tbuckley/cabot-search huggingface dataset:
Cancer Signature Investigation:<i>ERBB2</i>(<i>HER2</i>)-Activating Mutation and Amplification-Positive Breast Carcinoma Mimicking Lung Primary
Authors: Jennifer Shih, Babar Bashir, Karen S. Gustafson, Mark Andrake, Roland L. Dunbrack, Lori J. Goldstein, Yanis Boumber
Journal: Journal of the National Comprehensive Cancer Network (2015)

Next-generation sequencing of primary and metachronous metastatic cancer lesions may impact patient care. We present a case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma. A 72-year-old, never-smoker woman with a protracted cough was found to have a large lung mass and regional lymphadenopathy on a chest CT. Lung mass biopsy showed adenocarcinoma with focal TTF-1 (thyroid transcription factor 1) positivity, favoring a lung primary. In addition to stereotactic brain radiation for cerebral metastases, she was started on carboplatin/pemetrexed. As part of the workup, the tumor was analyzed by a 50-gene targeted mutation panel, which detected 3 somatic mutations: ERBB2 (HER2) D769H activating missense mutation, TP53 Y126 inactivating truncating mutation, and SMARCB1 R374Q missense mutation. Of note, the patient had a history of stage IIA triple-negative grade 3 invasive ductal carcinoma of the left breast 1.5 years ago and received neoadjuvant chemotherapy and adjuvant radiation, and underwent a lumpectomy. Further analysis of her primary breast tumor showed a mutational profile identical to that of the lung tumor. Fluorescence in situ hybridization revealed HER2 amplification in the lung tumor, with a HER2/CEP17 ratio of 3.9. The patient was diagnosed with recurrent HER2-positive metastatic breast carcinoma with a coexisting ERBB2 (HER2) activating mutation. Chemotherapy was adjusted to include dual HER2-targeted therapy containing trastuzumab and pertuzumab, resulting in an ongoing partial response. This case demonstrates that a unique genetic mutational profile can clarify whether a tumor represents a metastatic lesion or new malignancy when conventional morphological and immunohistochemical methods are indeterminate, and can directly impact treatment decisions.
Sixty seconds on . . . pre-exposure prophylaxis
Authors: Nigel Hawkes
Journal: BMJ (2015)

Then here’s one. Should the NHS in England spend up to £4500 (€6400; $6800) a year per patient providing a pre-exposure prophylaxis (PrEP) drug to healthy gay men and injecting drug users so that they can lower their risk of being infected with HIV?

That is the heart of the dilemma. Some right wing columnists …
Genome Editing Technologies and Human Germline Genetic Modification: The Hinxton Group Consensus Statement
Authors: Sarah Chan, Peter J. Donovan, Thomas Douglas, Christopher Gyngell, John Harris, Robin Lovell-Badge, Debra J. H. Mathews, Alan Regenberg
Journal: The American Journal of Bioethics (2015)

The prospect of using genome technologies to modify the human germline has raised profound moral disagreement but also emphasizes the need for wide-ranging discussion and a well-informed policy res...
Our Experience With Photodynamic Diagnosis and Photodynamic Therapy for Lung Cancer
Authors: Harubumi Kato
Journal: Journal of the National Comprehensive Cancer Network (2012)

The diagnosis of lung cancer was significantly enhanced by the development of the fiberoptic bronchoscope in 1965. Since then, advances in photosensitizers and light sources have brought photodynamic medicine into the light. This article offers an historic overview of the emergence of photodynamic medicine through the perspective of a pioneer with more than 30 years’ experience. Along with a discussion of photodynamic diagnosis of lung cancers via optical coherence tomography, the curative, palliative, and neoadjuvant roles of photodynamic therapy for early and advanced lung cancers are explored. An emerging strategy of using PDM to treat peripheral early-stage lung tumors is briefly discussed.
Answer to ‘A 28-year-old snowboarder presents with chronic ankle pain’
Authors: Lawrence B Josey, Christian Kirkpatrick, Gordon Andrews, Bruce B Forster
Journal: British Journal of Sports Medicine (2013)

See page 1588 for the question. 

Osteochondral lesion of the talus.

The initial MRI (figure 3) identified subchondral oedema-like signal of the medial talus on the fluid-sensitive short tau inversion recovery (STIR) sequence. The T1-weighted sequence was normal. A small effusion was present and the talar cartilage, ligaments and tendons were normal (not shown).



Figure 3 
(A) Coronal short tau inversion recovery  at initial presentation shows diffuse oedema-like signal involving the subchondral bone of the superomedial talar dome. (B) The sagittal T1 is normal, area within the dashed line corresponds to the oedema-like signal region observed in (A).



Anteroposterior and lateral plain radiographs obtained at 18 months (figure 4) identified a 7 mm subchondral cyst within the medial talar dome. The talar dome was intact and there was no collapse of the cortex.



Figure 4 
(A) Anteroposterior radiograph performed 18 months after initial presentation demonstrated a well-demarcated lucency within the superomedial talar dome (arrow head ) , the overlying cortex is intact. (B) Lateral radiograph identified lucency within the mid zone of the talar dome (dashed line ) .



The second MRI (figure 5) showed a predominately high-T2 signal, low-T1 signal lesion within the subcortical bone corresponding to the original area of oedema-like signal in the presentation MRI (figure 3) and the cystic lucency on the 18 months radiograph (figure 4). A curvilinear focus of high signal immediately beneath the hyaline cartilage (figure 5A,B) was a component of the subchondral cyst rather than chondral separation. The joint effusion had increased marginally in size and small loose bodies were present (not shown).



Figure 5 
(A,B) Coronal short tau inversion recovery and T2 sequences 18 months after initial presentation showed a well-demarcated, high-signal lesion involving the superomedial talar dome (arrow heads) . Diffuse oedema-like signal surrounded the lesion. (C) Sagittal T2 fat saturation sequence demonstrates the depth and anteroposterior extent of the …
Paradoxical Reaction During a Course of Terbinafine Treatment of<i>Trichophyton interdigitale</i>Infection in a Child
Authors: Anita Hryncewicz-Gwózdz, Marta Wojciechowska-Zdrojowy, Joanna Maj, Wojciech Baran, Tomasz Jagielski
Journal: JAMA Dermatology (2015)

Paradoxical Reaction During a Course of Terbinafine Treatment of Trichophyton interdigitale Infection in a ChildWe describe for the first time, to our knowledge, a paradoxical reaction to terbinafine treatment in the context of dermatophyte infection due to Trichophyton interdigitale.
Respiratory muscle and pulmonary function in polymyositis and other proximal myopathies
Journal: Thorax (1983)

We studied 53patients withproximal myopathy todetermine atwhatlevel ofmuscle weakness hypercapnic respiratory failure islikely, andwhichtestsofpulmonary function or respiratory muscle strength wouldbest suggest this development. Respiratory muscle strength was determined frommaximal static efforts andinhalf thepatients, bothinspiratory andexpiratory muscle strengths wereless than50%ofnormal. Inthe37patients without lungdisease respiratory muscle weakness was accompanied bysignificant decreases invital capacity, total lungcapacity, andmaximumvoluntary ventilation; bysignificant increases inresidual volume andarterial carbon dioxide tension (Paco2); andgreater likelihood ofdependence on ventilators, atelectasis, and pneumonia. Hypercapnia was particularly likely whenrespiratory muscle strength was less than 30%ofnormal inuncomplicated myopathy, andwhenvital capacity was less than55%ofthe predicted value inanypatient. Myopathies which affect proximal limbmuscles may alsoaffect respiratory muscles;'-' buttherelation- ships between theextent towhichrespiratory muscles areaffected, abnormality ofpulmonary function, andtheonset ofrespiratory failure havenot beendefined. We addressed these questions ina groupof 53 patients withvarious proximal
Sinus histiocytosis with massive lymphadenopathy: complete response to low-dose interferon-alpha.
Authors: L Palomera, J M Domingo, T Olave, S Romero, M Gutiérrez
Journal: Journal of Clinical Oncology (1997)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1997.15.5.2176 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9164237 Sinus histiocytosis with massive lymphadenopathy: complete response to low-dose interferon-alpha. L PalomeraxL PalomeraSearch for articles by this author , J M DomingoxJ M DomingoSearch for articles by this author , T OlavexT OlaveSearch for articles by this author , S RomeroxS RomeroSearch for articles by this author , M GutiérrezxM GutiérrezSearch for articles by this author https://doi.org/10.1200/JCO.1997.15.5.2176 PDF "Sinus histiocytosis with massive lymphadenopathy: complete response to low-dose interferon-alpha.." Journal of Clinical Oncology, 15(5), p. 2176© 1997 by American Society of Clinical Oncology
PHOSPHOINOSITIDE 3 KINASE BETA ATTENUATES INFLAMMATION AND FIBROSIS IN A BLEOMYCIN MODEL OF ACUTE LUNG INJURY
Authors: Vito Fanelli, Elisa Ciraolo, Martino Bosco, L Delsedime, A Mensa, El Martin, Lorenzo Del Sorbo, Barbara Assenzio, Ml Campanari, Emilio Hirsch, Vito Marco Ranieri
Journal: Intensive Care Medicine (2009)
Regulation of aldose reductase, sorbitol dehydrogenase, and taurine cotransporter mRNA in rat medulla.
Authors: S Martial, S R Price, J M Sands
Journal: Journal of the American Society of Nephrology (1995)

The regulation of mRNA for aldose reductase, sorbitol dehydrogenase, and the Na+/Cl-/taurine cotransporter was studied with three in vivo models in which urinary concentration is reduced: Sprague-Dawley rats undergoing a water diuresis or fed a low-protein diet or Brattleboro rats. In Sprague-Dawley rats, 3 days of water diuresis reduced inner medullary aldose reductase mRNA abundance 6.5-fold compared with untreated rats, whereas sorbitol dehydrogenase and taurine cotransporter mRNA were unchanged. When water diuretic rats were acutely deprived of water, urine osmolality increased significantly after 4 h but aldose reductase mRNA did not increase until 12 h. Heat shock protein-70 mRNA was not increased by water deprivation. Second, in rats fed a low-protein diet for 3 wk, aldose reductase mRNA increased two-fold, whereas sorbitol dehydrogenase and taurine cotransporter mRNA were unchanged. Finally, in Brattleboro rats, urine osmolality and levels of aldose reductase and taurine cotransporter mRNA increased in response to 1 day of water deprivation, whereas sorbitol dehydrogenase mRNA was unchanged. Administering vasopressin (1 U/day) to Brattleboro rats for 8 days also increased urine osmolality and aldose reductase mRNA but did not alter sorbitol dehydrogenase or taurine cotransporter mRNA. This result is consistent with the hypothesis that changes in urine osmolality induce changes in aldose reductase mRNA abundance that are independent of vasopressin. It was concluded that, in rat inner medulla: (1) aldose reductase mRNA abundance varies with changes in water balance or dietary protein, whereas sorbitol dehydrogenase and taurine cotransporter mRNA do not; and (2) heat shock protein-70 mRNA abundance is not increased during acute osmotic stress.
NCCN Guidelines Insights: Central Nervous System Cancers, Version 1.2017
Authors: Louis Burt Nabors, Jana Portnow, Mario Ammirati, Joachim Baehring, Henry Brem, Nicholas Butowski, Robert A. Fenstermaker, Peter Forsyth, Jona Hattangadi-Gluth, Matthias Holdhoff, Steven Howard, Larry Junck, Thomas Kaley, Priya Kumthekar, Jay S. Loeffler, Paul L. Moots, Maciej M. Mrugala, Seema Nagpal, Manjari Pandey, Ian Parney, Katherine Peters, Vinay K. Puduvalli, John Ragsdale, Jason Rockhill, Lisa Rogers, Chad Rusthoven, Nicole Shonka, Dennis C. Shrieve, Allen K. Sills, Lode J. Swinnen, Christina Tsien, Stephanie Weiss, Patrick Yung Wen, Nicole Willmarth, Mary Anne Bergman, Anita Engh
Journal: Journal of the National Comprehensive Cancer Network (2017)

For many years, the diagnosis and classification of gliomas have been based on histology. Although studies including large populations of patients demonstrated the prognostic value of histologic phenotype, variability in outcomes within histologic groups limited the utility of this system. Nonetheless, histology was the only proven and widely accessible tool available at the time, thus it was used for clinical trial entry criteria, and therefore determined the recommended treatment options. Research to identify molecular changes that underlie glioma progression has led to the discovery of molecular features that have greater diagnostic and prognostic value than histology. Analyses of these molecular markers across populations from randomized clinical trials have shown that some of these markers are also predictive of response to specific types of treatment, which has prompted significant changes to the recommended treatment options for grade III (anaplastic) gliomas.
Evolutionary implication of heterogeneity of the nontranscribed spacer region of ribosomal DNA repeating units in various subspecies of Mus musculus.
Authors: H Suzuki, N Miyashita, K Moriwaki, R Kominami, M Muramatsu, T Kanehisa, F Bonhomme, M L Petras, Z C Yu, D Y Lu
Journal: Molecular Biology and Evolution (1986)

Genetic variability of the nontranscribed spacer (NTS) region within ribosomal DNA repeating units in the various subspecies of Mus musculus was determined. Mice belonging to several laboratory mouse strains were examined by means of Southern blot hybridization with a mouse ribosomal DNA probe. This probe encompasses the 3' end of the 28S ribosomal RNA (rRNA) gene and the following spacer. Restriction enzyme digestions of the liver DNAs from various wild mice revealed that each of the subspecies has a unique pattern in the spacer encompassing a distance approximately 10 kb downstream from the ribosomal gene. These restriction patterns permit the classification of mouse subspecies and also provide insights into the origin of the laboratory mouse strains.
Gadd45<i>γ</i>regulates cardiomyocyte death and post-myocardial infarction left ventricular remodelling
Authors: Alexandre Lucas, Jeanne Mialet-Perez, Danièle Daviaud, Angelo Parini, Michael S. Marber, Pierre Sicard
Journal: Cardiovascular Research (2015)

Post-infarction remodelling is accompanied and influenced by perturbations in mitogen-activated protein kinase (MAPK) signalling. The growth arrest and DNA-damage-inducible 45 (Gadd45) proteins are small acidic proteins involved in DNA repair and modulation of MAPK activity. Little is known about the role of Gadd45 in the heart. Here, we explored the potential contribution of Gadd45 gamma (γ) isoform to the acute and late phase of heart failure (HF) after myocardial infarction (MI) and determined the mechanisms underlying Gadd45γ actions. The Gadd45γ isoform is up-regulated in murine cardiomyocytes subjected to simulated ischaemia and in the mouse heart during MI. To mimic the situation observed during MI, we enhanced Gadd45γ content in cardiomyocytes with a single injection of an adeno-associated viral (AAV9) vector encoding Gadd45γ under the cTNT promoter. Gadd45γ overexpression induces cardiomyocyte apoptosis, fibrosis, left ventricular dysfunction, and HF. On the other hand, genetic deletion of Gadd45γ in knockout mice confers resistance to ischaemic injury, at least in part by limiting cardiomyocyte apoptosis. Mechanistically, Gadd45γ activates receptor-interacting protein 1 (RIP1) and caspase-8 in a p38 MAPK-dependent manner to promote cardiomyocyte death. This work is the first to demonstrate that Gadd45γ accumulation during MI promotes the development and persistence of HF by inducing cardiomyocyte apoptosis in a p38 MAPK-dependent manner. We clearly identify Gadd45γ as a therapeutic target in the development of HF.
The estrous cycle surpasses sex differences in regulating the transcriptome in the rat medial prefrontal cortex and reveals an underlying role of early growth response 1
Authors: Florian Duclot, Mohamed Kabbaj
Journal: Genome biology (2015)

Males and females differ in cognitive functions and emotional processing, which in part have been associated with baseline sex differences in gene expression in the medial prefrontal cortex. Nevertheless, a growing body of evidence suggests that sex differences in medial prefrontal cortex-dependent cognitive functions are attenuated by hormonal fluctuations within the menstrual cycle. Despite known genomic effects of ovarian hormones, the interaction of the estrous cycle with sex differences in gene expression in the medial prefrontal cortex remains unclear and warrants further investigations. We undertake a large-scale characterization of sex differences and their interaction with the estrous cycle in the adult medial prefrontal cortex transcriptome and report that females with high and low ovarian hormone levels exhibited a partly opposed sexually biased transcriptome. The extent of regulation within females vastly exceeds sex differences, and supports a multi-level reorganization of synaptic function across the estrous cycle. Genome-wide analysis of the transcription factor early growth response 1 binding highlights its role in controlling the synapse-related genes varying within females. We uncover a critical influence of the estrous cycle on the adult rat medial prefrontal cortex transcriptome resulting in partly opposite sex differences in proestrus when compared to diestrus females, and we discovered a direct role for Early Growth Response 1 in this opposite regulation. In addition to illustrating the importance of accounting for the estrous cycle in females, our data set the ground for a better understanding of the female specificities in cognition and emotional processing.
CLINICAL STUDIES OF THE BLOOD VOLUME. VI. CHANGES IN BLOOD VOLUME IN PERNICIOUS ANEMIA IN RELATION TO THE HEMATOPOIETIC RESPONSE TO INTRA-MUSCULAR LIVER EXTRACT THERAPY 1
Authors: John G. Gibson
Journal: Journal of Clinical Investigation (1939)

The blood volume in pernicious anemia has been studied repeatedly by a variety of methods and all authors have commented upon the extremely low level of the total volume of circulating red cells found in the severe stages of this disease.There is less unanimity of opinion as regards the ab- normality of both the plasma and total blood vol- ume at various levels of anemia, the relationship between the severity of the disease and the degree of hypovolemia, and the changes in plasma, red cell, and total blood volume that occur during the course of successful liver therapy.Plasma volume was thought to be normal by Bock (1), Denny (2), and Murphy, et al. (3), or higher than normal, Keith (4), Rusynak (5), and De Wesselow and Bamforth (6).Denny (2) found no relation between the severity of the anemia and the total blood volume level, whereas Smith (7) noted that the total amount of hemoglobin was reduced in proportion to the severity of the dis- ease.During treatment with liver the total blood volume was found to increase, due chiefly to a great increase in the red cell volume (6) which may be three or fourfold (3).The plasma vol- ume was found to fall (6), during recovery, or in- crease .(8),or remain fairly constant (3).H61boll (8) could not find any relationship between the observed changes in the total blood volume and either the hematocrit or hemoglobin content of the blood, but De Wesselow and Bamforth (6) stated that the " increase in percentage of red cell vol- ume and hemoglobin estimations gives an accurate index of the actual increase in red cell substance and hemoglobin during treatment."
Representation of Patients With Kidney Disease in Trials of Cardiovascular Interventions
Authors: Ioannis Konstantinidis, Girish N. Nadkarni, Rabi Yacoub, Aparna Saha, Priya Simoes, Chirag R. Parikh, Steven G. Coca
Journal: JAMA Internal Medicine (2015)

Conflict of Interest Disclosures: Dr Mor reported performing research in a related area to that of several different paid activities; periodically serving as a paid speaker at national conferences where he discusses trends and research findings in long-term and postacute care but never any specific product or service provider; founding and previously owning stock of unknown value and sitting on the board of PointRight, Inc, an information services company that provides advice and consultation to various components of the long-term care and postacute care industries, including suppliers and insurers, and sells information on the measurement of nursing home quality to nursing homes and liability insurers; chairing the independent quality committee for HRC Manor Care, Inc, a nursing home chain, for which he receives compensation ranging from $20 000 to $40 000 per year; serving as chair of a scientific advisory committee for NaviHealth, a postacute care service organization, for which he also receives compensation ranging from $20 000 to $40 000 per year; serving as a compensated speaker at the nonacademic National Long Term Care Quality Meeting in 2014; serving as a technical expert on several Centers for Medicare & Medicaid Services quality measurement panels; and serving as a member of the board of directors for Tufts Health Plan Foundation, Hospice Care of Rhode Island, and the Jewish Alliance of Rhode Island.No other disclosures were reported.
Professional Rugby Union players have a 60% greater risk of time loss injury after concussion: a 2-season prospective study of clinical outcomes
Authors: Matthew Cross, Simon Kemp, Andrew Smith, Grant Trewartha, Keith Stokes
Journal: British Journal of Sports Medicine (2015)

To investigate incidence of concussion, clinical outcomes and subsequent injury risk following concussion.In a two-season (2012/2013, 2013/2014) prospective cohort study, incidence of diagnosed match concussions (injuries/1000 h), median time interval to subsequent injury of any type (survival time) and time spent at each stage of the graduated return to play pathway were determined in 810 professional Rugby Union players (1176 player seasons).Match concussion incidence was 8.9/1000 h with over 50% occurring in the tackle. Subsequent incidence of any injury for players who returned to play in the same season following a diagnosed concussion (122/1000 h, 95% CI 106 to 141) was 60% higher (IRR 1.6, 95% CI 1.4 to 1.8) than for those who did not sustain a concussion (76/1000 h, 95% CI 72 to 80). Median time to next injury following return to play was shorter following concussion (53 days, 95% CI 41 to 64) than following non-concussive injuries (114 days, 95% CI 85 to 143). 38% of players reported recurrence of symptoms or failed to match their baseline neurocognitive test during the graduated return to play protocol.Players who returned to play in the same season after a diagnosed concussion had a 60% greater risk of time-loss injury than players without concussion. A substantial proportion of players reported recurrence of symptoms or failed to match baseline neurocognitive test scores during graduated return to play. These data pave the way for trials of more conservative and comprehensive graduated return to play protocols, with a greater focus on active rehabilitation.
Constrained spheroids for prolonged hepatocyte culture
Authors: Wen Hao Tong, Yu Fang, Jie Yan, Xin Hong, Nisha Hari Singh, Shu Rui Wang, Bramasta Nugraha, Lei Xia, Eliza Li Shan Fong, Ciprian Iliescu, Hanry Yu
Journal: Biomaterials (2015)