tbuckley/cabot-search huggingface dataset:
The Needs for Inpatient Care and Treatment of Mentally Ill Children in the Commonwealth of Massachusetts
Authors: Thaddeus P. Krush
Journal: New England Journal of Medicine (1949)

IN PSYCHIATRY in the past thirty years there has been a gradual, increasing interest in progressing downward along the chronologic scale toward childhood to seek out the earlier phases of personality deviations. To search for a means of straightening the bent twig while it is still in the process of bending appears all too obvious, but the surprising feature is the fact that it has taken so long to turn attention in this general direction. That the "hopeful" aspect of psychiatry exists in child psychiatry should be reasonably apparent to anyone who has spent long hours in individual or group . . .
Afatinib Activity in Platinum-Refractory Metastatic Urothelial Carcinoma in Patients With <i>ERBB</i> Alterations
Authors: Noura J. Choudhury, Alexa Campanile, Tatjana Antic, Kai Lee Yap, Carrie A. Fitzpatrick, James L. Wade, Theodore Karrison, Walter M. Stadler, Yusuke Nakamura, Peter H. O’Donnell
Journal: Journal of Clinical Oncology (2016)

Somatic mutations and copy number variation in the ERBB family are frequent in urothelial carcinoma (UC) and may represent viable therapeutic targets. We studied whether afatinib (an oral, irreversible inhibitor of the ErbB family) has activity in UC and if specific ERBB molecular alterations are associated with clinical response.In this phase II trial, patients with metastatic platinum-refractory UC received afatinib 40 mg/day continuously until progression or intolerance. The primary end point was 3-month progression-free survival (PFS3). Prespecified tumor analysis for alterations in EGFR, HER2, ERBB3, and ERBB4 was conducted.The first-stage enrollment goal of 23 patients was met. Patient demographic data included: 78% male, median age 67 years (range, 36 to 82 years), hemoglobin < 10 g/dL in 17%, liver metastases in 30%, median time from prior chemotherapy of 3.6 months, and Eastern Cooperative Oncology Group performance status ≤ 1 in 100%. No unexpected toxicities were observed; two patients required dose reduction for grade 3 fatigue and rash. Overall, five of 23 patients (21.7%) met PFS3 (two partial response, three stable disease). Notably, among the 21 tumors analyzed, five of six patients (83.3%) with HER2 and/or ERBB3 alterations achieved PFS3 (PFS = 10.3, 7.0, 6.9, 6.3, and 5.0 months, respectively) versus none of 15 patients without alterations (P < .001). Three of four patients with HER2 amplification and three of three patients with ERBB3 somatic mutations (G284R, V104M, and R103G) met PFS3. One patient with both HER2 amplification and ERBB3 mutation never progressed on therapy, but treatment was discontinued after 10.3 months as a result of depressed ejection fraction. The median time to progression/discontinuation was 6.6 months in patients with HER2/ERBB3 alterations versus 1.4 months in patients without alterations (P < .001).Afatinib demonstrated significant activity in patients with platinum-refractory UC with HER2 or ERBB3 alterations. The potential contribution of ERBB3 to afatinib sensitivity is novel. Afatinib deserves further investigation in molecularly selected UC.
Empiric Therapy with Carbenicillin and Gentamicin for Febrile Patients with Cancer and Granulocytopenia
Authors: Stephen Schimpff, Winston Satterlee, Viola Mae Young, Arthur Serpick
Journal: New England Journal of Medicine (1971)

Seventy-five acutely ill, febrile patients with cancer and granulocytopenia were treated empirically with a combination of carbenicillin and gentamicin for presumed bacterial infection. Cultures taken before the initiation of antibiotics subsequently documented the presence of infection in 48 of these patients, of whom 21 were shown to have Pseudomonas aeruginosa infections. Fourteen of these patients with pseudomonas infections had complete improvement, three improved temporarily but later died of infection, two had no improvement, and two could not be evaluated. This antibiotic combination was less promising for the infections caused by other gram-negative bacteria, especially klebsiella. Superinfection occurred in eight patients. Combination carbenicillin and gentamicin is of value as initial antibiotic therapy for suspected Ps. aeruginosa infection in granulocytopenic patients with cancer but only after careful examination and extensive culturing.
Abstract 1636: A model-based approach toward clinical pipeline optimization
Authors: Jackson Burton, William Antebi, Christopher J. Zopf, Dean Bottino, Shu-Wen Teng, Ryan Nolan, Arijit Chakravarty
Journal: Cancer Research (2015)

Abstract Introduction What is the optimal “shape” for a drug pipeline: A flute? A megaphone? A trumpet? In other words, what set of stringencies for passage of candidates to the next stage in development maximizes the value of the pipeline as a whole, and how do assays predicting drug quality influence this optimum? Methods A linear programming formulation was developed for four phases of a drug pipeline: Preclinical, Phase I, Phase II, and Phase III, with variables including: the total budget for the entire pipeline (B), and the number (Ni), cost (ci), and net present value (vi) of drugs in each phase (i). The model is subject to two constraints: (1) the pipeline must reduce in size with each subsequent phase (i.e. Npre≥ N1 ≥ N2 ≥ N3), and (2) the sum total of the cost times the number of drugs in each phase must be less than or equal to the total budget (i.e. cpreNpre + c1N1 + c2N2 + c3N3 ≤ B). The overall goal is to maximize the total value of drugs progressing through the pipeline (i.e. maximize vtot = vpreNpre + v1N1 + v2N2 + v3N3). Additionally, pipeline evolution was modeled to evaluate the implications of a “predictive” drug quality assay. Hypothetical “drug quality scores” were drawn from normal distributions which reflect industry probabilities of success between phases. Drugs that are above a cutoff stringency advance forward, with the process repeated for all phases. The cost of each phase and value for successful drugs are recorded for each simulation. The process is repeated many times, with the expected value calculated at each iteration. Results Beginning with a pool of drug candidates, the optimal pipeline structure should approach equal sized pipeline widths as rapidly as possible. Monte Carlo simulations demonstrated that increasing the stringency of a “quality assay” in Phase I results in a linear increase in expected value. Additionally, if the quality test is improved, e.g. by reducing the variability of the assay, the improvement in expected value will increase in an exponential manner. Conclusions The simulations predict that to maximize pipeline value, drug companies should: (a) pick the winners as early as possible (i.e. Preclinical or Phase I), (b) set stringent go/no-go criteria in Preclinical and Phase I development, and (c) perform prospective clinical trial simulations (Preclinical to Phase I, Phase I to Phase II, Phase II to Phase III) to improve the ability to predict winners. Citation Format: Jackson Burton, William Antebi, Christopher J. Zopf, Dean Bottino, Shu-Wen Teng, Ryan Nolan, Arijit Chakravarty. A model-based approach toward clinical pipeline optimization. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1636. doi:10.1158/1538-7445.AM2015-1636
Testing for viral material in water of public bathing areas of the Danube during summer, Vojvodina, Serbia, 2014
Authors: Aleksandra Jovanović Galović, Sanja Bijelović, Vesna Milošević, Ivana Hrnjaković Cvjetkovic, Milka Popović, Gordana Kovačević, Jelena Radovanov, Nataša Dragić, Vladimir Petrović
Journal: Eurosurveillance (2016)

From August to September 2014 a water quality study was conducted on five popular public Danube beaches in Vojvodina, Serbia. To assess the safety of Danube water for bathing, physical, chemical, bacteriological tests were performed. While many parameters for monitoring the quality of water are regulated by law, there are neither national nor international legislations addressing the presence of viruses in recreational waters. In this study, we performed analyses that surpassed national requirements, and investigated if adenovirus, enterovirus or rotavirus genetic material was present in samples of recreational water collected for quality monitoring. Of 90 water samples obtained during the study, enterovirus material was not found in any sample, but adenovirus and rotavirus genetic materials were respectively detected in 60 and 31 samples. Statistical analyses showed a significant correlation between adenovirus DNA and total coliforms in the water. Even when water samples were adequate for recreational use, adenoviruses were detected in 75% (57/76) of such samples. Our results indicate that implementation of viral indicators in recreational water might be helpful to better assess public health safety. This might be particularly relevant in areas where urban wastewater treatment is insufficient and surface waters affected by wastewater are used for recreation.
Endogenous Creatinine Clearance
Authors: G. James Tobias, Richard F. McLaughlin, James Hopper
Journal: New England Journal of Medicine (1962)

FOR many years crcatinine clearance has been used as an estimate of glomerular filtration rate. In 1926 Rehberg1 first suggested that exogenous creatinine clearance could be used for this purpose. Shannon,2 however, in 1935, demonstrated exogenous creatinine clearance at high plasma levels of creatinine to be greater than inulin, because of tubular excretion of some creatinine at these high levels. Two years later Popper and Mandel3 first suggested the use of endogenous creatinine clearance (Ccr) as a measure of glomerular filtration rate. In 1938 Miller and Winkler4 were able to measure accurately the normal low serum levels of . . .
Use of pheophorbide a, an ABCG2 specific substrate, to probe for ABCG2 expression and function
Authors: Robert W. Robey, Kenneth Steadman, Orsolya Polgar, Margaret Blayney, Prakash Mistry, Susan E. Bates
Journal: Cancer Research (2004)

509  Pheophorbide a (PhA), a chlorophyll catabolite, was shown to be an ABCG2 substrate by Jonker et al, based on Abcg2-/- knockout mouse studies (Jonker et al., Proc. Natl. Acad. Sci. USA 99:15649-15654, 2003). Seeking a potential ABCG2-specific substrate, we developed a functional assay for ABCG2 using PhA and the ABCG2 specific inhibitor fumitremorgin C (FTC). In studies with selected cell lines expressing high levels of P-glycoprotein (Pgp), multidrug resistance associated protein 1 (MRP1), or ABCG2, PhA transport was detected only in cells expressing ABCG2 suggesting that, among the three transporters implicated in multidrug resistance, PhA is specific for ABCG2. FTC-inhibitable PhA transport was found to correlate with cell surface ABCG2 expression as measured by the anti-ABCG2 antibody 5D3. Additionally, PhA transport was found to be unaffected by the ABCG2 mutations at amino acid 482 that are known to affect substrate specificity. Using PhA as a model to screen for potential ABCG2 inhibitors, we found that 100 μM of the cyclin-dependent kinase inhibitor UCN-01 or 1 μM of the Pgp inhibitor tariquidar inhibited ABCG2-mediated PhA transport. The interaction of these two compounds with ABCG2 was confirmed in 4-day cytotoxicity assays. ABCG2-mediated resistance to SN-38 and topotecan was abrogated in ABCG2-transfected cells treated with 1 μM tariquidar, and ABCG2-transfected cells were 6- to 7-fold resistant to UCN-01. PhA is an ABCG2-specific substrate with potential value in measuring ABCG2 function and expression in clinical samples. Further studies exploring the potential of tariquidar as a multispecific blocker for Pgp and ABCG2 are warranted.
580_PR: Clinical and demographic features that influence EGFR mutation detection in plasma from patients (pts) with aNSCLC: The ASSESS experience
Authors: N. Normanno, H. Brown, V. Haddad, M. Ratcliffe, R. McCormack, S. Tjulandin, K. Hagiwara, B. Han, M. Reck
Journal: Journal of Thoracic Oncology (2016)
70P Identification of a novel microRNA signature: Potential diagnostic biomarkers and predictors of cisplatin response?
Authors: M.P. Barr, L. MacDonagh, S.G. Gray, M. Reidy, J. Sze Yin Sui, S. Nicholson, N. Leonard, K. O'Byrne, S. Cuffe, S. Finn
Journal: Journal of Thoracic Oncology (2016)
Outcomes Of Allogeneic Cord Blood Transplantation For Leukodystrophies; A Joint Study of Eurocord and “Inborn Errors WP-EBMT”
Authors: Hol Janna, Annalisa Ruggeri, Vanderson Rocha, Gerard Michel, Mouhab Ayas, Tracey O'Brien, Gergely Krivan, Bordon Victoria, Rik Schots, Rovelli Attilio, Elorza Izaskun, Jose M Moraleda, Peter J. Shaw, Marleen Renard, Karl-Walter Sykora, Reuven Or, Tsila Zuckerman, Manuel Abecasis, Bredius Robbert, M. Akif Yesilipek, Miguel Angel Diaz, Gennery Andy, Eliane Gluckman, Jaap Jan Boelens
Journal: Blood (2013)
P-306 A phase II biopsy-driven study to identify biomarkers predictive of clinical response to second-line regorafenib in patients with metastatic colorectal cancer
Authors: A. Schab, M. Abdelsalam, F. Aubin, A. Langleben, F. Couture, A. Gologan, A. Constantin, E. Camlioglu, C. Hoffert, G. Batist, P. Kavan
Journal: Annals of Oncology (2015)
Abstract IA18: Children, adolescents, and young adult ALL: Translating novel discoveries into therapeutic opportunities
Authors: Mignon L. Loh
Journal: Cancer Research (2016)

Abstract Acute lymphoblastic leukemia (ALL) is a genetically complex disease that remains a major cause of childhood cancer-related mortality. Some subsets of ALL can be successfully treated with traditional cytotoxic chemotherapy while others remain at high risk of relapse. Specifically, adolescents and young adults have higher relapse rates than younger children and also experience increased toxicity with cytotoxics. Major advances in genomic profiling through the application of next generation sequencing technologies in these high risk patients have uncovered recurrent mutations in key pathways that may be targeted with the addition of signal transduction inhibitors to chemotherapy. Such therapeutic approaches will mandate genetically precise risk stratification of patients. The Children's Oncology Group (COG) is poised to act in real time to identify these high risk subsets and will be introducing relevant signal transduction inhibitors in clinical trials shortly. Relapsed ALL remains a significant therapeutic challenge additional genomic analyses have shed light on new events that occur at relapse, but these may be difficult to individually target. Indeed, immunotherapeutic approaches are being harnessed to focus on eradicating the malignant B-cell without regard to genetic lesions, which may be useful in relapsed ALL. This discussion will review genomic data generated through large scale collaborations with the COG ALL committee and also present an overview of the clinical trials that will capitalize on these recent discoveries. Citation Format: Mignon L. Loh. Children, adolescents, and young adult ALL: Translating novel discoveries into therapeutic opportunities. [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 IA18.
Sequential Therapy Combining Clofarabine and HLA-Haploidentical Hematopoietic Stem Cell Transplantation In The Treatment Of Refractory and Advanced Lymphoma: Feasibility, Toxicity and Early Outcome
Authors: Anna-Katharina Zoellner, Susanne Fritsch, Dusan Prevalsek, Nicole Engel, Roland Reibke, Christina T Rieger, Georg Ledderose, Wolfgang Hiddemann, Martin Dreyling, Andreas Hausmann, Johanna Tischer
Journal: Blood (2013)
Single-Day Praziquantel Therapy for Neurocysticercosis
Authors: Teresa Corona, Roberto Lugo, Roberto Medina, Julio Sotelo
Journal: New England Journal of Medicine (1996)

To the Editor: Administration of praziquantel for 15 days is effective therapy for patients with parenchymal brain cysticercosis.1 Because the plasma and cerebrospinal fluid concentrations of prazi...
Inhibition by Retinoids of the Growth of Azaserine-Induced Foci in the Rat Pancreas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: B. D. Roebuck, Karen J. Baumgartner, C. Dennis Thron, Daniel S. Longnecker
Journal: JNCI Journal of the National Cancer Institute (1984)

The usefulness of a short-term azaserine [CAS: 115-02-6; diazoacetate serine (ester)]-rat model for the screening of retinoids (known chemopreventive agents) and the effect of two retinoids on the growth of azaserine-induced, presumptive preneoplastic foci of acinar cells were examined. At 14 days of age, male Lewis rats were each given injections of a single dose of 30 mg azaserine/kg body weight. These rats were weaned to test diets to which retinoids were added. At 4 months post initiation, pancreata were examined by quantitative stereologic methods to determine number and mean size of foci. Two phenotypically different populations of foci were observed and characterized as acidophilic or basophilic. Retinylidene dimedone and N-2-hydroxyethylretinamide decreased the number and size of the acidophilic foci but not the basophilic foci. The inhibition of growth of the acidophilic foci correlates well with the known effects of these retinoids in long-term carcinogenicity studies.
Reduction by Granulocyte Colony-Stimulating Factor of Fever and Neutropenia Induced by Chemotherapy in Patients with Small-Cell Lung Cancer
Authors: Jeffrey Crawford, Howard Ozer, Ronald Stoller, David Johnson, Gary Lyman, Imad Tabbara, Mark Kris, John Grous, Vincent Picozzi, Gregory Rausch, Roy Smith, William Gradishar, Anne Yahanda, Martha Vincent, Morgan Stewart, John Glaspy
Journal: New England Journal of Medicine (1991)

Neutropenia and infection are major dose-limiting side effects of chemotherapy. Previous studies have suggested that recombinant methionyl granulocyte colony-stimulating factor (G-CSF) can reduce chemotherapy-related neutropenia in patients with cancer. We conducted a randomized clinical trial to test this hypothesis and the clinical implications.
Apolipoprotein E, Dementia, and Cortical Deposition of β-Amyloid Protein
Authors: Tuomo Polvikoski, Raimo Sulkava, Matti Haltia, Katariina Kainulainen, Alpo Vuorio, Auli Verkkoniemi, Leena Niinistö, Pirjo Halonen, Kimmo Kontula
Journal: New England Journal of Medicine (1995)

The ε4 allele of apolipoprotein E has been associated with an increased risk of late-onset Alzheimer's disease. In a cohort of elderly subjects we prospectively investigated the relation between the apolipoprotein E genotype, dementia, and the accumulation of β-amyloid protein in the cerebral cortex.
AB0715 Acute Stress: Is it a Risk Factor for the Development of Systemic Sclerosis?:
Authors: M. Vasile, G. Valesini, V. Riccieri
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Several risk factors, such as genetic, infections, sexual hormones and stress, have been frequently considered in the pathogenesis of autoimmune diseases. Stress has nowadays gained more attention, as it is able to influence the close relationships existing between hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system and immune system. The stress response results in the release of neurotransmitters (norepinephrine), hormones (cortisol) and immune cells which serve to send an efferent message from the brain to the periphery (1). <h3>Objectives</h3> Our aim was to investigate for the presence of acute stressful events in a cohort of Systemic Sclerosis (SSc) patients referring to our out-patient clinic. We investigated for events occurring before the onset of the disease symptoms. <h3>Methods</h3> We reported for any acute stress events preexisting the onset of the disease symptoms since six months before, collecting these data from the medical history of 70 SSc patients. Thus we fulfilled the Psychosocial Stress Severity Scale of DSM III-R for adults (Tab. 1) (2). <h3>Results</h3> We evaluated 64 women and 6 men, mean age 61 years; 44 had a limited cutaneous SSc, 26 had a diffuse form. Forty patients (57%) had an acute stressing event in their medical history, before the disease onset. Among these 40 SSc patients, 2 of them reported a catastrophic event, 18 an extreme event, 5 a severe event, 10 a moderate event, 5 a mild event (Table 1). <h3>Conclusions</h3> Our preliminary results point out a high prevalence of acute stressful events, preceding the disease onset, in SSc. These results straighten the importance of acute stress in autoimmune conditions. Further investigations focusing on persistent chronic stressful events are needed to better define their possible role in the pathogenesis of this disease. <h3>References</h3> Straub RH, Cutolo M: Does stress influence the course of rheumatic diseases? Clin Exp Rheumatolog 2006. Frances et al: Diagnostic and statistical manual of mental disorders. American Psychiatric Association 1987. <h3>Disclosure of Interest</h3> None declared
Case 33-2011
Authors: Clemens Bergwitz, Michael T. Collins, Ravi S. Kamath, Andrew E. Rosenberg
Journal: New England Journal of Medicine (2011)

A 56-year-old man presented with recurrent bone pain, stress fractures, and hypophosphatemia. A tumor of the jaw had been resected in the past, with resolution of symptoms. Studies of the jaw revealed no recurrent tumor. Diagnostic tests were performed.
Mesencephalic Astrocyte–Derived Neurotrophic Factor as a Urine Biomarker for Endoplasmic Reticulum Stress–Related Kidney Diseases
Authors: Yeawon Kim, Heedoo Lee, Scott R. Manson, Maria Lindahl, Bradley Evans, Jeffrey H. Miner, Fumihiko Urano, Ying Maggie Chen
Journal: Journal of the American Society of Nephrology (2016)

Endoplasmic reticulum (ER) stress and disrupted proteostasis contribute to the pathogenesis of a variety of glomerular and tubular diseases. Thus, it is imperative to develop noninvasive biomarkers for detecting ER stress in podocytes or tubular cells in the incipient stage of disease, when a kidney biopsy is not yet clinically indicated. Mesencephalic astrocyte–derived neurotrophic factor (MANF) localizes to the ER lumen and is secreted in response to ER stress in several cell types. Here, using mouse models of human nephrotic syndrome caused by mutant laminin β 2 protein–induced podocyte ER stress and AKI triggered by tunicamycin– or ischemia-reperfusion–induced tubular ER stress, we examined MANF as a potential urine biomarker for detecting ER stress in podocytes or renal tubular cells. ER stress upregulated MANF expression in podocytes and tubular cells. Notably, urinary MANF excretion concurrent with podocyte or tubular cell ER stress preceded clinical or histologic manifestations of the corresponding disease. Thus, MANF can potentially serve as a urine diagnostic or prognostic biomarker in ER stress–related kidney diseases to help stratify disease risk, predict disease progression, monitor treatment response, and identify subgroups of patients who can be treated with ER stress modulators in a highly targeted manner.