tbuckley/cabot-search huggingface dataset:
Molecular profiling of hormone receptor-positive, HER2-negative breast cancers from patients treated with neoadjuvant endocrine therapy in the CARMINA 02 trial (UCBG-0609)
Authors: Xu Liang, Adrien Briaux, Véronique Becette, Camille Benoist, Anais Boulai, Walid Chemlali, Anne Schnitzler, Sylvain Baulande, Sofia Rivera, Marie-Ange Mouret-Reynier, Laurence Venat Bouvet, Thibaut De La Motte Rouge, Jérôme Lemonnier, Florence Lerebours, Céline Callens
Journal: Journal of Hematology & Oncology (2018)

Postmenopausal women with large, hormone receptor (HR)-positive/HER2-negative and low-proliferative breast cancer derived a benefit from neoadjuvant endocrine therapy (NET) in the CARMINA02 trial. This study was designed to correlate gene expression and mutation profiles with both response to NET and prognosis. Gene expression profiling using RNA sequencing was performed in 86 pre-NET and post-NET tumor samples. Targeted next-generation sequencing of 91 candidate breast cancer-associated genes was performed on DNA samples from 89 patients. Molecular data were correlated with radiological response and relapse-free survival. The transcriptional profile of tumors to NET in responders involved immune-associated genes enriched in activated Th1 pathway, which remained unchanged in non-responders. Immune response was confirmed by analysis of tumor-infiltrating lymphocytes (TILs). The percentage of TILs was significantly increased post-NET compared to pre-NET samples in responders (p = 0.0071), but not in non-responders (p = 0.0938). Gene expression revealed that lipid metabolism was the main molecular function related to prognosis, while PPARγ is the most important upstream regulator gene. The most frequently mutated genes were PIK3CA (48.3%), CDH1 (20.2%), PTEN (15.7%), TP53 (10.1%), LAMA2 (10.1%), BRCA2 (9.0%), MAP3K1 (7.9%), ALK (6.7%), INPP4B (6.7%), NCOR1 (6.7%), and NF1 (5.6%). Cell cycle and apoptosis pathway and PIK3CA/AKT/mTOR pathway were altered significantly more frequently in non-responders than in responders (p = 0.0017 and p = 0.0094, respectively). The average number of mutations per sample was significantly higher in endocrine-resistant tumors (2.88 vs. 1.64, p = 0.03), but no difference was observed in terms of prognosis. ESR1 hotspot mutations were detected in 3.4% of treatment-naive tumors. The Th1-related immune system and lipid metabolism appear to play key roles in the response to endocrine therapy and prognosis in HR-positive/HER2-negative breast cancer. Deleterious somatic mutations in the cell cycle and apoptosis pathway and PIK3CA/AKT/mTOR pathway may be relevant for clinical management. This trial is registered with ClinicalTrials.gov ( NCT00629616 ) on March 6, 2008, retrospectively registered.
GW29-e1728 The Application of Extracorporeal Membrane Oxygenation Combined with Intra-aortic Balloon Pump for High-risk Percutaneous Coronary Intervention
Authors: Yigang Qiu, Zhengming Xu, Xu Pan, Zhichao Wang, Ning Xue, Haitao Chi, Jianyong Zheng, Han Li, Jiangchun He, Zhong Yin, Chuzhong Tang, Tian-chang Li
Journal: Journal of the American College of Cardiology (2018)
Adult rhabdomyosarcoma in Tunisia: Clinical presentation, treatment and outcome
Authors: M. Saadi, D. Tajina, F. Letaief-Ksontini, K. Meddeb, A. Gabsi, Y. Yahyaoui, A. Mokrani, M. Ayadi, N. Chraiet, H. Rais, A. Mezlini
Journal: Annals of Oncology (2018)
SP0018 Smart wearables and health apps – the right tool for health monitoring and improving quality of health?
Authors: M. Silva
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> What role can technology play in enabling a shift from a traditional paternalistic model of care to a model based on empowered patient sharing ownership? In the traditional model, patients are fully reliant on the healthcare professional for information, diagnosis and treatment, with complexity to navigate through the ecosystem and where physicians are empowered rather than patients. Patient empowerment is enhanced thanks to technology enabled care, in which patients have access to their medical files, can use tools that allow them to be proactive and focus on prevention and where self-management is supported across the treatment pathway. Smart wearables and health apps are becoming more widespread and a commodity, while more and more research is being performed on the effectiveness of such devices on the quality of life of patients. The design of wearables and health apps itself can be approached in a patient-centric way, to maximise the benefits for patients and the uptake by patients. This presentation will discuss some evidences of the impact of technology on improvement of quality of life and how patients should be included in the design process. <h3>Disclosure of Interest</h3> M. Silva Shareholder of: Esperity SPRL, Simperium BVBA, Grant/research support from: EUPATI Belgium VZW, Consultant for: Janssen Pharmaceutics, Novartis, Sanofi, Pfizer, ReumaNet
Pan-cancer assessment of BRCA1/2 genomic alterations (GAs) by comprehensive genomic profiling (CGP) of tissue and circulating tumor DNA (ctDNA)
Authors: N. Agarwal, E.S. Sokol, P. Lara, J.S. Ross, V.A. Miller, A.W. Welsh, J.P. Gregg, G.M. Frampton, S.M. Ali, J. Chung
Journal: Annals of Oncology (2018)
Statins, saphenous vein endothelial function, and C-Reactive Protein in patients with coronary artery disease
Authors: A U Momin, N Melikian, S Wheatcroft, D Grieve, L John, A El-Gamel, M Marrinan, J Desai, C Driver, R Sherwood, A Shah, M Kearney
Journal: Journal of the American College of Cardiology (2006)
Circular RNA YAP1 inhibits the proliferation and invasion of gastric cancer cells by regulating the miR-367-5p/p27 Kip1 axis
Authors: Hui Liu, Yuan Liu, Zhaolian Bian, Jing Zhang, Rui Zhang, Xiaoyu Chen, Yanxia Huang, Yang Wang, Jinshui Zhu
Journal: Molecular Cancer (2018)

Circular RNAs (circRNAs) are a new type of non-coding RNAs and their functions in gastric cancer (GC) remain unclear. Recent studies have revealed that circRNAs play an important role in cancer development and certain types of pathological responses, acting as microRNA (miRNA) sponges to regulate gene expression. CircNet was used to screen potential circRNAs and validated circYAP1 expression levels in 17 GC tissues by quantitative real-time PCR (qRT-PCR) and another 80 paired GC tissues by FISH. CircYAP1 overexpression and knockdown experiments were conducted to assess the effects of circYAP1 in vitro and in vivo, and its molecular mechanism was demonstrated by RNA in vivo precipitation assays, western blotting, luciferase assay and rescue experiments. CircYAP1 expression level was significantly lower in GC tissues than the adjacent normal tissues, and GC patients with circYAP1 low expression had shorter survival times as compared with those with circYAP1 high expression. Functionally, circYAP1 overexpression inhibited cell growth and invasion in vitro and in vivo, but its knockdown reversed these effects. Further analysis showed that circYAP1 sponged miR-367-5p to inhibit p27 Kip1 expression and GC progression. Our findings demonstrate that circYAP1 functions as a tumor suppressor in GC cells by targeting the miR-367-5p/p27 Kip1 axis and may provide a prognostic indicator of survival in GC patients.
Normal human skin is superior to monkey oesophagus substrate for detection of circulating <scp>BP</scp> 180‐ <scp>NC</scp> 16A‐specific IgG antibodies in bullous pemphigoid
Authors: S. Emtenani, H. Yuan, C. Lin, M. Pan, J.E. Hundt, E. Schmidt, L. Komorowski, J.R. Stanley, C.M. Hammers
Journal: British Journal of Dermatology (2018)

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering skin disease. Two antigens have been identified as targets of circulating autoantibodies (autoAbs) - BP180 and BP230 - with BP180 being a critical transmembrane adhesion protein of basal keratinocytes of the epidermis. The noncollagenous domain 16A (NC16A) of BP180 is the immunodominant epitope in patients with BP, and anti-BP180-NC16A IgG antibodies (Abs) correlate to disease activity. Routine serological testing and follow-up of BP relies on indirect immunofluorescence (IIF) of serum Abs, commonly performed on monkey oesophagus (ME), and/or enzyme-linked immunosorbent assay (ELISA) testing on recombinantly produced fragments of BP180 and BP230 (BP180-NC16A, BP230-C/N).To determine if NC16A epitopes are well represented on ME substrate.Sera from different BP cohorts were tested by IIF on ME and normal human skin (NHS). To confirm findings, affinity-purified anti-BP180-NC16A/BP230 polyclonal Abs and recombinant anti-BP180-NC16A/BP230 monoclonal antibodies (mAbs) were used.For sensitive detection of BP180-NC16A-specific IgG Abs, sections of NHS are superior to the widely used ME. Confirmation comes from polyclonal affinity-purified anti-BP180-NC16A/BP230 Abs, and by mAbs cloned from a patient with active BP.Use of NHS is preferable over ME in routine IIF testing for BP. These results are of clinical relevance because anti-BP180-NC16A IgG titres are correlated to disease activity and detecting them reliably is important for screening, diagnosis and follow-up of patients with BP.
A Phase I Dose-Escalation Study of Veliparib Combined with Carboplatin and Etoposide in Patients with Extensive-Stage Small Cell Lung Cancer and Other Solid Tumors
Authors: Florence Atrafi, Harry J.M. Groen, Lauren A. Byers, Elena Garralda, Martijn P. Lolkema, Randeep S. Sangha, Santiago Viteri, Young Kwang Chae, D. Ross Camidge, Nashat Y. Gabrail, Beibei Hu, Tian Tian, Silpa Nuthalapati, Elizabeth Hoening, Lei He, Philip Komarnitsky, Antonio Calles
Journal: Clinical Cancer Research (2018)

This study examined safety, pharmacokinetics, and efficacy of veliparib, a PARP inhibitor, combined with carboplatin and etoposide in patients with extensive-stage (ED) small cell lung cancer (SCLC) and other solid tumors.The 3 + 3 design was used for dose escalation of oral veliparib in combination with carboplatin (AUC 5 on day 1) and etoposide (100 mg/m2 on days 1-3) in 21-day cycles. Veliparib dose was explored from 80 to 240 mg b.i.d. on 7-day, 14-day, or continuous schedules. Patients without disease progression continued on maintenance monotherapy (veliparib 400 mg b.i.d.) until disease progression or unacceptable toxicity.Thirty-nine patients were enrolled to determine the recommended phase II dose of 240 mg veliparib for 14 days combined with carboplatin and etoposide based on long-term tolerability. Dose-limiting toxicity occurred in 1 patient (grade 2 toxic motor polyneuropathy) at veliparib 240 mg b.i.d. for 7 days. Most common adverse events related to veliparib were nausea (39%), fatigue (39%), and hematologic toxicities. Continuous dosing of veliparib 240 mg b.i.d. with carboplatin and etoposide resulted in excessive chemotherapy dose delays due to hematologic toxicity (grade 3/4 neutropenia/thrombocytopenia). Etoposide pharmacokinetics was not affected by veliparib. Confirmed responses occurred in 17 of 39 (44%) and 16 of 25 (64%) of all enrolled and ED SCLC patients, respectively. At the RP2D, confirmed responses occurred in 6 of 13 (46%) and 5 of 6 (83%) of all enrolled and ED SCLC patients, respectively.Veliparib (240 mg b.i.d. 14 days) plus carboplatin/etoposide can be safely combined. Phase II of this study is ongoing in first-line patients with ED SCLC.
Professor must be supervised for three years after improperly pursuing emotional relationship with patient
Authors: Clare Dyer
Journal: BMJ (2018)

A professor of clinical nephrology at King’s College Hospital in London who told a patient that he was “a bit infatuated” with her must work under supervised conditions for three years after a medical practitioners’ tribunal accepted his claim that he did not want a sexual relationship, but found that he had improperly pursued an emotional one.

Iain Macdougall, 57, telephoned five times and left a voicemail over a few days in 2016, telling a patient who struggled with alcoholism that “you kind of, slightly, got under my skin” and that “you should take it as a massive compliment that you attract doctors.”

The 62 year old woman recorded some of the calls and reported Macdougall to the hospital. The medical practitioners’ tribunal in Manchester heard the …
GW29-e1070 Prognostic value of heart rate by dynamic electrocardiogram in hospitalized heart failure patients with atrial fibrillation
Authors: Wenjia Guo, Fei She, Haotian Wang, Rong He, Yuanwei Liu, Tingting Lv, Kun Li, Siyuan Li, Ruiqi Zhang, Ping Zhang
Journal: Journal of the American College of Cardiology (2018)
Metronomic capecitabine plus cyclophosphamide in unresectable or relapsed pseudomyxoma peritonei
Authors: A. Raimondi, S. Corallo, M. Niger, M. Antista, G. Randon, F. Morano, C. Cremolini, M. Di Bartolomeo, F.G.M. de Braud, F. Pietrantonio
Journal: Annals of Oncology (2018)
Tumour microenvironment and metabolic plasticity in cancer and cancer stem cells: Perspectives on metabolic and immune regulatory signatures in chemoresistant ovarian cancer stem cells
Authors: Nuzhat Ahmed, Ruth Escalona, Dilys Leung, Emily Chan, George Kannourakis
Journal: Seminars in Cancer Biology (2018)

Cancer stem cells (CSCs) are a sub-population of tumour cells, which are responsible to drive tumour growth, metastasis and therapy resistance. It has recently been proposed that enhanced glucose metabolism and immune evasion by tumour cells are linked, and are modulated by the changing tumour microenvironment (TME) that creates a competition for nutrient consumption between tumour and different sub-types of cells attracted to the TME. To facilitate efficient nutrient distribution, oncogene-induced inflammatory milieu in the tumours facilitate adaptive metabolic changes in the surrounding non-malignant cells to secrete metabolites that are used as alternative nutrient sources by the tumours to sustain its increasing energy needs for growth and anabolic functions. This scenario also affects CSCs residing at the primary or metastatic niches. This review summarises recent advances in our understanding of the metabolic phenotypes of cancer cells and CSCs and how these processes are affected by the TME. We also discuss how the evolving TME modulates tumour cells and CSCs in cancer progression. Using previously described proteomic and genomic platforms, ovarian cancer cell lines and a mouse xenograft model we highlight the existence of metabolic and immune regulatory signatures in chemoresistant ovarian CSCs, and discuss how these processes may affect recurrence in ovarian tumours. We propose that progress in cancer control and eradication may depend not only on the elimination of highly chemoresistant CSCs, but also in designing novel strategies which would intervene with the tumour-promoting TME factors.
GW29-e1351 low-level vagus nerve stimulation inhibit atrial electronic and neural remodeling in atrial fibrillation induced by obstructive sleep apnea
Authors: Ling Zhang, Xianhui Zhou, Yanmei Lu, Yaodong Li, Qiang Xing, Jianghua Zhang, Baopeng Tang
Journal: Journal of the American College of Cardiology (2018)
Abstract 18399: Polyethylene Glycol-20k Improves Microcirculation in a Rat Model of Cardiopulmonary Resuscitation
Authors: Jin Yang, Navami Ravindra, Changqing Miao, Yan Xiao, Weiping Huang, Zhangle Hu, Qinyue Guo, Xiaobo Wu, Jennifer Bradley, Mary Ann Peberdy, Joseph P Ornato, Martin Mangino, Wanchun Tang
Journal: Circulation (2017)

Introduction: Polyethylene Glycol-20K (PEG-20K) improves the microcirculation by alleviating ischemia-induced cell swelling, decompressing capillaries, and enhancing capillary oxygen transfer in a ...
Abstract 14823: Adult Congenital Heart Disease is Associated With a Decreased Prevalence of Morbid Obesity
Authors: Joseph B Lerman, John T Doucette, Ira A Parness, Rajesh U Shenoy
Journal: Circulation (2015)

Introduction: Obesity may be associated with greater morbidity in adults with Congenital Heart Disease (ACHD), than in the general population. While obesity prevalence in pediatric CHD has been well studied, the prevalence of obesity in the American ACHD population is unknown. Our study seeks to determine the prevalence of obesity (BMI &gt; 30) and morbid obesity (BMI &gt; 35) in a cohort of ACHD patients, as compared to matched controls. Hypothesis: We assessed the hypothesis that ACHD is associated with a higher prevalence of obesity compared to controls. Methods: Retrospective analysis was performed on all ACHD patients (identified via ICD-9 coding) seen at a tertiary center in 2013. A control group without CHD was randomly created, matching for age, sex, and ethnicity. Results: 1459 ACHD patients met inclusion criteria. ACHD patients had a lower mean BMI than controls (-0.650 kg/m2, 95% CI -1.068 to -0.231, p &lt;0.002). Obesity prevalence did not differ significantly between groups: 25.6% in ACHD, 27.4% in controls (OR 0.909, 95% CI 0.766 to 1.079, p = 0.285). ACHD was associated with lower prevalence of morbid obesity (OR =0.656, CI 0.511 to 0.841, p &lt; 0.0001), and higher prevalence of being underweight (BMI &lt; 18.5) (OR 1.709, 95% CI 1.098 to 2.663, p &lt; 0.016). ACHD was also associated with a lower prevalence of obesity amongst 41-65 year olds (OR = 0.722, 95% CI from 0.561 to 0.929, p &lt; 0.011). Severity of CHD (classified as simple vs. complex) was not significantly related to obesity prevalence. Conclusion: In conclusion, ACHD is associated with a decreased prevalence of morbid obesity, and an increased prevalence of being underweight. ACHD is not significantly associated with obesity prevalence.
Whither pulmonary rehabilitation? Will alternative modes help or hurt?
Authors: Richard Casaburi
Journal: European Respiratory Journal (2018)

<b>Pulmonary rehabilitation is available to only a sliver of COPD patients. Studies have explored less resource intensive approaches. Unless they prove to be at least as effective, traditional pulmonary rehabilitation availability may be further reduced.</b>http://ow.ly/fyh930lYFo2
Abstract 11592: Lipid Droplet Associated Hydrolase (LDAH) Enhances Triacylglycerol Accumulation by Antagonizing Adipose Triglyceride Lipase (ATGL)
Authors: Younghwa Goo, Sehee Son, Antoni Paul
Journal: Circulation (2015)

Lipid droplets (LDs) are lipid storage depots as well as metabolically dynamic organelles. LD-associated hydrolase (LDAH) is a newly identified protein that is highly expressed in liver and adipose tissues, where triacylglycerol (TAG) is the main form of lipid stored in LDs. However, to date the role of LDAH in TAG metabolism has not been reported. In this study we show that upon oleic acid loading LDAH translocalizes from the endoplasmic reticulum (ER) to the LD surface, and increases the size of LDs by promoting fusion in a tubulin-dependent fashion. LDAH overexpression in HEK 293 cells increased the net TAG content, while LDAH knockdown decreased TAG levels. Mutations in two predicted acyltransferase motifs aiming to assess if changes in TAG content is due to LDAH’s direct enzymatic activity did not affect TAG levels. However, an LDAH splicing variant missing 90 amino acid at C-terminus also localized to LDs, but failed to increase both LD fusion and TAG levels. Consistent with the increase in LD size and area, LDAH increased the level of Perilipin3, a major LD associated protein in HEK293 cells, but decreased the level of adipose triglyceride lipase (ATGL) that regulates rate-limiting step of TAG hydrolysis. ATGL ubiquitination, which ultimately leads to protein degradation, was higher in LDAH-overexpressing cells, and treatment with MG132 to block the activity of the 26S proteasome complex attenuated the reduction in ATGL. Coexpression of ATGL with LDAH reduced LDAH-mediated increase in LD size, total area of LDs, and TAG content. Alternatively, LDAH delayed TAG hydrolysis by ATGL upon treatment with β-adrenergic agonists. In conclusion, the data support a role of LDAH in facilitating LD growth and TAG accumulation, and uncover a mutually antagonistic interaction between LDAH and the catabolic enzyme ATGL.
Deregulation of neuronal miRNAs induced by amyloid-β or TAU pathology
Authors: Annerieke Sierksma, Ashley Lu, Evgenia Salta, Elke Vanden Eynden, Zsuzsanna Callaerts-Vegh, Rudi D’Hooge, David Blum, Luc Buée, Mark Fiers, Bart De Strooper
Journal: Molecular Neurodegeneration (2018)
Pharmacokinetics, pharmacodynamics and safety of aptamers
Authors: Katarina D. Kovacevic, James C. Gilbert, Bernd Jilma
Journal: Advanced Drug Delivery Reviews (2018)

Aptamers are synthetic molecules structured as single-stranded DNA or RNA oligonucleotides that can be designed to mimic the functional properties of monoclonal antibodies. They bind to the target molecules (typically soluble or cell-bound proteins) with high affinity (with picomolar to low nanomolar range) and specificity, and therefore can be an alternative to therapeutic antibodies or peptide ligands. This paper reviews published data regarding pharmacokinetics, pharmacodynamics and safety of aptamers from preclinical and clinical studies. Aptamers have been developed for the treatment of a variety of diseases, including cancer, macular degeneration,g cardiovascular disease, diabetes and anaemia of chronic diseases. There are several preclinical studies with unmodified aptamers, but the vast majority of aptamer trials in humans have been conducted with modified aptamers, because unmodified aptamers demonstrate metabolic instability, as well as rapid renal filtration and elimination. Various strategies have been developed to improve the pharmacokinetic profile of aptamers. Aside from chemical modification of nucleotides in order to stabilize them against nuclease degradation, the main modification to extend the half-life is pegylation. Therefore, the process of pegylation as well as its benefits and possible shortcomings will briefly be discussed.
Abstract 20232: Regulation of Cell Cycle to Stimulate Adult Cardiomyocyte Proliferation and Cardiac Regeneration
Authors: Tamer M Mohamed, Yen-Sin Ang, Ethan Radzinsky, Ping Zhou, Yu Huang, Arye Elfenbein, Amy Foley, Sergey Magnitsky, Deepak Srivastava
Journal: Circulation (2017)

Background: Heart failure is often caused by loss of cardiac cells that are unable to re-enter the cell cycle for regeneration. Numerous attempts to identify such cell cycle regulators that could i...
Lead author of Cochrane HPV review did not breach conflicts policy, find arbiters
Authors: Nigel Hawkes
Journal: BMJ (2018)

Cochrane has determined that the lead author of its review on human papillomavirus vaccine, Marc Arbyn, did not breach its rules on commercial sponsorship by not declaring his involvement in two organisations funded in whole or part by industry.

The complaints about alleged conflicts of interest undisclosed by Arbyn, of the Belgian Cancer Centre in Brussels, were made by several organisations and individuals after the review was published in May 2018.1 The first complaint seems to have come from the Japanese organisation Yakugai, which published a critique of the review on 7 June.2

Yakugai has campaigned against use of the vaccine, holding meetings at which people claiming to have been injured by the vaccine …