tbuckley/cabot-search huggingface dataset:
Long‐term effectiveness of oral second‐generation antipsychotics in patients with schizophrenia and related disorders: a systematic review and meta‐analysis of direct head‐to‐head comparisons
Authors: Taishiro Kishimoto, Katsuhiko Hagi, Masahiro Nitta, John M. Kane, Christoph U. Correll
Journal: World Psychiatry (2019)

Second‐generation antipsychotics (SGAs) are recommended for maintenance treatment in schizophrenia. However, comparative long‐term effectiveness among SGAs is unclear. Here we provide a systematic review and meta‐analysis of randomized trials lasting ≥⃒6 months comparing SGAs head‐to‐head in schizophrenia and related disorders. The primary outcome was all‐cause discontinuation. Secondary outcomes included efficacy and tolerability, i.e., psychopathology, inefficacy‐related and intolerability‐related discontinuation, relapse, hospitalization, remission, functioning, quality of life, and adverse events. Pooled risk ratio and standardized mean difference were calculated using random‐effects models. Across 59 studies (N=45,787), lasting 47.4±32.1 weeks (range 24‐186), no consistent superiority of any SGA emerged across efficacy and tolerability outcomes. Regarding all‐cause discontinuation, clozapine, olanzapine and risperidone were significantly (p&lt;0.05) superior to several other SGAs, while quetiapine was inferior to several other SGAs. As to psychopathology, clozapine and olanzapine were superior to several other SGAs, while quetiapine and ziprasidone were inferior to several other SGAs. Data for other efficacy outcomes were sparse. Regarding intolerability‐related discontinuation, risperidone was superior and clozapine was inferior to several other SGAs. Concerning weight gain, olanzapine was worse than all other compared non‐clozapine SGAs, and risperidone was significantly worse than several other SGAs. As to prolactin increase, risperidone and amisulpride were significantly worse than several other SGAs. Regarding parkinsonism, olanzapine was superior to risperidone, without significant differences pertaining to akathisia. Concerning sedation and somnolence, clozapine and quetiapine were significantly worse than some other SGAs. In summary, different long‐term SGA efficacy and tolerability patterns emerged. The long‐term risk‐benefit profiles of specific SGAs need to be tailored to individual patients to optimize maintenance treatment outcomes.
Abstract B15: RSK2 signals through stathmin to promote microtubule dynamics and tumor metastasis
Authors: Gina Alesi, Lingtao Jin, Dan Li, Kelly Magliocca, Yibin Kang, Zhuo G. Chen, Dong M. Shin, Fadlo R. Khuri, Sumin Kang
Journal: Cancer Research (2016)

Abstract Metastasis is responsible for over 90% of cancer related deaths. Complex signaling in cancer cells orchestrates the progression from a primary to a metastatic cancer. However, the mechanisms of these cellular changes remain elusive. We previously demonstrated that p90 ribosomal S6 kinase 2 (RSK2) promotes tumor metastasis. Here, we investigated the role of RSK2 in the regulation of microtubule dynamics and its potential implication in cancer cell invasion and tumor metastasis. Stable knockdown of RSK2 disrupted microtubule stability and decreased phosphorylation of stathmin, a microtubule destabilizing protein, at serine 16 in metastatic human cancer cells. We found that RSK2 directly binds and phosphorylates stathmin at the leading edge of cancer cells. Phosphorylation of stathmin by RSK2 reduced stathmin-mediated microtubule depolymerization. Moreover, overexpression of phospho-mimetic mutant stathmin S16D significantly rescued the decreased invasive and metastatic potential mediated by RSK2 knockdown in vitro and in vivo. Furthermore, stathmin phosphorylation positively correlated with RSK2 expression and metastatic cancer progression in primary patient tumor samples. Our finding demonstrates that RSK2 directly phosphorylates stathmin and regulates microtubule polymerization to provide a pro-invasive and pro-metastatic advantage to cancer cells. Therefore, the RSK2-stathmin pathway represents a promising therapeutic target and a prognostic marker for metastatic human cancers. Citation Format: Gina Alesi, Lingtao Jin, Dan Li, Kelly Magliocca, Yibin Kang, Zhuo G. Chen, Dong M. Shin, Fadlo R. Khuri, Sumin Kang. RSK2 signals through stathmin to promote microtubule dynamics and tumor metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B15.
Abstract OT1-09-01: Phase II trial assessing accuracy of tumor bed biopsies in predicting pathologic response in patients with clinical/radiological complete response after neoadjuvant chemotherapy in order to explore the feasibility of breast-conserving surgery without surgery: NRG Oncology BR005
Authors: M Basik, JP Costantino, JF De Los Santos, HR Umphrey, TB Julian, EP Mamounas, JR White, PC Lucas, JL Wagner, JA Tjoe, AM Thompson, N Wolmark
Journal: Cancer Research (2019)

Abstract The increased use of neoadjuvant chemotherapy (NCT) has enabled higher rates of breast-conserving surgery (BCS) as well as provided prognostic information for women with breast cancer. High pathological complete response (pCR) rates question the requirement for surgery, with its attendant morbidity. In order to avoid surgery, the ability to predict pCR prior to it must be very high. Trimodality imaging alone is inadequate to predict pCR prior to surgery. We hypothesize that performing core-needle biopsy (bx) of the tumor bed in addition to trimodality imaging in patients (pts) having had a clinical complete response (cCR) will increase the ability to predict pCR. Utilizing predetermined imaging response criteria of complete or near-complete response coupled with a stereotactic core-needle bx of the tumor bed, BR005 aims to determine the predictive value of imaging followed by tumor bed bx for pCR and demonstrate its reproducibility across a multi-institutional setting. Methods: 175 pts with operable focal or multifocal (T1-T3), stage II/IIIA invasive ductal carcinoma (all receptor subtypes) will be entered. Pts must have completed a minimum of 8 wks of standard NCT and achieved a complete or near-complete radiologic tumor response on breast imaging with mammogram, ultrasound, and MRI, and undergo BCS. Following cCR and prior to surgery, pts will undergo a stereotactic-vacuum-assisted breast bx with clip placement. The primary endpoint is the proportion of pts with post-NCT neg image-directed bx who have a pCR. Residual cancer burden scores and core bx pathology will be collected along with trimodality imaging data. Evaluation after 135 pts will allow for the possibility of early termination of the study. Results will provide the first step toward a paradigm change in the treatment of breast cancer, enabling a study to assess the criteria for successful avoidance of surgery in pts with high response rates to NCT. Accrual as of 6-15-18: 39 (22.3%). Support: U10CA180868, -180822, UG1CA189867. Citation Format: Basik M, Costantino JP, De Los Santos JF, Umphrey HR, Julian TB, Mamounas EP, White JR, Lucas PC, Wagner JL, Tjoe JA, Thompson AM, Wolmark N. Phase II trial assessing accuracy of tumor bed biopsies in predicting pathologic response in patients with clinical/radiological complete response after neoadjuvant chemotherapy in order to explore the feasibility of breast-conserving surgery without surgery: NRG Oncology BR005 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-09-01.
Malnutrition in idiopathic pulmonary fibrosis: the great forgotten comorbidity!
Authors: Stéphane Jouneau, Mathieu Lederlin, Laurent Vernhet, Ronan Thibault
Journal: European Respiratory Journal (2019)

The publication by Torrisi et al . [1] in the European Respiratory Journal evaluated the ability of comorbidities to improve the prediction of survival of idiopathic pulmonary fibrosis (IPF) patients. These variables are in addition to those in the best validated Gender-Age-Physiology (GAP) multivariable prediction model for mortality in IPF. The authors have added to the four parameters (age, sex, forced vital capacity per cent predicted and diffusing capacity of the lung for carbon monoxide per cent predicted) of the GAP model [2] comorbidities such as gastro-oesophageal reflux, pulmonary hypertension, lung cancer, valvular heart disease and atrial arrhythmias, which were found to have a significant impact on survival. They showed that the inclusion of comorbidities in TORVAN models significantly improved the prediction of the risk of death. BMI/nutritional assessment should be part of the evaluation of IPF patients, since it has an impact on prognosis <http://ow.ly/BBe930ocgx5>
Abstract B38: Molecular mechanisms and therapeutic implications of argininosuccinate synthesis 1 regulation in targeted arginine- and glutamine-starvation cancer therapy
Authors: Macus Tien Kuo, Wen-Bin Tsai, Yan Long
Journal: Clinical Cancer Research (2018)

Abstract Argininosuccinate synthetase 1 (ASS1) is the rate-limiting enzyme that catalyzes the biosynthesis of arginine (Arg). Many malignant human tumors are auxotrophic for Arg because ASS1 is silenced. We previously demonstrated that ASS1 is a sensor of Arg auxotrophic response and a chemosensitivity marker for Arg starvation therapy. Upregulation of ASS1 is the primary mechanism of resistance to Arg starvation therapy using Arg-depleting recombinant protein, pegylated arginine deiminase (ADI-PEG20). We will present in this conference that ASS1 is also a sensor for glutamine (Gln)-deprivation response, and that upregulation of ASS1 expression is associated with resistance to Gln-starvation treatments. Knockdown of ASS1 expression resulted in increased sensitivity to both Arg- and Gln-starvation, whereas increased ASS1 expression by ectopic transfection is associated with resistance to both Arg- and Gln-starvation. The addition of permeable fumarate, a metabolite that bridges the tricarboxylic acid and urea cycles, resulted in downregulation of ASS1 expression and increased sensitivity to both Arg- and Gln-deprivation treatments. Metabolically, ASS1 sits in the middle of several metabolic pathways linking Gln and ASS1 metabolism. This may explain how ASS1 can sense both Gln- and Arg-starvation from opposite directions. Mechanistically, the Gln-deprivation response, like the Arg-auxotrophic response, downregulates HIF-1α resulting in de-repression of ASS1. In the meantime, an activator, c-Myc, is upregulated; and the upregulated c-Myc transcriptionally turns on ASS1 expression. We further also demonstrate that Arg starvation-induced c-Myc activation is regulated by the signaling transduction pasthway involving Gas/Axl → PI3 kinase → Akt → GSK3beta → cMyc. Collectively, our results have revealed the molecular basis of auxotropic responses to Arg- and Gln-deprivation, and provided preclinical implications for improving the treatment efficacy of Arg- and Gln-starvation therapies which have been in several current clinical trials. (Supported by NCI grant R01 CA149260.) Note: This abstract was not presented at the conference. Citation Format: Macus Tien Kuo, Wen-Bin Tsai, Yan Long. Molecular mechanisms and therapeutic implications of argininosuccinate synthesis 1 regulation in targeted arginine- and glutamine-starvation cancer therapy [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B38.
Abstract 17003: Development of a Mouse Model of Metabolic Syndrome, Pulmonary Hypertension, and Heart Failure With Preserved Ejection Fraction (PH-HFpEF)
Authors: Yen-Chun Lai, Qingqing Meng, Neil Kelly, Marta Bueno, Jeffery Baust, Timothy Bachman, Rebecca Vanderpool, Josiah Radder, Jian Hu, Alison Morris, Ana Mora, Mark Gladwin
Journal: Circulation (2016)

Introduction: Pulmonary hypertension associated with heart failure and preserved ejection fraction (PH-HFpEF; WHO Group II) secondary to left ventricular diastolic dysfunction is the most frequent ...
Abstract P6-21-10: Not presented
Authors: R Pacaud, S Thomas, E Roche, N Pawlowska, P Munster
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Pacaud R, Thomas S, Roche E, Pawlowska N, Munster P. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-21-10.
Association of Psoriasis With Mental Health Disorders in South Korea
Authors: Chul Hwan Bang, Jae Woong Yoon, Jae Heon Chun, Ju Hee Han, Young Min Park, Suk Jun Lee, Ji Hyun Lee
Journal: JAMA Dermatology (2019)

This case-control study uses population-based data to examine the association of psoriasis with mental health disorders, and to identify trends in their rates of occurrence and times to onset after diagnosis of psoriasis.
Abstract P2-08-32: Withdrawn
Authors: SP Perimbeti, R Shrivastav, K Ward, M Styler
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Perimbeti SP, Shrivastav R, Ward K, Styler M. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-32.
Importance of Nonobstructive Coronary Artery Disease in the Prognosis of Patients With Heart Failure
Authors: Juarez R. Braga, Peter C. Austin, Heather J. Ross, Jack V. Tu, Douglas S. Lee
Journal: JACC Heart Failure (2019)

This study sought to examine the prognostic significance of nonobstructive coronary artery disease (CAD) in patients with heart failure (HF), as a distinct category apart from those with normal coronary arteries.Individuals with HF are often dichotomized into ischemic versus nonischemic categories according to the underlying etiology. This binary classification creates a heterogeneous group, combining individuals with nonobstructive CAD with those with normal coronary arteries under the nonischemic label.A cohort of individuals with HF and reduced ejection fraction undergoing invasive coronary angiography was examined and linked to administrative databases for outcomes evaluation. Patients were divided into those with normal coronary arteries, nonobstructive disease, and obstructive disease. The primary outcome was the composite of cardiovascular death, nonfatal acute myocardial infarction, nonfatal stroke, or HF hospitalization.Of 12,814 individuals, 2,656 (20.7%) had normal coronary arteries, 2,254 (17.6%) had nonobstructive CAD, and 7,904 (61.7%) had obstructive CAD. The risk of the primary outcome was increased in the nonobstructive group (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.04 to 1.32; p = 0.01) relative to those with normal coronary arteries. Nonobstructive CAD was associated with an increased hazard of cardiovascular death (HR: 1.82; 95% CI: 1.27 to 2.62; p = 0.001) and death of any cause (HR: 1.18; 95% CI: 1.05 to 1.33; p = 0.005). There were no significant differences in the rate of acute myocardial infarction, stroke, or HF hospitalization.Among HF patients with reduced ejection fraction, the presence of nonobstructive CAD was independently associated with an increased hazard of the primary composite outcome and death of any cause.
Abstract B59: Role of Dicer on human melanoma progression and resistance
Authors: Nathalia Cruz de Victo, Sandy Adjemian, Romulo dos Santos Sobreira Nunes, Rildo Aparecido Volpini, Mara Huffenbaecher Giavina-Bianchi, Cyro Festa Neto, Niels Olsen Saraiva Câmara, Gustavo Pessini Amarante-Mendes, Jacqueline de Fátima Jacysyn
Journal: Clinical Cancer Research (2018)

Abstract Melanoma is a serious public health problem that affects the population of Latin America and is increasing rapidly compared to other types of tumors. The growth or change in this type of tumor is progressive and is in the horizontal and/or vertical direction. Breslow thickness (vertical staging) is the tumor thickness in the dermis where patients with lesion thickness less than 0.75 mm have good prognosis, unlike lesion thickness larger than 3 mm. This stage is classified into T (primary tumor): T0 (with no evidence of primary tumor); Tis (in situ melanoma); T1 (1 mm); T2 (1.01 to 2 mm); T3 (2.01 to 4 mm); and T4 (above 4 mm). Knowing some molecular markers of melanoma is essential for the identification of genetically predisposed individuals, as well as early detection of the disease. Recent works has demonstrated that microRNAs may be involved in modulation of melanoma. Dicer is an essential member of the RNase III family which controls maturation of miRNAs in the cytoplasm from microRNA precursors (pre-miRNAs). The upregulation of Dicer is associated with aggressive features and proliferation of melanoma and no other skin tumors such as carcinomas and sarcoma. In our present study, we found that the knockdown expression of Dicer using the CRISPR/CAS9 in melanoma cell line induced more chemosensitivity to cisplatin and these changes correlated with the downregulation of Dicer. We examined the consequence of Dicer knockdown on melanoma cell proliferation, clonogenic assays, and overall survival. We also compared Dicer in tissue from patients diagnosed with melanoma in different stages with the prognosis of these patients, suggesting that the reduction in Dicer expression is associated with melanoma progression. Considering the fundamental and multiple biologic roles of Dicer in various cellular processes, our results suggest that modulation of Dicer in melanoma should become a promising therapeutic candidate for further clinical application. Note: This abstract was not presented at the conference. Citation Format: Nathalia Cruz de Victo, Sandy Adjemian, Romulo dos Santos Sobreira Nunes, Rildo Aparecido Volpini, Mara Huffenbaecher Giavina-Bianchi, Cyro Festa Neto, Niels Olsen Saraiva Câmara, Gustavo Pessini Amarante-Mendes, Jacqueline de Fátima Jacysyn. Role of Dicer on human melanoma progression and resistance [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B59.
ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach
Authors: C. Luchini, F. Bibeau, M.J.L. Ligtenberg, N. Singh, A. Nottegar, T. Bosse, R. Miller, N. Riaz, J.-Y. Douillard, F. Andre, A. Scarpa
Journal: Annals of Oncology (2019)
Phosphorylation-dependent Regnase-1 release from endoplasmic reticulum is critical in IL-17 response
Authors: Hiroki Tanaka, Yasunobu Arima, Daisuke Kamimura, Yuki Tanaka, Noriyuki Takahashi, Takuya Uehata, Kazuhiko Maeda, Takashi Satoh, Masaaki Murakami, Shizuo Akira
Journal: The Journal of Experimental Medicine (2019)

Regnase-1 (also known as Zc3h12a or MCPIP-1) is an endoribonuclease involved in mRNA degradation of inflammation-associated genes. Regnase-1 is inactivated in response to external stimuli through post-translational modifications including phosphorylation, yet the precise role of phosphorylation remains unknown. Here, we demonstrate that interleukin (IL)-17 induces phosphorylation of Regnase-1 in an Act1-TBK1/IKKi–dependent manner, especially in nonhematopoietic cells. Phosphorylated Regnase-1 is released from the endoplasmic reticulum (ER) into the cytosol, thereby losing its mRNA degradation function, which leads to expression of IL-17 target genes. By using CRISPR/Cas-9 technology, we generated Regnase-1 mutant mice, in which IL-17–induced Regnase-1 phosphorylation is completely blocked. Mutant mice (Regnase-1AA/AA and Regnase-1ΔCTD/ΔCTD) were resistant to the IL-17–mediated inflammation caused by T helper 17 (Th17) cells in vivo. Thus, Regnase-1 plays a critical role in the development of IL-17–mediated inflammatory diseases via the Act1-TBK1-IKKi axis, and blockade of Regnase-1 phosphorylation sites may be promising for treatment of Th17-associated diseases.
Bacterial TLR4 and NOD2 signaling linked to reduced mitochondrial energy function in active inflammatory bowel disease
Authors: Emmanuelle Ruiz, Harrison M. Penrose, Sandra Heller, Hani Nakhoul, Melody Baddoo, Erik F. Flemington, Emad Kandil, Suzana D. Savkovic
Journal: Gut Microbes (2019)

Inflammatory bowel disease (IBD) has been linked to active signaling with bacterial components and reduced mitochondrial ATP production; however, synergism between both of these disease characteristics remains unclear. We aimed to determine in human IBD transcriptomes the link between a transcriptional signature unique to intestinal cells (ICs) with reduced mitochondrial ATP production (Mito-0) and bacteria triggered signaling using a bioinformatics approach. We generated an IC Mito-0 panel comprised of 199 differentially expressed (DE) transcripts mediated by reduced mitochondrial ATP function (DEGseq, log2 fold-change > |2|, p < .001). Transcripts from this panel were involved in diverse biological functions including regulation of mitochondrial energy (lower ATP), extracellular matrix, cell–cell contact, cytoskeleton, growth, metabolism, and inflammation. Next, unsupervised hierarchical clustering showed that the Mito-0 panel distinctly separated inflamed IBD from non-inflamed transcriptomes, which was also supported by principal component analysis (PCA) revealing distinct variation between sample types based on presence of the Mito-0 signature (PCA, p = 8.77e–09). Utilizing three independent IBD cohorts, we validated that 60 novel transcripts from the Mito-0 panel were significantly increased in inflamed tissue. Subsequently, KEGG generated bacterial TLR4 and NOD2 transcriptional signatures strongly associated with inflamed IBD transcriptomes and with the Mito-0 signature as determined by Spearman's analysis (coefficient of correlation, r = 0.92, p < .05). Herein, using a comprehensive analysis we demonstrated existence of an axis between bacteria triggered signaling and reduced mitochondrial energy function. Furthermore, we identified and validated novel transcripts within this axis as potential drivers and therapeutic targets for human IBD.
Abstract OT2-07-08: Withdrawn
Authors: E Paplomata, V Borges, S Loi, V Abramson, E Hamilton, S Hurvitz, N Lin, L Walker, RK Murthy
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Paplomata E, Borges V, Loi S, Abramson V, Hamilton E, Hurvitz S, Lin N, Walker L, Murthy RK. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-07-08.
Eliciting allergens and treatment of anaphylaxis: Report of the finnish national anaphylaxis registry
Authors: Sanna M. Edelman, Anna Kaarina Kukkonen, Mika J. Mäkelä
Journal: Allergy (2019)

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