tbuckley/cabot-search huggingface dataset:
Randomized Phase III Study of Erlotinib Versus Observation in Patients With No Evidence of Disease Progression After First-Line Platin-Based Chemotherapy for Ovarian Carcinoma: A European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group, and Gynecologic Cancer Intergroup Study
Authors: Ignace B. Vergote, Antonio Jimeno, Florence Joly, Dionyssios Katsaros, Corneel Coens, Evelyn Despierre, Christian Marth, Marcia Hall, Christopher B. Steer, Nicoletta Colombo, Anne Lesoin, Antonio Casado, Alexander Reinthaller, John Green, Martin Buck, Isabelle Ray-Coquard, Annamaria Ferrero, Laure Favier, Nick Simon Reed, Hervé Curé, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2013)

This trial evaluated the efficacy of maintenance erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, after first-line chemotherapy.Eligible patients had high-risk International Federation of Gynecology and Obstetrics stage I or stage II to IV epithelial ovarian, primary peritoneal, or fallopian tube cancer and were not selected for EGFR expression. All patients underwent first-line platinum-based chemotherapy (CT) and showed no signs of progression at the end of CT. Patients were randomly assigned to maintenance erlotinib 150 mg orally daily for 2 years or to observation. EGFR immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and mutation analyses were performed in 318 patients.Between October 2005 and February 2008, 835 patients were randomly assigned (median follow-up, 51 months). Twenty-six percent of the patients stopped erlotinib as a result of adverse effects (of these, 67% were due to rash). For erlotinib and observation, respectively, the median progression-free survival was 12.7 and 12.4 months (hazard ratio [HR], 1.05; 95% CI, 0.90 to 1.23), and the median overall survival was 50.8 and 59.1 months (HR, 0.99; 95% CI, 0.81 to 1.20 months), respectively. No subgroup could be identified with improved effect of erlotinib, based on IHC or FISH for EGFR, or mutations in genes related to the EGFR pathway, or on rash during erlotinib therapy. However, patients with a positive FISH EGFR score had a worse overall survival (46.1 months) than those with a negative score (67.0 months; HR, 1.56; 95% CI, 1.01 to 2.40; P = .044). Global health/quality-of-life scores showed a significant difference during the first year (P = .0102) in favor of the observation arm.Maintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free or overall survival.
Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression.
Authors: L P Walsh, C McCormick, C Martin, D M Stocco
Journal: Environmental Health Perspectives (2000)

Recent reports demonstrate that many currently used pesticides have the capacity to disrupt reproductive function in animals. Although this reproductive dysfunction is typically characterized by alterations in serum steroid hormone levels, disruptions in spermatogenesis, and loss of fertility, the mechanisms involved in pesticide-induced infertility remain unclear. Because testicular Leydig cells play a crucial role in male reproductive function by producing testosterone, we used the mouse MA-10 Leydig tumor cell line to study the molecular events involved in pesticide-induced alterations in steroid hormone biosynthesis. We previously showed that the organochlorine insecticide lindane and the organophosphate insecticide Dimethoate directly inhibit steroidogenesis in Leydig cells by disrupting expression of the steroidogenic acute regulatory (StAR) protein. StAR protein mediates the rate-limiting and acutely regulated step in steroidogenesis, the transfer of cholesterol from the outer to the inner mitochondrial membrane where the cytochrome P450 side chain cleavage (P450scc) enzyme initiates the synthesis of all steroid hormones. In the present study, we screened eight currently used pesticide formulations for their ability to inhibit steroidogenesis, concentrating on their effects on StAR expression in MA-10 cells. In addition, we determined the effects of these compounds on the levels and activities of the P450scc enzyme (which converts cholesterol to pregnenolone) and the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) enzyme (which converts pregnenolone to progesterone). Of the pesticides screened, only the pesticide Roundup inhibited dibutyryl [(Bu)(2)]cAMP-stimulated progesterone production in MA-10 cells without causing cellular toxicity. Roundup inhibited steroidogenesis by disrupting StAR protein expression, further demonstrating the susceptibility of StAR to environmental pollutants.
Transverse myelopathy in systemic lupus erythematosus: an analysis of 14 cases and review of the literature
Authors: Birgit Kovacs, Thomas L Lafferty, Lawrence H Brent, Raphael J DeHoratius
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> To give a comprehensive review of transverse myelopathy (TM), a rare but serious condition reported in 1–2% of patients with systemic lupus erythematosus (SLE). <h3>METHODS</h3> 14 patients with SLE and TM were evaluated and 91 additional cases published in the English and German literature reviewed. <h3>RESULTS</h3> TM presented either as the initial manifestation or within five years of the diagnosis of SLE. Most patients presented with a detectable sensory deficit at the thoracic level. In our 14 patients, 22% of the patients showed complete neurological recovery, whereas in the total patient population of 105 (our cases plus those reviewed in the literature), complete recovery was observed in 50%, partial recovery in 29% and no improvement or deterioration in 21%. Treatment with intravenous methylprednisolone followed by cyclophosphamide seemed to be most effective. Seventy per cent of the total patient population had abnormal magnetic resonance imaging findings. In our group of 14 patients, those with higher disease activity (measured by the SLAM) at onset of TM were treated more aggressively (for example, with plasmapheresis and intravenous pulse cyclophosphamide). TM in our patients was associated with antiphospholipid antibodies in 43% of the cases as compared with 64% of the total patient population. Optic neuritis occurred in 48% of the total patient population with SLE and TM, suggesting an association. <h3>CONCLUSIONS</h3> TM in SLE is a poorly understood entity. Outcome might be more favourable than previously suggested. There is an association of TM with antiphospholipid antibodies in SLE patients. Treatment including intravenous cyclophosphamide may improve the final outcome. This report emphasises the need for multicentre trials to establish guidelines for optimal treatment.
Population phylogenomic analysis of mitochondrial DNA in wild boars and domestic pigs revealed multiple domestication events in East Asia
Authors: Gui-Sheng Wu, Yong-Gang Yao, Kai-Xing Qu, Zhao-Li Ding, Hui Li, Malliya G Palanichamy, Zi-Yuan Duan, Ning Li, Yao-Sheng Chen, Ya-Ping Zhang
Journal: Genome biology (2007)

Abstract Background Previously reported evidence indicates that pigs were independently domesticated in multiple places throughout the world. However, a detailed picture of the origin and dispersal of domestic pigs in East Asia has not yet been reported. Results Population phylogenomic analysis was conducted in domestic pigs and wild boars by screening the haplogroup-specific mutation motifs inferred from a phylogenetic tree of pig complete mitochondrial DNA (mtDNA) sequences. All domestic pigs are clustered into single clade D (which contains subclades D1, D2, D3, and D4), with wild boars from East Asia being interspersed. Three haplogroups within D1 are dominant in the Mekong region (D1a2 and D1b) and the middle and downstream regions of the Yangtze River (D1a1a), and may represent independent founders of domestic pigs. None of the domestic pig samples from North East Asia, the Yellow River region, and the upstream region of the Yangtze River share the same haplogroup status with the local wild boars. The limited regional distributions of haplogroups D1 (including its subhaplogroups), D2, D3, and D4 in domestic pigs suggest at least two different in situ domestication events. Conclusion The use of fine-grained mtDNA phylogenomic analysis of wild boars and domestic pigs is a powerful tool with which to discern the origin of domestic pigs. Our findings show that pig domestication in East Asia mainly occurred in the Mekong region and the middle and downstream regions of the Yangtze River.
Trying to Save a Health Care System: Colombian Residents Go on Strike
Authors: Sarah R. Gottfried
Journal: Annals of Internal Medicine (2014)

On Being a Doctor5 August 2014Trying to Save a Health Care System: Colombian Residents Go on StrikeSarah R. Gottfried, MD, MPHSarah R. Gottfried, MD, MPHFrom Yale New Haven Hospital, New Haven, Connecticut.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M14-0203 Audio Reading - “Trying to Save a Health Care System: Colombian Residents Go on Strike” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Trying to Save a Health Care System: Colombian Residents Go on Strike," by S.R. Gottfried. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail It was mid morning on Tuesday, October 29. We had just finished rounds at the Hospital Universitario del Valle (HUV) in Cali, Colombia. To my surprise, the resident, Diego, turned to me and said, “I have to go now—the strike is beginning.”He grabbed a rolled-up hand-painted banner and, along with nearly every resident in the hospital, headed out to the street. At the same moment, thousands of residents all over Colombia, from Cali to Bogotá to Medellín, stepped away from morning rounds to begin a nationwide strike.Unlike many resident strikes that have happened globally, this strike was not ... Author, Article, and Disclosure InformationAffiliations: From Yale New Haven Hospital, New Haven, Connecticut.Corresponding Author: Sarah R. Gottfried, MD, MPH, Everett Family Health Center, Cambridge Health Alliance, 391 Broadway, Suite 204, Everett, MA 02149; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Trying to Save a Health Care System: Colombian Residents Go on Strike” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Trying to Save a Health Care System: Colombian Residents Go on Strike," by S.R. Gottfried. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Cited byHow to Get Involved in Global Health 5 August 2014Volume 161, Issue 3Page: 228-229KeywordsDiagnostic techniquesHealth careLegislationPatient Protection and Affordable Care ActPatientsPrevention, policy, and public healthResidencySkeletonSurgeonsTongue ePublished: 5 August 2014 Issue Published: 5 August 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Comparison of epigenetic versus standard induction chemotherapy for newly diagnosed acute myeloid leukemia patients ≥60 years old
Authors: Neha Gupta, Austin Miller, Shipra Gandhi, Laurie A. Ford, Carlos E. Vigil, Elizabeth A. Griffiths, James E. Thompson, Meir Wetzler, Eunice S. Wang
Journal: American Journal of Hematology (2015)

Older patients with acute myeloid leukemia (AML) have poor outcomes with standard induction chemotherapy. We retrospectively reviewed our institute's experience with epigenetic (Epi) versus cytarabine‐ and anthracycline‐based intensive chemotherapy (IC) as induction in newly diagnosed AML patients aged 60 years and older. One hundred sixty‐seven patients ( n = 84, IC; n = 83, Epi) were assessed; 69 patients received decitabine and 14 azacitidine. Baseline characteristics between the IC and Epi patient cohorts were not statistically different except for age, initial white blood cell count, and comorbidity index. Overall response rate (ORR, 50% vs. 28%, respectively, P &lt; 0.01) and complete response rate (CRR, 43% vs. 20%, respectively, P &lt; 0.01) were superior following IC vs. Epi. Although univariate analysis demonstrated longer overall survival after IC (10.7 vs. 9.1 months, P = 0.012), multivariate analysis showed no independent impact of induction treatment. Treatment‐related mortality was not statistically different in the two groups. Outcomes of patients with secondary, poor cytogenetic risk, FLT‐3 mutated AML, or relapsed/refractory disease after IC or Epi were not significantly different. Outcomes of patients receiving IC versus a 10‐day decitabine regimen ( n = 63) also were not significantly different. Our results suggest that IC and Epi therapy are clinically equivalent approaches for upfront treatment of older patients with AML and that other factors (feasibility, toxicity, cost, etc.) should drive treatment decisions. Prospective randomized trials to determine the optimal induction approach for specific patient subsets are needed. Am. J. Hematol. 90:639–646, 2015. © 2015 Wiley Periodicals, Inc.
Neural Expression and Increased Lavage Fluid Levels of Secretoneurin in Seasonal Allergic Rhinitis
Authors: Magnus Korsgren, Jonas S. Erjefält, Josef Hinterhölzl, Reiner Fischer-Colbrie, Cecilia Ahlström Emanuelsson, Morgan Andersson, Carl G. A. Persson, Alan Mackay-Sim, Frank Sundler, Lennart Greiff
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Secretoneurin is a neuropeptide potentially involved in migration of eosinophils, monocytes, and dendritic cells. Whether secretoneurin is present in the human airway mucosa and whether it is released at ongoing allergic airway inflammation is currently unknown. In patients with allergic rhinitis, we have explored the occurrence of secretoneurin in nasal mucosal biopsies and lavage fluids before and during natural allergen exposure. Immunohistochemical analysis revealed an abundance of nerves displaying secretoneurin immunoreactivity, which were distributed predominantly around blood vessels and submucosal glands. A majority of nerve fibers containing vesicular acetylcholine transporter, tyrosine hydroxylase, calcitonin gene–related peptide, and vasoactive intestinal peptide were also secretoneurin-immunoreactive, indicating a localization of secretoneurin in cholinergic, adrenergic, and sensory nerves. Lavage fluid levels of secretoneurin were increased at allergen exposure (p < 0.01–0.05). Levels of secretoneurin did not correlate with eosinophil cationic protein (ρ = 0.1, p = 0.7). We conclude that secretoneurin has a widespread occurrence in nasal mucosal nerves of patients with seasonal allergic rhinitis and that increased nasal lavage fluid levels of secretoneurin may characterize ongoing allergen exposure. These data favor a role of secretoneurin in the local traffic of immune cells in human airway mucosa.
Molecular Basis of the Waxy Endosperm Starch Phenotype in Broomcorn Millet (Panicum miliaceum L.)
Authors: H. V. Hunt, K. Denyer, L. C. Packman, M. K. Jones, C. J. Howe
Journal: Molecular Biology and Evolution (2010)

Waxy varieties of the tetraploid cereal broomcorn millet (Panicum miliaceum L.) have endosperm starch granules lacking detectable amylose. This study investigated the basis of this phenotype using molecular and biochemical methods. Iodine staining of starch granules in 72 plants from 38 landrace accessions found 58 nonwaxy and 14 waxy phenotype plants. All waxy types were in plants from Chinese and Korean accessions, a distribution similar to that of the waxy phenotype in other cereals. Granule-bound starch synthase I (GBSSI) protein was present in the endosperm of both nonwaxy and waxy individuals, but waxy types had little or no granule-bound starch synthase activity compared with the wild types. Sequencing of the GBSSI (Waxy) gene showed that this gene is present in two different forms (L and S) in P. miliaceum, which probably represent homeologues derived from two distinct diploid ancestors. Protein products of both these forms are present in starch granules. We identified three polymorphisms in the exon sequence coding for mature GBSSI peptides. A 15-bp deletion has occurred in the S type GBSSI, resulting in the loss of five amino acids from glucosyl transferase domain 1 (GTD1). The second GBSSI type (L) shows two sequence polymorphisms. One is the insertion of an adenine residue that causes a reading frameshift, and the second causes a cysteine-tyrosine amino acid polymorphism. These mutations appear to have occurred in parallel from the ancestral allele, resulting in three GBSSI-L alleles in total. Five of the six possible genotype combinations of the S and L alleles were observed. The deletion in the GBSSI-S gene causes loss of protein activity, and there was 100% correspondence between this deletion and the waxy phenotype. The frameshift mutation in the L gene results in the loss of L-type protein from starch granules. The L isoform with the tyrosine residue is present in starch granules but is nonfunctional. This loss of function may result from the substitution of tyrosine for cysteine, although it could not be determined whether the cysteine isoform of L represents the functional type. This is the first characterization of mutations that occur in combination in a functionally polyploid species to give a fully waxy phenotype.
Oral Cancer Diagnosis by Mechanical Phenotyping
Authors: Torsten W. Remmerbach, Falk Wottawah, Julia Dietrich, Bryan Lincoln, Christian Wittekind, Jochen Guck
Journal: Cancer Research (2009)

Oral squamous cell carcinomas are among the 10 most common cancers and have a 50% lethality rate after 5 years. Despite easy access to the oral cavity for cancer screening, the main limitations to successful treatment are uncertain prognostic criteria for (pre-)malignant lesions. Identifying a functional cellular marker may represent a significant improvement for diagnosis and treatment. Toward this goal, mechanical phenotyping of individual cells is a novel approach to detect cytoskeletal changes, which are diagnostic for malignant change. The compliance of cells from cell lines and primary samples of healthy donors and cancer patients was measured using a microfluidic optical stretcher. Cancer cells showed significantly different mechanical behavior, with a higher mean deformability and increased variance. Cancer cells (n approximately 30 cells measured from each patient) were on average 3.5 times more compliant than those of healthy donors [D(normal) = (4.43 +/- 0.68) 10(-3) Pa(-1); D(cancer) = (15.8 +/- 1.5) 10(-3) Pa(-1); P < 0.01]. The diagnosis results of the patient samples were confirmed by standard histopathology. The generality of these findings was supported by measurements of two normal and four cancer oral epithelial cell lines. Our results indicate that mechanical phenotyping is a sensible, label-free approach for classifying cancer cells to enable broad screening of suspicious lesions in the oral cavity. It could in principle be applied to any cancer to aid conventional diagnostic procedures.
The Pathogenesis of Lupus Nephritis
Authors: Maciej Lech, Hans-Joachim Anders
Journal: Journal of the American Society of Nephrology (2013)

Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. The extrarenal etiology of systemic lupus is based on multiple combinations of genetic variants that compromise those mechanisms normally assuring immune tolerance to nuclear autoantigens. This loss of tolerance becomes clinically detectable by the presence of antinuclear antibodies. In addition, nucleic acids released from netting or apoptotic neutrophils activate innate and adaptive immunity via viral nucleic acid-specific Toll-like receptors. Therefore, many clinical manifestations of systemic lupus resemble those of viral infection. In lupus, endogenous nuclear particles trigger IFN-α signaling just like viral particles during viral infection. As such, dendritic cells, T helper cells, B cells, and plasma cells all contribute to the aberrant polyclonal autoimmunity. The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. Here we provide an update on the pathogenic mechanisms that lead to lupus nephritis and provide the rationale for the latest and novel treatment strategies.
Effects of low-level lead exposure on pyrimidine 5'-nucleotidase and other erythrocyte enzymes. Possible role of pyrimidine 5'-nucleotidase in the pathogenesis of lead-induced anemia.
Authors: D E Paglia, W N Valentine, J G Dahlgren
Journal: Journal of Clinical Investigation (1975)

Similarities between lead-induced anemia and a new hereditary erythorenzymopathy involving pyrimidine-specific 5'-nucleotidase prompted studies of the effects of lead on this and other erythrocyte enzymes. In vitro incubations of normal mature erythrocytes demonstrated that significant inhibition of pyrimidine 5'-nucleotidase occurred in the presence of lead at concentrations that had minimal effects on many other erythrocyte enzymes assayed simultaneously. Similarly, subjects with chronic lead intoxication secondary to industrial exposure exhibited substantial and consistent impairment of erythrocyte pyrimidine-5'-nucleotidase activity. Results suggest that lead-induced deficiency of this enzyme in maturing erythroid elements could, if sufficiently severe, result in induction of basophilic stippling and premature erythrocyte hemolysis analogous to that encountered in the genetically induced enzyme-deficiency syndrome.