tbuckley/cabot-search huggingface dataset:
Prevalence of synchronous metastases of breast cancer depends both on tumor subtypes and tumor burden.
Authors: C. Boutros, C. Mazouni, M. Saghatchian, J. Domont, C. Balleyguier, C. Bourgier, M. C. Mathieu, M. Spielmann, S. Delaloge
Journal: Journal of Clinical Oncology (2011)

1096 Background: Synchronous distant metastases (SDM) at diagnosis of breast cancer account for 5% of cases in ancient series. It is unclear what the recent prevalence of this condition is and whether it depends on tumor subtypes. Individual prediction of detectable SDM may lead to avoid unnecessary work-ups. Methods: We assessed the prevalence of synchronous distant metastases among patients from the community all seen in a unique One Stop Unit of a Comprehensive Cancer center where their initial diagnosis of BC was made between April, 2004 and March, 2010. All pts diagnosed with invasive breast cancer underwent an initial standardized work-up including clinical examination, blood tests, bone scintigraphy, chest X-ray and abdominal and pelvic ultrasound. They had all data prospectively recorded. Univariate comparisons were conducted and multivariate logistic regression analyses were used to built a predictive nomogram. Results: 2,411 pts had an initial diagnostic of invasive breast cancer. 12% had triple-negative cancer, and 12% Her2-positive disease. 106 pts were found to have synchronous distant metastases (SDM) at initial work-up (4.4%). The median age of patients did not differ between pts with and without SDM (61 and 60 years respectively). Median clinical size of lesions in SM pts was 35 mm (8-120), while it was 15 mm in SM-negative pts (p< 0.001). 7% of pts with triple-negative breast cancer, 6% with Her2-positive cancers, but only 3.7% of HR-positive Her2-negative pts had synchronous distant metastases (p=0.04). A nomogram could be built to assess for individual prediction of SM. It is currently under validation and will be presented at the meeting. Conclusions: Synchronous distant metastatic status relies both on breast cancer subtype and tumor burden at diagnosis but does not exceed 7% in triple-negative breast cancer in the modern era. Initial work-up may be discussed according to the individual probability of SM through the use of a nomogram.
Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury
Authors: Simone Alidori, Nima Akhavein, Daniel L. J. Thorek, Katja Behling, Yevgeniy Romin, Dawn Queen, Bradley J. Beattie, Katia Manova-Todorova, Magnus Bergkvist, David A. Scheinberg, Michael R. McDevitt
Journal: Science Translational Medicine (2016)

Fibrillar carbon nanotubes simultaneously deliver two small interfering RNAs, which safely prevent acute kidney injury and prolong survival in mice.
Dysmorphophobia: symptom or disease?
Authors: N C Andreasen, J Bardach
Journal: American Journal of Psychiatry (1977)

Although dysmorphophobia, a subjective feeling of ugliness in a person of normal appearance, constitutes a distinctive symptom cluster occasionally seen in patients requesting cosmetic surgery, it is not included in current major psychiatric diagnostic systems. Patients with dysmorphophobia are usually young and perfectionistic and have both schizoid and narcissistic traits. The authors present two representative case histories and suggest that study of more patients with dysmorphophobia is needed to determine whether it is a symptom of an underlying disease or is itself a separate disease entity.
Phase II trial of oxaliplatin, 5-FU, and leucovorin chemotherapy for the previously treated patients with advanced gastric cancer
Authors: S. C. Oh, Y. Kim, J. Kim, I. Choi, H. Sung, H. Seo, S. Shin
Journal: Journal of Clinical Oncology (2007)

15138 Background: The effect of chemotherapy for advanced gastric cancer was disappointing. Most of patients have progressed after treatment of first line chemotherapy. So, many trials searching for effective combination chemotherapy to these patients are warranted. We conducted this study to ascertain the efficacy and toxicity of oxaliplatin, 5FU, and leucovorin combination chemotherapy for the previously treated patients with advanced gastric cancer. Methods: In all, 48 patients received course of oxaliplatin 100mg/m 2 intravenously (i.v) for 2hour and leucovorin at 100mg/m 2 intravenously (i.v) for 2hour on day 1, then 5FU 2.4 g/m2 i.v for 46 hour continuous infusion on day 1 and 2. This regimen was repeated every 2 weeks. Results: A total 220 courses were administered as second line (64.6%) and third line (29.2%), and median number of courses per patient was four. No complete response was reported and 7 partial responses (14.6%) were achieved, giving an overall disease stabilizing rate of 52.2% (95% Confidence interval, 37.85 % to 66.6%). The major toxicity was neutropenia, which reached grade 3/4 in 8 patients (16.7%). Median time to progression was 3 months (0.6 to 8 months), median survival duration was 8 months (0.5+ to 14.5 months), and median response duration was 3 months (1.6–4.3 months). Conclusions: We conclude that oxaliplatin, 5-FU, leucovorin combination chemotherapy for the treatment of previously treated advanced gastric cancer has a role for disease stabilizing and toxicity was tolerable to most of patients. No significant financial relationships to disclose.
&lt;italic&gt;Hartmandia&lt;/italic&gt; sp. &lt;italic&gt;(acanthamoeba)&lt;/italic&gt; as a Tissue Culture Contaminant&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Alice E. Moore, John Hlinka
Journal: JNCI Journal of the National Cancer Institute (1968)

An occasional tissue culture contaminant, Hartmanella sp. (acanthamoeba), can be confused with tissue cells or viruses. Its similarities to tissue cells and macrophages have been recorded by cinematography. It was found to destroy tissue-cultured cells by proceeding rapidly around them until the cultured cells rounded up and were then pulled out of the field by the amebas. The relationship of the trophozoite form to the encysted form was found to vary in a reciprocal and cyclical fashion. Under adverse conditions, such as cold or lack of medium change, the cystic form predominated, whereas the trophozoite form was more numerous under good conditions. The emergence of the active trophozoite form from the cyst, leaving the empty shell behind, was recorded cinematographically. The film showing these events is available from the film library of the Tissue Culture Association.
Pigmented Silk Nanofibrous Composite for Skeletal Muscle Tissue Engineering
Authors: Shivaprasad Manchineella, Greeshma Thrivikraman, Khadija K. Khanum, Praveen C. Ramamurthy, Bikramjit Basu, T. Govindaraju
Journal: Advanced Healthcare Materials (2016)

Skeletal muscle tissue engineering (SMTE) employs designed biomaterial scaffolds for promoting myogenic differentiation of myoblasts to functional myotubes. Oxidative stress plays a significant role in the biocompatibility of biomaterials as well as in the fate of myoblasts during myogenesis and is also associated with pathological conditions such as myotonic dystrophy. The inherent electrical excitability of muscle cells inspired the use of electroactive scaffolds for SMTE. Conducting polymers attracted the attention of researchers for their use in muscle tissue engineering. However, poor biocompatibility, biodegradability and development of oxidative stress associated immunogenic response limits the extensive use of synthetic conducting polymers for SMTE. In order to address the limitations of synthetic polymers, intrinsically electroactive and antioxidant silk fibroin/melanin composite films and electrospun fiber mats were fabricated and evaluated as scaffolds for promoting myogenesis in vitro. Melanin incorporation modulated the thermal stability, electrical conductivity of scaffolds, fiber alignment in electrospun mats and imparted good antioxidant properties to the scaffolds. The composite electrospun scaffolds promoted myoblast assembly and differentiation into uniformly aligned high aspect ratio myotubes. The results highlight the significance of scaffold topography along with conductivity in promoting myogenesis and the potential application of silk nanofibrous composite as electoractive platform for SMTE.
LUX-breast 2: Phase II, open-label study of oral afatinib in HER2-overexpressing metastatic breast cancer (MBC) patients (pts) who progressed on prior trastuzumab (T) and/or lapatanib (L).
Authors: Tamas Hickish, Ling-Ming Tseng, Ajay O. Mehta, Janice Tsang, Nadezhda Kovalenko, Dmitry Udovitsa, Katy Pelling, Martina Maria Uttenreuther-Fischer, Chiun-Sheng Huang
Journal: Journal of Clinical Oncology (2012)

TPS651 Background: Management of HER2-overexpressing MBC has improved over the past decade. However, pts still develop resistance to currently available HER2-targeted therapies and novel effective treatments are increasingly required as dual targeted combinations are given in early treatment lines already. Current therapies focus on targeting HER2 and do not inhibit all relevant ErbB Family dimers. Afatinib is an oral, irreversible ErbB Family Blocker that inhibits signaling through activated EGFR (ErbB1), HER2 (ErbB2) and ErbB4 receptors and transphosphorylation of ErbB3. Preclinical studies have demonstrated efficacy in T-sensitive and T-resistant human BC xenograft models dependent on ErbB signaling. Efficacy of afatinib in a T-resistant SUM 190 xenograft model has been shown to be increased by addition of IV vinorelbine (V). Afatinib monotherapy has shown promising clinical benefit in 46% of HER2-overexpressing MBC pts who progressed on prior T, with 10% of pts achieving PR. Methods: This open-label Phase II trial (NCT01271725) investigates efficacy and safety of afatinib alone (40 mg/d) followed by afatinib ‘beyond progression’ plus chemotherapy in 120 pts with HER2-overexpressing MBC, who progressed on prior neoadjuvant and/or adjuvant T and/or L. Pts who progress on afatinib monotherapy receive afatinib plus either weekly paclitaxel (P) 80 mg/m 2 or V 25 mg/m 2 . Eligible pts have confirmed HER2-overexpressing BC, stage IV disease measurable by RECIST 1.1, progressed on T and/or L therapy in either neoadjuvant and/or adjuvant setting, are eligible for retreatment with P or V and should not have been pretreated with P (≤12 months) or V, respectively. Exclusion criteria: inadequate cardiac, renal, hepatic and hematological function, pre-existing gastrointestinal dysfunction, rapidly progressing visceral disease, ILD and active brain metastases. The primary endpoint is objective response (OR) and secondary endpoints include best overall response, duration of OR and PFS; safety will be assessed separately for afatinib mono- and combination therapy. Patient enrollment began in May 2011 in ~35 sites and 5 countries.
Abstract 220: Intralipid Fails to Rescue Bupivacaine-Induced Cardiotoxicity in the Presence of the Opioid Antagonist Naloxone
Authors: Parisa Partownavid, Soban Umar, Siamak Rahman, Salil Sharma, Mansoureh Eghbali
Journal: Circulation (2012)

Introduction: Exogenous opioids such as morphine protect the heart against I/R injury. This action is mediated through opioid receptors as Naloxone, an opioid receptor antagonist, inhibits the cardioprotective effect of ischemic preconditioning. Here we explored the involvement of opioid receptors in lipid-mediated rescue of Bupivacaine-induced cardiac toxicity. Methods: Young male SD rats (300-350 g) were anesthetized with ketamine (80 mg/kg) and xylazine (8 mg/kg) and ventilated with a ventilator. The M-mode echocardiography and Electrocardiograms were acquired throughout the experiment. Asystole was achieved with a single injection of Bupivacaine (10mg/kg over 20 s, intravenously), and resuscitation with Intralipid (5ml/kg bolus, and 0.5ml/kg/min maintenance) along with cardiac massage was started immediately. Some rats were pre-treated with different doses of Naloxone (1 mg/kg, 10 µg/kg, 5 µg/kg and 1 µg/kg) 2 min prior to inducing asystole with Bupivacaine. Results: Administration of Bupivacaine resulted in asystole and Intralipid therapy improved the heart rate gradually within 10 min: 73.3±3.3 beats/min at 1min (23% recovery), 180±23 beats/min at 5 min (56% recovery), and 243±20 beats/min at 10 min (76% recovery, n=6). The left ventricular systolic function was also fully recovered in all rats within 5 min of lipid treatment as the ejection fraction (EF) and fractional shortening (FS) were similar to their baseline values (EF=70±3%, FS=40±3%, n=6)., Interestingly, Intralipid failed to rescue Bupivacaine overdose in rats pretreated with a high dose of Naloxone (1mg/kg) as there was no recovery of cardiac function within 10 min of lipid therapy (n=5). In rats pretreated with lower doses of Naloxone of 5 µg /kg and 10 µg /kg (n=4/group), the heart rate and cardiac function were partially recovered. Lowering the dose of Naloxone further to 1 µg /kg resulted in 76% recovery of the heart rate at 10 min. Complete recovery of the left ventricular systolic function was observed in this group within 10 min of lipid treatment as EF and FS were similar to their baseline values (EF= 73±3%, FS=43±3, n=4). . Conclusions: The opioid receptor antagonist Naloxone abolishes lipid rescue of Bupivacaine-induced cardiotoxicity in a dose-dependent manner.
Characteristics of the &lt;italic&gt;In Vitro&lt;/italic&gt; Assay of Murine Sarcoma Virus (Moloney) and Virus-Infected Cells
Authors: R. Bather, A. Leonard, J. Yang
Journal: JNCI Journal of the National Cancer Institute (1968)

A number of conditions are critical to the sensitivity and reliability of in vitro assay of murine sarcoma virus (MSV) (Moloney) and MSV (Moloney) infected cells. The age of the mouse embryos used as the source of indicator cells, the ability of the cells to multiply, the time of virus adsorption, and volume of inoculum are all important and must be standardixed if results are to be reproducible. Optimum conditions now in routine use in our laboratory are described, including the use of 15-day embryos as a source of primary cells, infection at the time the secondary cultures are planted, and allowing the inoculum to be left in contact with the indicator cells. Results indicate that virus adsorption to normal cells and release from infected cells are slow and inefficient. Infected cells are incapable of the sustained division necessary to form foci, and the most important factors in focus formation appear to be virus release and reinfection of neighboring cells. Over 90% of tumor cells up to the twelfth transplant generation and in vitro transformed cells to the sixth generation maintain the diploid chromosome number, although as many as 61% of the latter register as infectious centers.
The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls
Authors: Martin Kummen, Kristian Holm, Jarl Andreas Anmarkrud, Ståle Nygård, Mette Vesterhus, Marte L Høivik, Marius Trøseid, Hanns-Ulrich Marschall, Erik Schrumpf, Bjørn Moum, Helge Røsjø, Pål Aukrust, Tom H Karlsen, Johannes R Hov
Journal: Gut (2016)

<h3>Objective</h3> Gut microbiota could influence gut, as well as hepatic and biliary immune responses. We therefore thoroughly characterised the gut microbiota in primary sclerosing cholangitis (PSC) compared with healthy controls (HC) and patients with ulcerative colitis without liver disease. <h3>Design</h3> We prospectively collected 543 stool samples. After a stringent exclusion process, bacterial DNA was submitted for 16S rRNA gene sequencing. PSC and HC were randomised to an exploration panel or a validation panel, and only significant results (p&lt;0.05, Q<sub>FDR</sub>&lt;0.20) in both panels were reported, followed by a combined comparison of all samples against UC. <h3>Results</h3> Patients with PSC (N=85) had markedly reduced bacterial diversity compared with HC (N=263, p&lt;0.0001), and a different global microbial composition compared with both HC (p&lt;0.001) and UC (N=36, p&lt;0.01). The microbiota of patients with PSC with and without IBD was similar. Twelve genera separated PSC and HC, out of which 11 were reduced in PSC. However, the <i>Veillonella</i> genus showed a marked increase in PSC compared with both HC (p&lt;0.0001) and UC (p&lt;0.02). Using receiver operating characteristic analysis, <i>Veillonella</i> abundance yielded an area under the curve (AUC) of 0.64 to discriminate PSC from HC, while a combination of PSC-associated genera yielded an AUC of 0.78. <h3>Conclusions</h3> Patients with PSC exhibited a gut microbial signature distinct from both HC and UC without liver disease, but similar in PSC with and without IBD. The <i>Veillonella</i> genus, which is also associated with other chronic inflammatory and fibrotic conditions, was enriched in PSC.
Disulfiram when Combined with Copper Enhances the Therapeutic Effects of Temozolomide for the Treatment of Glioblastoma
Authors: Xueqing Lun, J. Connor Wells, Natalie Grinshtein, Jennifer C. King, Xiaoguang Hao, Ngoc-Ha Dang, Xiuling Wang, Ahmed Aman, David Uehling, Alessandro Datti, Jeffrey L. Wrana, Jacob C. Easaw, Artee Luchman, Samuel Weiss, J. Gregory Cairncross, David R. Kaplan, Stephen M. Robbins, Donna L. Senger
Journal: Clinical Cancer Research (2016)

Glioblastoma is one of the most lethal cancers in humans, and with existing therapy, survival remains at 14.6 months. Current barriers to successful treatment include their infiltrative behavior, extensive tumor heterogeneity, and the presence of a stem-like population of cells, termed brain tumor-initiating cells (BTIC) that confer resistance to conventional therapies.To develop therapeutic strategies that target BTICs, we focused on a repurposing approach that explored already-marketed (clinically approved) drugs for therapeutic potential against patient-derived BTICs that encompass the genetic and phenotypic heterogeneity of glioblastoma observed clinically.Using a high-throughput in vitro drug screen, we found that montelukast, clioquinol, and disulfiram (DSF) were cytotoxic against a large panel of patient-derived BTICs. Of these compounds, disulfiram, an off-patent drug previously used to treat alcoholism, in the presence of a copper supplement, showed low nanomolar efficacy in BTICs including those resistant to temozolomide and the highly infiltrative quiescent stem-like population. Low dose DSF-Cu significantly augmented temozolomide activity in vitro, and importantly, prolonged in vivo survival in patient-derived BTIC models established from both newly diagnosed and recurrent tumors. Moreover, we found that in addition to acting as a potent proteasome inhibitor, DSF-Cu functionally impairs DNA repair pathways and enhances the effects of DNA alkylating agents and radiation. These observations suggest that DSF-Cu inhibits proteasome activity and augments the therapeutic effects of DNA-damaging agents (temozolomide and radiation).DSF-Cu should be considered as an adjuvant therapy for the treatment of patients with glioblastoma in both newly diagnosed and recurrent settings. Clin Cancer Res; 22(15); 3860-75. ©2016 AACR.
Abstract 18716: Survival for Infants with Critical Congenital Heart Defects in Atlanta, Georgia, 1979-2005: Temporal Trends and Prognostic Factors
Authors: Matthew E Oster, Kyung A Lee, Margaret A Honein, Tiffany Colarusso, Mikyong Shin, Adolfo Correa
Journal: Circulation (2012)

Matthew E Oster, 2012 Finalist and Presenting Author
Preventing Transmission of Zika Virus in Labor and Delivery Settings Through Implementation of Standard Precautions — United States, 2016
Authors: Christine K. Olson, Martha Iwamoto, Kiran M. Perkins, Kara N.D. Polen, Jeffrey Hageman, Dana Meaney-Delman, Irogue I. Igbinosa, Sumaiya Khan, Margaret A. Honein, Michael Bell, Sonja A. Rasmussen, Denise J. Jamieson
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Zika virus transmission was detected in the Region of the Americas (Americas) in Brazil in May 2015, and as of March 21, 2016, local mosquito-borne transmission of Zika virus had been reported in 32 countries and territories in the Americas, including Puerto Rico and the U.S. Virgin Islands.* Most persons infected with Zika virus have a mild illness or are asymptomatic. However, increasing evidence supports a link between Zika virus infection during pregnancy and adverse pregnancy and birth outcomes (1), and a possible association between recent Zika virus infection and Guillain-Barré syndrome has been reported (2). Although Zika virus is primarily transmitted through the bite of Aedes species of mosquitoes, sexual transmission also has been documented (3). Zika virus RNA has been detected in a number of body fluids, including blood, urine, saliva, and amniotic fluid (3-5), and whereas transmission associated with occupational exposure to these body fluids is theoretically possible, it has not been documented. Although there are no reports of transmission of Zika virus from infected patients to health care personnel or other patients, minimizing exposures to body fluids is important to reduce the possibility of such transmission. CDC recommends Standard Precautions in all health care settings to protect both health care personnel and patients from infection with Zika virus as well as from blood-borne pathogens (e.g., human immunodeficiency virus [HIV] and hepatitis C virus [HCV]) (6). Because of the potential for exposure to large volumes of body fluids during the labor and delivery process and the sometimes unpredictable and fast-paced nature of obstetrical care, the use of Standard Precautions in these settings is essential to prevent possible transmission of Zika virus from patients to health care personnel.
L-tryptophan: a rational hypnotic with clinical potential
Authors: E Hartmann
Journal: American Journal of Psychiatry (1977)

The author states that the use of the amino acid L-tryptophan as a hypnotic might avoid the problems of nonspecificity in the currently used CNS depressants because L-tryptophan is chosen on the basis of the chemistry of normal sleep rather than on a purely empirical basis. He reviews nine studies from his laboratory dealing with the effects of L-tryptophan on sleep. Studies in rats, normal human subjects, and subjects with mild insomnia all demonstrate that L-tryptophan reduces sleep latency. Polygraphic studies demonstrate that L-tryptophan, unlike hypnotics, does not produce distortions of sleep physiology when first administered, on long-term administration, or after withdrawal.
Adjuvant chemotherapy with fluorouracil and levamisole alone or in combination with 6-S-leucovorin for the treatment of colon cancer: randomized multicenter trial of the Italian Intergroup (INTACC)
Authors: F. Di Costanzo, A. Sobrero, S. Gasperoni, L. Dogliotti, L. Frassinetti, A Falcone
Journal: Annals of Oncology (2003)
Personality and the prediction of long-term outcome of depression
Authors: M M Weissman, B A Prusoff, G L Klerman
Journal: American Journal of Psychiatry (1978)

In a follow-up study of 150 women who had undergone treatment on an outpatient basis for acute depression, it was found that the most important predictor of their long-term clinical outcome (8, 20, and 48 months after the acute episode) was personality as measured by the Neuroticism Scale of the Maudsley Personality Inventory (MPI-N). Age, race, social class, marital status, religion, number of previous depressions or suicide attempts, diagnosis, history of early deaths of or separations from significant others, history of neurotic traits as a child, amount and type of stress in the 6 months before onset, and severity and pattern of pretreatment symptoms were not predictive of outcome.
Impact Of Initial FGD-PET CT and Serum Free Light Chain On Transformation Of Solitary Plasmacytoma To MM
Authors: Guillemette Fouquet, Stéphanie Guidez, Charles Herbaux, Zoé Van de Wyngaert, Sarah Bonnet, David Beauvais, Helene Demarquette, Bénédicte Hivert, Mathieu Wemeau, Louis Terriou, Valérie Coiteux, Margaret Macro, Olivier Decaux, Thierry Facon, Damien Huglo, Xavier Leleu
Journal: Blood (2013)