tbuckley/cabot-search huggingface dataset:
Gal-Gal Binding and Hemolysin Phenotypes and Genotypes Associated with Uropathogenic<i>Escherichia coli</i>
Authors: Peter O'Hanley, David Low, Irevis Romero, David Lark, Kenneth Vosti, Stanley Falkow, Gary Schoolnik
Journal: New England Journal of Medicine (1985)

To determine whether uropathogenic strains of Escherichia coli exhibit a distinctive constellation of phenotypes, we examined 44 urinary isolates from women with radiologically normal urinary tracts and pyelonephritis, cystitis, or asymptomatic bacteriuria and 73 fecal isolates from healthy control subjects. The strains were characterized by their O serogroup, by their binding specificity (as determined by adhesins), and by their production of hemolysin and colicin V. In addition, the strains were assessed for homologous gene sequences by means of DNA-hybridization probes prepared from cistrons that encode hemolysin and the Gal-Gal binding adhesin--two determinants of virulence, which cause tissue injury and promote bacterial colonization of uroepithelia, respectively. In contrast to most isolates from normal feces and from the urine of patients with asymptomatic bacteriuria, pyelonephritis strains belong to a small number of O serogroups; all express the Gal--Gal binding adhesin and 75 per cent are hemolytic. A gene probe for the Gal--Gal binding adhesin, derived from the chromosome of one strain from a patient with pyelonephritis, hybridized with the DNA of all other pyelonephritis strains. The probe for the hemolysin gene hybridized with DNA from all other hemolytic strains. These data indicate that most cases of pyelonephritis are due to a small number of pathogenic clones that express critical determinants of virulence, and that the nucleotide sequences for hemolysin and the Gal--Gal binding adhesin in heterologous strains share homology. We are tempted to speculate that the gene products of these shared regions of the genome might form the basis for a vaccine against pyelonephritis.
Case 32-1981
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Robert J. Krane, Theresa L. Perrone
Journal: New England Journal of Medicine (1981)

Presentation of CaseA 20-year-old man was admitted to the hospital because of abdominal pain.He was well until six months earlier, when he experienced the onset of weakness, fatigue, and anorexia, with subsequent loss of 18 kg in weight. One month before admission he began to have constant pain in the right testis, with intermittent exacerbations. One week before entry the testicular pain disappeared. On the day of admission sharp pain occurred in the right upper abdominal quadrant, accompanied by pleuritic pain in the right anterior portion of the chest.There was no history of fever, chills, dysuria, hematuria, . . .
Abstract B12: The ALK inhibitor PF-06463922 shows significant response as a single agent in ALK/MYCN driven models of neuroblastoma
Authors: J. Guan, L. Danielson, D. Chand, Y. Jamin, K. Ruuth, E. Tucker, G. Umapathy, A. El Wakil, B. Witek, T. W. Johnson, T. Smeal, L. Chesler, R. H. Palmer, B. Hallberg
Journal: Cancer Research (2016)

Abstract ALK inhibitors such as the ALK/MET/ROS1 inhibitor crizotinib (Xalkori) have shown clinical efficacy in a number of tumour types. However, in ALK positive neuroblastoma treatment with the ALK inhibitor crizotinib has proved more difficult, highlighting the exploration of new drugs as a clinical priority. A recent report of an increased percentage of ALK positive cases in the relapsed neuroblastoma patient population, together with the increased repertoire of ALK inhibitors now available, led to the investigation of alternative ALK inhibitors with potential for use in treatment of neuroblastoma. Here we report an investigation of the activity of a next generation ALK inhibitor in a range of in vitro and pre-clinical ALK driven neuroblastoma models. Initially PF-06463922 was tested in various neuroblastoma cell lines and a range of gain-of-function ALK neuroblastoma mutations were subsequently analyzed in more detail in engineered Ba/F3 and PC12 cell models and by in vitro kinase assays, comparing the effect of PF-06463922 in abrogating cell growth and induced pharmacodynamics markers of response with the ALK inhibitor crizotinib. These results clearly show PF-06463922 to be a superior inhibitor of ALK kinase activity inhibiting all neuroblastoma mutant ALK forms assayed. Finally, single agent oral administration of PF-06463922 lead to induction of apoptosis and a dramatic reduction in tumour volume in a genetically engineered mouse model of treatment-resistant high-risk neuroblastoma driven by aberrant expression of MYCN and activated ALK. Taken together, our results suggest that PF-06463922 represents an important potential step forward in the treatment of relapsed neuroblastoma with mutated ALK. Statement of significance: Our results together with PK/PD analysis of PF-06463922 suggest future clinical trial investigation of ALK positive neuroblastoma Citation Format: J. Guan, L. Danielson, D. Chand, Y. Jamin, K. Ruuth, E. Tucker, G. Umapathy, A. El Wakil, B. Witek, T. W. Johnson, T. Smeal, L. Chesler, R. H. Palmer, B. Hallberg. The ALK inhibitor PF-06463922 shows significant response as a single agent in ALK/MYCN driven models of neuroblastoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B12.
Financial burden from wage losses after early breast cancer: Extent and determinants among Canadian women
Authors: S. Lauzier, E. Maunsell, M. Drolet, N. Hébert-Croteau, J. Brisson, D. Coyle, B. Masse, B. Abdous, A. Robidoux, J. Robert
Journal: Journal of Clinical Oncology (2007)

9000 Background: Wage losses after breast cancer may result in considerable financial burden. More women now participate in the workforce and breast cancer is managed using multiple treatment modalities that could lead to long work absences. We evaluated the burden from wage losses and determinants among Canadian women in the first 12 months after newly diagnosed non-metastatic breast cancer. Methods: This prospective cohort study was conducted among 800 women from 8 hospitals (participation 83%) of whom 459 were working at diagnosis. For these latter women, information on potential determinants of wage losses, work absences, compensation received and perception of financial situation was collected by 3 telephone interviews over the year. Information on medical characteristics came from medical files. The main outcome was the relative loss, namely wages lost divided by annual wages the woman would have earned had she not been absent from work. ANOVA was used to identify determinants. Results: The median relative loss in the first year after diagnosis for the 403 women reporting an absence or reduced work hours was 19% or $5,502 (Can dollars). Multivariate analysis showed that the mean relative loss was 13% for women who reported that breast cancer was not at all costly compared to 22%, 33% and 38% among women who said that breast cancer was a bit, quite or very costly, respectively (ptrend&lt;0.0001). A higher relative loss was significantly associated with a lower level of education (difference between lowest and highest levels = 8 %, ptrend=0.0016), living =50 km from the surgery hospital (diff = 6%, p=0.0697), lower social support (diff = 8%, p=0.0119), invasive disease (diff = 6%, p=0.0861), chemotherapy (diff = 17%, p&lt;0.0001), self-employment (diff= 17%, p&lt;0.0001), shorter tenure in the job (diff between lowest and highest levels = 12%, ptrend&lt;0.0001) and part-time work (diff = 10%, p=0.0003). Conclusions: Financial effects of wage losses could add to the overall burden of breast cancer. Clinicians and policy makers should be sensitized further to the fact that financial burden may be important for working women having more aggressive treatment and precarious work situations. No significant financial relationships to disclose.
Maternal Hydramnios and Congenital Anomalies of the Central Nervous System
Authors: Richard A. Prindle, Theodore H. Ingalls, Samuel B. Kirkwood
Journal: New England Journal of Medicine (1955)

THE association of hydramnios with congenital anomalies, long recognized, was confirmed once again by a previous investigation into antecedent (prenatal) factors influencing tracheoesophageal fistula; hydramnios was present in 20 of the 107 cases.1 The meaning of this association was obscure, and clarification is now sought reversing the approach by studying the results of 145 pregnancies complicated by hydramnios. These pregnancies terminated in the delivery of 68 defective infants, including 45 with anencephalus, 8 with spina bifida, 6 with hydrocephalus and 4 with mongolism.The Group StudiedThe patients studied were for the most part residents of Boston; some came from . . .
Multiple Congenital Defects Following Maternal Varicella
Authors: Eugene G. Laforet, Charles L. Lynch
Journal: New England Journal of Medicine (1947)

INVESTIGATION of the factors responsible for congenital malformations received tremendous impetus in 1941 with the classic report by Gregg,1 of Australia, of a series of cases in which maternal rubella was followed by a variety of anomalies in the offspring, particularly such ocular defects as cataract. Previously, it had been generally accepted that malformations do not result from environmental factors that operate for the first time after fertilization.2 Attention, therefore, had been directed chiefly at possible preconceptual causes. The studies of Gregg1 and of numerous subsequent workers, however, emphasized the necessity of according careful consideration to environmental conditions obtaining after . . .
Recognizing Data Generation
Authors: Mette Kalager, Hans-Olov Adami, Michael Bretthauer
Journal: New England Journal of Medicine (2016)

To the Editor: The International Committee of Medical Journal Editors (ICMJE) recently announced data-sharing requirements for member journals.1 Among the issues that were raised is giving adequate academic credit to the people who design clinical trials, enroll and treat patients, and curate the resulting data. Two main parties are involved in data sharing: those who have performed a clinical trial and possess the data (data generators) and those who want to use those data for other purposes (data reanalysts). Data-sharing requirements need to ensure that the interests of both parties are protected. Data-sharing requirements may discourage researchers from initiating and . . .
Targeting of MyD88 Homodimerization by Novel Synthetic Inhibitor TJ-M2010-5 in Preventing Colitis-Associated Colorectal Cancer
Authors: Lin Xie, Feng-Chao Jiang, Li-Min Zhang, Wen-Tao He, Jian-Hua Liu, Ming-Qiang Li, Xue Zhang, Shuai Xing, Hui Guo, Ping Zhou
Journal: JNCI Journal of the National Cancer Institute (2015)

The TLR/MyD88 signaling pathway is an important driver of inflammation and cancer and is a possible target for antitumor therapy.We generated a MyD88 inhibitor (TJ-M2010-5), which was designed to bind to the TIR domain of MyD88 to interfere with its homodimerization, and the TLR/MyD88 signal pathway. We utilized a mouse model of azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colitis-associated cancer (CAC) in combination with TJ-M2010-5 administration to investigate the anti-inflammation-related cancer effect of MyD88 inhibitor in vivo. Data were analyzed with one-way and repeated measures analysis of variance. Differences in survival between groups were compared using the log rank test. All statistical tests were two-sided.TJ-M2010-5 inhibited MyD88 homodimerization in transfected HEK293 cells in a concentration-dependent manner and suppressed MyD88 signaling in LPS-responsive RAW 264.7 cells in vitro. In a 10-week CAC mouse model (n = 30 per group), TJ-M2010-5 treatment statistically significantly reduced AOM/DSS-induced colitis and completely prevented CAC development with less related body mass loss, resulted in 0% mortality of treated mice (compared with 53% mortality of control mice), decreased cell proliferation, and increased apoptosis in colon tissue. TJ-M2010-5 treatment also inhibited production of inflammatory cytokines and chemokines (TNF-α, IL-6,G-CSF, MIP-1β, TGF-β1, IL-11, IL-17A, IL-22 and IL-23) and infiltration of immune cells (macrophages, dendritic cells, neutropihls and CD(+)4 T cells) in colon tissues of mice.Our findings suggest that TLR/MyD88 signaling may be a therapeutic target for CAC intervention and MyD88 inhibitors may be a promising therapeutic modality for treating patients with colitis or CAC.
Case 7-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Ethan A. Lerner, Franz C. von Lichtenberg
Journal: New England Journal of Medicine (1991)

Presentation of CaseA 21-year-old woman was admitted to the hospital because of a persistent rash on her elbow.The patient was well until five weeks earlier, shortly before the end of a six-month stay in Costa Rica, when she became aware of a skin lesion on the right elbow. One day after her return to Massachusetts she consulted her physician. Physical examination showed a localized rash (Fig. 1 and 2), 5 or 6 cm, on a crusted extensor surface of the elbow; a shallow ulcerated area in the center was irregularly rounded and had raised margins; several discrete satellite lesions . . .
Cat Scratch Disease, Bacillary Angiomatosis, and Other Infections Due to Rochalimaea
Authors: Karim A. Adal, Clay J. Cockerell, William A. Petri
Journal: New England Journal of Medicine (1994)

In 1982 a 32-year-old married bricklayer was admitted to a hospital in Rochester, New York, because of fever and subcutaneous nodules. The nodules were firm, 2 to 6 cm in diameter, and nontender and had appeared in the three weeks before admission. The patient's CD4+ lymphocyte count was 40 cells per cubic millimeter. During the first several days of hospitalization additional nodules appeared and the original nodules increased in size. Histologic examination demonstrated angioproliferation, and bacillary forms were identified in the lesions by Warthin-Starry staining, although standard bacterial cultures were negative. The patient was treated with oral erythromycin, and the . . .
Testosterone in Human Plasma
Authors: W. S. Coppage, A. E. Cooner
Journal: New England Journal of Medicine (1965)

TESTOSTERONE is the most potent of naturally occurring androgens, but attempts to measure testosterone in human peripheral venous plasma by standard chemical technics have generally been unsuccessful.1 This lack of success has been thought to be due to low circulating concentration of testosterone. The concentration of the free hormone in peripheral plasma appears to reflect more nearly the quantity available for tissue activity than the amount of hormone in urine or other body fluids. The majority of the 17-ketosteroids found in urine are the metabolic products of other less potent androgens than testosterone, and their measurement is a nearly useless . . .
Ventricular Fibrillation and Competitive Pacing
Authors: Michael Bilitch, Richard S. Cosby, Edwin A. Cafferky
Journal: New England Journal of Medicine (1967)

SUDDEN death in persons with artificial pacemakers is a continuing and disturbing problem. Causes include pacemaker-catheter displacement, electric-component failure, broken wires and rising pacing threshold. Each of these may be resolved in a relatively simple fashion once recognized.1 , 2 More of an unsolved problem is that of competitive rhythm between pacemaker-induced impulses and the patient's own intrinsic focus or foci. Sowton,3 comparing mortality rates between patients with competitive and noncompetitive rhythms, found the rate five times higher in the former. Individual case reports4 , 5 have documented the onset of ventricular fibrillation or tachycardia, or both, at the moment of inscription of the . . .
Studies of a Family with the Oral-Facial-Digital Syndrome
Authors: Theodore C. Doege, Horace C. Thuline, Jean H. Priest, Darwin E. Norby, Jean S. Bryant
Journal: New England Journal of Medicine (1964)

IN 1954 a syndrome characterized by cleft tongue and jaw, cleft lip and palate and digital malformation was described in 8 female patients by Papillon-Léage and Psaume.1 The terms "oral-facial-digital syndrome"2 and "orodigitofacial dysostosis"3 were later proposed for this condition.During a visit to a general pediatric clinic at Children's Orthopedic Hospital 3 members in different generations of a family were noted to have cleft tongue, cleft or pseudocleft palate and tongue tumors. Investigation of this family has disclosed the oral-facial-digital syndrome** in 15 females in 4 generations and 89 births. Studies are consistent with the hypothesis that this condition . . .
Prolyl hydroxylation regulates protein degradation, synthesis, and splicing in human induced pluripotent stem cell-derived cardiomyocytes
Authors: Andrea Stoehr, Yanqin Yang, Sajni Patel, Alicia M. Evangelista, Angel Aponte, Guanghui Wang, Poching Liu, Jennifer Boylston, Philip H. Kloner, Yongshun Lin, Marjan Gucek, Jun Zhu, Elizabeth Murphy
Journal: Cardiovascular Research (2016)

Protein hydroxylases are oxygen- and α-ketoglutarate-dependent enzymes that catalyse hydroxylation of amino acids such as proline, thus linking oxygen and metabolism to enzymatic activity. Prolyl hydroxylation is a dynamic post-translational modification that regulates protein stability and protein–protein interactions; however, the extent of this modification is largely uncharacterized. The goals of this study are to investigate the biological consequences of prolyl hydroxylation and to identify new targets that undergo prolyl hydroxylation in human cardiomyocytes. We used human induced pluripotent stem cell-derived cardiomyocytes in combination with pulse-chase amino acid labelling and proteomics to analyse the effects of prolyl hydroxylation on protein degradation and synthesis. We identified 167 proteins that exhibit differences in degradation with inhibition of prolyl hydroxylation by dimethyloxalylglycine (DMOG); 164 were stabilized. Proteins involved in RNA splicing such as serine/arginine-rich splicing factor 2 (SRSF2) and splicing factor and proline- and glutamine-rich (SFPQ) were stabilized with DMOG. DMOG also decreased protein translation of cytoskeletal and sarcomeric proteins such as α-cardiac actin. We searched the mass spectrometry data for proline hydroxylation and identified 134 high confidence peptides mapping to 78 unique proteins. We identified SRSF2, SFPQ, α-cardiac actin, and cardiac titin as prolyl hydroxylated. We identified 29 prolyl hydroxylated proteins that showed a significant difference in either protein degradation or synthesis. Additionally, we performed next-generation RNA sequencing and showed that the observed decrease in protein synthesis was not due to changes in mRNA levels. Because RNA splicing factors were prolyl hydroxylated, we investigated splicing ± inhibition of prolyl hydroxylation and detected 369 alternative splicing events, with a preponderance of exon skipping. This study provides the first extensive characterization of the cardiac prolyl hydroxylome and demonstrates that inhibition of α-ketoglutarate hydroxylases alters protein stability, translation, and splicing.
Case 25-1997
Authors: Anthony D. Elias, Eugene J. Mark
Journal: New England Journal of Medicine (1997)

Presentation of CaseA 60-year-old man was admitted to the hospital because of a pulmonary infiltrate.The patient had been well until 16 months earlier, when he was found to have a cervical soft-tissue mass, 3 cm by 3 cm by 2 cm, with an adjacent osteolytic lesion of the C6 vertebra. A diagnosis of multiple myeloma was made. The neck was stabilized by a cervical laminectomy with an iliac-bone autograft; radiotherapy was administered postoperatively.Ten months before admission, a mass was discovered in the right flank, with osteolytic lesions in a rib and the left iliac crest. The IgG . . .
Cortisone and ACTH as an Adjunct to the Surgery of Craniopharyngiomas
Authors: Franc D. Ingraham, Donald D. Matson, Robert L. McLaurin
Journal: New England Journal of Medicine (1952)

THE surgical management of craniopharyngiomas, whether radical or conservative, has always been hazardous. Gordy, Peet and Kahn1 reported a series of 51 cases in which the operative mortality was 41 per cent, due principally to severe hypothalamic reactions incident to the surgical manipulation. Grant,2 in summarizing the results of 40 operations on 30 patients, found a case mortality of 35 per cent and an operative mortality of 25 per cent. He noted generalized endocrine glandular atrophy in many of the fatal cases and stated that "the problem in surgical treatment of craniopharyngioma is threefold: to escape hyperthermia from damage to . . .
PTU-322 Longitudinal study investigating the role of social factors in hospital re-admissions for alcohol detox
Authors: PS Sidhu, S Lin, A Tipton, S Peagram, R Karwa, A Agrawal
Journal: Gut (2015)

<h3>Introduction</h3> The National Health Service expenditure on alcohol services is estimated to be £2.7 billion with over 78% of costs incurred from hospital-based care.<sup>1</sup>Patients with alcohol problems are major contributors to hospital readmission,<sup>2</sup>reduction of which is also a key government objective. We aim to investigate the social and lifestyle factors that predict alcohol re-admissions. <h3>Method</h3> Discharge summaries, case-notes and blood results were reviewed for patients requiring in-hospital Alcohol Detox (AD) between 1/10/2013 and 1/3/2014. They were then followed up to 1/8/2014. Data was collected on emergency Department (ED) re-presentation, hospital re-admission, community alcohol services (CAS) engagement, reasons for drinking alcohol and Childs-Pugh Score. <h3>Results</h3> 189 patients were admitted and required input from alcohol liaison team, 76% (n = 144) of these required AD. Of these, 35% (n = 51 patients) required further admissions during the study period which accounted for 149 ED presentation episodes and 92 re-admission episodes. Within this cohort, admission in 58% (n = 30) of individuals were secondary to alcohol with 57 such episodes. Reasons for re-admission in this group included alcohol withdrawal symptoms (51%, n = 29), seizures (25%, n = 14), decompensated liver disease (14%, n = 8), gastrointestinal bleeding (n = 7) and alcoholic hepatitis (n = 3). Re-admission rates between this group and those admitted for other reasons and requiring AD was similar. Child-Pugh Score of A, B and C was noted in 71%, 14% and 15% of patients respectively. Identified social factors associated with alcohol excess were habitual alcohol consumption (82%), bereavement (4%), stress (28%), drug abuse (10%), social isolation (39%), unemployment (55%), started drinking at early age (65%) and CAS engagement (12%). Paradoxically admitting to alcohol dependence (51%, p &lt; 0.001) and engagement with community alcohol services (12%, p = 0.04) led to higher chance of readmission and this could be due to greater healthcare seeking behaviour and awareness of their condition. <h3>Conclusion</h3> This study identified social factors that associate with re-admission to hospital secondary to alcohol related diseases. Addressing these factors proactively may lead to better outcomes and reduction in hospital re-admissions for patients. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Alcohol related disease: meeting the challenge of improved quality of care and better use of resources (2010). A joint position paper by BSG/BASL/AHA. www.bsg.co.uk NHS Confederation and Royal College of Physicians. Briefing 2010. Too much of the hard stuff: what alcohol costs the NHS. London: The NHS Confederation, 2010