tbuckley/cabot-search huggingface dataset:
Acute hepatitis A, B and C but not D is still prevalent in Mongolia: a time trend analysis
Authors: Oidov Baatarkhuu, Hye Won Lee, Jacob George, Dashchirev Munkh-Orshikh, Baasankhuu Enkhtuvshin, Sosorbaram Ariunaa, Mohammed Eslam, Sang Hoon Ahn, Kwang-Hyub Han, Do Young Kim
Journal: Clinical and Molecular Hepatology (2017)

Mongolia has one of the highest hepatitis A, C, B and D infection incidences worldwide. We sought to investigate changes in the proportion of acute viral hepatitis types in Mongolia over the last decade.The cohort comprised 546 consecutive patients clinically diagnosed with acute viral hepatitis from January 2012 to December 2014 in Ulaanbaatar Hospital, Mongolia. A time trend analysis investigating the change in proportion of acute hepatitis A virus, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis delta virus (HDV) infection among the cohort with respect to a previous published study was undertaken.Acute hepatitis A, B and C was diagnosed in 50.9%, 26.2% and 6.0% of the cohort. Notably, 16.8% of the cohort had a dual infection. The etiologies of acute viral hepatitis were varied by age groups. The most common cause of acute viral hepatitis among 2-19 year olds was hepatitis A, HBV and superinfection with HDV among 20-40 year olds, and HCV among 40-49 year olds. Patients with more than one hepatitis virus infection were significantly older, more likely to be male and had a higher prevalence of all risk factors for disease acquisition. These patients also had more severe liver disease at presentation compared to those with mono-infection.Acute viral hepatitis is still prevalent in Mongolia. Thus, the need for proper infection control is increasing in this country.
FOXP1 suppresses chemokine genes critical for TIL migration and function in breast tumors
Authors: P. De Silva, S. Garaud, C. Solinas, A. Boisson, A. De Wind, G. Van den Eyden, C. Naveaux, D. Hugues, M. Piccart-Gebhart, K. Willard-Gallo
Journal: Annals of Oncology (2017)
Potentially modifiable factors contributing to sepsis-associated encephalopathy
Authors: Romain Sonneville, Etienne de Montmollin, Julien Poujade, Maïté Garrouste-Orgeas, Bertrand Souweine, Michael Darmon, Eric Mariotte, Laurent Argaud, François Barbier, Dany Goldgran-Toledano, Guillaume Marcotte, Anne-Sylvie Dumenil, Samir Jamali, Guillaume Lacave, Stéphane Ruckly, Bruno Mourvillier, Jean-François Timsit
Journal: Intensive Care Medicine (2017)
Dioxins and related environmental contaminants increase TDP-43 levels
Authors: Peter E. A. Ash, Elizabeth A. Stanford, Ali Al Abdulatif, Alejandra Ramirez-Cardenas, Heather I. Ballance, Samantha Boudeau, Amanda Jeh, James M. Murithi, Yorghos Tripodis, George J. Murphy, David H. Sherr, Benjamin Wolozin
Journal: Molecular Neurodegeneration (2017)

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative condition that is characterized by progressive loss of motor neurons and the accumulation of aggregated TAR DNA Binding Protein-43 (TDP-43, gene: TARDBP). Increasing evidence indicates that environmental factors contribute to the risk of ALS. Dioxins, related planar polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that activate the aryl hydrocarbon receptor (AHR), a ligand-activated, PAS family transcription factor. Recently, exposure to these toxicants was identified as a risk factor for ALS.We examined levels of TDP-43 reporter activity, transcript and protein. Quantification was done using cell lines, induced pluripotent stem cells (iPSCs) and mouse brain. The target samples were treated with AHR agonists, including 6-Formylindolo[3,2-b]carbazole (FICZ, a potential endogenous ligand, 2,3,7,8-tetrachlorodibenzo(p)dioxin, and benzo(a)pyrene, an abundant carcinogen in cigarette smoke). The action of the agonists was inhibited by concomitant addition of AHR antagonists or by AHR-specific shRNA.We now report that AHR agonists induce up to a 3-fold increase in TDP-43 protein in human neuronal cell lines (BE-M17 cells), motor neuron differentiated iPSCs, and in murine brain. Chronic treatment with AHR agonists elicits over 2-fold accumulation of soluble and insoluble TDP-43, primarily because of reduced TDP-43 catabolism. AHR antagonists or AHR knockdown inhibits agonist-induced increases in TDP-43 protein and TARDBP transcription demonstrating that the ligands act through the AHR.These results provide the first evidence that environmental AHR ligands increase TDP-43, which is the principle pathological protein associated with ALS. These results suggest novel molecular mechanisms through which a variety of prevalent environmental factors might directly contribute to ALS. The widespread distribution of dioxins, PCBs and PAHs is considered to be a risk factor for cancer and autoimmune diseases, but could also be a significant public health concern for ALS.
Ubiquitination of STING at lysine 224 controls IRF3 activation
Authors: Guoxin Ni, Hiroyasu Konno, Glen N. Barber
Journal: Science Immunology (2017)

Cytosolic DNA species derived from invading microbes or leaked from the nuclear or mitochondrial compartments of the cell can trigger the induction of host defense genes by activating the endoplasmic reticulum-associated protein STING (stimulator of interferon genes). Using a mass spectrometry-based approach, we show that after association with cyclic dinucleotides, delivery of Tank-binding kinase 1 to interferon regulatory factors (IRFs), such as IRF3, relies on K63-linked ubiquitination of K224 on STING. Blocking K224 ubiquitination specifically prevented IRF3 but not nuclear factor κB activation, additionally indicating that STING trafficking is not required to stimulate the latter signaling pathway. By carrying out a limited small interfering RNA screen, we have identified MUL1 (mitochondrial E3 ubiquitin protein ligase 1) as an E3 ligase that catalyzes the ubiquitination of STING on K224. These data demonstrate the critical role of K224 ubiquitination in STING function and provide molecular insight into the mechanisms governing host defense responses.
Relation of Mitral Valve Surgery Volume to Repair Rate, Durability, and Survival
Authors: Joanna Chikwe, Nana Toyoda, Anelechi C. Anyanwu, Shinobu Itagaki, Natalia N. Egorova, Percy Boateng, Ahmed El-Eshmawi, David H. Adams
Journal: Journal of the American College of Cardiology (2017)

Degenerative mitral valve repair rates remain highly variable, despite established benefits of repair over replacement. The contribution of surgeon-specific factors is poorly defined. This study evaluated the influence of surgeon case volume on degenerative mitral valve repair rates and outcomes. A mandatory New York State database was queried and 5,475 patients were identified with degenerative mitral disease who underwent mitral valve operations between 2002 and 2013. Mitral repair rates, mitral reoperations within 12 months of repair, and survival were analyzed using multivariable Cox modeling and restricted cubic spline function. Median annual surgeon volume of any mitral operations was 10 (range 1 to 230), with a mean repair rate of 55% (n = 20,797 of 38,128). In the subgroup of patients with degenerative disease, the mean repair rate was 67% (n = 3,660 of 5,475), with a range of 0% to 100%. Mean repair rates ranged from 48% (n = 179 of 370) for surgeons with total annual volumes of ≤10 mitral operations to 77% (n = 1,710 of 2,216) for surgeons with total annual volumes of >50 mitral operations (p < 0.001). Higher total annual surgeon volume was associated with increased repair rates of degenerative mitral valve disease (adjusted odds ratio [OR]: 1.13 for every additional 10 mitral operations; 95% confidence interval [CI]: 1.10 to 1.17; p < 0.001); a steady decrease in reoperation risk until 25 total mitral operations annually; and improved 1-year survival (adjusted hazard ratio: 0.95 for every additional 10 operations; 95% CI: 0.92 to 0.98; p = 0.001). For surgeons with a total annual volume of ≤25 mitral operations, repair rates were higher (63.8%; n = 180 of 282) if they operated in the same institution as a surgeon with total annual mitral volumes of >50 and degenerative mitral valve repair rates of >70%, compared with surgeons operating in the other institutions (51.3%; n = 580 of 1,130) (adjusted OR: 1.79; 95% CI: 1.24 to 2.60; p < 0.001). This study suggests that individual surgeon volume is a determinant of not only mitral repair rates, but also freedom from reoperation, and survival. The data from this study support the guideline's concept of reference referral to experienced mitral surgeons to improve outcomes in patients with degenerative mitral valve disease.
Predictors of deep vein thrombosis (DVT) in newly diagnosed multiple myeloma (MM) patients with and without prophylactic recombinant erythropoietin (EPO) therapy
Authors: E. A. Coleman, E. J. Anaissie, R. L. Kennedy, K. D. Lockhart, C. B. Stewart, C. Bailey
Journal: Journal of Clinical Oncology (2009)

9554 Background: DVT, a complication among newly diagnosed MM patients, is most common during the first 3–4 months of therapy. EPO, given to treat anemia in patients receiving chemotherapy, has been associated with increased DVT risk and the mechanism, thought to be related to rise in hemoglobin, remains unknown. Methods: All 604 patients with newly diagnosed MM who completed the induction phase (∼ 3–4 months) of treatment were included. Induction consisted of multiagent chemotherapy with upfront randomization to thalidomide (THAL) or no THAL. 122 patients were also enrolled in an exercise study that included prophylactic EPO. Venous thromboembolism, defined as Doppler confirmed DVT and/or pulmonary embolus during induction, was the primary endpoint. Univariate analyses provided group comparisons. Logistic regression analysis determined predictors of DVT. Results: EPO and No EPO groups were similar for THAL use, age, race, gender, BMI, DVT history, and key baseline laboratory values except for lower cytogenetics risk score (p = 0.010) and higher albumin (p = 0.005), hemoglobin (p = 0.025) and fibrinogen (p = 0.0005) in the EPO group. EPO patients had a higher incidence of DVT 25 (20.5%) vs. 47 (9.8%) (p = 0.001). Risk factors for DVT by univariate analysis were THAL (p =0.001) and baseline platelets &gt; 350,000/μL (p = 0.018) but not hemoglobin (at baseline or throughout study). There were no significant differences in MM response or survival between the groups with and without DVT. Compared to the No EPO group, EPO-treated patients had a better MM response (p = 0.023) and a higher survival (p = 0.0005). The main predictors of DVT by logistic regression were THAL and prophylactic EPO. Conclusions: THAL and prophylactic EPO predict for higher risk of DVT among newly diagnosed MM patients. Hemoglobin levels were not related to higher risk of DVT. DVT and EPO did not decrease treatment response or survival. No significant financial relationships to disclose.
Formula one: best is no formula
Authors: Andrew Bush, Adnan Custovic
Journal: European Respiratory Journal (2017)

“Begin at the beginning,” the King said, very gravely, “and go on till you come to the end: then stop” (Lewis Carroll, Alice in Wonderland). Sometimes, however, ignoring this excellent advice may be beneficial to the editorialist. So, starting at the end, how do patients reach a point of premature airflow obstruction (or chronic obstructive pulmonary disease (COPD) to those who think that an arbitrary physiological ratio in spirometric measures of lung function is a disease, even though it may be within the normal range for age)? For a long time, the prevailing view was that most individuals achieve normal or near-normal maximal lung function in early adult life, following which those who go on to develop COPD suffer a rapid decline as a result of various environmental exposures (predominantly smoking) [1]. However, the crucial importance of the level of lung function attained in early adulthood has been highlighted in a recent study, which demonstrated that the level of lung function in early adult age, at its physiological plateau, is as important in the genesis of COPD as its rapid decline in later years. The manuscript describes two trajectories to a reduced forced expired volume in 1 s/forced vital capacity (FEV1/FVC) ratio [2]. In the first, there was failure to reach the normal plateau of maximally attained spirometric function in early adulthood (at age 20–25 years), with a subsequent normal rate of decline. In the second, the group attained a normal plateau, but declined more rapidly. Individuals who did not reach the expected lung function plateau had a 26% chance of going below the “magic” FEV1/FVC of 70%, while among those in whom a normal plateau was reached, the risk was 8%. Importantly, both trajectories contributed equally to the community burden of COPD. Of note, neither this nor any of four other major studies of decline in lung function with age [3–6] managed to find consistent associates of accelerated lung function decline (including smoking, politically unpalatable though this statement may be). Indeed, data from the CAMP [7] and Tucson cohort (which identified a group of individuals with a persistently low lung function trajectory between ages 11 and 32 years, which comprised nearly 1 in 10 participants) [8] confirmed that abnormal lung growth patterns are established early in life. Clearly, starting at the end turns the spotlight firmly on the beginning: early life, which is where efforts at prevention of COPD must be focused if they are to have any chance of success. Breast is best; formula is worst: in between, there may be a typically British compromise! <http://ow.ly/o1to309Wf6F>
Plasma VEGF-a, angiopoietin-2 (ANG2) and soluble(s)TIE2 in patients (pts) with HER2-negative locally recurrent or metastatic breast cancer (LR/MBC) treated with first-line bevacizumab (A) and paclitaxel (T) without or with capecitabine (X).
Authors: Siu W. Lam, Steffen M. de Groot, Aafke H. Honkoop, Nienke M. Nota, A. Jager, Ankie M.T. van der Velden, Monique M.E.M. Bos, Sabine C. Linn, J. Van Den Bosch, Judith R. Kroep, J. J. Braun, Richard R. de Haas, Carolien H. Smorenburg, Hiltje de Graaf, Johanna Elisabeth A. Portielje, Maartje Los, Domingo de Gooyer, Harm van Tinteren, Epie Boven
Journal: Journal of Clinical Oncology (2013)

1072 Background: In the randomized phase II ATX trial, pts with HER2-negative LR/MBC were treated with first-line AT or ATX. We determined the prognostic value for outcome of VEGF-A, ANG2 and sTIE2 measured at baseline on cycle 1 day 1 (C1D1) and after cycle 1 (C2D1). Methods: 312 pts were randomized in 1:1 ratio to AT (T 90 mg/m 2 on d1, 8, 15 and A 10 mg/kg on d1, 15 q4w x 6 cycles, followed by A 15 mg/kg on d1 q3w for next cycles) or ATX (T 90 mg/m 2 on d1, 8, A 15 mg/kg on d1 and X 825 mg/m 2 bid on d1–14 q3w x 8 cycles, followed by the same dose of A and X q3w for next cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), response duration (RD), overall survival (OS) and safety. Plasma proteins on C1D1 (N = 173) and on C2D1 (N = 142) were measured by ELISA. The association of protein levels (continuous variable) with PFS and OS was evaluated by Cox proportional hazards model and Martingale residual plot. Results: At a median follow-up of 39 months (mo), there were 292 PFS events and 242 deaths. ATX significantly improved PFS as compared to AT (median 11 vs. 8.4 mo, stratified HR = 0.52; 95% CI, 0.41 – 0.67; P &lt; .001). The confirmed ORR in measurable disease (N = 268) was 67% in ATX vs. 50% in AT. Median RD was 6.4 mo (95% CI, 6.1 – 8.3) in ATX v 5.4 mo (95% CI, 5.1 – 6.0) in AT. Median OS was 24.1 mo in ATX vs. 23.1 mo in AT (P= .44). The aselected ‘biomarker’ cohort (N = 173) and overall trial cohort had similar baseline characteristics. ANG2 on C1D1 moderately correlated with sTIE2 on C1D1 (Pearson’s r = .44, P &lt; .001). High ANG2 on C1D1 was significantly associated with poor OS (HR = 1.6; 95% CI, 1.1 – 2.3; P = .01), but not with poor PFS (HR = 1.3; 95% CI, 1.0 – 1.3; P = .07). ANG2 on C2D1 was not significantly associated with OS (HR = 1.55; 95% CI, 0.99 – 2.4; P = .057) or with PFS (P= .6). sTIE2 and VEGF-A were not associated with outcome. All pts had very low levels of free VEGF-A on C2D1 (median 8 pg/ml). Conclusions: In HER2-negative LR/MBC, ATX is more effective (PFS, ORR and RD) than AT. A very high plasma level of ANG2 at baseline indicates a high risk for poor survival. Clinical trial information: NTR1348.
In Virologically Suppressed HIV+ Patients, High CD4/CD8 Ratio and Length of Treatment Independently Correlate to the Intracellular Content of Proviral HIV-DNA in Different Types of CD4+ T Cells
Authors: Andrea Cossarizza, Sara De Biasi, Elena Bianchini, Margherita Digaetano, Simone Pecorini, Marcello Pinti, Lara Gibellini, Vanni Borghi, Cristina Mussini, Milena Nasi
Journal: Blood (2016)
Characterization of antigen-processing machinery in human monocyte-derived immature and mature dendritic cells
Authors: Theresa L. Whiteside, Joanna D. Stanson, Michael Shurin, Soldano Ferrone
Journal: Cancer Research (2004)

1230  Efficient antigen processing and presentation are the major function of dendritic cells (DC) and are clearly dependent on the integrity of the entire antigen processing machinery (AMP) pathway in these cells. The panel of monoclonal antibodies developed for recognition of APM components in fixed paraffin-embedded tissues was used to evaluate expression of each of the components in human immature (iDC) and matured (mDC) dendritic cells. A flow cytometry-based method was developed for quantitative detection (MESF units) of individual APM components, and DC generated from peripheral blood monocytes of normal donors (ND; n = 12) and patients with melanoma and head neck cancer (n = 6) were compared. We also compared two methods for cell permeabilization: the microwave treatment and the incubation of cells in the presence of 0.25% saponin solution. Co-incubation of tumor cell lines with iDC were performed in microwells or transwell system to evaluate effects of tumor cells on the APM component expression. Our results show that the microwave treatment of DC was necessary to achieve optimal staining, as the percentage of positive cells was consistently higher in microwave-treated DC than saponin-permeabilized DC in all experiments performed. A considerable variability was observed among ND in expression of the APM components in DC. i DC were found to have lower (p
r-HuEPO 40,000 U one time/week before high-dose melphalan allows a tandem autologous peripheral stem-cell transplantation without red blood cell transfusion in multiple myeloma patients: A pilot study
Authors: M. V. Martino, G. Console, E. Massara, T. Moscato, I. Callea, F. Gatto, G. Pucci, A. Dattola, E. Spiniello, P. Iacopino
Journal: Journal of Clinical Oncology (2007)

7103 Purpose: To decrease red blood cell (RBC) transfusion requirements during a tandem high-dose melphalan (HDM) for multiple myeloma (MM) patients (PTS), we conducted a pilot study to assess the effect of high-dose of recombinant human erythropoietin (rHuEpo) started during chemotherapy before the first HDM and autologous peripheral blood stem-cell transplantation (APBSCT). Patients and Methods: After induction chemotherapy with VAD, 14 consecutive PTS with MM, stage III, median age 58 years (range 42–62), were mobilized with cyclophosphamide (3–4 g/m 2 ) to collect peripheral blood stem cells (PBSC) and entered a study consisting of two HDM (200 mg/m 2 ) with APBSCT. Enrolled patients received rHuEpo (40,000 U subcutaneously one time/week) as soon as their hemoglobin (Hb) level fell &lt;11 g/dl during induction chemotherapy. rHuEpo was continued at the same dose during PBSC collection and was reintroduced at the time of discharge after the first transplant up to the admission for the second one. If the Hb level exceeded 13 g/dl at any time, rHuEpo was withheld until the concentration decreased to &lt;11 g/dl, at which time it was restarted. Results were compared to those of 20 tandem HDM and APBSCT performed in 15 consecutive historical MM controls matched for hematological parameters. Results: rHuEpo increased the hemoglobin (Hb) level from 10.1 ± 2.5 g/dl at diagnosis to 12.8 ± 2 g/dl at the time of the first HDM; no major adverse effects occurred. Compared to historical controls (46.6%, 7/15), RBC transfusion requirements were significantly lower for rHuEpo recipients (6.6%, 1/14) (P=0.00001). After the tandem HDM and APSCT, fewer RBC transfusions were needed: 3.3 and 1 RBC units for controls and rHuEpo recipients, respectively (P=0.006). Conclusion: The administration of high dose of rHuEpo during induction chemotherapy and interval beetween the first and second HDM cycle permit the realitazion of tandem chemotherapic program with a reduction of blood product support. No significant financial relationships to disclose.
Fingolimod and Teriflunomide Attenuate Neurodegeneration in Mouse Models of Neuronal Ceroid Lipofuscinosis
Authors: Janos Groh, Kristina Berve, Rudolf Martini
Journal: Molecular Therapy (2017)

CLN diseases are rare lysosomal storage diseases characterized by progressive axonal degeneration and neuron loss in the CNS, manifesting in disability, blindness, and premature death. We have previously demonstrated that, in animal models of infantile and juvenile forms of CLN disease (CLN1 and CLN3, respectively), secondary neuroinflammation in the CNS substantially amplifies neural damage, opening the possibility that immunomodulatory treatment might improve disease outcome. First, we recapitulated the inflammatory phenotype, originally seen in mice in autopsies of CLN patients. We then treated mouse models of CLN1 and CLN3 disease with the clinically approved immunomodulatory compounds fingolimod (0.5 mg/kg/day) and teriflunomide (10 mg/kg/day) by consistent supply in the drinking water for 5 months. The treatment was well tolerated and reduced T cell numbers and microgliosis in the CNS of both models. Moreover, axonal damage, neuron loss, retinal thinning, and brain atrophy were substantially attenuated in both models, along with reduced frequency of myoclonic jerks in Ppt1-/- mice. Based on these findings, and because side effects were not detected, we suggest that clinically approved immune modulators such as fingolimod and teriflunomide may be suitable to attenuate progression of CLN1 and CLN3 disease and, possibly, other orphan diseases with pathogenically relevant neuroinflammation.
Following Autologous Stem Cell Transplantation (1 Yr) Mesenchymal Stem Cells Are Functionally Impaired with Reduced Hematopoietic Support
Authors: Catharina Hazenberg, Fiona A.J. van den Heuvel, Edo Vellenga, Annet Z. Brouwers-Vos, Gerbrig Berger, Jan Jacob Schuringa
Journal: Blood (2016)
Holistic hamstring health: not just the Nordic hamstring exercise
Authors: Aiden J Oakley, Jacob Jennings, Chris J Bishop
Journal: British Journal of Sports Medicine (2017)

Hamstring strain injuries (HSIs) are the most prevalent in team sports, accounting for 12%–26% of injuries in Australian rules football, American football, football, rugby and track and field.1 The biceps femoris is the most commonly injured muscle with 53%–68% of injuries occurring during sprinting.1 In European football, the incidence and recurrence of HSI has continued to rise, while in Australian rules football, a notable reduction in HSI recurrences has been reported.1 It is possible that evidence-based hamstring injury prevention is not adopted or adhered to in some elite level football teams,2 which may explain the rise in HSI.

Although not an exhaustive list, HSI risk factors include: age, previous injury, strength imbalance, flexibility, fatigue1 and low eccentric strength.3 There is a growing body of evidence on the Nordic hamstring exercise (NHE) and its impact on HSI reduction.4 However, there may be misconceptions (fuelled by social media) that this is the only exercise used …