tbuckley/cabot-search huggingface dataset:
Research based recommendations on management of sport related concussion: summary of the National Athletic Trainers’ Association position statement
Authors: K M Guskiewicz, S L Bruce, R C Cantu, M S Ferrara, J P Kelly, M McCrea, M Putukian, T C Valovich McLeod
Journal: British Journal of Sports Medicine (2005)

Sport related concussion should always be treated seriously and systematically

Sport related concussion has received considerable attention in both the lay media and medical literature in recent years. As a result, clinicians, coaches, parents, and athletes at all levels of competition are becoming educated about the necessity to treat concussions seriously. In time, this will help to create a safer playing environment for athletes at all levels of competition. Despite an array of complexities associated with studying sport related concussion, new scientific research and clinically based literature have provided sports medicine professions with a wealth of updated information on the treatment of sport related concussion.

For example, there is now sufficient literature supporting the notion that once you experience a concussion, you are more likely to sustain future concussions1,2; and a strong likelihood exists that the symptoms following these repeat concussions may be more serious and resolve at a slower rate.1,3 Several recent research papers and consensus statements indicate the necessity to use a systematic approach to evaluating the severity and duration of all possible signs and symptoms after a concussion, and to be cautious of not returning players to competition too quickly.4,5,6,7,8,9,10,11,12,13,14,15,16 Loss of consciousness and amnesia are two important parameters associated with cerebral concussion, but headaches, dizziness/balance deficits, concentration deficits, and feeling “slowed down” are more common.1,2,6,9,14,17–20 Extensive research has also been conducted on neuropsychological testing17,19–34 and postural stability testing,20,35–37 both of which are considered to be key markers for tracking recovery after cerebral concussion. Recent concussion publications on topics such as physician referral and home care,13,38 youth athletes,39,40 and protective equipment41 …
Effects of Carbohydrate Counting on Glucose Control and Quality of Life Over 24 Weeks in Adult Patients With Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion
Authors: Andrea Laurenzi, Andrea M. Bolla, Gabriella Panigoni, Valentina Doria, AnnaChiara Uccellatore, Elena Peretti, Alessandro Saibene, Gabriella Galimberti, Emanuele Bosi, Marina Scavini
Journal: Diabetes Care (2011)

OBJECTIVE Few studies have assessed the efficacy of carbohydrate counting in type 1 diabetes, and none have validated its efficacy in patients who are treated with continuous subcutaneous insulin infusion (CSII). The aim of our study was to test the effect of carbohydrate counting on glycemic control and quality of life in adult patients with type 1 diabetes who are receiving CSII. RESEARCH DESIGN AND METHODS Sixty-one adult patients with type 1 diabetes treated with CSII were randomly assigned to either learning carbohydrate counting (intervention) or estimating pre-meal insulin dose in the usual empirical way (control). At baseline and 12 and 24 weeks, we measured HbA1c, fasting plasma glucose, BMI, waist circumference, recorded daily insulin dose, and capillary glucose data, and administered the Diabetes-Specific Quality-of-Life Scale (DSQOLS) questionnaire. RESULTS Intention-to-treat analysis showed improvement of the DSQOLS score related to diet restrictions (week 24 – baseline difference, P = 0.008) and reduction of BMI (P = 0.003) and waist circumference (P = 0.002) in the intervention group compared with control subjects. No changes in HbA1c, fasting plasma glucose, daily insulin dose, and hypoglycemic episodes (&amp;lt;2.8 mmol/L) were observed. Per-protocol analysis, including only patients who continuously used carbohydrate counting and CSII during the study, confirmed improvement of the DSQOLS score and reduction of BMI and waist circumference, and showed a significant reduction of HbA1c (−0.35% vs. control subjects, P = 0.05). CONCLUSIONS Among adult patients with type 1 diabetes treated with CSII, carbohydrate counting is safe and improves quality of life, reduces BMI and waist circumference, and, in per-protocol analysis, reduces HbA1c.
Periarticular fibrous nodules in Lyme borreliosis
Authors: A. ESPANA, A. TORRELO, A. GUERRERO, J. SUAREZ, A. ROCAMORA, A. LEDO
Journal: British Journal of Dermatology (1991)

Periarticular fibrous nodules have been described in patients with late‐phase acrodermatitis chronica atrophicans (ACA) in the setting of Lyme borreliosis. We report the clinical and histopathological study of two patients with periarticuiar fibrous nodules and with Lyme borreliosis and discuss the relationship between these nodules and ACA.
Incidence of recombinant erythropoietin (EPO) hyporesponse, EPO-associated antibodies, and pure red cell aplasia in dialysis patients
Authors: Aantje V Kharagjitsingh, Joke C Korevaar, Jan P Vandenbroucke, Elisabeth W Boeschoten, Raymond T Krediet, Mohammed R Daha, Friedo W Dekker
Journal: Kidney International (2005)
Tissue Biomarkers for Prognosis in Cutaneous Melanoma: A Systematic Review and Meta-analysis
Authors: Bonnie E. Gould Rothberg, Michael B. Bracken, David L. Rimm
Journal: JNCI Journal of the National Cancer Institute (2009)

In the clinical management of early-stage cutaneous melanoma, it is critical to determine which patients are cured by surgery alone and which should be treated with adjuvant therapy. To assist in this decision, many groups have made an effort to use molecular information. However, although there are hundreds of studies that have sought to assess the potential prognostic value of molecular markers in predicting the course of cutaneous melanoma, at this time, no molecular method to improve risk stratification is part of recommended clinical practice. To help understand this disconnect, we conducted a systematic review and meta-analysis of the published literature that reported immunohistochemistry-based protein biomarkers of melanoma outcome. Three parallel search strategies were applied to the PubMed database through January 15, 2008, to identify cohort studies that reported associations between immunohistochemical expression and survival outcomes in melanoma that conformed to the REMARK criteria. Of the 102 cohort studies, we identified only 37 manuscripts, collectively describing 87 assays on 62 distinct proteins, which met all inclusion criteria. Promising markers that emerged included melanoma cell adhesion molecule (MCAM)/MUC18 (all-cause mortality [ACM] hazard ratio [HR] = 16.34; 95% confidence interval [CI] = 3.80 to 70.28), matrix metalloproteinase-2 (melanoma-specific mortality [MSM] HR = 2.6; 95% CI = 1.32 to 5.07), Ki-67 (combined ACM HR = 2.66; 95% CI = 1.41 to 5.01), proliferating cell nuclear antigen (ACM HR = 2.27; 95% CI = 1.56 to 3.31), and p16/INK4A (ACM HR = 0.29; 95% CI = 0.10 to 0.83, MSM HR = 0.4; 95% CI = 0.24 to 0.67). We further noted incomplete adherence to the REMARK guidelines: 14 of 27 cohort studies that failed to adequately report their methods and nine studies that failed to either perform multivariable analyses or report their risk estimates were published since 2005.
Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation
Authors: Payal Kapur, Samuel Peña-Llopis, Alana Christie, Leah Zhrebker, Andrea Pavía-Jiménez, W Kimryn Rathmell, Xian-Jin Xie, James Brugarolas
Journal: The Lancet Oncology (2013)
Patient and Hospital Differences Underlying Racial Variation in Outcomes After Coronary Artery Bypass Graft Surgery
Authors: Suma H. Konety, Mary S. Vaughan Sarrazin, Gary E. Rosenthal
Journal: Circulation (2005)

Background— Few studies have examined the association of race and outcomes after coronary artery bypass graft (CABG) surgery while controlling for both patient and hospital effects. Methods and Results— We retrospectively analyzed data on a cohort of 566 785 white and 24 354 black Medicare beneficiaries 65 years old and older undergoing CABG in 1091 US hospitals from 1997 to 2000. Mortality and repeat revascularization rates were examined after sequential adjustment for patient and hospital differences by use of generalized estimating equations. Unadjusted mortality was higher ( P &lt;0.001) in black than in white patients at 30 (6.4% versus 5.2%), 90 (8.3% versus 6.6%), and 365 days (13.5% versus 9.8%) after surgery. Black patients were more likely ( P &lt;0.001) to undergo CABG at hospitals with the highest mortality (56% versus 47%) and at hospitals in the lowest volume quintile (24% versus 20%). Adjusted only for patient characteristics, mortality was 8%, 11%, and 25% higher in black patients at 30, 90, and 365 days. After adjustment for hospital effects, 30 and 90 day mortality was similar but 17% higher in black patients at 365 days. Racial differences in mortality were greater in men than in women. On adjustment for patient and hospital effects, repeat revascularization rates were similar in black and white patients. Conclusions— Racial disparities in CABG outcomes are sensitive to the effects of sex and duration of postsurgical follow-up. The increasing disparity in outcomes as follow-up increased is consistent with the hypothesis that black patients have less access to secondary prevention and rehabilitation services after surgery.
Phase I Study of the Antiangiogenic Antibody Bevacizumab and the mTOR/Hypoxia-Inducible Factor Inhibitor Temsirolimus Combined with Liposomal Doxorubicin: Tolerance and Biological Activity
Authors: John Moroney, Siqing Fu, Stacy Moulder, Gerald Falchook, Thorunn Helgason, Charles Levenback, David Hong, Aung Naing, Jennifer Wheler, Razelle Kurzrock
Journal: Clinical Cancer Research (2012)

Preclinical data suggest that combining the mTOR/hypoxia-inducible factor (HIF) inhibitor temsirolimus and the antiangiogenesis antibody bevacizumab may augment antitumor activity as well as resensitize cells to anthracyclines.We initiated a phase I study of bevacizumab and temsirolimus plus liposomal doxorubicin in patients with advanced malignancies. Patients (N = 136) were enrolled according to a modified 3 + 3 design plus dose expansion in responsive tumor types.The most common cancers were breast (n = 29), epithelial ovarian (n = 23), and colorectal cancer (n = 17). The median number of prior chemotherapy regimens was four (range: 0-16). Grade 3 or higher adverse events (> 5%) included pancytopenia, mucositis, hand-foot syndrome, hypertension, and fistula. This regimen led to a 21% (n = 28) stable disease (SD) ≥ 6 months and 21% (n = 29) rate of partial or complete remission [PR/CR; (total SD ≥ 6 months/PR/CR = 42% (n = 57)]. PR/CR was most common in parotid gland adenocarcinoma (4/6, 67%), metaplastic breast cancer (5/12, 42%), endometrial endometrioid carcinoma (6/15, 40%), and in patients with a PIK3CA mutation and/or a PTEN mutation/loss (11/28, 39%). The maximum tolerated dose was liposomal doxorubicin 30 mg/m(2) and bevacizumab 15 mg/kg every three weeks with temsirolimus 25 mg weekly.Patients tolerated bevacizumab and temsirolimus together with liposomal doxorubicin. Further evaluation, especially in patients with parotid, metaplastic breast, and endometrial endometrioid cancer, and in patients with PIK3CA and/or PTEN aberrations is warranted.
A second rabbit kappa isotype.
Authors: A Benammar, P A Cazenave
Journal: The Journal of Experimental Medicine (1982)

Immunoglobulin G (IgG) from the rabbit strain Basilea was previously shown to contain two distinct populations of molecules one with light chain belonging to the known lambda isotype and the others to a new kappa-like L chain type. Alloantisera prepared against the Basilea IgG are directed against the kappa-like light chain (anti-bas antisera). All Basilea rabbits express kappa-like chains recognized by anti-bas sera, but IgG from other domestic rabbits did not react with these antisera. Genetic studies of wild rabbits belonging to different populations show that the bas+ phenotype could be found in heterozygous rabbits as well as those homozygous at the b locus. The gene encoding the bas+ light chain is closely linked to the b locus. Moreover, antigenic determinants recognized by anti-bas antibodies and antigenic determinants recognized by antibodies directed against allotypic determinants of the b series are located on distinct IgG molecules. These results show that there are two rabbit kappa isotypes: the kappa 1 isotype, bearing allotypic determinants of the b series, and the kappa 2 isotype, for which bas+ chain is one of the allotypic forms. The kappa 1 and kappa 2 isotypes are controlled by closely linked genes.
Lats2 Is a Negative Regulator of Myocyte Size in the Heart
Authors: Yutaka Matsui, Noritsugu Nakano, Dan Shao, Shumin Gao, Wenting Luo, Chull Hong, Peiyong Zhai, Eric Holle, Xianzhong Yu, Norikazu Yabuta, Wufan Tao, Thomas Wagner, Hiroshi Nojima, Junichi Sadoshima
Journal: Circulation Research (2008)

Mammalian sterile 20–like kinase (Mst)1 plays an important role in mediating apoptosis and inhibiting hypertrophy in the heart. Because Hippo, a Drosophila homolog of Mst1, forms a signaling complex with Warts, a serine/threonine kinase, which in turn stimulates cell death and inhibits cell proliferation, mammalian homologs of Warts, termed Lats1 and Lats2, may mediate the function of Mst1. We here show that Lats2, but not Lats1, dose-dependently increased apoptosis in cultured cardiac myocytes. Lats2 also dose-dependently reduced [ 3 H]phenylalanine incorporation and cardiac myocyte size, whereas dominant negative Lats2 (DN-Lats2) increased them, suggesting that endogenous Lats2 negatively regulates myocyte growth. DN-Lats2 significantly attenuated induction of apoptosis and inhibition of hypertrophy by Mst1, indicating that Lats2 mediates the function of Mst1 in cardiac myocytes. Cardiac specific overexpression of Lats2 in transgenic mice significantly reduced the size of left and right ventricles, whereas that of DN-Lats2 caused hypertrophy in both ventricles. Overexpression of Lats2 reduced left ventricular systolic and diastolic function without affecting baseline levels of myocardial apoptosis. Expression of endogenous Lats2 was significantly upregulated in response to transverse aortic constriction. Overexpression of DN-Lats2 significantly enhanced cardiac hypertrophy and inhibited cardiac myocyte apoptosis induced by transverse aortic constriction. These results suggest that Lats2 is necessary and sufficient for negatively regulating ventricular mass in the heart. Although Lats2 is required for cardiac myocyte apoptosis in response to pressure overload, it was not sufficient to induce apoptosis at baseline. In conclusion, Lats2 affects both growth and death of cardiac myocytes, but it primarily regulates the size of the heart and acts as an endogenous negative regulator of cardiac hypertrophy.
Magnetic Resonance Neuroimaging Study of Brain Structural Differences in Diabetic Peripheral Neuropathy
Authors: Dinesh Selvarajah, Iain D. Wilkinson, Michael Maxwell, Jennifer Davies, Adhithya Sankar, Elaine Boland, Rajiv Gandhi, Irene Tracey, Solomon Tesfaye
Journal: Diabetes Care (2014)

OBJECTIVE Diabetic peripheral neuropathy (DPN) has hitherto been considered a disease of the peripheral nervous system only, with central nervous system (CNS) involvement largely overlooked. The aim of this study was to investigate any differences in brain structure in subjects with DPN. RESEARCH DESIGN AND METHODS Thirty-six subjects with type 1 diabetes (No DPN [n = 18], Painful DPN [n = 9], Painless DPN [n = 9]) underwent neurophysiological assessment to quantify the severity of DPN. All subjects, including 18 healthy volunteers (HVs), underwent volumetric brain magnetic resonance imaging at 3 Tesla. RESULTS Adjusted peripheral gray matter volume was statistically significantly lower in subjects with painless and painful DPN (mean 599.6 mL [SEM 9.8 mL] and 585.4 mL [10.0 mL], respectively) compared with those with No DPN (626.5 mL [5.7 mL]) and HVs (639.9 mL [7.2 mL]; ANCOVA, P = 0.001). The difference in adjusted peripheral gray matter volume between subjects with No DPN and HVs and those with Painful DPN and Painless DPN was not statistically significant (P = 0.16 and 0.30, respectively). Voxel-based morphometry analyses revealed greater localized volume loss in the primary somatosensory cortex, supramarginal gyrus, and cingulate cortex (corrected P &amp;lt; 0.05) in DPN subjects. CONCLUSIONS This is the first study to focus on structural changes in the brain associated with DPN. Our findings suggest increased peripheral gray matter volume loss, localized to regions involved with somatosensory perception in subjects with DPN. This may have important implications for the long-term prognosis of DPN.
Scleraxis Is Required for Cell Lineage Differentiation and Extracellular Matrix Remodeling During Murine Heart Valve Formation In Vivo
Authors: Agata K. Levay, Jacqueline D. Peacock, Yinhui Lu, Manuel Koch, Robert B. Hinton, Karl E. Kadler, Joy Lincoln
Journal: Circulation Research (2008)

Heart valve structures, derived from mesenchyme precursor cells, are composed of differentiated cell types and extracellular matrix arranged to facilitate valve function. Scleraxis (scx) is a transcription factor required for tendon cell differentiation and matrix organization. This study identified high levels of scx expression in remodeling heart valve structures at embryonic day 15.5 through postnatal stages using scx-GFP reporter mice and determined the in vivo function using mice null for scx. Scx(-/-) mice display significantly thickened heart valve structures from embryonic day 17.5, and valves from mutant mice show alterations in valve precursor cell differentiation and matrix organization. This is indicated by decreased expression of the tendon-related collagen type XIV, increased expression of cartilage-associated genes including sox9, as well as persistent expression of mesenchyme cell markers including msx1 and snai1. In addition, ultrastructure analysis reveals disarray of extracellular matrix and collagen fiber organization within the valve leaflet. Thickened valve structures and increased expression of matrix remodeling genes characteristic of human heart valve disease are observed in juvenile scx(-/-) mice. In addition, excessive collagen deposition in annular structures within the atrioventricular junction is observed. Collectively, our studies have identified an in vivo requirement for scx during valvulogenesis and demonstrate its role in cell lineage differentiation and matrix distribution in remodeling valve structures.
Gut-adipose tissue axis in hepatic fat accumulation in humans
Authors: Eveliina Munukka, Satu Pekkala, Petri Wiklund, Omid Rasool, Ronald Borra, Lingjia Kong, Xiaowei Ojanen, Shu Mei Cheng, Christophe Roos, Soile Tuomela, Markku Alen, Riitta Lahesmaa, Sulin Cheng
Journal: Journal of Hepatology (2014)
Altered composition of urinary heparan sulfate in patients with COPD.
Authors: C H van de Lest, E M Versteeg, J H Veerkamp, J H Berden, J van den Born, L Heunks, J W Lammers, C L van Herwaarden, P N Dekhuijzen, T H van Kuppevelt
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

In patients with emphysema the integrity of the extracellular matrix (connective tissue skeleton) is compromised. In this study we analyzed glycosaminoglycans, which are main constituents of this matrix, in urines from patients with chronic obstructive pulmonary disease (COPD)/emphysema. Glycosaminoglycans (GAGs) were purified by anion exchange chromatography and quantified using the 1,9-dimethylmethylene blue assay. Heparan sulfate (HS) was assayed using three different chemical methods: digestion with heparitinase or with nitrous acid and by use of an adapted 1,9-dimethylmethylene blue assay. A specific epitope on the HS molecule, defined by the monoclonal antibody JM403, was determined using an inhibition enzyme immunoassay. In patients with COPD total urinary glycosaminoglycan and HS content were not altered. The JM403 epitope of HS, however, was greatly decreased in patients (0.6 versus 4.1 units/mg creatinine for control subjects, p < 0.0001). A similar pattern was observed when patients with bronchial carcinoma with and without emphysema were compared (0.4 versus 2.4 units/mg creatinine respectively, p < 0.0005). Patients with sarcoidosis did not show a decreased epitope content. These results indicate a structural change or an altered processing of the HS molecule in patients with emphysema. Taking into consideration the importance of HS for the stability of the alveolar extracellular matrix, this change may be associated with the pathogenesis of emphysema.
Inhibitors of apoptosis proteins in asthmatic airway inflammation
Authors: James Reihill, Catriona Kelly, Wang Sm, Michael Shields, Bettina Schock
Journal: European Respiratory Journal (2013)

Background: In atopic asthma aero-allergens and infections cause chronic airway inflammation, even when ‘well’. Transcription factor NF-kB is central in the response, but its regulation is compromised in asthma leading to constitutive activation. Inhibitors of Apoptosis (IAPs) may regulate NF-kB inflammation via TRAF6 activation. Endogenous IAP antagonist (Smac) regulates IAPs and pharmacological depletion by Smac-mimetics inhibits NF-kB and inflammation. IAPs may significantly contribute to the innate immune response in asthma.

Methods: Adult Primary Nasal Epithelial cells (PNECs, atopic asthma, non-asthmatic controls, n=3) were stimulated with LPS (P.aeruginosa, 100ng/ml) or PolyI:C (50μg/ml). Protein and mRNA expression of IAPs/Smac and NF-kB p65 mRNA were determined. Cells were pre-incubated with smac-mimetic SM164 and IL-8 analysed.

Results: Basal IAP1/2 and p65 mRNA are increased in atopic-asthmatics (all p<0.05), Smac is significantly lower. LPS had little effect on IAPs/Smac, but PolyI:C caused a time-dependent increase in cIAP2 mRNA (p<0.01), which was higher in controls (p<0.001). p65 mRNA was significantly higher in atopic-asthmatics. IAP proteins were only detectable after immunoprecipitation: PolyI:C induced cIAP2 in controls and significantly less in atopic-asthmatics. IL-8 release after PolyI:C was higher in controls and was significantly reduced by SM164.

Conclusion: Although atopic asthmatics have increased basal levels of IAPs, they show a blunted cIAP2 response to PolyI:C. Degradation of IAP1/2 only reduces the inflammatory response in controls, suggest a beneficial role for increased cIAP2 in airway epithelium. The role of the natural inhibitor Smac in atopic asthma needs further investigation.
Progressive Multifocal Leukoencephalopathy: Why Gray and White Matter
Authors: Sarah Gheuens, Christian Wüthrich, Igor J. Koralnik
Journal: Annual Review of Pathology Mechanisms of Disease (2012)

Since it was first described in 1958, progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the brain caused by the polyomavirus JC (JCV), has evolved tremendously. It was once considered a noninflammatory disease that affected exclusively oligodendrocytes and astrocytes in the white matter of immunosuppressed individuals and was almost always fatal. Today, we understand that PML can present during the course of an immune reconstitution inflammatory syndrome and that it affects a broader range of individuals, including patients with minimal immunosuppression and those who are treated with novel immunomodulatory medications. Furthermore, JCV-infected glial cells are frequently located at the gray matter-white matter junction or within the gray matter, causing demyelinating lesions within cortical areas. Finally, JCV variants can also infect neurons, leading to the recognition of two distinct clinical entities: JCV granule cell neuronopathy and JCV encephalopathy.