tbuckley/cabot-search huggingface dataset:
Dermoscopy of subungual haemorrhage: its usefulness in differential diagnosis from nail-unit melanoma
Authors: J.-H. Mun, G.-W. Kim, S.-W. Jwa, M. Song, H.-S. Kim, H.-C. Ko, B.-S. Kim, M.-B. Kim
Journal: British Journal of Dermatology (2013)

Subungual haemorrhages are characterized by well-circumscribed dots or blotches with a red to red-black pigmentation, but some cases can be difficult to distinguish from subungual melanoma by the naked eye alone. Dermoscopy has proven to be a useful, noninvasive tool in the diagnosis of pigmented lesions in the nail; however, few dermoscopic studies of subungual haemorrhages have been reported.To investigate characteristic dermoscopic patterns of subungual haemorrhages, and to find distinctive features that can differentiate them from nail-unit melanomas.Patients with a confirmed diagnosis of either subungual haemorrhage or nail-unit melanoma at a tertiary university hospital were included in the study. Clinical features and dermoscopic patterns were evaluated.Sixty-four patients with a total of 90 lesions of subungual haemorrhage were enrolled in the study. The majority of cases (84%) showed combinations of more than one colour, while 16% had only one colour. The most common colour of the subungual haemorrhages was purple-black, in 37% of cases. A homogeneous pattern was observed in 92% of cases, globular patterns in 42% and streaks in 39%. Peripheral fading and periungual haemorrhages were found in 54% and 22% of cases, respectively. Destruction or dystrophy of the nail plate was observed in 16% of cases. In the 16 cases of nail-unit melanomas, Hutchinson sign, longitudinal irregular bands or lines, triangular shape of bands, vascular pattern, and ulcerations were found in 100%, 81%, 25%, 6% and 81% of cases, respectively. In contrast, these features were not found in subungual haemorrhages.Dermoscopy provides valuable information for the diagnosis of subungual haemorrhage and aids in the differential diagnosis from nail-unit melanoma.
Psychiatric complications of multiple myeloma
Authors: P M Silberfarb, G M Bates
Journal: American Journal of Psychiatry (1983)

Multiple myeloma is an uncommon cancer, but of eight patients with multiple myeloma admitted to a general hospital over 5 months, five had psychiatric illness, and four of the five had delirium. Consulting psychiatrists should be aware of the common occurrence of impaired cognition in patients with multiple myeloma.
Genes affecting mRNA stability and metalloproteinase inhibitor RECK are down-regulated in patients with COPD
Authors: Zdenka Navratilova, Tereza Krsjakova, Eva Novosadova, Jaromir Zatloukal, Vitezslav Kolek, Martin Petrek
Journal: European Respiratory Journal (2013)

The local lung inflammatory response in chronic obstructive pulmonary disease (COPD) has proteolytic nature with elevated activity of matrix metalloproteinases (MMPs). As with other genes, the expression of MMPs and their inhibitors is affected by mRNA stability. Our aim was, therefore, to investigate the expression of two inhibitors of MMPs (RECK and PTEN) and of RNA-binding proteins affecting mRNA stability (AUF1, HuR and PCBP2) in bronchoalveolar cells from COPD patients. Real time-PCR method with PSMB2 as reference gene was used to quantify the relative expression of the tested genes in 11 non-smoking controls, 11 smoking controls, 8 non-smoking COPD patients and 22 smoking patients. The relative expression of RECK was decreased in COPD patients compared to healthy controls (p=0.004). Sub-analysis among the four subject groups stratified based on their smoking status showed that the RECK expression was decreasing gradually in the direction from non-smoking controls to smoking COPD patients (p=0.01). Of RNA-binding proteins, the numbers of AUF1 (p=0.01) and HuR (p=0.03) mRNA transcripts were lower in COPD patients than those in healthy control subjects. There was a positive correlation between RECK expression and AUF1 (p =0.001), PCBP2 (p =0.001) and HuR (p=0.02), respectively. In conclusion, altered expression of the MMPs inhibitor and deregulated mRNA stability observed in this study may be involved to COPD pathogenesis. Further studies are required to clarify the relationship between RECK and RNA-binding proteins in COPD.  Acknowledgment: Grant support IGA PU LF 2013_009 and CZ.1.05./2.1.00/01.0030.
Imaging of primary and metastatic liver cancer with 131I monoclonal and polyclonal antibodies against alphafetoprotein.
Authors: D M Goldenberg, H Goldenberg, E Higginbotham-Ford, D Shochat, E Ruoslahti
Journal: Journal of Clinical Oncology (1987)

Thirteen patients with a history of confirmed liver carcinoma were given either I131 goat polyclonal or murine monoclonal antibodies against alpha-fetoprotein (AFP), and then scanned with a gamma camera. In order to reduce background, nontarget activity, especially in the liver, blood pool, and reticuloendothelial system, 99mTc imaging agents were used for tumor image enhancement by computer-assisted subtraction. A sensitivity of 91% for the primary site, 50% for the lungs (33% for the chest area), and 75% for the abdomen and pelvis was achieved, with a specificity of 100%, 94%, and 100% for these sites, respectively. The accuracy was determined to be 93% for the liver, 86% for the lungs (77% for the chest), and 85% for the abdominal and pelvic area, resulting in an overall accuracy rate for imaging primary and metastatic hepatocellular cancer of 84% (90% if bone metastases are excluded). In two of the 13 patients, lesions that had been missed by conventional liver scintigraphy and transmission computed tomography (CT) were first shown by radioimmunodetection (RAID).
Abstract 189: βAR Resensitization At The Plasma Membrane Provides Beneficial Cardiac Remodeling
Authors: Elizabeth E Martelli, Neelakantan T Vasudevan, John George, Maradumane L Mohan, Manveen K Gupta, Sathyamangla V Naga Prasad
Journal: Circulation Research (2014)

βAR downregulation and desensitization are hallmarks of heart failure. Agonist occupied βARs undergo desensitization through phosphorylation by G-protein coupled receptor kinases leading to βAR internalization. Phosphorylated βAR becomes resensitized following dephosphorylation by PP2A in the endosomes. In contrast to this paradigm our recent studies have shown that resensitization of βARs can occur at the plasma membrane through the inhibition of PP2A activity by I2PP2A. We generated a stable HEK cell line expressing short hairpin RNA targeting I2PP2A (shRNA-I2PP2A). Confocal microscopy studies show cells expressing shRNA-I2PP2A resulted in significant loss of receptor phosphorylation despite the presence of the agonist. Radioligand binding and confocal imaging also showed marked inhibition of receptor internalization upon depletion of I2PP2A with significant PP2A activation. We also observed preservation of βAR function despite the presence of agonist measured by cAMP generation and adenylyl cyclase activity. To further dissect the interaction of I2PP2A-PP2A we generated mutants of PP2A from amino acids 263-309. Over expression of these PP2A mutant peptides significantly reversed receptor phosphorylation upon isoproterenol (ISO) stimulation compared to full length PP2A. Also, expression of PP2A mutant showed marked increase in adenylyl cyclase activity in response ISO stimulation suggesting that this mutant I2PP2A competes out inhibitory I2PP2A interaction with PP2A. To test whether alteration in βAR resensitization contributes to cardiac dysfunction with stress we generated transgenic (Tg) mice with cardiac specific over expression of wt I2PP2A and mutant I2PP2A (phopspho- and dephospho-). ISO treatment of wt I2PP2A Tg and littermate controls showed that wt I2PP2A Tg mice had significant βAR dysfunction and cardiac hypertrophy. Assessment of age dependent cardiac function of these mice showed that wt I2PP2A Tg and phospho-I2PP2A Tg mice have cardiac hypertrophic response followed by dilated cardiomyopathy; expression of dephospho-I2PP2A mutant reversed this phenotype. These studies suggest targeting I2PP2A alters receptor function and may have implications in cardiac remodeling and hypertrophy with cardiac stress.
The comparative effectiveness of oral versus subcutaneous methotrexate for the treatment of early rheumatoid arthritis
Authors: Glen S Hazlewood, J Carter Thorne, Janet E Pope, Daming Lin, Diane Tin, Gilles Boire, Boulos Haraoui, Carol A Hitchon, Edward C Keystone, Shahin Jamal, Vivian P Bykerk
Journal: Annals of the Rheumatic Diseases (2015)

Objective To determine the comparative effectiveness of oral versus subcutaneous methotrexate (MTX) as initial therapy for patients with early rheumatoid arthritis (ERA). Methods Patients with ERA (symptoms ≤1 year) initiating MTX therapy were included from a multicentre, prospective cohort study. We compared the effectiveness between starting with oral versus subcutaneous MTX over the first year. Longitudinal multivariable models, adjusted for potential baseline and time-varying confounders, were used to compare treatment changes due to inefficacy or toxicity and treatment efficacy (Disease Activity Score-28 (DAS-28), DAS-28 remission and Health Assessment Questionnaire-Disability Index (HAQ-DI)). Results 666 patients were included (417 oral MTX, 249 subcutaneous MTX). Patients prescribed subcutaneous MTX were prescribed a higher dose of MTX (mean dose over first three months 22.3 mg vs 17.2 mg/week). At 1 year, 49% of patients initially treated with subcutaneous MTX had changed treatment compared with 77% treated with oral MTX. After adjusting for potential confounders, subcutaneous MTX was associated with a lower rate of treatment failure ((HR (95% CI) 0.55 (0.39 to 0.79)). Most treatment failures were due to inefficacy with no difference in failure due to toxicity. In multivariable models, subcutaneous MTX was also associated with lower average DAS-28 scores (mean difference (−0.38 (95% CI −0.64 to −0.10)) and a small difference in DAS-28 remission (OR 1.2 (95% CI 1.1 to 1.3)). There was no significant difference in sustained remission or HAQ-DI (p values 0.43 and 0.75). Conclusions Initial treatment with subcutaneous MTX was associated with lower rates of treatment changes, no difference in toxicity and some improvements in disease control versus oral MTX over the first year in patients with ERA.
Computer Program to Assist in Making Decisions About Adjuvant Therapy for Women With Early Breast Cancer
Authors: Peter M. Ravdin, Laura A. Siminoff, Greg J. Davis, Mary Beth Mercer, Joan Hewlett, Nancy Gerson, Helen L. Parker
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The goal of the computer program Adjuvant! is to allow health professionals and their patients with early breast cancer to make more informed decisions about adjuvant therapy. METHODS: Actuarial analysis was used to project outcomes of patients with and without adjuvant therapy based on estimates of prognosis largely derived from Surveillance, Epidemiology, and End-Results data and estimates of the efficacy of adjuvant therapy based on the 1998 overviews of randomized trials of adjuvant therapy. These estimates can be refined using the Prognostic Factor Impact Calculator, which uses a Bayesian method to make adjustments based on relative risks conferred and prevalence of positive test results. RESULTS: From the entries of patient information (age, menopausal status, comorbidity estimate) and tumor staging and characteristics (tumor size, number of positive axillary nodes, estrogen receptor status), baseline prognostic estimates are made. Estimates for the efficacy of endocrine therapy (5 years of tamoxifen) and of polychemotherapy (cyclophosphamide/methotrexate/fluorouracil–like regimens, or anthracycline-based therapy, or therapy based on both an anthracycline and a taxane) can then be used to project outcomes presented in both numerical and graphical formats. Outcomes for overall survival and disease-free survival and the improvement seen in clinical trials, are reasonably modeled by Adjuvant!, although an ideal validation for all patient subsets with all treatment options is not possible. Additional speculative estimates of years of remaining life expectancy and long-term survival curves can also be produced. Help files supply general information about breast cancer. The program’s Internet links supply national treatment guidelines, cooperative group trial options, and other related information. CONCLUSION: The computer program Adjuvant! can play practical and educational roles in clinical settings.
Paradigm shifts in cardioprotection research: the importance of the MPTP as a therapeutic target: AUTHORS' RETROSPECTIVE
Authors: D. J. Hausenloy, H. L. Maddock, G. F. Baxter, D. M. Yellon
Journal: Cardiovascular Research (2012)

This editorial refers to an article by D.J. Hausenloy et al . [12][1] published in Cardiovascular Research in 2002 (see [Box 1][2]). It is accompanied by an editorial by M. Ruiz-Meana, pp. 157–159, this issue, as part of this Spotlight on Landmark Papers in Cardiovascular Research .

Our interest in the mitochondrial permeability transition pore (MPTP) as a target for cardioprotection was first aroused by a seminar given at University College London by John Lemasters and during one of our weekly journal clubs, back in early 2001. The research article which attracted our attention was by two pioneers in MPTP research, Fabio Di Lisa and Paulo Bernardi at the University of Padova.1 In their experimental study, they had demonstrated that pre-treating isolated perfused rat hearts with the immunosuppressant agent cyclosporin-A (CsA) could decrease myocardial injury (measured by lactate dehydrogenase release) following an episode of acute lethal ischaemia and reperfusion injury (IRI) and that the cardioprotective effect was associated with inhibition of MPTP opening at the time of myocardial reperfusion. At that time, our research group had been keen to discover novel therapeutic agents which were able to prevent lethal myocardial reperfusion injury and limit myocardial infarct (MI) size when administered at the onset of myocardial reperfusion. In addition, we were keen to unravel the mechanistic pathways underlying the phenomenon of ischaemic preconditioning (IPC),2 in which the heart could be rendered resistant to an episode of acute lethal ischaemia and reperfusion by preconditioning it with one or more brief cycles of non-lethal ischaemia and reperfusion. Therefore, the suggestion that the opening of the MPTP at the onset of reperfusion was a critical mediator of lethal myocardial reperfusion injury made it an obvious target for investigation.

This was the first time our research group had come across the MPTP, and so we …

 [1]: #ref-12
 [2]: #F1
Ciclesonide and tiotropium synergistically inhibit airway eosinophilia in a guinea pig model of chronic asthma
Authors: Sophie Bos, Herman Meurs, Harm Maarsingh, Marieke Smit, Annet Zuidhof, Reinoud Gosens
Journal: European Respiratory Journal (2013)

Rationale:  Using tiotropium, we previously established that acetylcholine regulates allergen-induced airway inflammation and remodelling in guinea pigs. The effect of the combination of a glucocorticosteroid with tiotropium on these processes is currently unknown.  Methods:  We investigated the effects of tiotropium, alone and in combination with ciclesonide on airway inflammation and remodelling in guinea pigs. Animals were sensitized to ovalbumin and challenged with ovalbumin once (acute model) or once per week for twelve weeks (chronic model).  Results:  Ovalbumin challenge induced eosinophilia in the acute model. Surprisingly, tiotropium (0.01 – 0.3 mM; nebulizer concentrations) had no effect on airway inflammation in the acute model, whereas ciclesonide (instilled dose range 0.001-1 mg/kg) only had a small anti-inflammatory effect. The combination of tiotropium with ciclesonide showed no anti-inflammatory activity. In striking contrast, both tiotropium and ciclesonide had profound dose-dependent anti-inflammatory effects in the chronic model. Further, both tiotropium and ciclesonide dose-dependently inhibited airway smooth muscle thickening in the chronic model. Importantly, whereas a low dose of tiotropium (0.01 mM) and a low dose of ciclesonide (0.01 mg/kg) each had minimal effects on airway inflammation, they had highly synergistic effects on airway eosinophilia when administered in combination.  Conclusion:  Tiotropium and ciclesonide inhibit chronic, but not acute, allergen-induced inflammation and airway remodelling. The combination of these drugs produces synergistic anti-inflammatory effects in the chronic model.
Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group Study.
Authors: G A Omura, B N Bundy, J S Berek, S Curry, G Delgado, R Mortel
Journal: Journal of Clinical Oncology (1989)

A randomized clinical trial was conducted in women with stage III ovarian carcinoma (less than or equal to 1 cm residual lesions), using cyclophosphamide plus cisplatin (CP) with or without doxorubicin. There were 349 evaluable patients, of whom 176 received CP while 173 patients received CP plus doxorubicin (CAP). Hematologic toxicity was almost identical. There was no significant difference in progression-free interval (PFI) (median, 22.7 months and 24.6 months), frequency of negative second-look laparotomy (30.2% and 32.8%), or survival (median, 31.2 months and 38.9 months) between CP and CAP, respectively. Thus, doxorubicin in the dose schedule employed does not improve combination chemotherapy of optimal stage III ovarian carcinoma. Several other findings, independent of treatment arm, were of interest. There was a significant difference in PFI and survival by residual disease category (yes v no) and by grade of differentiation (1 v 2 + 3). In multivariate analysis, age, residual disease at entry, cell type (clear cell carcinoma), and time from surgery to initiation of chemotherapy were significant predictors of survival. There was no difference in outcome comparing those who refused second-look with those who had a second-look.
Endothelin-1 (ET-1) is a useful biomarker for early detection of ventilator-assotiated pneumonia (VAP) in mehanical ventilation children
Authors: Dmytro Dmytriiev, Kateryna Dmytriieva, Oleksander Katilov, Oleksander Nazarchuk, Anatoliy Staradub, Oleksander Mazulov, Konstantin Dmytriiev
Journal: European Respiratory Journal (2011)

Objectives:  VAP is a severe complication limiting survival children. ET-1 is a peptide produced by pulmonary vascular endothelial cells that play a role in the pathophysiology of lung dysfunction. Whether ET-1 could predict VAP development is unknown.   Methods:  Transbronchial biopsy specimens and serum and bronchoalveolar lavage were obtained from 23 children with VAP and 24 without VAP. The serum and bronchoalveolar lavage ET-1 concentrations were measured by enzyme-linked immunosorbent assay, and the ET-1 mRNA expression in the transbronchial biopsy specimens was examined using real-time polymerase chain reaction.   Results:  ET-1 serum concentrations were greater in the patients with VAP (P=0.02); and ET-1 mRNA was significantly in the lung of those with versus those without VAP at 3 and 12 day after start mehanical ventilation (P=0.01). At 3 and 12 days after start mehanical ventilation, the ET-1 concentrations were significantly elevated in the serum (P    Conclusions:  Elevated serum ET-1 concentrations were predictive of VAP, and the assessment of circulating ET-1 might be beneficial in diagnosing and monitoring VAP.
Exploitation, Violence, and Suicide Risk Among Child and Adolescent Survivors of Human Trafficking in the Greater Mekong Subregion
Authors: Ligia Kiss, Katherine Yun, Nicola Pocock, Cathy Zimmerman
Journal: JAMA Pediatrics (2015)

IMPORTANCE Human trafficking and exploitation of children have profound health consequences.To our knowledge, this study represents the largest survey on the health of child and adolescent survivors of human trafficking.OBJECTIVE To describe experiences of abuse and exploitation, mental health outcomes, and suicidal behavior among children and adolescents in posttrafficking services.We also examine how exposures to violence, exploitation, and abuse affect the mental health and suicidal behavior of trafficked children. DESIGN, SETTING, AND PARTICIPANTSA survey was conducted with 387 children and adolescents aged 10 to 17 years in posttrafficking services in Cambodia, Thailand, or Vietnam, which along with Laos, Myanmar, and Yunnan Province, China, compose the Greater Melong Subregion.Participants were interviewed within 2 weeks of entering services from October 2011 through May 2013.MAIN OUTCOMES AND MEASURES Depression, posttraumatic stress disorder, anxiety, suicidal ideation, self-injury, and suicide attempts.RESULTS Among the 387 children and adolescent study participants, most (82%) were female.Twelve percent had tried to harm or kill themselves in the month before the interview.Fifty-six percent screened positive for depression, 33% for an anxiety disorder, and 26% for posttraumatic stress disorder.Abuse at home was reported by 20%.Physical violence while trafficked was reported by 41% of boys and 19% of girls.Twenty-three percent of girls and 1 boy reported sexual violence.Mental health symptoms were strongly associated with recent self-harm and suicide attempts.Severe physical violence was associated with depression (adjusted odds ratio [AOR], 3.55; 95% CI, 1.64-7.71),anxiety (AOR, 2.13; 95% CI, 1.12-4.05),and suicidal ideation (AOR, 3.68; 95% CI, 1.77-7.67).Sexual violence while trafficked was associated with depression (AOR, 2.27; 95% CI, 1.22-4.23)and suicidal ideation (AOR, 3.43; 95% CI, 1.80-6.54). CONCLUSIONS AND RELEVANCEChildren and adolescents in posttrafficking care showed high symptom levels of depression, anxiety, and posttraumatic stress disorder, which are strongly associated with self-harm or suicidal behaviors.Mental health screening and reintegration risk assessments are critical components of posttrafficking services, especially in planning for family reunification and other social integration options.
Irradiation in the setting of collagen vascular disease: acute and late complications.
Authors: M M Morris, S N Powell
Journal: Journal of Clinical Oncology (1997)

PURPOSE Based on reports of greater toxicity from radiation therapy, collagen vascular diseases (CVDs) have been considered a contraindication to irradiation. We assessed the complications of radiation therapy in patients with CVD. PATIENTS AND METHODS A total of 209 patients with documented CVD were irradiated between 1960 and 1995. One hundred thirty-one had rheumatoid arthritis (RA), 25 had systemic lupus erythematosus (SLE); 17 had polymyositis or dermatomyositis; 16 had scleroderma; eight had ankylosing spondylitis; five had juvenile RA; three had discoid lupus erythematosus; and four had 4 mixed connective tissue disorders (MCTD). The mean follow-up duration of curative cases was more than 6 years. Doses ranged from 10 to 87.6 Gy, with a median of 45 Gy. RESULTS Overall, 263 sites were assessable in 209 patients. Significant (&gt; or = grade 3) acute toxicity was seen in 10% of irradiated sites. Severe late effects were associated with significant acute reactions and with non-RA CVDs (6% v 21% at 5 years). No difference was seen in late effects according to timing of CVD onset, presence of concurrent vascular insults, radiation dose, or other technical factors, or by measures of disease activity. CONCLUSION RA does not appear to have an elevated rate of late toxicity. While non-RA CVD is significantly associated with increased radiation late effects at standard doses, radiation-related mortality remains exceedingly rare. The choice of therapeutic modality in this radiosensitive group of patients should be made on a case-by-case basis.