tbuckley/cabot-search huggingface dataset:
Association of polymorphisms with tumor response in rectal cancer patients treated with capecitabine +/- oxaliplatine and radiation: Pharmacogenetic analysis of ACCORD-12/PRODIGE-2 trial.
Authors: Valerie Boige, Caroline Mollevi, David Azria, Sophie Gourgou, Jean Francois Seitz, Marc Vincent, Ludovic Bigot, Beata Juzyna, Isabelle Miran, Jean-Pierre Gerard, Pierre Laurent-Puig
Journal: Journal of Clinical Oncology (2016)

3583 Background: We examined whether 66 germline polymorphisms (SNPs) in 10 candidate genes (ERCC1, ERCC2, ERCC4, GSTP1, MTHFR, SOD2, TYMS, XPA, XRRC1, and XRCC3) would predict clinical outcome in the ACCORD-12 phase III trial which randomly compared neoadjuvant radiotherapy (RT) plus capecitabine (CAP45) with dose-intensified radiotherapy plus capecitabine and oxaliplatin (CAPOX50) in T3-4 Nx M0 resectable rectal cancer. Methods: A candidate-gene association study was conducted in 316 patients (n = 161 in the CAPOX50 and n = 155 in the CAP45 arm). The primary end-point was response according to the Dworak score in each arm. Logistic regressions were used to assess univariate/multivariate associations. The Storey and Tibshirani method based on the control of false discovery rate was used (q-value < 0.10 (adjusted p-value) considered as true discovery). Multivariate models adjusted on treatment arm and T stage were performed to determine prognostic and predictive values of SNPs for tumor response. Results: In univariate analysis, five SNPs in ERCC2 (rs1799787: OR = 3.46 [1.76; 6.79] and rs13181: OR = 0.28 [0.14; 0.58]), XPA (rs3176683: OR = 0.18 [0.05; 0.66]), MTHFR (rs7553194: OR = 4.60 [1.48; 14.3]) and ERCC1 (rs10412761: OR = 0.34 [0.17; 0.68]) were significantly associated with the Dworak score in the CAPOX50 arm, and none in the CAP45 arm. All but one (XPA) were confirmed in the multivariate analysis. Interaction was significant for ERCC2 (rs1799787, p= 0.05) and XPA (rs3176683, p= 0.008), and marginally significant for MTHFR (rs7553194, p= 0.053), suggesting a predictive effect of these SNPs for response to oxaliplatin-based chemoRT, and a prognostic effect of ERCC1 rs10412761 for response to chemoRT (+/- oxaliplatin). MTHFRrs7553194 was associated with overall survival in the multivariate analysis. Conclusions: This pharmacogenetic analysis shows that SNPs in four DNA repair/folate metabolic pathways genes have a significant association with response to chemoRT in patients with locally advanced rectal cancer. The predictive effect of ERCC2 and XPA may identify patients who benefit from oxaliplatin-based chemoRT.
Virus Filtration: Highly Efficient Virus Rejection with Self-Organized Membranes Based on a Crosslinked Bicontinuous Cubic Liquid Crystal (Adv. Healthcare Mater. 14/2017)
Authors: Nicolas Marets, Daniel Kuo, Jason R. Torrey, Takeshi Sakamoto, Masahiro Henmi, Hiroyuki Katayama, Takashi Kato
Journal: Advanced Healthcare Materials (2017)

For the first time, liquid-crystalline composite membrane for virus filtration in water treatment is reported by Hiroyuki Katayama, Takashi Kato, and co-workers in article number 1700252. The self-assembling liquid crystal forms uniform nanostructured bicontinuous cubic separation layer, minimizes the defect potentials and shows more than 99.9999% removal toward the virus. This development may spark more innovative designs for the future water treatment membrane.
Abstract P080: Bestrophin: A Potential Mediator of Cardiac Calcium Handling
Authors: Fiona C Britton, Steeven John, Kate E O'Driscoll, Martha Baring
Journal: Circulation Research (2011)

Bestrophins are a family of transmembrane proteins expressed in heart. We reported that Bestrophin 1 and 3 cloned from mouse heart function as calcium-activated chloride channels. We hypothesized that bestrophin channels may function in a macromolecule complex similar to other cardiac ion channels. To identify proteins that bind Bestrophin 3 channel, we screened a mouse heart cDNA library using 4 different cytosolic cDNA fragments as bait. Yeast two-hybrid assays were performed with the GAL4 system. Using bait consisting of C-terminus amino acid residues 386 to 669 of the Best3 channel (Best3-C2), we obtained positive interactions with the histidine-rich calcium binding protein (hrc). Hrc is a component of the SR complex involved in calcium handling in the heart. Eleven independent clones represented a fragment encoding the cysteine rich domain of hrc previously shown to interact with triadin. To further map the interaction sites between Best3-C2 and hrc, we subdivided this region into three fragments and tested these baits for interaction with hrc. Two Best3 fragments (residues 541–600 and residues 601–669) displayed strong interaction with hrc, while Best3 bait (residues 386–540) failed to interact. This region of Best3 contains a KEKE protein binding motif. In a similar manner C-terminal Best 1 fragments were confirmed to also interact with hrc. In this study we report that Bestrophin channels interact with hrc, a cardiac calcium handling protein. Calcium-activated chloride channels play a critical role in excitation-contraction coupling in the SR by balancing charge movement during calcium release and reuptake. Recent evidence confirms Bestrophin 1 is located in the ER membrane in association with Stim1 and facilitates calcium cycling. Future in vivo investigations will examine the role of bestrophins as potential mediators of calcium handling in heart.
Covalent coupling of high-affinity ligands to the surface of viral vector particles by protein trans-splicing mediates cell type-specific gene transfer
Authors: Alexander Muik, Johanna Reul, Thorsten Friedel, Anke Muth, Karen Patricia Hartmann, Irene C. Schneider, Robert C. Münch, Christian J. Buchholz
Journal: Biomaterials (2017)
Can We Reap the Benefits of Regionalization Without Paying the Price?
Authors: Peter A. Najjar, Stanley W. Ashley
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Ultrasound non-invasive measurement of intracranial pressure in neurointensive care: A prospective observational study
Authors: Chiara Robba, Danilo Cardim, Tamara Tajsic, Justine Pietersen, Michael Bulman, Joseph Donnelly, Andrea Lavinio, Arun Gupta, David K. Menon, Peter J. A. Hutchinson, Marek Czosnyka
Journal: PLoS Medicine (2017)

Background The invasive nature of the current methods for monitoring of intracranial pressure (ICP) has prevented their use in many clinical situations. Several attempts have been made to develop methods to monitor ICP non-invasively. The aim of this study is to assess the relationship between ultrasound-based non-invasive ICP (nICP) and invasive ICP measurement in neurocritical care patients. Methods and findings This was a prospective, single-cohort observational study of patients admitted to a tertiary neurocritical care unit. Patients with brain injury requiring invasive ICP monitoring were considered for inclusion. nICP was assessed using optic nerve sheath diameter (ONSD), venous transcranial Doppler (vTCD) of straight sinus systolic flow velocity (FVsv), and methods derived from arterial transcranial Doppler (aTCD) on the middle cerebral artery (MCA): MCA pulsatility index (PIa) and an estimator based on diastolic flow velocity (FVd). A total of 445 ultrasound examinations from 64 patients performed from 1 January to 1 November 2016 were included. The median age of the patients was 53 years (range 37–64). Median Glasgow Coma Scale at admission was 7 (range 3–14), and median Glasgow Outcome Scale was 3 (range 1–5). The mortality rate was 20%. ONSD and FVsv demonstrated the strongest correlation with ICP (R = 0.76 for ONSD versus ICP; R = 0.72 for FVsv versus ICP), whereas PIa and the estimator based on FVd did not correlate with ICP significantly. Combining the 2 strongest nICP predictors (ONSD and FVsv) resulted in an even stronger correlation with ICP (R = 0.80). The ability to detect intracranial hypertension (ICP ≥ 20 mm Hg) was highest for ONSD (area under the curve [AUC] 0.91, 95% CI 0.88–0.95). The combination of ONSD and FVsv methods showed a statistically significant improvement of AUC values compared with the ONSD method alone (0.93, 95% CI 0.90–0.97, p = 0.01). Major limitations are the heterogeneity and small number of patients included in this study, the need for specialised training to perform and interpret the ultrasound tests, and the variability in performance among different ultrasound operators. Conclusions Of the studied ultrasound nICP methods, ONSD is the best estimator of ICP. The novel combination of ONSD ultrasonography and vTCD of the straight sinus is a promising and easily available technique for identifying critically ill patients with intracranial hypertension.
Long noncoding RNA TSLNC8 is a tumor suppressor that inactivates the interleukin‐6/STAT3 signaling pathway
Authors: Jiwei Zhang, Zhe Li, Longzi Liu, Qifeng Wang, Shengli Li, Di Chen, Zhixiang Hu, Tao Yu, Jie Ding, Jinjun Li, Ming Yao, Shenglin Huang, Yingjun Zhao, Xianghuo He
Journal: Hepatology (2017)

Long noncoding RNAs can serve as oncogenes or tumor suppressors in human cancer; however, their biological functions and underlying mechanism in hepatocarcinogenesis are largely unknown. Here, we report a novel tumor suppressor long noncoding RNA on chromosome 8p12 (termed TSLNC8 ) that is frequently deleted and down‐regulated in hepatocellular carcinoma (HCC) tissues. The loss of TSLNC8 is highly associated with the malignant features of HCC and serves as a prognostic indicator for HCC patients. TSLNC8 significantly suppresses the proliferation and metastasis of HCC cells in vitro and in vivo . TSLNC8 exerts its tumor suppressive activity by competitively interacting with transketolase and signal transducer and activator of transcription 3 (STAT3) and modulating the STAT3‐Tyr705 and STAT3‐Ser727 phosphorylation levels and STAT3 transcriptional activity, thus resulting in inactivation of the interleukin‐6–STAT3 signaling pathway in HCC cells. Conclusion: TSLNC8 is a promising prognostic predictor for patients with HCC, and the TSLNC8–transketolase–STAT3 axis is a potential therapeutic target for HCC treatment. (H epatology 2018;67:171‐187).
Use of Prescription Smoking Cessation Medications After Myocardial Infarction Among Older Patients in Community Practice
Authors: Neha J. Pagidipati, Anne Hellkamp, Laine Thomas, Martha Gulati, Eric D. Peterson, Tracy Y. Wang
Journal: JAMA Cardiology (2017)

This population-based study uses the Acute Coronary Treatment and Intervention Outcomes Network Registry to evaluate the prevalence of smoking cessation medication use among patients following myocardial infarction.
Risk of cancer in patients with psoriasis on biological therapies: a systematic review
Authors: E. Peleva, L.S. Exton, K. Kelley, C.E. Kleyn, K.J. Mason, C.H. Smith
Journal: British Journal of Dermatology (2017)

Biological therapies are highly effective in psoriasis, but have profound effects on innate and adaptive immune pathways that may negatively impact on cancer immunosurveillance mechanisms.To investigate the risk of cancer in patients with psoriasis treated with biological therapy.We searched MEDLINE, Embase, and the Cochrane Library (up to August 2016) for randomized controlled trials, prospective cohort studies and systematic reviews that reported cancer incidence in people exposed to biological therapy for psoriasis compared with a control population.Eight prospective cohort studies met our inclusion criteria. All the evidence reviewed related to tumour necrosis factor inhibitors (TNFi) with the exception of one study on ustekinumab. An increased risk of nonmelanoma skin cancer (NMSC), particularly squamous cell carcinoma, was reported with TNFi compared with both a general United States population and a rheumatoid arthritis population treated with TNFi. No evidence for increased risk of cancers (reported as all cancers, lymphoma, melanoma, prostate, colorectal and breast cancer) other than NMSC was identified.There were important limitations to the studies identified including choice of comparator arms, inadequate adjustment for confounding factors and failure to account for latency periods of cancer. There remains a need for ongoing pharmacovigilance in relation to cancer risk and biological therapy; the NMSC signal requires further investigation to determine the risk specifically attributable to biological therapy using prospectively collected data with adjustment for known NMSC risk factors.
Antipsychotic drugs for the acute treatment of patients with a first episode of schizophrenia: a systematic review with pairwise and network meta-analyses
Authors: Yikang Zhu, Marc Krause, Maximilian Huhn, Philipp Rothe, Johannes Schneider-Thoma, Anna Chaimani, Chunbo Li, John M Davis, Stefan Leucht
Journal: The Lancet Psychiatry (2017)
Human induced pluripotent stem cell-derived vascular smooth muscle cells: differentiation and therapeutic potential
Authors: Sohrab Ayoubi, Søren P. Sheikh, Tilde V. Eskildsen
Journal: Cardiovascular Research (2017)

Cardiovascular diseases remain the leading cause of death worldwide and current treatment strategies have limited effect of disease progression. It would be desirable to have better models to study developmental and pathological processes and model vascular diseases in laboratory settings. To this end, human induced pluripotent stem cells (hiPSCs) have generated great enthusiasm, and have been a driving force for development of novel strategies in drug discovery and regenerative cell-therapy for the last decade. Hence, investigating the mechanisms underlying the differentiation of hiPSCs into specialized cell types such as cardiomyocytes, endothelial cells, and vascular smooth muscle cells (VSMCs) may lead to a better understanding of developmental cardiovascular processes and potentiate progress of safe autologous regenerative therapies in pathological conditions. In this review, we summarize the latest trends on differentiation protocols of hiPSC-derived VSMCs and their potential application in vascular research and regenerative therapy.
Cardiovascular Disease Among Transgender Adults Receiving Hormone Therapy
Authors: Carl G. Streed, Omar Harfouch, Francoise Marvel, Roger S. Blumenthal, Seth S. Martin, Monica Mukherjee
Journal: Annals of Internal Medicine (2017)

Recent reports estimate that 0.6% of adults in the United States, or approximately 1.4 million persons, identify as transgender. Despite gains in rights and media attention, the reality is that transgender persons experience health disparities, and a dearth of research and evidence-based guidelines remains regarding their specific health needs. The lack of research to characterize cardiovascular disease (CVD) and CVD risk factors in transgender populations receiving cross-sex hormone therapy (CSHT) limits appropriate primary and specialty care. As with hormone therapy in cisgender persons (that is, those whose sex assigned at birth aligns with their gender identity), existing research in transgender populations suggests that CVD risk factors are altered by CSHT. Currently, systemic hormone replacement for cisgender adults requires a nuanced discussion based on baseline risk factors and age of administration of exogenous hormones because of concern regarding an increased risk for myocardial infarction and stroke. For transgender adults, CSHT has been associated with the potential for worsening CVD risk factors (such as blood pressure elevation, insulin resistance, and lipid derangements), although these changes have not been associated with increases in morbidity or mortality in transgender men receiving CSHT. For transgender women, CSHT has known thromboembolic risk, and lower-dose transdermal estrogen formulations are preferred over high-dose oral formulations. In addition, many studies of transgender adults focus predominantly on younger persons, limiting the generalizability of CSHT in older transgender adults. The lack of randomized controlled trials comparing various routes and formulations of CSHT, as well as the paucity of prospective cohort studies, limits knowledge of any associations between CSHT and CVD.
Comment on Harlan. Islet Transplantation for Hypoglycemia Unawareness/Severe Hypoglycemia: Caveat Emptor. Diabetes Care 2016;39:1072–1074
Authors: Bernhard J. Hering, Nancy D. Bridges, Thomas L. Eggerman, Camillo Ricordi
Journal: Diabetes Care (2017)

Harlan (1) states that the benefits of islet transplantation in type 1 diabetes (T1D) are limited to patients already taking immunosuppressive agents because of having received a kidney transplant. We strongly disagree. The Clinical Islet Transplantation Consortium phase 3 trial (CIT-07) demonstrated the effectiveness of islet transplantation in restoring near normoglycemia, hypoglycemia awareness, and protection from severe hypoglycemic events in T1D patients with persistent severe hypoglycemic episodes (SHE) who are immunosuppressed only for the purpose of protecting the islet graft from rejection and autoimmune recurrence (2). The position of Harlan (1) seems to be that the morbidity and mortality of T1D complicated by persistent and unpredictable SHE are not sufficiently high to justify the immunosuppressive risks associated with an islet transplant–based approach. We disagree, and we feel that consideration of the risks and benefits of islet transplantation will result in a net benefit for some carefully selected patients. That evaluation and decision must be made on an individual basis, by a patient and …
Evaluation of immunological efficacy of Japanese herbal medicine, hochu-ekki-to and keishi-bukuryo-gan, in patients with castration-resistant prostate cancer under personalized peptide vaccination.
Authors: Noriko Koga, Fukuko Moriya, Kayoko Waki, Akira Yamada, Kyogo Itoh, Masanori Noguchi
Journal: Journal of Clinical Oncology (2017)

e16584 Background: This randomized phase II study investigated the immunological efficacy of herbal medicines (HMs) using Hochu-ekki-to and Keishi-bukuryo-gan, in combination with personalized peptide vaccination (PPV) for castration-resistant prostate cancer (CRPC). Methods: Seventy patients with CRPC were randomly assigned (1:1) to receive PPV plus HMs, or PPV alone. PPV treatment used a maximum of four peptides chosen from 31 peptides derived from cancer antigens according to human leukocyte antigen types and antigen-specific humoral immune responses before PPV, for 8 subcutaneous weekly injections. Peptide-specific cytotoxic T lymphocyte (CTL), immunoglobulin G (IgG), regulatory T cells (Treg), monocytic myeloid-derived suppressor cells (Mo-MDSC) and interleukin-6 (IL-6) responses were measured before and 8th vaccination. Clinical outcomes were also analyzed. Results: The combination therapy of PPV with HMs was well tolerated without severe adverse events but had no significant impact on antigen-specific IgG and CTL, Treg and clinical outcomes. The combination therapy of PPV with HMs stabilized the frequency of M0-MDSCs (1.91% to 1.92%, p = 0.96) and serum levels of IL-6 (19.2 pg/ml to 16.1 pg/ml, p = 0.63). On the other hand, the frequency of Mo-MDSC and levels of IL-6 in the PPV alone were significantly increased (0.91% to 1.49% for Mo-MDSC and 9.2 pg/ml to 19.4 pg/ml for IL-6, respectively). Conclusions: These results suggested that the combination usage of HMs reveals a potential to prevent the immunosuppression induced by Mo-MDSC or IL-6 during the immunotherapy. More research is needed to validate the findings of the present study. Clinical trial information: 000010290.
Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease
Authors: Jérôme Harambat, Kevin Kunzmann, Karolis Azukaitis, Aysun K. Bayazit, Nur Canpolat, Anke Doyon, Ali Duzova, Anna Niemirska, Betul Sözeri, Daniela Thurn-Valsassina, Ali Anarat, Lucie Bessenay, Cengiz Candan, Amira Peco-Antic, Alev Yilmaz, Sibylle Tschumi, Sara Testa, Augustina Jankauskiene, Hakan Erdogan, Alejandra Rosales, Harika Alpay, Francesca Lugani, Klaus Arbeiter, Francesca Mencarelli, Aysel Kiyak, Osman Dönmez, Dorota Drozdz, Anette Melk, Uwe Querfeld, Franz Schaefer
Journal: Kidney International (2017)
Abstract 130: Secretion of Angiogenic and Anti-apoptotic Factors Accompanies Mesenchymal Stem Cell-mediated Enhancement of Contractile Function in Engineered Cardiac Tissues
Authors: Timothy Cashman, Joshua Mayourian, Kevin D Costa
Journal: Circulation Research (2013)

Previous studies using three-dimensional engineered cardiac tissues (ECT) demonstrated beneficial effects of mesenchymal stem cells (MSC) on contractile function, recapitulating findings in animal studies and in clinical trials. But the mechanisms by which MSC effect this functional enhancement remain unclear. This study tested the hypothesis that MSC-mediated enhancement of ECT function involves paracrine signaling, independent of direct cell-cell interaction with cardiomyocytes (CM). To create ECT, CM were isolated from neonatal rat ventricles, mixed with 2.0 mg/ml bovine type I collagen and 0.9 mg/ml Matrigel, and pipetted into a custom elastomeric mold with integrated force sensing end-posts. Two types of ECT were created: one containing 1.5 million CM (“CM-only”) and the other containing 1.5 million CM supplemented with 150,000 MSC (“MSC-CM hybrid”). Contractile function of CM-only ECT was then assessed during 2-Hz pacing either in the presence or absence of hybrid tissues sharing the same media. Media surrounding the tissues was also collected and analyzed via protein microarray (RayBiotech) combined with Ingenuity Pathway Analysis software. CM-only ECT cultured for 5 days showed aligned and compacted structure with a cross-sectional area of 0.39 ± 0.03 mm 2 and a twitch force of 4.7 ± 0.7 N (mean ± SD; n = 6). In CM-only tissues co-cultured for 5 days in shared media alongside hybrid tissues, cross-sectional area was unchanged (0.42 ± 0.02 mm 2 , p = 0.17, n=3), but twitch force increased two-fold to 9.8 ± 6.5 N (p = 0.08). Threshold voltage for electrical pacing of CM-only ECT also decreased from 0.54 ± 0.12 V/mm to 0.39 ± 0.07 V/mm when co-cultured with hybrid ECT (p = 0.097). Protein microarray analysis of the shared co-culture conditioned media showed enrichment (relative to CM-only conditioned media) of the angiogenic factors VEGF (1240x) and IL-1 (8.6x) as well as the cardiac anti-apoptotic/pro-survival factors TNF (194x), bFGF (55x), and bNGF (14.9x). In conclusion, these findings support paracrine signaling, independent of direct cell-cell contact, as one mechanism of MSC-mediated enhancement of CM function in rat ECT. Identification and isolation of defined cardiotropic factors may lead to novel molecular therapies for cardiac repair.