tbuckley/cabot-search huggingface dataset:
Antipsychotic Polypharmacy for the Management of Schizophrenia: Evidence and Recommendations
Authors: Markku Lähteenvuo, Jari Tiihonen
Journal: Drugs (2021)

Schizophrenia is a debilitating illness with a lifetime prevalence estimate of 0.6% and consists of symptoms from the positive, negative, and cognitive domains. Social support, therapy, psychoeducation, and overall case management are very important aspects of the treatment of schizophrenia. However, as abnormalities in neurotransmission are one of the key findings of schizophrenia pathology, pharmacotherapies are cornerstones of the management of schizophrenia. Antipsychotics have been used as the primary pharmacological treatment of schizophrenia. These agents often have a good effect on reducing positive symptoms, but may not markedly improve negative symptoms or cognitive defects. However, at least 20% of individuals with schizophrenia do not experience a substantial response from monotherapy with antipsychotics. Further, despite evolving treatment protocols and advances in early recognition of the disorder, 70% of patients with schizophrenia require long-term, even lifetime, medication to control their symptoms and do not achieve complete recovery. To address these shortcomings, clinicians and research scientists have explored different combinations of treatments, polypharmacy, to improve the treatment of patients. Antipsychotic polypharmacy has been shown to cause more side effects than monotherapy, which is the main reason why most treatment guidelines caution against it. Antipsychotic monotherapy should be strived for and clozapine should be tried at the latest if two monotherapy trials with other antipsychotics have failed and no absolute contraindications exist. If residual symptoms exist despite trials of adequate dose and duration, other reasons that may reduce treatment effect should be ruled out. Long-acting injectables or blood concentration measurements should be considered to affirm compliance and proper serum levels. Antipsychotic polypharmacy should be considered and discussed with patients from whom the aforementioned procedures do not produce a satisfactory treatment result. In some cases, antipsychotic polypharmacy may produce better results than other forms of treatment augmentation, such as benzodiazepines. In particular, combining aripiprazole with clozapine may be effective in reducing treatment side effects or residual symptoms, and this is likely to hold true for combining other partial dopamine D2 agonists with clozapine as well, although currently scant data exist. More research is needed, both in controlled but also real-world settings, to define optimal antipsychotic polypharmacy and/or other psychotropic treatment augmentation strategies for specific patient groups and situations.
免疫-ソノダイナミック抗癌療法のための腫瘍微小環境に対する二重感受性を有するナノ薬物【JST・京大機械翻訳】
Authors: Huang Jinsheng, Xiao Zecong, An Yongcheng, Han Shisong, Wu Wei, Wang Yong, Guo Yu, Shuai Xintao
Journal: Biomaterials (2021)
Abstract 445: Cardiopulmonary Resuscitation Training for Families of Cardiac Patients Before Hospital Discharge Using a Mobile Application
Authors: Audrey L Blewer, Shaun K McGovern, Andrew D Murray, Marion Leary, Mary Putt, Barbara Riegel, Judy A Shea, Robert Berg, Asch A David, Raina Merchant, Vinay Nadkarni, Anthony Viera, Benjamin Abella
Journal: Circulation (2019)

Introduction: Since over 75% of sudden cardiac arrest events occur in the home where family members may be first responders, broad cardiopulmonary resuscitation (CPR) training for family members of high-risk cardiac patients represents a promising intervention. The use of mobile application-based (mApp) CPR training may facilitate this, but data on the approach are limited. Objectives: We compared CPR skill retention among those trained with an mApp and hypothesized that training with the mApp would be non-inferior to training with a well-established video self-instruction (VSI) kit. As a secondary analysis, we examined dissemination via the “multiplier rate” (i.e., those additionally trained by primary trainees) by intervention. Methods: We conducted a multicenter pragmatic, randomized control trial assessing non-inferiority of training family members of cardiac patients in CPR with an mApp (video, but no practice manikin) to training with an established VSI method (video and manikin). Subject’s CPR skills were tested 6-months post-training. We hypothesized that mApp training would be non-inferior to VSI training, with a non-inferiority margin set at 5 chest compressions (cc) per min. Results: From 01/2016-01/2018, 1446 subjects were enrolled at 8 hospitals with 685 trained with VSI, and 761 trained with the mApp. Of those, 541 were included in the skills analysis (275 VSI, 266 App). The mean age was 52±16 years and 69% were female. Mean cc rate was 85±34 per min; mean cc depth was 40±14 mm. When stratified by intervention arm, those trained with VSI had a mean rate of 86 per min (83, 90), compared to 88 per min (84, 92) with the mApp; those trained with VSI had a mean depth of 42 mm (41, 44), compared to 39 mm (38, 41) with the mApp. Findings were similar when accounting for loss to follow-up. We concluded non-inferiority of the mApp with a mean difference of 1 (-5, 7) cc per min for rate. Subjects trained with VSI shared with an additional 2±4 individuals compared to 1±2 (p&lt;0.01) of those trained with the mApp. Conclusion: In this large prospective trial of CPR skill retention, the mApp CPR training approach was non-inferior to VSI training for family members of cardiac patients. Future work may include evaluating additional means for adoption and dissemination of the mApp.
Efficacy Analysis of Comparison of CAMS (Chinese Academy of Medical Sciences)—2005 Trial and CAMS-2009 Trial for Pediatric Acute Myeloid Leukemia
Authors: Min Ruan, Xiaojuan Chen, Ye Guo, Li Zhang, Fang Liu, Wenbin An, Wenyu Yang, Yao Zou, Yumei Chen, Xiaofan Zhu
Journal: Blood (2017)
Effect of Age (≧75 Years) on Long-term Outcomes and Device-delivered Therapies after Cardiac Resynchronization Therapy with Defibrillator Implantation
Authors: Suehiro Hideya, Adachi Kazumasa, Hirayama Yasutaka, Matsuura Takeshi, Kintsu Masayuki, Kodara Mutsuki, Akita Tomomi, Kato Yukinori, Sogabe Koji, Takigami Masao, Kamemura Kohei, Matsuura Akira, Kawata Masahito, Sakamoto Susumu
Journal: Circulation (2016)
Abstract 14368: Long Noncoding RNA Tykril Plays a Role in Pulmonary Hypertension by Controlling the p53 Mediated Regulation of PDGFRβ
Authors: Christoph M Zehendner, Chanil Valasarajan, Serge Thal, Astrid Werner, Jes-Niels Boeckel, Florian C Bischoff, David John, Tyler Weirick, Simone-Franziska Glaser, Oliver Rossbach, Nicolas Jaé, Shemsi Demolli, Regina Hummel, Karl-Friedrich Kreitner, Christian Möllmann, Katharina M Michalik, Wei Chen, Werner Seeger, Shizuka Uchida, Andreas M Zeiher, Stefanie Dimmeler, Soni Pullamsetti
Journal: Circulation (2019)

Background: In recent years, understanding the role of epigenetic regulators in disease pathogenesis has gained interest. The role of long non coding RNA (LncRNA), which functions as epigenetic reg...
Anisometric Microstructures to Determine Minimal Critical Physical Cues Required for Neurite Alignment
Authors: Sitara Vedaraman, Amaury Perez‐Tirado, Tamas Haraszti, Jose Gerardo‐Nava, Akihiro Nishiguchi, Laura De Laporte
Journal: Advanced Healthcare Materials (2021)

Abstract In nerve regeneration, scaffolds play an important role in providing an artificial extracellular matrix with architectural, mechanical, and biochemical cues to bridge the site of injury. Directed nerve growth is a crucial aspect of nerve repair, often introduced by engineered scaffolds imparting linear tracks. The influence of physical cues, determined by well‐defined architectures, has been mainly studied for implantable scaffolds and is usually limited to continuous guiding features. In this report, the potential of short anisometric microelements in inducing aligned neurite extension, their dimensions, and the role of vertical and horizontal distances between them, is investigated. This provides crucial information to create efficient injectable 3D materials with discontinuous, in situ magnetically oriented microstructures, like the Anisogel. By designing and fabricating periodic, anisometric, discreet guidance cues in a high‐throughput 2D in vitro platform using two‐photon lithography techniques, the authors are able to decipher the minimal guidance cues required for directed nerve growth along the major axis of the microelements. These features determine whether axons grow unidirectionally or cross paths via the open spaces between the elements, which is vital for the design of injectable Anisogels for enhanced nerve repair.
Abstract 350: Chromosome Content of Cardiac Progenitor Cells Influence on Regenerative Potential in the Heart
Authors: Kathleen Broughton, Tiffany Khieu, Nicky Nguyen, Sadia Mohsin, Pearl Quijada, Jessica Wang, Megan Monsanto, Natalie Gude, Mark Sussman
Journal: Circulation Research (2016)

Discovery of endogenous stem cells found within the heart, cardiac progenitor cells (CPC), has prompted intense basic discovery in multiple experimental animal models and clinical trials in heart failure patients. A survey of the literature reveals animal or cellular models exhibiting regenerative properties are also characterized by genome duplication or polyploidization. Our lab recently discovered a fundamental difference between large and small mammalian CPCs through karyotype analysis: rodent (rat, mouse) CPCs possess mononuclear tetraploid (4n) chromosome content, whereas large animal (human, swine) CPCs are mononuclear diploid (2n). This primary distinction between large and small animals prompts provocative questions regarding regenerative potential as well as the translational applicability of regenerative studies performed in rodent models. To expand on this finding, CPCs were isolated from eight human tissue samples (normal and heart failure), two swine strains (Gottingen and Yorkshire) six mice strains (FVB, C57, CAST, SPRET, SAMP6, and SAMR1), and seven rat clonal lines (Sprague Dawley), which confirmed karyotyped ploidy content per species as characterized through flow cytometry and confocal microscopy techniques. The large (human, swine) and small (rat, mouse) mammal CPCs maintained stable chromosome content through increased passaging and positive correlations appears between chromosome content and growth rate through increased passages as well as chromosome content and unrestrained growth through increased passages. The ploidy content of endogenous CPCs was investigated in situ with heart tissue sections with comparable ploidy determinations to that of cultured CPCs. Furthermore, the unique tetraploid content of murine CPCs is reinforced by comparison with ckit+ progenitor cells of secondary tissues (intestine and bone marrow) and cardiomyocytes in situ and in vitro that exhibit mostly diploid (2n) chromosome content per nuclei. These studies suggest ploidy may play a significant role in the biological capacity of the CPC and the endogenous stem cell pool may influence the regenerative capacity of the heart. Future directions will focus on defining the advantage of polyploid content in mediating regeneration.
Whole-Genome Mate Pair Sequencing Transforms Cytogenetic Analysis of Hematologic Malignancies: Development of a Targeted Panel to Detect Diagnostic/Prognostic Chromosomal Rearrangements and Copy Number Changes in AML
Authors: Umut Aypar, George Vasmatzis, Sarah K Johnson, James Smadbeck, Stephanie A. Smoley, Hutton Kearney, William Sukov, Rhett P. Ketterling, Katherine Geiersbach, Daniel L. Van Dyke, Robert Jenkins, Patricia Greipp, Erik Thorland, Nicole Hoppman, Linda B Baughn
Journal: Blood (2017)
Abstract 14721: Phenotypic Variability in Atherosclerosis Burden Despite Genetic and Lifestyle Homogeneity in an Old-Order Amish Family With Homozygous Sitosterolemia
Authors: Amy L Peterson, James DeLine, Ann M Dodge, JoAnne Weber, Claudia E Korcarz, Kristin Hansen, Claire Sandrock, James H Stein
Journal: Circulation (2018)

Introduction: Sitosterolemia is an atherogenic sterol storage disorder with <100 cases reported worldwide. Due to lack of genetic and lifestyle variability, we hypothesized that in a nuclear family...
Blockade of checkpoint receptor PVRIG unleashes anti-tumor immunity of NK cells in murine and human solid tumors
Authors: Yangyang Li, Yu Zhang, Guoshuai Cao, Xiaodong Zheng, Cheng Sun, Haiming Wei, Zhigang Tian, Weihua Xiao, Rui Sun, Haoyu Sun
Journal: Journal of Hematology & Oncology (2021)

Abstract Background Although checkpoint-based immunotherapy has shown exciting results in the treatment of tumors, around 70% of patients have experienced unresponsiveness. PVRIG is a recently identified immune checkpoint receptor and blockade of which could reverse T cell exhaustion to treat murine tumor; however, its therapeutic potential via NK cells in mice and human remains seldom reported. Methods In this study, we used patient paraffin-embedded colon adenocarcinoma sections, various murine tumor models (MC38 colon cancer, MCA205 fibrosarcoma and LLC lung cancer), and human NK cell- or PBMC-reconstituted xenograft models (SW620 colon cancer) to investigate the effect of PVRIG on tumor progression. Results We found that PVRIG was highly expressed on tumor-infiltrating NK cells with exhausted phenotype. Furthermore, either PVRIG deficiency, early blockade or late blockade of PVRIG slowed tumor growth and prolonged survival of tumor-bearing mice by inhibiting exhaustion of NK cells as well as CD8 + T cells. Combined blockade of PVRIG and PD-L1 showed better effect in controlling tumor growth than using either one alone. Depletion of NK or/and CD8 + T cells in vivo showed that both cell types contributed to the anti-tumor efficacy of PVRIG blockade. By using Rag1 −/− mice, we demonstrated that PVRIG blockade could provide therapeutic effect in the absence of adaptive immunity. Further, blockade of human PVRIG with monoclonal antibody enhanced human NK cell function and inhibited human tumor growth in NK cell- or PBMC-reconstituted xenograft mice. Conclusions Our results reveal the importance of NK cells and provide novel knowledge for clinical application of PVRIG-targeted drugs in future.
当院における心臓再同期療法(CRT)の経験
Authors: 嶋根章, 島津修三, 出山順太郎, 橋口直貴, 矢野利明, 小野寺修一, 杉山博文, 村田耕一郎, 小野寺知哉, 滝澤明憲, 中井真尚, 山崎文郎
Journal: Circulation (2007)
Incidence and prognosis of clonal hematopoiesis in patients with chronic idiopathic neutropenia
Authors: Grigorios Tsaknakis, Anna Gallì, Stavros Papadakis, Peggy Kanellou, Chiara Elena, Gabriele Todisco, Elisa Bono, Ettore Rizzo, Elisabetta Molteni, Irene Fragiadaki, Irene Mavroudi, Charalampos Pontikoglou, Anastasios Batas, Stella Maxouri, Emmanouela Linardaki, Nektarios Tavernarakis, Luca Malcovati, Helen A. Papadaki
Journal: Blood (2021)
The Role of Imaging Studies in Favor of Possible Cerebellar Multiple System Atrophy
Authors: Ana Utrera-Costero, Begoña Martinez-Sanchis, Pablo Sopena-Novales, Pilar Bello-Arques
Journal: Clinical Nuclear Medicine (2021)

Abstract We report a 64-year-old woman whose history started with urinary incontinence and neurological symptoms (cognitive impairment, dysarthria, and gait difficulties). The 18 F-FDG PET/CT showed hypometabolism of the whole cerebellum. Then 6 months later, she developed tremor, postural instability, and ataxia, so she was hospitalized to complete study. Blood tests (antibodies, vitamin B12, copper, genetic test of spinocerebellar ataxia) did not have alterations, but imaging studies, along with clinical symptoms, provide the diagnosis of possible multiple system atrophy.
Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge
Authors: Rena D. Astronomo, Maria P. Lemos, Sandeep R. Narpala, Julie Czartoski, Lamar Ballweber Fleming, Kelly E. Seaton, Madhu Prabhakaran, Yunda Huang, Yiwen Lu, Katharine Westerberg, Lily Zhang, Mary K. Gross, John Hural, Hong-Van Tieu, Lindsey R. Baden, Scott Hammer, Ian Frank, Christina Ochsenbauer, Nicole Grunenberg, Julie E. Ledgerwood, Kenneth Mayer, Georgia Tomaras, Adrian B. McDermott, M. Juliana McElrath
Journal: Journal of Clinical Investigation (2021)

Background. VRC01, a potent, broadly neutralizing monoclonal antibody, inhibits simian-HIV infection in animal models. The HVTN 104 study assessed the safety and pharmacokinetics of VRC01 in humans. We extend the clinical evaluation to determine intravenously infused VRC01 distribution and protective function at mucosal sites of HIV-1 entry.
Abstract 373: Identification of Novel Anti-necrotic Factor TGN91
Authors: Jason Karch, Matthew J Brody, Onur Kanisicak, Michelle A Sargent, Jeffery D Molkentin
Journal: Circulation Research (2016)

Loss of cardiomyocytes by necrotic cell death is the direct mechanistic basis for mortality due to myocardial infarction injury, as well as ensuing heart failure associated with an array of cardiomyopathies. Further definition of the regulated necrotic pathway and identification of novel effectors will be essential in designing new therapies. To identify novel regulators of necrotic cell death we performed an unbiased lentiviral-based overexpression screen comprising of over 13,000 human cDNAs. In order to mimic an ischemic insult, the calcium ionophore ionomycin was used to induce necrotic cell death in conjunction with each individually encoded cDNA in the lentiviruses. After 24 hours of calcium overload cell viability was assessed to determine if a cDNA had a protective or maladaptive effect on necrotic cell death. One completely novel cDNA that we named Trans-Golgi Network protein 91 (TGN91) was found to be significantly protective against regulated necrosis. TGN91 is a multipass transmembrane protein that is conserved from humans to drosophila, although its function is unknown. TGN91 is most abundant in the heart compared to other tissues in the mouse and the protein resides within the Golgi. The expression of TGN91 increases in human ischemic failing hearts compared to non-ischemic failing and normal hearts. Lastly, we generated transgenic mice overexpressing TGN91 specifically in cardiomyocytes and our preliminary results suggest that these mice are protected against ischemic injury. The identification of TGN91 not only provides a novel putative regulator of the necrotic pathway, but also advocates for the Golgi as a regulatory site in necrotic cell death.
Reply
Authors: Tamara Rusman, Mignon A. C. van der Weijden, Michael T. Nurmohamed, Carmella M. A. van der Bijl, Conny J. van der Laken, Pierre M. Bet, Robert B. M. Landewé, Janneke J. H. de Winter, Bouke J. H. Boden, Irene E. van der Horst‐Bruinsma
Journal: Arthritis & Rheumatology (2021)
Trajectories of IgE sensitization to allergen molecules from childhood to adulthood and respiratory health in the EGEA cohort
Authors: Valérie Siroux, Anne Boudier, Jean Bousquet, Orianne Dumas, Jocelyne Just, Nicole Le Moual, Rachel Nadif, Raphaëlle Varraso, Rudolf Valenta, Isabelle Pin
Journal: Allergy (2021)

Longitudinal studies assessing the association of profiles of allergen-specific IgE (sIgE) sensitization to a large range of allergen molecules and respiratory health are rare. We aimed to assess trajectories of molecular sIgE sensitization profiles from childhood to adulthood and their associations with respiratory health.IgE reactivity to microarrayed allergen molecules were measured in childhood (EGEA1) and 12 years later in adult life (EGEA2) among 291 EGEA participants (152 with asthma). At each time point, sIgE sensitization profiles were identified by latent class analysis (LCA) by considering IgE-reactivity to the 38 most prevalent respiratory allergens. The LCA-defined profiles were then studied in association with respiratory health.At baseline, the mean (min-max) age of the population was 11 (4.5-16) years. The LCA identified four sIgE sensitization profiles which were very similar at both time points (% at EGEA1 and EGEA2); A: "no/few allergen(s)" (48%, 39%), B: "pollen/animal allergens" (18%, 21%), C: "most prevalent house dust mite allergens" (22%, 27%) and D: "many allergens" (12%, 13%). Overall, 73% of the participants remained in the same profile from childhood to adulthood. The profiles were associated with asthma and rhinitis phenotypes. Participants of profiles C and D had lower FEV1 % and FEF25-75 % as compared to profile A. Similar patterns of associations were observed for participants with asthma. There was no association with change in lung function.Using high-resolution sIgE longitudinal data, the LCA identified four molecular sensitization profiles, mainly stable from childhood to adulthood, that were associated with respiratory health.
Dual Inhibition of Aurora Kinase and BRD4 Leads to Improved Anti-Tumor Activity in Myc-Overexpressing Lymphoma Cells
Authors: Steven I Park, Carolina Lin, Lawrence J Druhan, Michael B Foote, Trevor Parton, Natalie Ren, Steven P Angus, Aadra P Bhatt, Scott C Jaros, Nilanjan Ghosh, Ryan Jacobs, Belinda Rene Avalos, Dirk P Dittmer, Norman E. Sharpless, Blossom A Damania
Journal: Blood (2017)
Abstract 314: The Impact of City-Level Public Health Interventions on Increased Bystander Cardiopulmonary Resuscitation
Authors: Audrey L Blewer, Andrew F Ho, Nur Shahidah Binte Ahamad, Alexander E White, Pin Pin Pek, Yih Yng Ng, Desmond Ren Hao Mao, Ling Tiah, Michael Yih-Chong Chia, Benjamin Sieu-Hon Leong, Si Oon Cheah, Lai Peng Tham, Phek Hui Jade Kua, Shalini Arulanandam, Truls Ostbye, Hayden B Bosworth, Marcus E Ong
Journal: Circulation (2019)

Introduction: Bystander cardiopulmonary resuscitation (B-CPR) may increase a victim’s chance of survival from sudden cardiac arrest (SCA), but B-CPR rates are low in many communities. Few studies have examined the association of city-wide public health interventions on B-CPR. Objectives: We sought to assess whether there is variation in B-CPR by intervention and location of arrest. We hypothesized that implementation of dispatch-assisted CPR (DA-CPR), CPR/AED training, and a first responder mobile application (myResponder) would increase B-CPR by two-fold. Methods: We conducted a retrospective study of adult, non-traumatic SCAs from the Singapore registry (4/2010-12/2016). Interventions included DA-CPR (7/2012 - present), CPR/AED training (04/2014 - present), and myResponder (4/2015 - present). Using logistic regression, we modeled the likelihood of receiving B-CPR by increased number of interventions over time. We examined these effects together, in the home, and public accounting for patient-level confounding. Results: From 2010-2016, the Singapore registry contained 12,546 SCA events. Excluding pediatric, EMS witnessed, and healthcare facility arrests, 7,476 were analyzed. Of these, mean age was 66±15 and 68% were male. B-CPR was administered in 45% of the events and varied by location (home: 43% v public: 52%). With implementation of DA-CPR, likelihood of B-CPR increased (OR: 3.5 (2.9-4.2) p&lt;0.01) compared to no intervention; with implementation of CPR/AED training, likelihood of B-CPR increased compared to no intervention (OR: 5.8 (4.8-7.0), p&lt;0.01). Lastly, implementation of myResponder resulted in a 7.09 increased likelihood of B-CPR compared to no intervention (OR: 7.1 (5.9-8.4), p&lt;0.01). Variation was seen when examining likelihood of B-CPR by all interventions compared to no intervention, in the home (OR: 8.7 (7.0-10.7)) and the public (OR: 4.0 (2.9-5.6)). Survival increased, corresponding to the increase in B-CPR. Conclusion: City-level public health interventions increased the likelihood of layperson B-CPR, while variation was seen in the home and public. Understanding the impact of public health interventions may shed light on strategies to increase B-CPR and inform targeted initiatives to improve survival from SCA.