tbuckley/cabot-search huggingface dataset:
Peroxisome proliferator-activated receptor β stimulation induces rapid cardiac growth and angiogenesis via direct activation of calcineurin
Authors: Nicole Wagner, Chantal Jehl-Piétri, Pascal Lopez, Joseph Murdaca, Christian Giordano, Chantal Schwartz, Pierre Gounon, Stéphane N. Hatem, Paul Grimaldi, Kay-Dietrich Wagner
Journal: Cardiovascular Research (2009)

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors. PPARβ agonists were suggested as potential drugs for the treatment of metabolic syndrome, but effects of PPARβ activation on cardiac growth and vascularization are unknown. Thus, we investigated the consequences of pharmacological PPARβ activation on the heart and the underlying molecular mechanisms. Male C57/Bl6 mice were injected with the specific PPARβ agonists GW0742 or GW501516, or vehicle. Cardiomyocyte size and vascularisation were determined at different time points. Expression differences were investigated by quantitative reverse transcriptase–polymerase chain reaction and western blotting. In addition, the effects of PPARβ stimulation were compared with hearts of mice undergoing long-term voluntary exercise or pharmacological PPARα activation. Five hours after GW0742 injection, we detected an enhanced angiogenesis compared with vehicle-injected controls. After 24 h, the heart-to-body weight ratios were higher in mice injected with either GW0742 or GW501516 vs. controls. The increased heart size was due to cardiomyocyte enlargement. No signs of pathological cardiac hypertrophy (i.e. apoptosis, fibrosis, or deteriorated cardiac function) could be detected. The effects are mediated via calcineurin A (CnA) activation as: (i) CnA was upregulated, (ii) GW0742 administration or co-transfection of PPARβ significantly stimulated the activity of the CnA promoter, (iii) PPARβ protein bound directly to the CnA promoter, (iv) the CnA target genes NFATc3, Hif-1α, and Cdk 9 were upregulated in response to PPARβ stimulation, and (v) the inhibition of CnA activity by cyclosporine A abolished the hypertrophic and angiogenic responses to PPARβ stimulation. Our data suggest PPARβ pharmacological activation as a novel approach to increase cardiac vascularization and cardiac muscle mass.
The ‘gender gap’ in authorship in nursing literature
Authors: Linda Shields, Jenny Hall, Abdulla A Mamun
Journal: Journal of the Royal Society of Medicine (2011)

Gender bias has been found in medical literature, with more men than women as first or senior authors of papers, despite about half of doctors being women. Nursing is about 90% female, so we aimed to determine if similar biases exist in nursing literature.Taking the eight non-specialist nursing journals with the highest impact factors for that profession, we counted the numbers of men and women first authors over 30 years.We used nursing journals from around the world which attract the highest impact factors for nursing publication.Eight journals qualified for entry, three from the United Kingdom, four from the United States of America, and one from Australia. MAIN OUTCOME MEASURES Using Chi-square and Fisher exact tests, we determined differences between the numbers of men and women across all the journals, between countries (USA, UK and Australia), changes over the 30 years, and changes within journals over time. RESULTS Despite the small proportion of men in the nursing workforce, up to 30% of first authors were men. UK journals were more likely to have male authors than USA journals, and this increased over time. USA journals had proportions of male first authors consistent with the male proportion of its nursing workforce. CONCLUSIONS In the UK (though not in the USA) gender bias in nursing publishing exists, even though the nursing workforce is strongly feminized. This warrants further research, but is likely to be due to the same reasons for the gender gap in medical publishing; that is, female nurses take time out to have families, and social and family responsibilities prevent them taking opportunities for career progression, whereas men's careers often are not affected in such ways.
A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with ‘good-risk’ metastatic non-seminomatious germ cell tumors
Authors: C. Bokemeyer, O. Köhrmann, J. Tischler, L. Weißbach, U. Räth, A. Haupt, P. Schöffski, A. Harstrick, H.-J. Schmoll
Journal: Annals of Oncology (1996)
Agonistic AT1 Receptor Autoantibody Increases in Serum of Patients with Refractory Hypertension and Improves Ca2+ Mobilization in Cultured Rat Vascular Smooth Muscle Cells
Authors: Feng Zhu, Yanxiang Sun, Yuhua Liao, Yumiao Wei, Ming Chen, Min Wang, Zihua Zhou
Journal: Cellular and Molecular Immunology (2008)
Utility of a Lung Biopsy for the Diagnosis of Idiopathic Pulmonary Fibrosis
Authors: GARY W. HUNNINGHAKE, M. BRIDGET ZIMMERMAN, DAVID A. SCHWARTZ, TALMADGE E. KING, JOSEPH LYNCH, RICHARD HEGELE, JAMES WALDRON, THOMAS COLBY, NESTOR MÜLLER, DAVID LYNCH, JEFF GALVIN, BARRY GROSS, JAMES HOGG, GALEN TOEWS, RICK HELMERS, J. ALLEN D. COOPER, ROBERT BAUGHMAN, CHARLIE STRANGE, MARK MILLARD
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

It is not known if a surgical lung biopsy is necessary in all patients for the diagnosis of idiopathic pulmonary fibrosis (IPF). We conducted a blinded, prospective study at eight referring centers. Initially, cases were evaluated by clinical history and examination, transbronchial biopsy, and high-resolution lung computed tomography scans. Pulmonologists at the referring centers then assessed their certainty of the diagnosis of IPF and provided an overall diagnosis, before surgical lung biopsy. The lung biopsies were reviewed by a pathology core and 54 of 91 patients received a pathologic diagnosis of IPF. The positive predictive value of a confident (certain) clinical diagnosis of IPF by the referring centers was 80%. The positive predictive value of a confident clinical diagnosis was higher, when the cases were reviewed by a core of pulmonologists (87%) or radiologists (96%). Lung biopsy was most important for diagnosis in those patients with an uncertain diagnosis and those thought unlikely to have IPF. These studies suggest that clinical and radiologic data that result in a confident diagnosis of IPF by an experienced pulmonologist or radiologist are sufficient to obviate the need for a lung biopsy. Lung biopsy is most helpful when clinical and radiologic data result in an uncertain diagnosis or when patients are thought not to have IPF.
Retrospective Study of Childhood Ganglioneuroma
Authors: Bruno De Bernardi, Claudio Gambini, Riccardo Haupt, Claudio Granata, Antonino Rizzo, Massimo Conte, Gian Paolo Tonini, Maurizio Bianchi, Maria Giuliano, Roberto Luksch, Arcangelo Prete, Elisabetta Viscardi, Alberto Garaventa, Angela Rita Sementa, Paolo Bruzzi, Paola Angelini
Journal: Journal of Clinical Oncology (2008)

To review a historical cohort of childhood ganglioneuroma (GN), the benign representative of the peripheral neuroblastic tumor (PNT) family.Of 2,286 PNTs enrolled between 1979 and 2005, 146 (6.4%) were registered as GN. Histological revision was carried out on 76 tumors. Diagnosis was confirmed in 45, while 27 were reclassified as ganglioneuroblastoma intermixed (GNBI) and four were reclassified as other PNT subtypes.GNs differed from other PNTs for sex, age, tumor site, stage, tumor markers, and scintigraphic results. Characteristics of 76 reviewed and 70 nonreviewed patients were comparable. Reviewed GN and GNBI patients were comparable except for homovanillic acid excretion, metaiodobenzylguanidine scintigraphy, and DNA content. Seven patients were only biopsied and 139 underwent surgery. Twenty-two patients suffered surgery-related complications, of which two were fatal and seven were severe. Radical tumor resection and surgery-related complication rates were comparable for GN, GNBI, and nonreviewed instances. Six patients developed tumor progression but survived. Two patients developed a late malignancy but survived. None of the 146 patients received chemotherapy. Of 146 patients, two died of surgery-related complications and 144 survived.Diagnosis was changed to GNBI for approximately one third of 76 reviewed tumors. Patients with confirmed GN, reclassified as GNBI, and nonreviewed histology presented with comparable clinical, biochemical, and biologic features. Surgical results, complication rate, number of progressions, and outcome were similar for the three groups. Surgery was associated with significant risk of complications. Survival was not influenced by extent of tumor resection. Aggressive surgical approach should not be recommended for childhood GN and GNBI.
Efficacy and Safety of Mirogabalin (DS-5565) for the Treatment of Diabetic Peripheral Neuropathic Pain: A Randomized, Double-Blind, Placebo- and Active Comparator–Controlled, Adaptive Proof-of-Concept Phase 2 Study
Authors: Aaron Vinik, Julio Rosenstock, Uma Sharma, Karen Feins, Ching Hsu, Domenico Merante
Journal: Diabetes Care (2014)

We aimed to identify doses of mirogabalin (DS-5565) providing clinically meaningful efficacy with manageable side effects for treatment of diabetic peripheral neuropathic pain (DPNP).Adults (≥18 years) with type 1 or 2 diabetes, HbA₁c ≤10% at screening, and DPNP for ≥6 months were eligible for study participation. Subjects (n = 452) were randomized (2:1:1:1:1:1:1 ratio) to placebo, dose-ranging mirogabalin (5, 10, 15, 20, and 30 mg/day), or pregabalin (300 mg/day) for 5 weeks. The primary end point was weekly change in average daily pain score (ADPS; 0 to 10 numeric rating scale) from baseline to week 5 (minimally meaningful effect, ≥1.0-point decrease versus placebo). ANCOVA was conducted using last observation carried forward, and treatment effect least squares (LS) means were provided for each contrast. Safety assessments included adverse events (AEs), clinical laboratory tests, and electrocardiograms.LS mean differences in change in ADPS from baseline to week 5 versus placebo were -0.22, -0.53, -0.94, -0.88, and -1.01 for the mirogabalin 5-, 10-, 15-, 20-, and 30-mg/day treatment groups, respectively, and -0.05 in the pregabalin group (P < 0.05 versus placebo for mirogabalin 15, 20, and 30 mg/day). Most frequent AEs (n = 277) were primarily mild to moderate dizziness (9.4%), somnolence (6.1%), and headache (6.1%); otherwise, mirogabalin was well tolerated.Mirogabalin 15, 20, and 30 mg/day had statistically significant reductions in ADPS versus placebo, and mirogabalin 30 mg/day also met the criteria of minimally meaningful effect. Mirogabalin may be a promising new treatment option for patients with DPNP.
II. Involutional Psychotic Reaction
Authors: EARL D. BOND
Journal: American Journal of Psychiatry (1954)

A series of 206 consecutive admissions of involutional psychotic reactions in 1940-46, when electric and other shock treatments were used (except in 24 where shock was contraindicated or refused) is compared to a control series of 141 consecutive admissions in 1925-34, under similar conditions without shock therapy. The shock treated series has over twice the percentage of recoveries both on discharge from the hospital and at 5 years after admission. The average stay in the Pennsylvania Hospital of the recoveries in the shock series was 2 months; the average stay of the control series was 12 months. The comparison is marred by the fact that only slightly more than half of the shock series could be followed for all of 5 years; however, the cases which were "lost" had, at last accounting, the same percentage of recoveries as those which could be followed.
Prophylactic Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor Decrease Febrile Neutropenia After Chemotherapy in Children With Cancer: A Meta-Analysis of Randomized Controlled Trials
Authors: Lillian Sung, Paul C. Nathan, Beverly Lange, Joseph Beyene, George R. Buchanan
Journal: Journal of Clinical Oncology (2004)

Purpose To determine whether prophylactic hematopoietic colony-stimulating factors (CSFs) used in children with cancer reduce the rate of febrile neutropenia, hospitalization duration, documented infection rate, parenteral antibiotic duration, amphotericin B use, or infection-related mortality. Methods We included studies in this meta-analysis if their populations consisted of children, if there was randomization between CSFs and placebo or no therapy, if CSFs were administered prophylactically (before neutropenia or febrile neutropenia), and if chemotherapy treatments preceding CSFs and placebo or no therapy were identical. From 971 reviewed study articles, 16 were included. Results The mean rate of febrile neutropenia in the control arms was 57% (range, 39% to 100%). Using a random effects model, CSFs were associated with a reduction in febrile neutropenia, with a rate ratio of 0.80 (95% CI, 0.67 to 0.95; P = .01), and a decrease in hospitalization length, with a weighted mean difference of −1.9 days (95% CI, −2.7 to −1.1 days; P &lt; .00001). CSF use was also associated with reduction in documented infections (rate ratio, 0.78; 95% CI, 0.62 to 0.97; P = .02) and reduction in amphotericin B use (rate ratio, 0.50; 95% CI, 0.28 to 0.87; P = .02). There was no difference in duration of parenteral antibiotic therapy (weighted mean difference, −4.3; 95% CI, −10.6 to 2.0 days; P = .2) or infection-related mortality (rate ratio, 1.02; 95% CI, 0.34 to 3.06; P = .97). Conclusion CSFs were associated with a 20% reduction in febrile neutropenia and shorter duration of hospitalization; however, CSFs did not reduce infection-related mortality.
Neuropilin-2 expression is inhibited by secreted Wnt antagonists and its down-regulation is associated with reduced tumor growth and metastasis in osteosarcoma
Authors: Tao Ji, Yi Guo, Kapjun Kim, Peter McQueen, Samia Ghaffar, Alexander Christ, Carol Lin, Ramez Eskander, Xiaolin Zi, Bang H Hoang
Journal: Molecular Cancer (2015)

Neuropilin 2 (NRP2) isa multi-functional co-receptor to many receptors, including VEGF receptor, c-Met and others. NRP2 has recently been implicated in tumor angiogenesis, growth, and metastasis of many other cancers. However, its role in osteosarcoma remains poorly understood.NRP2 was overexpressed in osteosarcoma cell lines and tissues, and associated with poor survival of osteosarcoma patients. Knockdown of NRP2 expression by short-hairpin (Sh) RNA resulted in reduced tumor growth, metastasis, and blood vessel formation of osteosarcoma. Knockdown of NRP2 expression by ShRNA also inhibited the recruitment of HUVEC cells to osteosarcoma cells. Inhibition of Wnt signaling by overexpression of secreted Wnt antagonists soluble LRP5, Frzb, and WIF1 markedly down-regulated mRNA and protein expression of NRP2 in osteosarcoma cell lines.Regulation of NRP2 receptor expression may represent a novel approach for treatment of osteosarcoma through retarding osteosarcoma growth, metastasis and blood vessel formation. In addition, down-regulation of NRP2 expression can be achieved by expression of secreted Wnt antagonists.
PARANEOPLASTIC SYNDROMES AFFECTING THE CENTRAL NERVOUS SYSTEM
Authors: Jerome B. Posner, MD, Josep O. Dalmau, MD, PhD
Journal: Annual Review of Medicine (1997)

▪ Abstract Paraneoplastic syndromes affecting the nervous system are rare neurologic syndromes caused by cancer but not ascribable to metastases. Any portion of the nervous system may be involved in a paraneoplastic syndrome. The pathogenesis of these disorders appears to be an immune reaction against antigens shared by the cancer and the nervous system. Some disorders, such as the Lambert-Eaton myasthenic syndrome, are effectively treated by removal of autoantibodies directed against the presynaptic cholinergic synapse. In other disorders, such as paraneoplastic cerebellar degeneration or paraneoplastic sensory neuronopathy, neither removal of the autoantibody nor treatment of the cancer is effective.
Male Breast Cancer Incidence Among Atomic Bomb Survivors
Authors: Elaine Ron, Takayoshi Ikeda, Dale L. Preston, Shoji Tokuoka
Journal: JNCI Journal of the National Cancer Institute (2005)

To learn more about the role of ionizing radiation in the development of male breast cancer, we evaluated male breast cancer incidence among 45 880 male members of the Life Span Study cohort of Japanese atomic bomb survivors. Male breast cancers, diagnosed between January 1, 1958, and December 31, 1998, were identified through the Hiroshima and Nagasaki Tumor Registries. Nine male breast cancers were diagnosed among exposed Life Span Study members (crude rate = 1.8 per 100,000 person-years), and three were diagnosed among nonexposed cohort members (crude rate = 0.5 per 100,000 person-years). A statistically significant dose-response relation was observed (excess relative risk per sievert = 8, 95% confidence interval = 0.8 to 48; P = .01). Our finding of a statistically significant association between ionizing radiation and male breast cancer incidence adds to the very limited information that shows an association between radiation exposure and an increased risk of male breast cancer.
Glycan Shielding of the Influenza Virus Hemagglutinin Contributes to Immunopathology in Mice
Authors: Keith Wanzeck, Kelli L. Boyd, Jonathan A. McCullers
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Pandemic influenza viruses historically have had few potential sites for N-linked glycosylation on the globular head of the hemagglutinin (HA) on emergence from the avian reservoir. Gain of glycans within antigenic sites of the HA during adaptation to the mammalian lung facilitates immune evasion.In this study, we sought to determine in mice how exposure to highly glycosylated viruses affects immunity to poorly glycosylated variants to model the emergence of a novel pandemic strain of a circulating subtype.We engineered the 1968 H3N2 pandemic strain to express an additional two or four potential sites for glycosylation on the globular head of the HA. Mice were infected sequentially with highly glycosylated variants followed by poorly glycosylated variants and monitored for immune responses and disease.The mutant with four additional glycosylation sites (+4 virus) elicited significantly lower antibody responses than the wild-type or +2 virus and was unable to elicit neutralizing antibodies. Mice infected with the +4 virus and then challenged with wild-type virus were not protected from infection and experienced significant T-cell-mediated immunopathology. Infection with a recent seasonal H1N1 virus followed by infection with the 2009 pandemic H1N1 elicited similar responses.These data suggest that sequential infection with viral strains with different surface glycosylation can prime the host for immunopathology if a neutralizing antibody response matching the T-cell response is not present. This mechanism may have contributed to severe disease in young adults infected with the 2009 pandemic virus.
Upper limb injuries in sports
Authors: B B Putty
Journal: British Journal of Sports Medicine (2010)

Injuries, either to the athletes, amateurs, trainees or professional players, are common in any sporting event. Injuries can be to the limbs or to the trunk; acute, chronic or repetitive, from mild to severely disabling in severity. The most commonly injured regions are knee (28%) followed by the upper limb (23%). The common upper extremity injuries are the shoulder, followed by elbow and wrist. The type, biomechanics and frequencies of the use of the body parts determine the injury patterns. Shoulder injuries are more common in cricket players, during delivery or follow through of the bowler or throw of the fielder, either acute or chronic. Pain in the upper extremity, to shoulder and elbow are common in throwing sports, racquet sports and swimming while wrist pain is common in young gymnasts. Elbow injuries are common in athletes with over the head and arm motions. In chronic conditions, either lateral or medial epicondylitis (50%), popularly known as tennis elbow or golfers elbow are due to repetitive valgus or varus stress impacts. This repetitive stress pathology from mild to severely disabling to the sportsman is a common challenge to clinicians or physiotherapists in management. The musculoskeletal disorders, general or related to tendons, muscular, joints nerves or vascular, need a variety of management skills involving clinicians, physiotherapists and rehabilitation specialists.
Relief of Feedback Inhibition of <i>HER3</i> Transcription by RAF and MEK Inhibitors Attenuates Their Antitumor Effects in <i>BRAF</i>-Mutant Thyroid Carcinomas
Authors: Cristina Montero-Conde, Sergio Ruiz-Llorente, Jose M. Dominguez, Jeffrey A. Knauf, Agnes Viale, Eric J. Sherman, Mabel Ryder, Ronald A. Ghossein, Neal Rosen, James A. Fagin
Journal: Cancer Discovery (2013)

The RAF inhibitor vemurafenib (PLX4032) increases survival in patients with BRAF-mutant metastatic melanoma, but has limited efficacy in patients with colorectal cancers. Thyroid cancer cells are also comparatively refractory to RAF inhibitors. In contrast to melanomas, inhibition of mitogen-activated protein kinase (MAPK) signaling by PLX4032 is transient in thyroid and colorectal cancer cells. The rebound in extracellular signal-regulated kinase (ERK) in thyroid cells is accompanied by increased HER3 signaling caused by induction of ERBB3 (HER3) transcription through decreased promoter occupancy by the transcriptional repressors C-terminal binding protein 1 and 2 and by autocrine secretion of neuregulin-1 (NRG1). The HER kinase inhibitor lapatinib prevents MAPK rebound and sensitizes BRAF-mutant thyroid cancer cells to RAF or MAP-ERK kinase inhibitors. This provides a rationale for combining ERK pathway antagonists with inhibitors of feedback-reactivated HER signaling in this disease. The determinants of primary resistance to MAPK inhibitors vary between cancer types, due to preferential upregulation of specific receptor tyrosine kinases, and the abundance of their respective ligands.