tbuckley/cabot-search huggingface dataset:
Comparison of New Pharmacologic Agents With Triptans for Treatment of Migraine
Authors: Chun-Pai Yang, Chih-Sung Liang, Ching-Mao Chang, Cheng-Chia Yang, Po-Hsuan Shih, Yun-Chain Yau, Kuo-Tung Tang, Shuu-Jiun Wang
Journal: JAMA Network Open (2021)

New therapeutic classes of migraine-specific treatment have been developed, including 5-hydroxytryptamine1F receptor agonists (lasmiditan) and calcitonin gene-related peptide antagonists (rimegepant and ubrogepant).To compare outcomes associated with the use of lasmiditan, rimegepant, and ubrogepant vs triptans for acute management of migraine headaches.The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to March 5, 2020.Double-blind randomized clinical trials examining current available migraine-specific acute treatments were included.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was applied to extract the data according to a predetermined list of variables of interest, and all network meta-analyses were conducted using a random-effects model.The primary outcome was the odds ratio (OR) for freedom from pain (hereafter referred to as pain freedom) at 2 hours after the dose, and the secondary outcomes were ORs for pain relief at 2 hours after the dose and any adverse events.A total of 64 randomized clinical trials were included (46 442 participants; 74%-87% women; age range, 36-43 years). Most of the included treatments were associated with reduced pain at 2 hours compared with placebo. Most triptans were associated with higher ORs for pain freedom at 2 hours compared with lasmiditan (range: OR, 1.72 [95% CI, 1.06-2.80] to OR, 3.40 [95% CI, 2.12-5.44]), rimegepant (range: OR, 1.58 [95% CI, 1.07-2.33] to OR, 3.13 [95% CI, 2.16-4.52]), and ubrogepant (range: OR, 1.54 [95% CI, 1.00-2.37] to OR, 3.05 [95% CI, 2.02-4.60]). Most triptans were associated with higher ORs for pain relief at 2 hours compared with lasmiditan (range: OR, 1.46 [95% CI, 1.09-1.96] to OR, 3.31 [95% CI, 2.41-4.55]), rimegepant (range: OR, 1.33 [95% CI, 1.01-1.76] to OR, 3.01 [95% CI, 2.33-3.88]), and ubrogepant (range: OR, 1.38 [95% CI, 1.02-1.88] to OR, 3.13 [95% CI, 2.35-4.15]). The comparisons between lasmiditan, rimegepant, and ubrogepant were not statistically significant for both pain freedom and pain relief at 2 hours. Lasmiditan was associated with the highest risk of any adverse events, and certain triptans (rizatriptan, sumatriptan, and zolmitriptan) were also associated with a higher risk of any adverse events than the calcitonin gene-related peptide antagonists.For pain freedom or pain relief at 2 hours after the dose, lasmiditan, rimegepant, and ubrogepant were associated with higher ORs compared with placebo but lower ORs compared with most triptans. However, the lack of cardiovascular risks for these new classes of migraine-specific treatments may offer an alternative to triptans.
P25.01 Efficacy of Weekly Paclitaxel-Bevacizumab Combination in Advanced NSCLC: AVATAX, A Retrospective Multicentric Study
Authors: G. Bilger, A.C. Toffart, M. Darrason, M. Duruisseaux, L. Ulmer, P. Wang, E. Giroux Leprieur, N. Girard, M.A. Massiani, P. Bore, R. Descourt, J. Pinsolle, S. Valery, I. Monnet, A. Swalduz, C. Tissot, P. Fournel, A. Baranzelli, A. Cortot, C. Decroisette
Journal: Journal of Thoracic Oncology (2021)
TNF-α-dependent neuronal necroptosis regulated in Alzheimer's disease by coordination of RIPK1-p62 complex with autophagic UVRAG
Authors: Chong Xu, Jialin Wu, Yiqun Wu, Zhichu Ren, Yuyuan Yao, Guobing Chen, Evandro F. Fang, Ji Heon Noh, Yong U. Liu, Libin Wei, Xijing Chen, Jian Sima
Journal: Theranostics (2021)

Background: Neuronal death is a major hallmark of Alzheimer's disease (AD). Necroptosis, as a programmed necrotic process, is activated in AD. However, what signals and factors initiate necroptosis in AD is largely unknown. Methods: We examined the expression levels of critical molecules in necroptotic signaling pathway by immunohistochemistry (IHC) staining and immunoblotting using brain tissues from AD patients and AD mouse models of APP/PS1 and 5×FAD. We performed brain stereotaxic injection with recombinant TNF-α, anti-TNFR1 neutralizing antibody or AAV-mediated gene expression and knockdown in APP/PS1 mice. For in vitro studies, we used TNF-α combined with zVAD-fmk and Smac mimetic to establish neuronal necroptosis models and utilized pharmacological or molecular biological approaches to study the signaling pathways. Results: We find that activated neuronal necroptosis is dependent on upstream TNF-α/TNFR1 signaling in both neuronal cell cultures and AD mouse models. Upon TNF-α stimulation, accumulated p62 recruits RIPK1 and induces its self-oligomerization, and activates downstream RIPK1/RIPK3/MLKL cascade, leading to neuronal necroptosis. Ectopic accumulation of p62 is caused by impaired autophagy flux, which is mediated by UVRAG downregulation during the TNF-α-promoted necroptosis. Notably, UVRAG overexpression inhibits neuronal necroptosis in cell and mouse models of AD. Conclusions: We identify a finely controlled regulation of neuronal necroptosis in AD by coordinated TNF-α signaling, RIPK1/3 activity and autophagy machinery. Strategies that could fine-tune necroptosis and autophagy may bring in promising therapeutics for AD.
Abstract 17851: Prognostic Factors and Outcomes of Patients With Vasospastic Angina Surviving Out-of-hospital Cardiopulmonary Arrest
Authors: Asami Kashiwa, Yukio Hosaka, Kazuyoshi Takahashi, Kazuyuki Ozaki, Keiichi Tsuchida, Yuki Fujihara, Norihito Nakamura, Jiro Hiroki, Hirotaka Oda
Journal: Circulation (2015)

Background: Vasospastic angina (VSA) is reported to cause sudden cardiac death (SCD) due to lethal ventricular arrhythmias, even while a patient is undergoing drug therapy with calcium channel blockers (CCB). The prognostic factors are not fully assessed and the indication of implantable cardioverter-defibrillator (ICD) for patients with VSA is still controversial. We assessed the prognostic factors and outcomes of patients with VSA surviving out-of-hospital cardiopulmonary arrest (OHCA). Methods: Between November 2007 and February 2014, 129 VSA patients were diagnosed by provocative tests using ergonovine during coronary angiographies. The patients were divided into two groups: OHCA group consisted of patients with VSA surviving OHCA (n=15, median age: 58.2 ± 12.2 years) and non-OHCA group (n=114, median age: 60.3 ± 0.9 years). We analyzed the appearance of J wave in the resting ECG and T wave augmentation (more than two times compared to resting) during treadmill exercise tests in three groups (OHCA group, non-OHCA group and Control group consisting of healthy subjects (n=25, median age: 57.9 ± 1.8years)). Results: In resting ECG analysis, J wave was found in 9/15 (60%) of OHCA group, 42/114 (37%) of non-OHCA group and 3/25 (12%) of Control group. There was no significant difference in the appearance of J wave among the three groups. In ECG analysis of treadmill exercise tests, T wave augmentation in non-OHCA group (15/38, 39%) was significantly more frequent than that of Control group (3/25, 12%) (p=0.04). Furthermore T wave augmentation in OHCA group (10/12, 83%) was significantly more frequent than that of non-OHCA group (p=0.008). In OHCA group, all patients began treatment with CCB. Twelve of 15 patients (87%) underwent ICD therapy. During a follow up of 38.7 ± 18.4 months, three of 15 patients (20%) in OHCA group had appropriate ICD therapy or died: one patient received an appropriate ICD therapy for VF and successfully resuscitated, and two patients died suddenly among 3 patients without ICD implantations. Conclusions: In the risk stratification of SCD in VSA patients, T wave augmentation during treadmill exercise tests might be a new prognostic factor. ICD might result in favorable clinical outcomes for high-risk VSA patients.
Mechanical Properties of Bioengineered Corneal Stroma (Adv. Healthcare Mater. 20/2021)
Authors: Nello Formisano, Cas van der Putten, Rhiannon Grant, Gozde Sahin, Roman K. Truckenmüller, Carlijn V. C. Bouten, Nicholas A. Kurniawan, Stefan Giselbrecht
Journal: Advanced Healthcare Materials (2021)

Corneas In article number 2100972, Stefan Giselbrecht and colleagues review existing approaches for bioengineering corneal stromal constructs. There is a high demand for bioengineered corneal constructs to overcome a global donor shortage, but unfortunately many of these bioengineered constructs fail clinical trials due to poor biomechanical performance. This review emphasizes the need to more critically design and analyze these properties in future stromal constructs.
MA09.02 SAKK 16/14 - T-Cell Receptor Repertoire Metrics Predict Response to Neoadjuvant Durvalumab in Patients With Stage IIIA(N2) NSCLC
Authors: I. Alborelli, K. Leonards, M. Manzo, E. Keller, P. Herzig, M. Trüb, D. Schmid, E. Eboulet, G. Godar, M. Pless, A. Zippelius, P. Jermann, S. Savic Prince, S. Rothschild
Journal: Journal of Thoracic Oncology (2021)
P59.17 EGFR Mutation Status, Liver Metastasis, and Overall Survival in Advanced Lung Adenocarcinoma Patients
Authors: P. Walia, L. Zhan, S. Schmid, M.C. Brown, K. Khan, M. Garcia, M. Chowdhury, J. Herman, A. Sabouhanian, E. Strom, D. Patel, S. Cheng, P. Bradbury, N. Leighl, A. Sacher, F.A. Shepherd, D. Shultz, G. Liu
Journal: Journal of Thoracic Oncology (2021)
Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders
Authors: Christoph Kornauth, Tea Pemovska, Gregory I. Vladimer, Günther Bayer, Michael Bergmann, Sandra Eder, Ruth Eichner, Martin Erl, Harald Esterbauer, Ruth Exner, Verena Felsleitner-Hauer, Maurizio Forte, Alexander Gaiger, Klaus Geissler, Hildegard T. Greinix, Wolfgang Gstöttner, Marcus Hacker, Bernd Lorenz Hartmann, Alexander W. Hauswirth, Tim Heinemann, Daniel Heintel, Mir Alireza Hoda, Georg Hopfinger, Ulrich Jaeger, Lukas Kazianka, Lukas Kenner, Barbara Kiesewetter, Nikolaus Krall, Gerhard Krajnik, Stefan Kubicek, Trang Le, Simone Lubowitzki, Marius E. Mayerhoefer, Elisabeth Menschel, Olaf Merkel, Katsuhiro Miura, Leonhard Müllauer, Peter Neumeister, Thomas Noesslinger, Katharina Ocko, Leopold Öhler, Michael Panny, Alexander Pichler, Edit Porpaczy, Gerald W. Prager, Markus Raderer, Robin Ristl, Reinhard Ruckser, Julius Salamon, Ana-Iris Schiefer, Ann-Sofie Schmolke, Ilse Schwarzinger, Edgar Selzer, Christian Sillaber, Cathrin Skrabs, Wolfgang R. Sperr, Ismet Srndic, Renate Thalhammer, Peter Valent, Emiel van der Kouwe, Katrina Vanura, Stefan Vogt, Cora Waldstein, Dominik Wolf, Christoph C. Zielinski, Niklas Zojer, Ingrid Simonitsch-Klupp, Giulio Superti-Furga, Berend Snijder, Philipp B. Staber
Journal: Cancer Discovery (2021)

Abstract Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. Significance: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer. See related commentary by Letai, p. 290. This article is highlighted in the In This Issue feature, p. 275
P07.04 Primary Lung Cancers in Patients With Head and Neck Cancer: Experience of a French Institution
Authors: C. Clément-Duchêne, J. Salleron, G. Dolivet, S. Cortses, R. Mastronicola, E. Beulque, L. Geoffrois, M. Kaminsky, J. Faivre
Journal: Journal of Thoracic Oncology (2021)
P01.01 LIBRETTO-432: A Placebo-Controlled Phase 3 Study of Adjuvant Selpercatinib in Stage IB-IIIA RET Fusion-Positive NSCLC
Authors: J. Goldman, B. Besse, Y. Wu, J.C. Yang, L. Paz-Ares, A. Drilon, M. Johnson, M. Xia, B.H. Chao, M. Tsuboi
Journal: Journal of Thoracic Oncology (2021)
Diet–Host–Microbiota Interactions Shape Aryl Hydrocarbon Receptor Ligand Production to Modulate Intestinal Homeostasis
Authors: Huajun Han, Stephen Safe, Arul Jayaraman, Robert S. Chapkin
Journal: Annual Review of Nutrition (2021)

The aryl hydrocarbon receptor (AhR) is a ligand-activated basic-helix-loop-helix transcription factor that binds structurally diverse ligands and senses cues from environmental toxicants and physiologically relevant dietary/microbiota-derived ligands. The AhR is an ancient conserved protein and is widely expressed across different tissues in vertebrates and invertebrates. AhR signaling mediates a wide range of cellular functions in a ligand-, cell type–, species-, and context-specific manner. Dysregulation of AhR signaling is linked to many developmental defects and chronic diseases. In this review, we discuss the emerging role of AhR signaling in mediating bidirectional host–microbiome interactions. We also consider evidence showing the potential for the dietary/microbial enhancement ofhealth-promoting AhR ligands to improve clinical pathway management in the context of inflammatory bowel diseases and colon tumorigenesis.
P08.01 Building Personalized Follow-Up Care Through AI by Bringing the Lung Cancer Patient, Data Scientist and Oncologist Together
Authors: M. Torrente, F. Franco, V. Calvo, A. Collazo Lorduy, E. Menasalvas, M.E. Vidal, P. Sousa, J. Pimentao, V. Novacek, P. Minervini, D. Fey, L. Costabello, M. Pocs, M. Provencio
Journal: Journal of Thoracic Oncology (2021)
The roles of GTPase-activating proteins in regulated cell death and tumor immunity
Authors: Hua He, Jingjing Huang, Sufang Wu, Shiyao Jiang, Lu Liang, Yueying Liu, Wenbing Liu, Li Xie, Yongguang Tao, Yiqun Jiang, Li Cong
Journal: Journal of Hematology & Oncology (2021)

Abstract GTPase-activating protein (GAP) is a negative regulator of GTPase protein that is thought to promote the conversion of the active GTPase-GTP form to the GTPase-GDP form. Based on its ability to regulate GTPase proteins and other domains, GAPs are directly or indirectly involved in various cell requirement processes. We reviewed the existing evidence of GAPs regulating regulated cell death (RCD), mainly apoptosis and autophagy, as well as some novel RCDs, with particular attention to their association in diseases, especially cancer. We also considered that GAPs could affect tumor immunity and attempted to link GAPs, RCD and tumor immunity. A deeper understanding of the GAPs for regulating these processes could lead to the discovery of new therapeutic targets to avoid pathologic cell loss or to mediate cancer cell death.
It Is Time to Inform Patients of Medical Imaging Risks
Authors: Carly Stewart, Rebecca Smith-Bindman
Journal: JAMA Network Open (2021)

Luca Bastiani, PhD; Fabio Paolicchi, RT; Lorenzo Faggioni, MD, PhD; Massimo Martinelli, PhD; Roberta Gerasia, RT; Chiara Martini, RT; Patrizia Cornacchione, RT; Matteo Ceccarelli, MP; Dante Chiappino, MD; Daniele Della Latta, BSc; Jacopo Negri, RT; Donatella Pertoldi, RT; Donato Negro, RT, MSc; Giovanni Nuzzi, RT; Vincenzo Rizzo, RT; Paola Tamburrino, RT; Chiara Pozzessere, MD; Giacomo Aringhieri, MD, PhD; Davide Caramella, MD
Covid-19: Fatal errors, not fatalism, created UK’s public health disaster
Authors: Kamran Abbasi
Journal: BMJ (2021)

Was it fatalism that allowed 138 000 covid deaths in the UK? Were these deaths bound or decreed to have happened? The answer is, simply, no. Did fatalism kill people in social care, or differentially target people who are disadvantaged? Were ethnic minorities victims of “covid fatalism”—and is it “career fatalism” that means that they are less likely to be shortlisted and appointed to medical jobs, as a new investigation reveals (doi:10.1136/bmj.n2460; doi:10.1136/bmj.n2451)?12

Was it fatalism that denied frontline health and social care professionals adequate personal protective equipment during the pandemic—and even now still exposes them to risks of airborne transmission and accusations of fakery (doi:10.1136/bmj.n2473)?3 The answers remain no. Fatalism, we’re told, ignored pandemic lessons of history and lessons from other countries. Fatalism failed to implement adequate contact tracing and border controls.

Fatalism sidelined local public health teams and institutions, pumped billions into private hospitals and private contractors (doi:10.1136/bmj.n2471),4 and …
The Multifaceted Biology of PCSK9
Authors: Nabil G Seidah, Annik Prat
Journal: Endocrine Reviews (2021)

This article reviews the discovery of PCSK9, its structure-function characteristics, and its presently known and proposed novel biological functions. The major critical function of PCSK9 deduced from human and mouse studies, as well as cellular and structural analyses, is its role in increasing the levels of circulating LDL-cholesterol (LDLc), via its ability to enhance the sorting and escort of the cell surface LDL receptor (LDLR) to lysosomes. This implicates the binding of the catalytic domain of PCSK9 to the EGF-A domain of the LDLR. This also requires the presence of the C-terminal Cys/His-rich domain (CHRD), its binding to the secreted cytosolic cyclase associated protein 1 (CAP-1), and possibly another membrane-bound "protein X". Curiously, in PCSK9-deficient mice, an alternative to the downregulation of the surface levels of the LDLR by PCSK9 is taking place in the liver of female mice in a 17β-estradiol-dependent manner by still an unknown mechanism. Recent studies have extended our understanding of the biological functions of PCSK9, namely its implication in septic shock, vascular inflammation, viral infections (Dengue; SARS-CoV-2) or immune checkpoint modulation in cancer via the regulation of the cell surface levels of the T-cell receptor and MHC-I, which govern the anti-tumoral activity of CD8 + T cells. Because PCSK9 inhibition may be advantageous in these processes, the availability of injectable safe PCSK9 inhibitors (PCSK9i) that reduces by 50-60% LDLc above the effect of statins is highly valuable. Indeed, injectable PCSK9 mAb or siRNA could be added to current immunotherapies in cancer/metastasis.
Implementation of non-communicable disease policies from 2015 to 2020: a geopolitical analysis of 194 countries
Authors: Luke N Allen, Simon Wigley, Hampus Holmer
Journal: The Lancet Global Health (2021)

BackgroundNon-communicable diseases (NCDs) are the leading cause of morbidity and mortality globally. We aimed to analyse trends in implementation of WHO-recommended population-level policies and associations with national geopolitical characteristics.MethodsWe calculated cross-sectional NCD policy implementation scores for all 194 WHO member states from the 2015, 2017, and 2020 WHO progress monitor reports, and examined changes over time as well as average implementation by geographical and geopolitical region and income level. We developed a framework of indicators of national characteristics hypothesised to influence policy implementation, including democracy, corporate permeation (an indicator of corporate influence), NCD burden, and risk factor prevalence. We used multivariate regression models to test our hypotheses.FindingsOn average, countries had fully implemented a third (32·8%, SD 18·2) of the 19 policies in 2020. Using aggregate policy scores, which include partially implemented policies, mean implementation had increased from 39·0% (SD 19·3) in 2015 to 45·9% (19·2) in 2017 and 47·0% (19·8) in 2020. Implementation was lowest for policies relating to alcohol, tobacco, and unhealthy foods, and had reversed for a third of all policies. Low-income and less democratic countries had the lowest policy implementation. Our model explained 64·8% of variance in implementation scores. For every unit increase in corporate permeation, implementation decreased by 5·0% (95% CI –8·0 to –1·9, p=0·0017), and for every 1% increase in NCD mortality burden, implementation increased by 0·9% (0·2 to 1·6, p=0·014). Democracy was positively associated with policy implementation, but only in countries with low corporate permeation.InterpretationImplementation of NCD policies is uneven, but broadly improving over time. Urgent action is needed to boost implementation of policies targeting corporate vectors of NCDs, and to support countries facing high corporate permeation.FundingThe National Institutes for Health Research, the Swedish Research Council, the Fulbright Commission, and the Swedish Society of Medicine.
Aquaporin-1 Expression and Ultrafiltration of the Peritoneal Membrane
Authors: Daniel G. Bichet
Journal: New England Journal of Medicine (2021)

Peritoneal dialysis in adults involves diffusion and osmosis through a peritoneal membrane, measuring 1 m2, that is highly vascularized (flow rate, 100 to 150 ml per minute) and has a total available capillary surface area of approximately 2 m2.1 For decades, glucose has been used as the prototypical crystalloid osmotic agent to drive water removal in peritoneal dialysis.2 Glucose is a small osmotic agent (molecular weight, 180 g per mole) that is prone to crystallization but easily diffuses across semipermeable membranes; hence, it is known as a crystalloid substance. In contrast, colloid and noncrystalline substances are retained by membranes because . . .
76P B7-H3 immune checkpoint protein expression is associated with immune exhaustion, overall survival and metastasis in clear cell renal cell carcinoma
Authors: C.E. Nunes-Xavier, M. Emaldi, T. Øyjord, G. Larrinaga, P. Errarte, J.C. Angulo, R. Llarena, G.M. Mælandsmo, Ø. Fodstad, R. Pulido, J.I. López
Journal: Annals of Oncology (2021)
Exploring Barriers and Facilitators to COVID-19 Vaccine Uptake Among Black and Latinx Communities
Authors: Stella A. Safo
Journal: JAMA Network Open (2021)

Lilanthi Balasuriya, MD; Alycia Santilli, MSW; Jennifer Morone, PhD, RN; Jessica Ainooson, BA; Brita Roy, MD, MHS; Anuli Njoku, DrPH; Andrea Mendiola-Iparraguirre, MD; Kathleen O'Connor Duffany, PhD; Bernard Macklin, PhD; Jackson Higginbottom, MPH; Celina Fernández-Ayala, BA; Genesis Vicente, BA; Arjun Venkatesh, MD, MBA, MHS