tbuckley/cabot-search huggingface dataset:
Genes To Mental Health (G2MH): A Framework to Map the Combined Effects of Rare and Common Variants on Dimensions of Cognition and Psychopathology
Authors: Sébastien Jacquemont, Guillaume Huguet, Marieke Klein, Samuel J.R.A. Chawner, Kirsten A. Donald, Marianne B.M. van den Bree, Jonathan Sebat, David H. Ledbetter, John N. Constantino, Rachel K. Earl, Donna M. McDonald-McGinn, Therese van Amelsvoort, Ann Swillen, Anne H. O’Donnell-Luria, David C. Glahn, Laura Almasy, Evan E. Eichler, Stephen W. Scherer, Elise Robinson, Anne S. Bassett, Christa Lese Martin, Brenda Finucane, Jacob A.S. Vorstman, Carrie E. Bearden, Raquel E. Gur
Journal: American Journal of Psychiatry (2022)

Rare genomic disorders (RGDs) confer elevated risk for neurodevelopmental psychiatric disorders. In this era of intense genomics discoveries, the landscape of RGDs is rapidly evolving. However, there has not been comparable progress to date in scalable, harmonized phenotyping methods. As a result, beyond associations with categorical diagnoses, the effects on dimensional traits remain unclear for many RGDs. The nature and specificity of RGD effects on cognitive and behavioral traits is an area of intense investigation: RGDs are frequently associated with more than one psychiatric condition, and those studied to date affect, to varying degrees, a broad range of developmental and cognitive functions. Although many RGDs have large effects, phenotypic expression is typically influenced by additional genomic and environmental factors. There is emerging evidence that using polygenic risk scores in individuals with RGDs offers opportunities to refine prediction, thus allowing for the identification of those at greatest risk of psychiatric illness. However, translation into the clinic is hindered by roadblocks, which include limited genetic testing in clinical psychiatry, and the lack of guidelines for following individuals with RGDs, who are at high risk of developing psychiatric symptoms. The Genes to Mental Health Network (G2MH) is a newly funded National Institute of Mental Health initiative that will collect, share, and analyze large-scale data sets combining genomics and dimensional measures of psychopathology spanning diverse populations and geography. The authors present here the most recent understanding of the effects of RGDs on dimensional behavioral traits and risk for psychiatric conditions and discuss strategies that will be pursued within the G2MH network, as well as how expected results can be translated into clinical practice to improve patient outcomes.
1609P COVID-19 outbreak repercussions on breast cancer diagnoses and access to treatment: Preliminary data from the COVID-DELAY study
Authors: R. Berardi, G. Mentrasti, S. Crocetti, N. La Verde, R. Chiari, M.S. Cona, L. Nicolardi, C. De Filippis, S. Oldani, F. Pecci, F. Venanzi, M.B.L. Rocchi, A. Savini, L. Cantini, M. Pistelli
Journal: Annals of Oncology (2021)
Mandibular advancement device design: A systematic review on outcomes in obstructive sleep apnea treatment
Authors: Julia A.M. Uniken Venema, Boudewijn R.A.M. Rosenmöller, Nico de Vries, Jan de Lange, Ghizlane Aarab, Frank Lobbezoo, Aarnoud Hoekema
Journal: Sleep Medicine Reviews (2021)

Obstructive Sleep Apnea (OSA) is often treated with Mandibular Advancement Devices (MADs). It is unclear whether particular design features are superior to others in terms of OSA alleviation. In order to facilitate clinical decision-making, this systematic review summarizes the objective and subjective outcomes of different available MAD designs. Studies comparing different MAD designs in OSA treatment were searched. After screening 1887 titles and abstracts, 20 original RCTs and six cohort studies were included. 14 articles were systematically reviewed in a meta-analysis. The decrease in AHI was significantly different between some of the MAD designs. The clinical relevance of the observed differences was however limited. Monoblock appliances performed more favorable, compared to bilateral thrust (effect size:-0.37; CI:-1.81 to 0.07). Midline traction appliances performed more favorable, compared to other designs. Custom appliances performed more favorable, compared to thermoplastic appliances (effect size:0.86; CI:-0.62 to 2.35). Furthermore, there were no clinically relevant differences between MAD designs in reduction of ESS, compliance, preference, side effects, and cost effectiveness. With respect to the included trials, presently there is not one superior custom MAD design in OSA treatment regarding the effect on AHI reduction, ESS improvement, compliance, preference, side effects, cost effectiveness, and other disease-related outcomes. We confirm custom MAD designs perform superior to thermoplastic MAD designs.
熊本県の急性心筋梗塞登録-熊本急性冠状動脈疾患(KACE)研究-
Authors: Kojima Sunao, Ogawa Hisao, Ogata Yasuhiro, Nakao Koichi, Fujimoto Kazuteru, Oshima Shuichi, Sakaino Naritsugu, Matsumura Toshiyuki, Oka Hideki, Koide Shunichi, Morikami Yasuhiro, Kajiwara Ichiro, Mizuno Yuji, Hirai Nobutaka, Biwa Takeshi, Sadanaga Tsuneaki, Misumi Ikuo, Maruyama Hideki, Haruguchi Hiroshi, Wakita Tomio, Horiuchi Kenji
Journal: Circulation (2010)
Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China
Authors: Xue Zhang, Fang Wang, Ye Shen, Xiaohua Zhang, Yuan Cen, Bin Wang, Songtao Zhao, Yi Zhou, Baoman Hu, Man Wang, Yuhui Liu, Hongming Miao, Paul Jones, Xiangyu Ma, Yong He, Guoqiang Cao, Lixia Cheng, Li Li
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The long-term health outcomes and symptom burden of COVID-19 remain largely unclear. <h3>Objective</h3> To evaluate health outcomes of COVID-19 survivors 1 year after hospital discharge and to identify associated risk factors. <h3>Design, Setting, and Participants</h3> This retrospective, multicenter cohort study was conducted at 2 designated hospitals, Huoshenshan Hospital and Taikang Tongji Hospital, both in Wuhan, China. All adult patients with COVID-19 discharged between February 12 and April 10, 2020, were screened for eligibility. Of a consecutive sample of 3988 discharged patients, 1555 were excluded (796 declined to participate and 759 were unable to be contacted) and the remaining 2433 patients were enrolled. All patients were interviewed via telephone from March 1 to March 20, 2021. Statistical analysis was performed from March 28 to April 18, 2021. <h3>Exposures</h3> COVID-19. <h3>Main Outcomes and Measures</h3> All patients participated in telephone interviews using a series of questionnaires for evaluation of symptoms, along with a chronic obstructive pulmonary disease (COPD) assessment test (CAT). Logistic regression models were used to evaluate risk factors for fatigue, dyspnea, symptom burden, or higher CAT scores. <h3>Results</h3> Of 2433 patients at 1-year follow-up, 1205 (49.5%) were men and 680 (27.9%) were categorized into the severe disease group as defined by the World Health Organization guideline; the median (IQR) age was 60.0 (49.0-68.0) years. In total, 1095 patients (45.0%) reported at least 1 symptom. The most common symptoms included fatigue, sweating, chest tightness, anxiety, and myalgia. Older age (odds ratio [OR], 1.02; 95% CI, 1.01-1.02;<i>P</i> &lt; .001), female sex (OR, 1.27; 95% CI, 1.06-1.52;<i>P</i> = .008), and severe disease during hospital stay (OR, 1.43; 95% CI, 1.18-1.74;<i>P</i> &lt; .001) were associated with higher risks of fatigue. Older age (OR, 1.02; 95% CI, 1.01-1.03;<i>P</i> &lt; .001) and severe disease (OR, 1.51; 95% CI, 1.14-1.99;<i>P</i> = .004) were associated with higher risks of having at least 3 symptoms. The median (IQR) CAT score was 2 (0-4), and a total of 161 patients (6.6%) had a CAT score of at least 10. Severe disease (OR, 1.84; 95% CI, 1.31-2.58;<i>P</i> &lt; .001) and coexisting cerebrovascular diseases (OR, 1.95; 95% CI, 1.07-3.54;<i>P</i> = .03) were independent risk factors for CAT scores of at least 10. <h3>Conclusions and Relevance</h3> This study found that patients with COVID-19 with severe disease during hospitalization had more postinfection symptoms and higher CAT scores.
Chronic liver disease enables gut Enterococcus faecalis colonization to promote liver carcinogenesis
Authors: Noriho Iida, Eishiro Mizukoshi, Tatsuya Yamashita, Masahiro Yutani, Jun Seishima, Ziyu Wang, Kuniaki Arai, Hikari Okada, Taro Yamashita, Yoshio Sakai, Yusuke Masuo, Rina Agustina, Yukio Kato, Yukako Fujinaga, Masanobu Oshima, Masao Honda, François Lebreton, Michael S. Gilmore, Shuichi Kaneko
Journal: Nature Cancer (2021)
1366TiP Tepotinib + osimertinib for EGFR-mutant NSCLC with resistance to first-line osimertinib due to MET amplification (METamp): INSIGHT 2
Authors: Y-L. Wu, C. Dooms, E. Nadal, J. Raskin, I. Demedts, J. Mazieres, M. Wislez, S. Abdul Shukor, L.M. Tho, C-C. Wang, S. Viteri, X. Le, S.H. How, D. Tan, M. Takeda, R. Veillon, N. Karachaliou, B. Ellers-Lenz, E.F.F. Smit
Journal: Annals of Oncology (2021)
948P Predicting the efficacy of lenvatinib plus anti-PD-1 antibodies in unresectable hepatocellular carcinoma (uHCC) using radiomics features of tumors extracted from baseline MRI
Authors: H. Sun, S-X. Rao, B. Xu, X-D. Zhu, S-Y. Dong, X-L. Li, C. Huang, Y-H. Shen, J-J. Zhu, M-L. Li, J. Liu, M-S. Zeng, J. Zhou, J. Fan
Journal: Annals of Oncology (2021)
A neurodevelopmental disorders perspective into music, social attention, and social bonding
Authors: Anna Kasdan, Reyna L Gordon, Miriam D Lense
Journal: Behavioral and Brain Sciences (2021)

Abstract Our commentary addresses how two neurodevelopmental disorders, Williams syndrome and autism spectrum disorder, provide novel insights into the credible signaling and music and social bonding hypotheses presented in the two target articles. We suggest that these neurodevelopmental disorders, characterized by atypical social communication, allow us to test hypotheses about music, social bonding, and their underlying neurobiology.
Assessing Microvascular Dysfunction in Angina With Unobstructed Coronary Arteries
Authors: Tijn P.J. Jansen, Regina E. Konst, Suzette E. Elias-Smale, Stijn C. van den Oord, Peter Ong, Annemiek M.J. de Vos, Tim P. van de Hoef, Valeria Paradies, Pieter C. Smits, Niels van Royen, Peter Damman
Journal: Journal of the American College of Cardiology (2021)
280P Intracranial activity of trastuzumab-deruxtecan (T-DXd) in HER2-positive breast cancer patients with active brain metastases: Results from the first stage of the phase II TUXEDO-1 trial
Authors: R. Bartsch, A.S. Berghoff, J. Furtner, E.S. Bergen, S. Roider-Schur, M. Marhold, A.M. Starzer, H. Forstner, B. Rottenmanner, K. Dieckmann, Z.A. Bago-Horvath, G. Widhalm, A. Ilhan-Mutlu, C. Minichsdorfer, T. Fuereder, C.F. Singer, A. Weltermann, M. Preusser
Journal: Annals of Oncology (2021)
Knowledge songs as an evolutionary adaptation to facilitate information transmission through music
Authors: Daniel J. Levitin
Journal: Behavioral and Brain Sciences (2021)

Abstract I propose an adjunct to the two models presented in the target articles, a function of music that is ubiquitous and would have solved a clear adaptive problem, that of transmitting important survival information among pre-literate humans. This class of knowledge songs uniquely preserved cultural, botanical, medical, safety, and practical information that increased the adaptive fitness of societies.
476P Open-label phase I/II study evaluating the tolerability and antitumor activity of selinexor (SEL) and pembrolizumab (pembro) in colorectal cancer (CRC)
Authors: T. Shentzer Kutiel, T. Golan, R. Geva, M. Gottfried, A. Zick, A. Shai, J. Dudnik, E. Netiv, F. Yang, S. Sharoni, C. Meng, P. Duic, D. Michel, E. Sbar, J. Shah, M.G. Kauffman, S. Shacham, A. Zer
Journal: Annals of Oncology (2021)
Bispecific prodrug nanoparticles circumventing multiple immune resistance mechanisms for promoting cancer immunotherapy
Authors: Jiayi Ye, Bo Hou, Fangmin Chen, Shunan Zhang, Muya Xiong, Tianliang Li, Yechun Xu, Zhiai Xu, Haijun Yu
Journal: Acta Pharmaceutica Sinica B (2021)

Cancer immunotherapy is impaired by the intrinsic and adaptive immune resistance. Herein, a bispecific prodrug nanoparticle was engineered for circumventing immune evasion of the tumor cells by targeting multiple immune resistance mechanisms. A disulfide bond-linked bispecific prodrug of NLG919 and JQ1 (namely NJ) was synthesized and self-assembled into a prodrug nanoparticle, which was subsequently coated with a photosensitizer-modified and tumor acidity-activatable diblock copolymer PHP for tumor-specific delivery of NJ. Upon tumor accumulation via passive tumor targeting, the polymeric shell was detached for facilitating intracellular uptake of the bispecific prodrug. NJ was then activated inside the tumor cells for releasing JQ1 and NLG919 via glutathione-mediated cleavage of the disulfide bond. JQ1 is a bromodomain-containing protein 4 inhibitor for abolishing interferon gamma-triggered expression of programmed death ligand 1. In contrast, NLG919 suppresses indoleamine-2,3-dioxygenase 1-mediated tryptophan consumption in the tumor microenvironment, which thus restores robust antitumor immune responses. Photodynamic therapy (PDT) was performed to elicit antitumor immunogenicity by triggering immunogenic cell death of the tumor cells. The combination of PDT and the bispecific prodrug nanoparticle might represent a novel strategy for blockading multiple immune evasion pathways and improving cancer immunotherapy.
Low neoantigen expression and poor T-cell priming underlie early immune escape in colorectal cancer
Authors: Peter M. K. Westcott, Nathan J. Sacks, Jason M. Schenkel, Zackery A. Ely, Olivia Smith, Haley Hauck, Alex M. Jaeger, Daniel Zhang, Coralie M. Backlund, Mary C. Beytagh, J. J. Patten, Ryan Elbashir, George Eng, Darrell J. Irvine, Omer H. Yilmaz, Tyler Jacks
Journal: Nature Cancer (2021)
893P Clinico-genetic profiling of HRAS mutant head and neck squamous cell carcinoma (HNSCC)
Authors: X. Le, K. Marcelo, N. Coleman, J. Hopkins, B. Balsara, M. Leoni, A.R. Spelman, D.S. Hong, L.A. Albacker, M. Gillison
Journal: Annals of Oncology (2021)
834P Role of assessment of IL-6, IL-15 and soluble PD-L1 levels as prognostic and predictive biomarkers in nivolumab-treated relapsed/refractory Hodgkin lymphoma
Authors: A. Chekalov, D. Shmidt, K. Lepik, N. Yolshin, N. Volkov, A. Muslimov, N. Mikhailova, E. Kondakova, L. Tsvetkova, Y. Zalyalov, E. Borzenkova, I. Moiseev, V. Baykov, T. Ionova, A. Kulagin
Journal: Annals of Oncology (2021)
1796P CXCL12-loaded-hydrogel (CLG) based 'pseudo niche': A new device for CTCs capturing and characterization
Authors: L. Portella, G. Guardascione, G. Bertolini, C. Ieranò, C. D'Alterio, G. Rea, S. Santagata, A.M. Trotta, R. Camerlingo, E. Scarpa, S.C. Cecere, A. Ottaiano, G. Palumbo, A. Morabito, R. Pacelli, S. Pignata, S. Scala
Journal: Annals of Oncology (2021)
Abstract 10612: Use of the AHA Pegasis Pipeline to Identify Genetic Associations With Severe 3-Vessel Coronary Artery Disease in High-Risk Pedigrees Free From Myocardial Infarction: The ProGENE Study
Authors: Stacey Knight, Raymond O McCubrey, Robert Sargent, Daniel Bride, Michael Madsen, John Gardner, Joseph B Muhlestein, Jeffrey L Anderson, Benjamin D Horne, Nicola Camp, Kirk U Knowlton
Journal: Circulation (2019)

Introduction: To develop new strategies and medications to more precisely treat cardiac patients, it is critical to not only continue discovering genes that increase risk of disease, but also find ...
Bioequivalence assessment of high-capacity polymeric micelle nanoformulation of paclitaxel and Abraxane® in rodent and non-human primate models using a stable isotope tracer assay
Authors: Duhyeong Hwang, Natasha Vinod, Sarah L. Skoczen, Jacob D. Ramsey, Kelsie S. Snapp, Stephanie A. Montgomery, Mengzhe Wang, Chaemin Lim, Jonathan E. Frank, Marina Sokolsky-Papkov, Zibo Li, Hong Yuan, Stephan T. Stern, Alexander V. Kabanov
Journal: Biomaterials (2021)
Regional vaccine production is key to ensuring equity
Authors: Shanthi Mendis
Journal: BMJ (2021)

Ensuring equal access to vaccines for rich and poor countries is of utmost importance to humanity.1 Standing by as millions of people succumb to “preventable death” is unethical. 

When the pandemic began, millions of people died (including in rich countries) as the result of a lack of emergency preparedness and inadequate investment in public health infrastructure.2 Now, millions of people are dying in poorer countries as the result of insufficient access to vaccines. Meanwhile, the virus continues to …
Remodeling “cold” tumor immune microenvironment via epigenetic-based therapy using targeted liposomes with in situ formed albumin corona
Authors: Yang He, Yuefei Fang, Meng Zhang, Yuge Zhao, Bin Tu, Mingjie Shi, Bahtiyor Muhitdinov, Akmal Asrorov, Qin Xu, Yongzhuo Huang
Journal: Acta Pharmaceutica Sinica B (2021)

There is a close connection between epigenetic regulation, cancer metabolism, and immunology. The combination of epigenetic therapy and immunotherapy provides a promising avenue for cancer management. As an epigenetic regulator of histone acetylation, panobinostat can induce histone acetylation and inhibit tumor cell proliferation, as well as regulate aerobic glycolysis and reprogram intratumoral immune cells. JQ1 is a BRD4 inhibitor that can suppress PD-L1 expression. Herein, we proposed a chemo-free, epigenetic-based combination therapy of panobinostat/JQ1 for metastatic colorectal cancer. A novel targeted binary-drug liposome was developed based on lactoferrin-mediated binding with the LRP-1 receptor. It was found that the tumor-targeted delivery was further enhanced by in situ formation of albumin corona. The lactoferrin modification and endogenous albumin adsorption contribute a dual-targeting effect on the receptors of both LRP-1 and SPARC that were overexpressed in tumor cells and immune cells (e.g., tumor-associated macrophages). The targeted liposomal therapy was effective to suppress the crosstalk between tumor metabolism and immune evasion via glycolysis inhibition and immune normalization. Consequently, lactic acid production was reduced and angiogenesis inhibited; TAM switched to an anti-tumor phenotype, and the anti-tumor function of the effector CD8+ T cells was reinforced. The strategy provides a potential method for remodeling the tumor immune microenvironment (TIME).
The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin
Authors: Martin Hoenigl, Rosanne Sprute, Matthias Egger, Amir Arastehfar, Oliver A. Cornely, Robert Krause, Cornelia Lass-Flörl, Juergen Prattes, Andrej Spec, George R. Thompson, Nathan Wiederhold, Jeffrey D. Jenks
Journal: Drugs (2021)

The epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug–drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available over the last 2 decades, and only one single new agent from a known antifungal class has been approved in the last decade. Nevertheless, there is hope on the horizon, with a number of new antifungal classes in late-stage clinical development. In this review, we describe the mechanisms of drug resistance employed by fungi and extensively discuss the most promising drugs in development, including fosmanogepix (a novel Gwt1 enzyme inhibitor), ibrexafungerp (a first-in-class triterpenoid), olorofim (a novel dihyroorotate dehydrogenase enzyme inhibitor), opelconazole (a novel triazole optimized for inhalation), and rezafungin (an echinocandin designed to be dosed once weekly). We focus on the mechanism of action and pharmacokinetics, as well as the spectrum of activity and stages of clinical development. We also highlight the potential future role of these drugs and unmet needs.
Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19
Authors: Tomer Merison, Adam Goldman, David Bomze
Journal: New England Journal of Medicine (2021)

19To the Editor: O'Brien et al. report that the combination of casirivimab and imdevimab (REGEN-COV) reduced the risk of symptomatic Covid-19 by 81.4% among persons exposed to SARS-CoV-2. 1 However, we question the decision to communicate the effect size almost exclusively with the use of the relative risk reduction, calculated as 1 minus the relative risk.The authors placed a strong emphasis on the relative risk reduction for both primary and secondary efficacy end points throughout the abstract and main text but did not provide a complementary, absolute measure.The Consolidated Standards of Reporting Trials guidelines recommend reporting both the absolute risk reduction and the relative risk reduction to fully describe the effectiveness of an intervention, as applied in many trials, including the recent trial of bamlanivimab-etesevimab combination for This practice is imperative, because the same relative risk reduction may represent very different absolute risk reductions -a relative risk reduction of 80% corresponds with an absolute risk reduction of 40% when the absolute risk decreases from 50% to 10% but with an absolute risk reduction of less than 1% when the absolute risk decreases from 1% to 0.2%.The provision of only the relative risk measure may lead clinicians, patients, and laypeople to overestimate treatment efficacy.
Optimal regenerative repair of large segmental bone defect in a goat model with osteoinductive calcium phosphate bioceramic implants
Authors: Wei Zhi, Xiaohua Wang, Dong Sun, Taijun Chen, Bo Yuan, Xiangfeng Li, Xuening Chen, Jianxin Wang, Zhao Xie, Xiangdong Zhu, Kai Zhang, Xingdong Zhang
Journal: Bioactive Materials (2021)

So far, how to achieve the optimal regenerative repair of large load-bearing bone defects using artificial bone grafts is a huge challenge in clinic. In this study, a strategy of combining osteoinductive biphasic calcium phosphate (BCP) bioceramic scaffolds with intramedullary nail fixation for creating stable osteogenic microenvironment was applied to repair large segmental bone defects (3.0 cm in length) in goat femur model. The material characterization results showed that the BCP scaffold had the initial compressive strength of over 2.0 MPa, and total porosity of 84%. The cell culture experiments demonstrated that the scaffold had the excellent ability to promote the proliferation and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs). The in vivo results showed that the intramedullary nail fixation maintained the initial stability and structural integrity of the implants at early stage, promoting the osteogenic process both guided and induced by the BCP scaffolds. At 9 months postoperatively, good integration between the implants and host bone was observed, and a large amount of newborn bones formed, accompanying with the degradation of the material. At 18 months postoperatively, almost the complete new bone substitution in the defect area was achieved. The maximum bending strength of the repaired bone defects reached to the 100% of normal femur at 18 months post-surgery. Our results demonstrated the good potential of osteoinductive BCP bioceramics in the regenerative repair of large load-bearing bone defects. The current study could provide an effective method to treat the clinical large segmental bone defects.