2 y; male/female 73.1 %/27.9 %; T distance from anal verge : <5 cm : 49.1%; 6–10 cm : 43.7 %; >10 cm : 6.46 %; NA : 0,8 %; T stage : T3 : 89.5 %; T4 : 10 %. NA : 0.5 %. A resection was performed in 476 pts (94.3 %) and 473 pts (99.5 %) in Group 1 and 2 respectively. Results: Group 1 vs Group 2 : Median tumour length (mm) : 30 vs 25 (p = <0.0001). Extension into rectal wall : T0 : 5.3 % vs 14 % (p = >0.0001); PT0–2 : 42.9 % vs 58.1 % (p = < 0.0001). Median depth invasion beyond muscularis propria (mm) : 3 vs 2 (p = 0.061). Veinous (V) invasion 13.9 % vs 9.1 % (p = 0.021). Perineural (N) invasion 14.3 % vs 7.6 % (p = 0.001). Lymphatic (L) invasion 17.4 % vs 11.4 % (p = 0.008). Nodal invasion : 26.9 % vs 20.9 % (p = 0.031). Conclusions: The addition of 5-FU-LV to preopRT significantly reduced tumor size and pTN stage, and significant decreased LVN invasion rates. Longer follow-up is needed to assess the true impact on local control and survival. Supported in part by a grant from the French Research Ministry (PHRC 1992) and by NCI grants 2U10-CA11488–22 through 5U10-CA11488–32. No significant financial relationships to disclose.
Abstract 3770: MLN4924, a neddylation inhibitor, abolishes chemoresistance of bladder cancer stem-like cells through suppression of stemness
Authors: Kuan-Lin Kuo, I-Lin Ho, Yeong-Shiau Pu, Yu-Chieh Tsai, Tsung-Hsien Shih, Kuo-How Huang
Journal: Cancer Research (2014)

Abstract Introduction: Bladder urothelial carcinoma (UC) ranks fourth in incidence among cancers in men and eighth in women in the United States, however, the chemotherapy response rate is only about half. The cancer stem cells (CSCs), which are believed as the driving force of tumor progression, have related to chemoresistance. Here we present the finding of CSC-like cells from human UC cell line NTUB1, and investigate the effect of MLN4924, a neddylation inhibitor on conquering chemoresistance in human UC. Materials &amp; methods: The CSC-like cells were enriched from its parental cell line NTUB1 by cisplatin selection consecutively for at least one year. The properties of CSC-like cells were demonstrated by colony formation assay, side population assay, and cell viability assay. The expression levels of specific stemness-related markers, EMT-related markers and cell death-related molecules were revealed by western blot. The ability of migration was analyzed by wound-healing assay and transwell assay. The MLN4924-induced apoptosis on CSC-like cells were determined by flow cytometry with annexin V and propidium iodide (PI) staining. Gene knockdown was performed with gene-specific siRNA. The in vitro findings were further confirmed in vivo via xenograft mouse model. Results: The CSC-like cells exhibited multiple drug resistance, highly expression level of stemness markers as well as EMT markers, and highly mobility. The treatment of MLN4924 repressed the expression of stemness markers and EMT markers and reduced cell mobility; meanwhile, it caused significant cell death in CSC-like cells. The knockdown of stemness markers diminished the drug resistance of CSC-like cells. And in the end, MLN4924 significantly inhibit tumor growth in xenograft models bladder cancer stem-like cells. Conclusion: Our data suggested that the drug resistance in UC may conferred by CSC-like cells via up-regulation of stemness markers, and the treatment of MLN4924 could abolish drug resistance through repression of stemness markers. This could provide a new remedy for bladder cancer treatment. Citation Format: Kuan-Lin Kuo, I-Lin Ho, Yeong-Shiau Pu, Yu-Chieh Tsai, Tsung-Hsien Shih, Kuo-How Huang. MLN4924, a neddylation inhibitor, abolishes chemoresistance of bladder cancer stem-like cells through suppression of stemness. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3770. doi:10.1158/1538-7445.AM2014-3770
Autoimmune hepatitis in a murine autoimmune polyendocrine syndrome type 1 model is directed against multiple autoantigens
Authors: Matthias Hardtke‐Wolenski, Richard Taubert, Fatih Noyan, Maren Sievers, Janine Dywicki, Jerome Schlue, Christine S. Falk, Brita Ardesjö Lundgren, Hamish S. Scott, Andreas Pich, Mark S. Anderson, Michael P. Manns, Elmar Jaeckel
Journal: Hepatology (2014)

Autoimmune polyendocrine syndrome type 1 (APS‐1) is caused by mutations of the autoimmune regulator ( AIRE) gene. Mouse studies have shown that this results in defective negative selection of T cells and defective early seeding of peripheral organs with regulatory T cells (Tregs). Aire deficiency in humans and mice manifests as spontaneous autoimmunity against multiple organs, and 20% of patients develop an autoimmune hepatitis (AIH). To study AIH in APS‐1, we generated a murine model of human AIH on a BALB/c mouse background, in which Aire is truncated at exon 2. A subgroup of 24% of mice is affected by AIH, characterized by lymphoplasmacytic and periportal hepatic infiltrates, autoantibodies, elevated aminotransferases, and a chronic and progressive course of disease. Disease manifestation was dependent on specific Aire mutations and the genetic background of the mice. Though intrahepatic Treg numbers were increased and hyperproliferative, the intrahepatic CD4/CD8 ratio was decreased. The targets of the adaptive autoimmune response were polyspecific and not focussed on essential autoantigens, as described for other APS‐1‐related autoimmune diseases. The AIH could be treated with prednisolone or adoptive transfer of polyspecific Tregs. Conclusion : Development of AIH in APS‐1 is dependent on specific Aire mutations and genetic background genes. Autoimmune response is polyspecific and can be controlled by steroids or transfer with Tregs. This might enable new treatment options for patients with AIH. (H epatology 2015;61:1295–1305)
Abstract 16219: Effects of Netrin-1 on Vascular Injury and Repair
Authors: Kin L Siu, Ji-Youn Youn, Jun Zhang, Hua L Cai
Journal: Circulation (2011)

Post-angioplasty restenosis is a major complication after angioplasty surgery. While several strategies exist to limit this phenomenon, they each have their own shortcomings. In this work, we tested whether netrin-1, which we have shown previously to be a powerful angiogenic and cardioprotective agent via production of nitric oxide (NO), can be used to prevent the typical phenotypes of restenosis using the femoral wire injury mice model. Animals were infused with either vehicle or netrin-1 (15 ng/day) via an osmotic pump for 14 days with the netrin-1 grouped started 2 days prior. On the second day, femoral artery injury was performed by passing a guide wire inside of the right femoral artery 3 times, each time held for 30 seconds. The artery was then ligated and checked for blood flow before closure of the wound site. Sham surgery was performed on the left femoral artery. Femoral arteries were harvested 12 days after the surgery, fixed in paraffin, and sectioned in paraffin. Visualization of the vessels using H & E and trichrome staining reveals neointimal formation when compared to uninjured controls, which was abolished in netrin-1 treated animals. This effect of netrin-1 was not observed in DCC+/- animals, which are deficient in the receptor for netrin-1. In additional experiments we found that netrin-1 potently and dose-dependently inhibited vascular smooth muscle cell (VSMC) migration and proliferation, which are hallmarks of neointimal formation and restenosis. These responses were also inhibited by pre-incubation of the cells with DCC-antibody. It has been shown that endothelial progenitor cells (EPCs) play an important in vascular repair. In parallel experiments we found that pre-treatment of bone marrow-derived EPCs with netrin-1 markedly attenuated hydrogen peroxide induced EPC apoptosis (14% dead cells from 45% in untreated group). In summary, netrin-1 appears to inhibit vascular injury and promote vascular repair via attenuation of VSMC migration and proliferation, as well as promotion of EPC survival, resulting in reduced neointimal formation and likely restenosis. These data represent the fist evidence that netrin-1 can be used as a powerful protector against vascular injury.
<scp>d-</scp>Serine Added to Clozapine for the Treatment of Schizophrenia
Authors: Guochuan E. Tsai, Pinchen Yang, Li-Chen Chung, I-Ching Tsai, Chung-Wen Tsai, Joseph T. Coyle
Journal: American Journal of Psychiatry (1999)

D-Serine is a full agonist at the glycine site on the N-methyl-D-aspartate (NMDA) receptor. Previous administration of D-serine to schizophrenic patients taking nonclozapine antipsychotics improved positive, negative, and cognitive symptoms, whereas the partial agonist D-cycloserine improved negative symptoms of patients taking conventional antipsychotics but worsened symptoms in clozapine-treated patients. To study the difference between full and partial agonists at the NMDA receptor glycine site, the clinical effects of adding D-serine to clozapine were assessed.In a 6-week double-blind trial, 20 schizophrenic patients received placebo or D-serine (30 mg/kg per day) in addition to clozapine. Clinical efficacy, side effects, and serum levels of D-serine were determined every other week.The patients exhibited no improvement with D-serine, nor did their symptoms worsen, as previously reported with D-cycloserine.The results suggest either that clozapine may have an agonistic effect on the NMDA system or that clozapine-treated patients do not respond to D-serine.