tbuckley/cabot-search huggingface dataset:
The Association between Long-Term Air Pollution and Urinary Catecholamines: Evidence from the Multi-Ethnic Study of Atherosclerosis
Authors: Anjum Hajat, Ana V. Diez Roux, Cecilia Castro-Diehl, Kristen Cosselman, Sherita Hill Golden, Marnie F. Hazlehurst, Adam Szpiro, Sverre Vedal, Joel D. Kaufman
Journal: Environmental Health Perspectives (2019)

Autonomic nervous system effects have been hypothesized as a mechanism of air pollutant health effects, though scant prior epidemiologic research has examined the association between air pollutants and catecholamines.
PROSPECTIVE EVALUATION OF CONTRAST-ENHANCED ENDOSCOPIC ULTRASOUND AND ELASTOGRAPHY FOR DEEP PELVIC ENDOMETRIOSIS WITH BOWEL INVOLVEMENT
Authors: C Fortier Beaulieu, M Chassang, M Le Maréchal, C Gomercic, M Barthet, T Piche, J Delotte, G Vanbiervliet
Journal: Endoscopy (2019)

Rectal endoscopic ultrasonography completes the iconographic assessment of Deep Pelvic Endometriosis (DPE) with a diagnostic sensitivity of 90% for bowel involvement. No study has evaluated the value of endoscopic ultrasound with elastography and contrast enhancement (CE-EUS) to characterize bowel lesions in DPE. The aim of this study was to characterize the bowel involvement of DPE by elastography and CE-EUS.
CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia
Authors: Jing Pan, Qing Niu, Biping Deng, Shuangyou Liu, Tong Wu, Zhiyong Gao, Zhaoli Liu, Yue Zhang, Xiaomin Qu, Yanlei Zhang, Shaohui Liu, Zhuojun Ling, Yuehui Lin, Yongqiang Zhao, Yanzhi Song, Xiyou Tan, Yan Zhang, Zhihui Li, Zhichao Yin, Bingzhen Chen, Xinjian Yu, Ju Yan, Qinlong Zheng, Xuan Zhou, Jin Gao, Alex H. Chang, Xiaoming Feng, Chunrong Tong
Journal: Leukemia (2019)

Abstract Despite worldwide promising clinical outcome of CD19 CAR-T therapy, relapse after this therapy is associated with poor prognosis and has become an urgent problem to be solved. We conducted a CD22 CAR T-cell therapy in 34 relapsed or refractory (r/r) B-ALL pediatric and adult patients who failed from previous CD19 CAR T-cell therapy. Complete remission (CR) or CR with incomplete count recovery (CRi) was achieved in 24 of 30 patients (80%) that could be evaluated on day 30 after infusion, which accounted for 70.5% of all 34 enrolled patients. Most patients only experienced mild cytokine-release syndrome and neurotoxicity. Seven CR patients received no further treatment, and 3 of them remained in remission at 6, 6.6, and 14 months after infusion. Eleven CR patients were promptly bridged to transplantation, and 8 of them remained in remission at 4.6 to 13.3 months after transplantation, resulted in 1-year leukemia-free survival rate of 71.6% (95% CI, 44.2–99.0). CD22 antigen loss or mutation was not observed to be associated with relapsed patients. Our study demonstrated that our CD22 CAR T-cells was highly effective in inducing remission in r/r B-ALL patients, and also provided a precious window for subsequent transplantation to achieve durable remission.
Enhancement of oral bioavailability and anti-Parkinsonian efficacy of resveratrol through a nanocrystal formulation
Authors: Sha Xiong, Wei Liu, Yile Zhou, Yousheng Mo, Yao Liu, Xiaojia Chen, Huafeng Pan, Dongsheng Yuan, Qi Wang, Tongkai Chen
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Resveratrol (RES), a non-flavonoid polyphenol extracted from a wide variety of plants, exhibits neuroprotective activities against Parkinson's disease (PD). However, undesirable water solubility of RES reduces its oral bioavailability and demonstrates low efficacy in blood and brain, thus limiting its application. In present study, a nanocrystal formulation of RES (RES-NCs) was developed to enhance its oral bioavailability and delivery into brain for PD treatment. RES-NCs were fabricated with hydroxypropyl methylcellulose (HPMC) stabilizer via antisolvent precipitation approach. The obtained RES-NCs displayed the particle size of 222.54 ± 1.66 nm, the PDI of 0.125 ± 0.035, the zeta potential of −9.41 ± 0.37 mV, and a rapid in vitro dissolution rate. Molecular dynamics simulation of RES and HPMC revealed an interaction energy of −68.09 kJ/mol and a binding energy of −30.98 ± 0.388 kJ/mol, indicating that the spontaneous binding between the two molecules is through van der Waals forces. RES-NCs conferred enhanced cellular uptake as well as improved permeability relative to pure RES. In addition, RES-NCs were able to protect neurons against cytotoxicity induced by MPP+. Meanwhile, RES-NCs exerted no significant toxic effects on zebrafish embryos and larvae, and did not influence their survival and hatching rates. When orally administered to rats, RES-NCs exhibited more favorable pharmacokinetics than pure RES, with higher plasma and brain concentrations. More importantly, MPTP-induced PD mice showed notable improvements in behavior, attenuated dopamine deficiency, and elevated levels of dopamine and its metabolites after the treatment with RES-NCs. Furthermore, immunoblot analysis revealed that the neuroprotective role of RES-NCs may be at least partially mediated by Akt/Gsk3β signaling pathway. Taken altogether, RES-NCs can serve as a potential treatment modality for PD, offering means of improving RES oral bioavailability and brain accumulation.
STIM1 at the plasma membrane as a new target in progressive chronic lymphocytic leukemia
Authors: Marjolaine Debant, Miguel Burgos, Patrice Hemon, Paul Buscaglia, Tinhinane Fali, Sarra Melayah, Nelig Le Goux, Christophe Vandier, Marie Potier-Cartereau, Jacques-Olivier Pers, Adrian Tempescul, Christian Berthou, Cristina Bagacean, Olivier Mignen, Yves Renaudineau
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Dysregulation in calcium (Ca<sup>2+</sup>) signaling is a hallmark of chronic lymphocytic leukemia (CLL). While the role of the B cell receptor (BCR) Ca<sup>2+</sup> pathway has been associated with disease progression, the importance of the newly described constitutive Ca<sup>2+</sup> entry (CE) pathway is less clear. In addition, we hypothesized that these differences reflect modifications of the CE pathway and Ca<sup>2+</sup> actors such as Orai1, transient receptor potential canonical (TRPC) 1, and stromal interaction molecule 1 (STIM1), the latter being the focus of this study. <h3>Methods</h3> An extensive analysis of the Ca<sup>2+</sup> entry (CE) pathway in CLL B cells was performed including constitutive Ca<sup>2+</sup> entry, basal Ca<sup>2+</sup> levels, and store operated Ca<sup>2+</sup> entry (SOCE) activated following B cell receptor engagement or using Thapsigargin. The molecular characterization of the calcium channels Orai1 and TRPC1 and to their partner STIM1 was performed by flow cytometry and/or Western blotting. Specific siRNAs for Orai1, TRPC1 and STIM1 plus the Orai1 channel blocker Synta66 were used. CLL B cell viability was tested in the presence of an anti-STIM1 monoclonal antibody (mAb, clone GOK) coupled or not with an anti-CD20 mAb, rituximab. The Cox regression model was used to determine the optimal threshold and to stratify patients. <h3>Results</h3> Seeking to explore the CE pathway, we found in untreated CLL patients that an abnormal CE pathway was (i) highly associated with the disease outcome; (ii) positively correlated with basal Ca<sup>2+</sup> concentrations; (iii) independent from the BCR-PLCγ2-InsP<sub>3</sub>R (SOCE) Ca<sup>2+</sup> signaling pathway; (iv) supported by Orai1 and TRPC1 channels; (v) regulated by the pool of STIM1 located in the plasma membrane (STIM1<sub>PM</sub>); and (vi) blocked when using a mAb targeting STIM1<sub>PM</sub>. Next, we further established an association between an elevated expression of STIM1<sub>PM</sub> and clinical outcome. In addition, combining an anti-STIM1 mAb with rituximab significantly reduced in vitro CLL B cell viability within the high STIM1<sub>PM</sub> CLL subgroup. <h3>Conclusions</h3> These data establish the critical role of a newly discovered BCR independent Ca<sup>2+</sup> entry in CLL evolution, provide new insights into CLL pathophysiology, and support innovative therapeutic perspectives such as targeting STIM1 located at the plasma membrane.
Comparaison de la coloscopie avec chromoendoscopie à l'indigo carmin à la coloscopie avec chromoendoscopie virtuelle au NBI de 3ème génération chez des patients ayant un syndrome de Lynch: étude Lynch-Chromo
Authors: E Samaha, C Colas, M Dhooge, JC Saurin, T Lecomte, E Coron, G Rahmi, G Perrod, C Savale, S Chaussade, J Bellanger, N Benech, M Le Rhun, JP Barbieux, H Pereira, G Chatellier, C Cellier
Journal: Endoscopy (2019)

La coloscopie avec chromoendoscopie à l'indigo carmin (CIC) améliore le taux de détection des adénomes (TDA) chez les patients ayant un syndrome de Lynch (SL). Néanmois, il s'agit d'une technique plus couteûse, qui nécessite un apprentissage dédié et un temps de procédure allongé. Le système de Narrow Band Imaging (NBI) est une technique de chromoendoscopie virtuelle qui met en reliefs l'architecture vasculaire muqueuse améliorant le contraste pour les adénomes. Nous avons mené une étude prospective multicentrique en tandem pour comparer le NBI de 3ème génération à la CIC pour la détection des adénomes coliques chez les patients ayant un SL.
Bullying and undermining by line managers in the NHS
Authors: Shyam Kumar
Journal: BMJ (2019)

I read Rimmer’s article titled “Tackling bullying in the NHS” with interest.1 Clare Marx rightly highlights the importance of good clinical leadership in tackling unprofessional behaviour, saying, “A big part of that is the development of leadership skills and crucially tackling unprofessional behaviour towards colleagues: anything from basic rudeness to outright bullying and undermining.”1

The debate, …
Abstract P012: The Effect of Vitamin D Supplementation on Epigenetic Aging: A Randomized Placebo-Controlled Clinical Trial
Authors: Li Chen, Yanbin Dong, Jigar Bhagatwala, Anas Raed, Ying Huang, Haidong Zhu
Journal: Circulation (2018)

Background: Vitamin D deficiency is associated with age-related diseases, such as cardiovascular disease, diabetes and cancer. We have previously shown that vitamin D plays a role in regulating human epigenome. Moreover, we have demonstrated that vitamin D supplementation increases telomerase activity, suggesting an anti-aging property. Epigenetic age acceleration, an emerging marker of biological aging, predicts cardiovascular mortality, morbidity and cancer. In this study, we tested the hypothesis that vitamin D supplementation would decelerate epigenetic aging. Methods: We have previously completed a 16 week randomized placebo-controlled clinical trial of vitamin D3 supplementation in overweight/obese African-Americans (NCT01583621). The participants were randomly assigned into four groups of placebo, 600 IU/day, 2000 IU/day, and 4000 IU/day of vitamin D supplements. A genome-wide methylation scan was performed using the Illumina Human Methylation 480K Bead Chip on peripheral blood mononuclear cell DNA. DNA methylation age of 52 participants was determined based on 353 CpG sites using the statistical pipeline developed by Horvath. Epigenetic aging, methylation-based age acceleration index (Δage) was defined as the difference between DNA methylation age and chronological age in years. Mixed-effects models were used to evaluate the treatment effects. Results: DNAm age was significantly correlated with chronological age (r=0.9082, p-value &lt; 0.001). The correlation was higher at baseline (r=0.9281, p-value &lt; 0.001) than at 16 weeks (r=0.8887, p-value &lt; 0.001), which implies that the 16 week treatment may drive the DNAm age deviated from the chronological age. Compared with placebo, vitamin D supplementation was also associated with decreased Δage after adjustment for sex, BMI, lymphocyte percentage, month and baseline 25(OH)D concentration (600 IU/day: β = 0.90, p-value = 0.325; 2000 IU/day: β= -1.21, p-value = 0.118; 4000 IU/day: β= -1.70, p-value = 0.035), but only the treatment effect of 4000 IU/day supplementation was significant. Conclusion: Our results suggest that vitamin D supplementation might decelerate epigenetic aging, further supporting the anti-aging effect of vitamin D supplementation in overweight/obese African Americans. Larger studies are needed to replicate the findings.
SUBMUCOSAL TUNNELING ENDOSCOPIC RESECTION (STER) FOR OBSTRUCTIVE DUODENAL LIPOMA
Authors: G Mavrogenis, F Bazerbachi, I Tsevgas, D Zachariadis
Journal: Endoscopy (2019)

A 35-year-old male presented with a 6-month history of postprandial epigastric pain and nausea. Gastroscopy revealed a 3 cm soft subepithelial mass that originated from the duodenal bulb and prolapsed into the antrum. Endoscopic ultrasonography showed a hyperechoic homogenous mass that originated from the submucosal layer of the duodenum, consistent with a lipoma. The mass had a broad base, preventing the application of endoscopic loop ligation. Therefore, submucosal tunneling endoscopic resection (STER) technique was applied. A mixture of hydroxyethyl starch (500 ml) with methylene blue (1 ml) and epinephrine (1 mg) was injected above the pylorus. Then, a submucosal pocket was created at the lesser curvature of the antrum that was extended all along the length of the superior wall of the duodenal bulb. The endoscope was advanced between the superior pole of the lesion and the duodenal wall. Dissection of the inferior and posterior part of the lesion was achieved with a blunt tip knife in order to diminish the risk of perforation due to poor visualization or due to tangential access. In addition, a tapered tip cap was used in order to push the endoscope into the tight space between the mass and the underlying duodenal mucosa. Finally, the lesion was completely resected and the specimen was retrieved with a basket. At the end of the procedure small incisions were made around the edges of the entrance of the tunnel. These superficial defects allowed clip grip for traction and apposition. Using two clips, the mucosal defect was partially closed. Complete closure was achieved with additional clips. The patient was discharged after 24 hours and had an uneventful recovery. At 10 months of follow up the patient remains asymptomatic and endoscopy showed a smooth passage of the gastroscope to the duodenum.
Abstract 19232: Pre-Implant Heart Failure Severity Predicts Quality of Life and Psychological Symptoms for Patient-Caregiver Dyads in Left Ventricular Assist Device Therapy
Authors: Julie T Bidwell, James O Mudd, Karen S Lyons, Kathleen L Grady, Jill M Gelow, Shirin O Hiatt, Christopher V Chien, Christopher S Lee
Journal: Circulation (2017)

Introduction: For heart failure (HF) patients requiring a left ventricular assist device (LVAD), illness severity likely influences outcomes not only for patients, but also for family caregivers wh...
Chronic HCV Infection and Autologous Stem Cell Transplantation for Multiple Myeloma
Authors: Cécile Gruchet, Stephanie Guidez, Guillemette Fouquet, Isabelle Azais, Geraldine Durand, Vincent Javaugue, Antoine Brigaud, Florent Plasse, Jeremie Diolez, Florence Sabirou, Niels Moya, Arthur Bobin, Thomas Systchenko, Antoine Machet, Deborah Desmier, Anthony Levy, Celine Dieval, Sylvain Primault, Jocelyn Barrier, Anne Corby, Claire Daras, Isabelle Princet, Delphine Bauwens, Valentine Richez, Paul Franques, Helene Gardeney, Sabrina Bouyer, Elodie Dindinaud, Herve Avet Loiseau, Franck Bridoux, Silvain Christine, Xavier Leleu
Journal: Blood (2018)
CAM-H2 effectively targets and treats HER2 positive brain lesions: A comparative preclinical study with trastuzumab
Authors: J. Puttemans, M. D’Huyvetter, B. Windhorst, T. Lahoutte, N. Devoogdt
Journal: Annals of Oncology (2019)

Background: Despite extensive research in systemic treatments for HER2 positive breast cancer brain metastases (BCBM), only limited benefits have been observed often at the cost of significant toxicities. Treatment failure is attributed to the limited capacity of drugs to cross the blood-tumor-barrier (BTB) or to resistance mechanisms in the brain lesion microenvironment. In this study we evaluate the radiolabeled drug CAM-H2 as a new systemic treatment for the irradiation of HER2 positive BCBM. Single domain antibody fragments (sdAbs) are small (15 kDa) heavy-chain-only antibody fragments. Due to their favorable pharmacokinetics, sdAbs are tested as targeting vehicles for the delivery of cytotoxic irradiation to cancer lesions inside and outside the brain. Here we measure the potential of CAM-H2 (131-Iodine conjugated anti-HER2 sdAb 2Rs15d) for targeting brain lesions with imaging and compare its therapeutic efficacy with Trastuzumab in a preclinical model. Methods: Tumors were inoculated through intracranial injection of HER2+SKOV3.ip1 or MDA-MB-231Br (MDA) cancer cells. Biodistribution of radiolabeled 2Rs15d and Trastuzumab was evaluated through in vivoSPECT/CT imaging at 1h and 72h post injection followed by ex vivotissue radioactivity counting. Five groups of MDA-tumor-bearing mice were treated with either CAM-H2, Trastuzumab plus CAM-H2, unlabeled 2Rs15d, Trastuzumab, or PBS. Results: Mice treated with CAM-H2 and the combination of CAM-H2 plus Trastuzumab showed a significant increase (p < 0.05) in median survival compared to the Trastuzumab only, unlabeled 2Rs15d or PBS. The addition of Trastuzumab did not significantly prolong survival, compared to cold 2Rs15d or PBS. SPECT/CT imaging of CAM-H2 treated animals showed specific uptake in the brain lesions up to 2 days after administration. Conclusions: CAM-H2 crosses the BTB and binds HER2 positive brain lesions. Treatment with therapeutic doses of CAM-H2 significantly increased survival compared to Trastuzumab. Systemically delivered cytotoxic irradiation conjugated to sdAbs has the potential to effectively treat cancer lesions inside the brain, with limited exposure to healthy brain. Clinical translation of CAM-H2 for treatment of BCBM is currently ongoing. Legal entity responsible for the study: Vrije Universiteit Brussel. Funding: Camel-IDS NV/SA. Disclosure: M. D'Huyvetter: Ownership interest, employee: Camel-IDS NV/SA. B. Windhorst: Editor in chief: Nuclear Medicine & Biology; Editor: Journal of Radiolabelled Compounds & Radiopharmaceuticals T. Lahoutte: Holds ownership interest, consultant: Camel-IDS NV/SA; Member of the scientific advisory board: Ion Beam Applications; Member of the strategic committee: IRE; Preclinical contract research: Roche, Telix Pharmaceuticals. N. Devoogdt: Ownership interest, consultant for Camel-IDS NV/SA; Preclinical contract research: Roche, Telix Pharmaceuticals. All other authors have declared no conflicts of interest.
Distinct Surface Expression of Activating Receptor Ly49H Drives Differential Expansion of NK Cell Clones upon Murine Cytomegalovirus Infection
Authors: Simon Grassmann, Ludwig O. Pachmayr, Justin Leube, Lorenz Mihatsch, Immanuel Andrae, Sophie Flommersfeld, Jennifer Oduro, Luka Cicin-Sain, Matthias Schiemann, Michael Flossdorf, Veit R. Buchholz
Journal: Immunity (2019)
ULTRASOUND-GUIDED TRANSORAL FUNDOPLICATION FOR THE TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE: RESULTS UP TO 24 MONTHS FROM A SINGLE-CENTER PROSPECTIVE STUDY
Authors: PA Testoni, G Mazzoleni, G Distefano, SGG Testoni, M Antonelli, L Fanti, S Passaretti
Journal: Endoscopy (2019)

Transoral incisionless fundoplication (TIF) with the MUSE system is a new ultrasound-guided intervention for the treatment of gastroesophageal reflux disease (GERD). Aim of this study was to assess the safety of TIF with MUSE and its effects on clinical, pathophysiological and endoscopic results.
Posthospital Fall Injuries and 30-Day Readmissions in Adults 65 Years and Older
Authors: Geoffrey J. Hoffman, Haiyin Liu, Neil B. Alexander, Mary Tinetti, Thomas M. Braun, Lillian C. Min
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Falls are common among older adults, particularly those with previous falls and cognitive impairment and in the postdischarge period. Hospitals have financial incentives to reduce both inpatient falls and hospital readmissions, yet little is known about whether fall-related injuries (FRIs) are common diagnoses for 30-day hospital readmissions. <h3>Objective</h3> To compare fall-related readmissions with other leading rehospitalization diagnoses, including for patients at greatest risk of readmission. <h3>Design, Setting, and Participants</h3> Retrospective cohort study of the Hospital Cost and Utilization Project's Nationwide Readmissions Database of nationally representative US hospital discharges among Medicare beneficiaries aged 65 years and older from January 1, 2013, to November 30, 2014. The prevalence and ranking of FRIs compared with other diagnostic factors for 30-day unplanned hospital-wide readmissions were determined, overall and for 2 acute geriatric cohorts, classified by fall injury or cognitive impairment diagnoses observed at the index admission. Analyses were also stratified by patient discharge disposition (home, home health care, skilled nursing facility). Analyses were conducted from February 1, 2018, to February 26, 2018. <h3>Main Outcomes and Measures</h3> Unplanned hospital-wide readmission within 30 days of discharge. <h3>Results</h3> From the database, 8 382 074 eligible index admissions were identified, including 746 397 (8.9%) in the FRI cohort and 1 367 759 (16.3%) in the cognitive impairment cohort. Among the entire 8 382 074-discharge cohort, mean (SD) age was 77.7 (7.8) years and 4 736 281 (56.5%) were female. Overall, 1 205 962 (14.4%) of index admissions resulted in readmission, with readmission rates of 12.9% for those with a previous fall and 16.0% for patients with cognitive impairment. Overall, FRIs ranked as the third-leading readmission diagnosis, accounting for 60 954 (5.1%) of all readmission diagnoses. Within the novel acute geriatric cohorts, FRIs were the second-leading diagnosis for readmission both for patients with an FRI at index admission (10.3% of all readmission diagnoses) and those with cognitive impairment (7.0% of all readmission diagnoses). For those with an FRI at index admission and discharged home or to home health care, FRIs were the leading readmission diagnosis. <h3>Conclusions and Relevance</h3> This study found that posthospital FRIs were a leading readmission diagnosis, particularly for patients originally admitted with a FRI or cognitive impairment. Targeting at-risk hospitalized older adults, particularly those discharged to home or home health care, is an underexplored, cost-effective mechanism with potential to reduce readmissions and improve patient care.
Long noncoding RNA Pvt1 regulates the immunosuppression activity of granulocytic myeloid-derived suppressor cells in tumor-bearing mice
Authors: Yu Zheng, Xinyu Tian, Tingting Wang, Xueli Xia, Fenghua Cao, Jie Tian, Ping Xu, Jie Ma, Huaxi Xu, Shengjun Wang
Journal: Molecular Cancer (2019)

Myeloid-derived suppressor cells (MDSCs) participate in tumor-elicited immunosuppression by dramatically blocking T-cell-induced antitumor responses, thereby influencing the effectiveness of cancer immunotherapies. Treatments that alter the differentiation and function of MDSCs can partially restore antitumor immune responses. The long noncoding RNA plasmacytoma variant translocation 1 (lncRNA Pvt1) is a potential oncogene in a variety of cancer types. However, whether lncRNA Pvt1 is involved in the regulation of MDSCs has not been thoroughly elucidated to date. MDSCs or granulocytic MDSCs (G-MDSCs) were isolated by microbeads and flow cytometry. Bone marrow derived G-MDSCs were induced by IL-6 and GM-CSF. The expression of lncRNA Pvt1 was measured by qRT-PCR. Specific siRNA was used to knockdown the expression of lncRNA Pvt1 in G-MDSCs. In this study, we found that knockdown of lncRNA Pvt1 significantly inhibited the immunosuppressive function of G-MDSCs in vitro. Additionally, lncRNA Pvt1 knockdown reduced the ability of G-MDSCs to delay tumor progression in tumor-bearing mice in vivo. Notably, lncRNA Pvt1 was upregulated by HIF-1α under hypoxia in G-MDSCs. Taken together, our results demonstrate a critical role for lncRNA Pvt1 in regulating the immunosuppression activity of G-MDSCs, and lncRNA Pvt1 might thus be a potential antitumor immunotherapy target.