tbuckley/cabot-search huggingface dataset:
Selective serotonin re-uptake inhibitor sertraline inhibits bone healing in a calvarial defect model
Authors: R. Nicole Howie, Samuel Herberg, Emily Durham, Zachary Grey, Grace Bennfors, Mohammed Elsalanty, Amanda C. LaRue, William D. Hill, James J. Cray
Journal: International Journal of Oral Science (2018)

Abstract Bone wound healing is a highly dynamic and precisely controlled process through which damaged bone undergoes repair and complete regeneration. External factors can alter this process, leading to delayed or failed bone wound healing. The findings of recent studies suggest that the use of selective serotonin reuptake inhibitors (SSRIs) can reduce bone mass, precipitate osteoporotic fractures and increase the rate of dental implant failure. With 10% of Americans prescribed antidepressants, the potential of SSRIs to impair bone healing may adversely affect millions of patients’ ability to heal after sustaining trauma. Here, we investigate the effect of the SSRI sertraline on bone healing through pre-treatment with (10 mg·kg -1 sertraline in drinking water, n = 26) or without (control, n = 30) SSRI followed by the creation of a 5-mm calvarial defect. Animals were randomized into three surgical groups: (a) empty/sham, (b) implanted with a DermaMatrix scaffold soak-loaded with sterile PBS or (c) DermaMatrix soak-loaded with 542.5 ng BMP2. SSRI exposure continued until sacrifice in the exposed groups at 4 weeks after surgery. Sertraline exposure resulted in decreased bone healing with significant decreases in trabecular thickness, trabecular number and osteoclast dysfunction while significantly increasing mature collagen fiber formation. These findings indicate that sertraline exposure can impair bone wound healing through disruption of bone repair and regeneration while promoting or defaulting to scar formation within the defect site.
Strong scientific theorizing is needed to improve replicability in psychological science
Authors: Timothy Carsel, Alexander P. Demos, Matt Motyl
Journal: Behavioral and Brain Sciences (2018)

The target article makes the important case for making replicability mainstream. Yet, their proposal targets a symptom, rather than the underlying cause of low replication rates. We argue that psychological scientists need to devise stronger theories that are more clearly falsifiable. Without strong, falsifiable theories in the original research, attempts to replicate the original research are nigh uninterpretable.
Testing Epinephrine for Out-of-Hospital Cardiac Arrest
Authors: Clifton W. Callaway, Michael W. Donnino
Journal: New England Journal of Medicine (2018)

The administration of epinephrine has been part of the resuscitation of patients with cardiac arrest since the 1960s. The rationale for the use of epinephrine includes evidence from studies in animals and from clinical trials in humans that increasing vasomotor tone during circulatory collapse and chest compressions improves coronary perfusion pressure, shunts more blood to the heart, and increases the likelihood of restoring spontaneous circulation.1 However, epinephrine also decreases microvascular blood flow in some organs, increases cardiac dysrhythmias, and increases myocardial oxygen demand during critical ischemia.2 These deleterious effects can result in long-term organ dysfunction or hypoperfusion of the heart . . .
Amiodarone-Induced Thyrotoxicosis
Authors: Simona Censi, Valentina Bodanza, Jacopo Manso, Sara Gusella, Sara Watutantrige-Fernando, Elisabetta Cavedon, Susi Barollo, Loris Bertazza, Diego Cecchin, Caterina Mian
Journal: Clinical Nuclear Medicine (2018)

Distinguishing between amiodarone-induced thyrotoxicosis (AIT) caused by excessive hormone synthesis (AIT-1) or by a destructive process (AIT-2) has important therapeutic implications, but is still difficult and debated. Tc-sestaMIBI thyroid scintigraphy (99m-STS) has been proposed as a tool for classifying the two forms.30 AIT patients (11 females and 19 males) who underwent 99m-STS were retrospectively assessed for the present study. For each patient, a target-to-background ratio (TBR) was obtained on planar images. The TBR was then correlated with the qualitative assessment of the scans and the final clinical diagnosis.Considering clinical response to treatment as the gold standard for differential diagnosis, 14 cases of AIT-1, 12 of AIT-2, and 4 mixed forms were identified. 99m-STS was able to qualitatively identify all the mixed forms, while 1/14 AIT-1 and 6/12 AIT-2 cases were misdiagnosed as mixed forms. When the quantitative index (the TBR) was compared with the final clinical diagnosis, ROC curve analysis enabled us to identify an IBR of 0.482 during 99m-STS as a cut-off capable of discriminating between AIT-1 and AIT-2, with 100% specificity and 91.7% sensitivity (P < 0.0001, area under the curve: 0.982).Taking the TBR into consideration, 99m-STS proved a very useful tool for distinguishing AIT-1 from AIT-2, and thus offering patients appropriate treatment as of their diagnosis. This approach can avoid pointless and potentially dangerous combined overtreatments, and may speed up the return to normal thyroid function, which is crucial in AIT patients suffering from heart disease.
Conventional and PD-L1-expressing Regulatory T Cells are Enriched During BCG Therapy and may Limit its Efficacy
Authors: Mathieu F. Chevalier, Anna K. Schneider, Valerie Cesson, Florence Dartiguenave, Ilaria Lucca, Patrice Jichlinski, Denise Nardelli-Haefliger, Laurent Derré
Journal: European Urology (2018)
Simple Scoring Scheme for Calculating the Risk of Acute Coronary Events Based on the 10-Year Follow-Up of the Prospective Cardiovascular Münster (PROCAM) Study
Authors: GerdAssmann, PaulCullen, HelmutSchulte
Journal: Circulation (2002)

Background— The absolute risk of an acute coronary event depends on the totality of risk factors exhibited by an individual, the so-called global risk profile. Although several scoring schemes have been suggested to calculate this profile, many omit information on important variables such as family history of coronary heart disease or LDL cholesterol. Methods and Results— Based on 325 acute coronary events occurring within 10 years of follow-up among 5389 men 35 to 65 years of age at recruitment into the Prospective Cardiovascular Munster (PROCAM) study, we developed a Cox proportional hazards model using the following 8 independent risk variables, ranked in order of importance: age, LDL cholesterol, smoking, HDL cholesterol, systolic blood pressure, family history of premature myocardial infarction, diabetes mellitus, and triglycerides. We then derived a simple point scoring system based on the β-coefficients of this model. The accuracy of this point scoring scheme was comparable to coronary event predi...
Radiology examinations: regulator calls for targets on reporting after finding delays
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The healthcare regulator has called for national standards for the time it should take for patients to receive results from radiology examinations after finding “significant variation” in reporting times across hospitals in England.

The Care Quality Commission (CQC) warned of delays to radiography results being shared with clinicians and of x ray films being examined by clinicians without specialist training in its report published on 19 July.1

The regulator said that it was concerned at the lack of agreed best practice and called for national standards for reporting turnaround times. It also called for …
Protecting Mothers and Babies — A Delicate Balancing Act
Authors: Sonja A. Rasmussen, Wanda Barfield, Margaret A. Honein
Journal: New England Journal of Medicine (2018)

Protecting Mothers and Babies A signal of a possible link between periconceptional use of the antiretroviral medication dolutegravir and neural tube defects warrants further rapid evaluation, but caution is needed before long-term changes in recommendations are made.
Use of Serum Mesothelin as an Indicator of Tumor Progression in Routine Clinical Practice of Malignant Pleural Mesothelioma Treatment
Authors: Antonella Vigani, Maria Pia Pistillo, Vincenzo Fontana, Ugo Giannoni, Ilan Rosenberg, Pier Aldo Canessa, Giovanni Berisso, Paola Ferro, Maria Cristiana Franceschini, Marika Tonarelli, Silvio Roncella
Journal: Journal of Thoracic Oncology (2018)
Acute lymphoblastic leukemia as a clonally unrelated second primary malignancy after multiple myeloma
Authors: Ibrahim Aldoss, Marzia Capelletti, Jihye Park, Romanos Sklavenitis Pistofidis, Raju Pillai, Tracey Stiller, James F. Sanchez, Stephen J. Forman, Irene M. Ghobrial, Amrita Krishnan
Journal: Leukemia (2018)
An intravascular magnetic wire for the high-throughput retrieval of circulating tumour cells in vivo
Authors: Ophir Vermesh, Amin Aalipour, T. Jessie Ge, Yamil Saenz, Yue Guo, Israt S. Alam, Seung-min Park, Charlie N. Adelson, Yoshiaki Mitsutake, Jose Vilches-Moure, Elias Godoy, Michael H. Bachmann, Chin Chun Ooi, Jennifer K. Lyons, Kerstin Mueller, Hamed Arami, Alfredo Green, Edward I. Solomon, Shan X. Wang, Sanjiv S. Gambhir
Journal: Nature Biomedical Engineering (2018)
Blood eosinophils in COPD and the future risk of pneumonia
Authors: Pierre Ernst
Journal: European Respiratory Journal (2018)

The eosinophil, whether in the blood or sputum, has been receiving increasing attention as a measure of treatment response or failure in patients with chronic obstructive pulmonary disease (COPD). A recent review by Bafadhel et al. [1] summarises the biology of the eosinophil, its role in airway disease, as well as the clinical data supporting the use of blood eosinophils as a biomarker in airway disease, and more specifically, COPD. To paraphrase their conclusions: while the role of eosinophils in COPD needs clarification, there is now the realisation that blood eosinophils may be a useful guide to therapy. There is, however, substantial within-person variation in blood eosinophil counts [2]. Despite this, there is a significant proportion of patients with COPD in whom blood eosinophil counts are consistently high or low: 65% consistently above or below 0.40×109 per L over a 1-year period in the Leicester cohort [1] and 51% at the 2% cut-off over a 3-year period in the ECLIPSE study [3]. Consistency also appears better when using absolute counts and at lower counts. For example, using a cut-off value of <0.15×109 per L, Southworth et al. [4] found 87% to be in the same category at 6 months and a similar proportion at >2 years of follow-up. It has further been suggested that higher blood eosinophil counts are predictive of future eosinophilic exacerbations [5] and this is supported by the better response to oral corticosteroids in patients with exacerbations characterised by higher blood eosinophils at presentation [1]. The broader importance of the eosinophil in the natural history of airway disease at an early stage is suggested by the predictive value of blood eosinophil counts on decline in forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity in young adults from the New Zealand birth cohort, an effect that is independent of asthma and cigarette smoking [6]. There is an increase in pneumonia risk in COPD patients who have higher blood eosinophil counts at baseline <http://ow.ly/XPVh30kvOpZ>
Abstract 18048: Essential Role of Heart AMP-Activated Protein Kinase to Maintain Mitochondrial Respiration, Decrease Mitochondrial Oxidative Stress and Inhibit Mitochondrial Transition Permeability Pore Opening after Ischemia-Reperfusion
Authors: Vlad G Zaha, Monica Palmeri, Hui-Young Lee, Jesse Rinehart, Xiaoyue Hu, Gerald Shulman, Lawrence H Young
Journal: Circulation (2012)

AMP-activated kinase (AMPK) is a stress responsive kinase essential to myocardial recovery following ischemia-reperfusion (IR). Recent studies suggest that AMPK signaling regulates mitochondrial in...
Has Access to Hepatitis C Virus Therapy Changed for Patients With Mental Health or Substance Use Disorders in the Direct‐Acting‐Antiviral Period?
Authors: Mamta K. Jain, Mae Thamer, George Therapondos, Mitchell L. Shiffman, Onkar Kshirsagar, Christopher Clark, Robert J. Wong
Journal: Hepatology (2018)

Direct‐acting antivirals (DAA) for hepatitis C virus (HCV) became available in 2014, but the role of mental health or substance use disorders (MH/SUD) on access to treatment is unknown. The objective of this study was to examine the extent and predictors of HCV treatment in the pre‐DAA and post‐DAA periods in four large, diverse health care settings in the United States. We conducted a retrospective analysis of 29,544 adults with chronic HCV who did or did not receive treatment from January 1, 2011, to February 28, 2017. Kaplan‐Meier curve was used to examine cumulative risk for receiving HCV treatment stratified by MH/SUD. Predictors of HCV treatment in the pre‐DAA (January 1, 2011, to December 31, 2013) and post‐DAA (January 1, 2014, to February 28, 2017) cohorts were analyzed using multivariate generalized estimating equations and a modified Poisson model. Overall, 21.7% (2,879/13,240) of those with chronic HCV post‐DAA were treated compared with 3.5% (574/16,304) in the pre‐DAA period. Compared with non‐Hispanic whites, Hispanic whites (adjusted odds ratio [AOR] 0.36; 95% confidence interval [CI], 0.25, 0.52) were less likely to be treated in the post‐DAA period. Those with concurrent nonalcoholic fatty liver disease (AOR 1.39; 95% CI, 1.05, 1.83), cirrhosis (AOR 2.00; 95% CI, 1.74, 2.31), and liver transplant (AOR 2.72; 95% CI, 1.87, 3.94) were more likely to be treated post‐DAA. Those with MH/SUD were less likely to be treated both before (AOR 0.46; 95% CI, 0.36, 0.60) and after (AOR 0.63; 95% CI, 0.55, 0.71) DAA therapy was available. Overall, the cumulative risk for receiving HCV treatment from 2011 to 2017 among those with versus without MH/SUD was 13.6% versus 21.6%, respectively (P < 0.001). Conclusion: The volume of patients treated for HCV has increased in the post‐DAA period, especially among those with liver‐related comorbidities, but disparities in access to treatment continue among those with MH/SUD.
Estrogen Prevents Oxidative Stress–Induced Endothelial Cell Apoptosis in Rats
Authors: NorikoSudoh, KenjiToba, MasahiroAkishita, JunyaAko, MasayoshiHashimoto, KatsuyaIijima, SeungbumKim, Yi-QiangLiang, YumikoOhike, TokumitsuWatanabe, IeharuYamazaki, MasaoYoshizumi, MasatoEto, YasuyoshiOuchi
Journal: Circulation (2001)

Background—Estrogen replacement attenuates the increased risk of cardiovascular disease in postmenopausal women. Recent studies using an in vitro culture system have shown that estrogen inhibits endothelial cell (EC) apoptosis. The in vivo relevance of this finding, however, is not defined. To do so, we have developed a rat vascular injury model in which EC apoptosis induced by hydrogen peroxide plays a role. Methods and Results—Intracarotid arterial administration of 0.01 mmol/L hydrogen peroxide for 5 minutes evoked EC apoptosis after 6 to 24 hours, determined by nuclear staining with Hoechst 33342, terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling, and electron microscopy. Apoptosis was associated with EC loss and was followed by EC regeneration at 72 hours and neointima formation at 1 to 2 weeks. Estradiol replacement in ovariectomized female Wistar rats decreased the rate of apoptotic ECs by ≈50%, assayed by nuclear morphology of en face specimens, resulting in increased remaining...
Phase III, randomised trial of avelumab versus physician’s choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300
Authors: Y.-J Bang, E.Yañez Ruiz, E. Van Cutsem, K.-W Lee, L. Wyrwicz, M. Schenker, M. Alsina, M.-H Ryu, H.-C Chung, L. Evesque, S.-E Al-Batran, S.H. Park, M. Lichinitser, N. Boku, M.H. Moehler, J. Hong, H. Xiong, R. Hallwachs, I. Conti, J. Taieb
Journal: Annals of Oncology (2018)

BackgroundThere currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician's choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC.Patients and methodsPatients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician's choice of chemotherapy (paclitaxel 80 mg/m2 on days 1, 8, and 15 or irinotecan 150 mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.ResultsA total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0 months; hazard ratio (HR)=1.1 [95% confidence interval (CI) 0.9–1.4]; P= 0.81} or the secondary end points of PFS [median, 1.4 versus 2.7 months; HR=1.73 (95% CI 1.4–2.2); P> 0.99] or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm.ConclusionsTreatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy.Trial registrationClinicalTrials.gov: NCT02625623.
Targeted combination prevention to support female sex workers in Zimbabwe accessing and adhering to antiretrovirals for treatment and prevention of HIV (SAPPH-IRe): a cluster-randomised trial
Authors: Frances M Cowan, Calum Davey, Elizabeth Fearon, Phillis Mushati, Jeffrey Dirawo, Sungai Chabata, Valentina Cambiano, Sue Napierala, Dagmar Hanisch, Ramona Wong-Gruenwald, Nyasha Masuka, Travor Mabugo, Karin Hatzold, Owen Mugurungi, Joanna Busza, Andrew Phillips, James R Hargreaves
Journal: The Lancet HIV (2018)

BackgroundStrengthening engagement of female sex workers with health services is needed to eliminate HIV. We assessed the efficacy of a targeted combination intervention for female sex workers in Zimbabwe.MethodsWe did a cluster-randomised trial from 2014 to 2016. Clusters were areas surrounding female sex worker clinics and were enrolled in matched pairs. Sites were randomly assigned (1:1) to receive usual care (free sexual-health services supported by peer educators, including HIV testing on demand, referral for antiretroviral therapy [ART], and health education) or an intervention that supported additional regular HIV testing, on-site initiation of ART, pre-exposure prophylaxis, adherence, and intensified community mobilisation. The primary outcome was the proportion of all female sex workers with HIV viral load 1000 copies per mL or greater, assessed through respondent-driven sampling surveys. We used an adapted cluster-summary approach to estimate risk differences. This trial is registered with Pan African Clinical Trials Registry, number PACTR201312000722390.ResultsWe randomly assigned 14 clusters to usual care or the intervention (seven in each group). 3612 female sex workers attended clinics in the usual-care clusters and 4619 in the intervention clusters during the study. Half as many were tested (1151 vs 2606) and diagnosed as being HIV positive (546 vs 1052) in the usual-care clusters. The proportion of all female sex workers with viral loads of 1000 copies per mL or greater fell in both study groups (from 421 [30%] of 1363 to 279 [19%] of 1443 in the usual-care group and from 399 [30%] of 1303 to 240 [16%] of 1439 in the intervention group), but with a risk difference at the end of the assessment period of only −2·8% (95% CI −8·1 to 2·5, p=0·23). Among HIV-positive women, the proportions with viral loads less than 1000 copies per mL were 590 (68%) of 869 in the usual-care group and 588 (72%) of 828 in the intervention group at the end of the assessment period, adjusted risk difference of 5·3% (95% CI −4·0 to 14·6, p=0·20). There were no adverse events.InterpretationOur intervention of a dedicated programme for female sex workers led to high levels of HIV diagnosis and treatment. Further research is needed to optimise programme content and intensity for the broader population.FundingUN Population Fund (through Zimbabwe's Integrated Support Fund funded by UK Department for International Development, Irish Aid, and Swedish International Development Cooperation Agency).
Tle corepressors are differentially partitioned to instruct CD8<sup>+</sup> T cell lineage choice and identity
Authors: Shaojun Xing, Peng Shao, Fengyin Li, Xudong Zhao, Wooseok Seo, Justin C. Wheat, Selvi Ramasamy, Jianfeng Wang, Xiang Li, Weiqun Peng, Shuyang Yu, Chengyu Liu, Ichiro Taniuchi, David A. Sweetser, Hai-Hui Xue
Journal: The Journal of Experimental Medicine (2018)

Tle/Groucho proteins are transcriptional corepressors interacting with Tcf/Lef and Runx transcription factors, but their physiological roles in T cell development remain unknown. Conditional targeting of Tle1, Tle3 and Tle4 revealed gene dose–dependent requirements for Tle proteins in CD8 + lineage cells. Upon ablating all three Tle proteins, generation of CD8 + T cells was greatly diminished, largely owing to redirection of MHC-I–selected thymocytes to CD4 + lineage; the remaining CD8-positive T cells showed aberrant up-regulation of CD4 + lineage-associated genes including Cd4 , Thpok , St8sia6 , and Foxp3 . Mechanistically, Tle3 bound to Runx-occupied Thpok silencer, in post-selection double-positive thymocytes to prevent excessive ThPOK induction and in mature CD8 + T cells to silence Thpok expression. Tle3 also bound to Tcf1-occupied sites in a few CD4 + lineage-associated genes, including Cd4 silencer and St8sia6 introns, to repress their expression in mature CD8 + T cells. These findings indicate that Tle corepressors are differentially partitioned to Runx and Tcf/Lef complexes to instruct CD8 + lineage choice and cooperatively establish CD8 + T cell identity, respectively.