tbuckley/cabot-search huggingface dataset:
Accuracy of central neuro-imaging review of DIPG compared with histopathology in the International DIPG Registry
Authors: Margot A Lazow, Christine Fuller, Mariko DeWire, Adam Lane, Pratiti Bandopadhayay, Ute Bartels, Eric Bouffet, Sylvia Cheng, Kenneth J Cohen, Tabitha M Cooney, Scott L Coven, Hetal Dholaria, Blanca Diez, Kathleen Dorris, Moatasem El-ayadi, Ayman El-Sheikh, Paul G Fisher, Adriana Fonseca, Mercedes Garcia Lombardi, Robert J Greiner, Stewart Goldman, Nicholas Gottardo, Sridharan Gururangan, Jordan R Hansford, Tim Hassall, Cynthia Hawkins, Lindsay Kilburn, Carl Koschmann, Sarah E Leary, Jie Ma, Jane E Minturn, Michelle Monje-Deisseroth, Roger Packer, Yvan Samson, Eric S Sandler, Gustavo Sevlever, Christopher L Tinkle, Karen Tsui, Lars M Wagner, Mohamed Zaghloul, David S Ziegler, Brooklyn Chaney, Katie Black, Anthony Asher, Rachid Drissi, Maryam Fouladi, Blaise V Jones, James L Leach
Journal: Neuro-Oncology (2021)

Diffuse intrinsic pontine glioma (DIPG) remains a clinico-radiologic diagnosis without routine tissue acquisition. Reliable imaging distinction between DIPG and other pontine tumors with potentially more favorable prognoses and treatment considerations is essential.Cases submitted to the International DIPG registry (IDIPGR) with histopathologic and/or radiologic data were analyzed. Central imaging review was performed on diagnostic brain MRIs (if available) by two neuro-radiologists. Imaging features suggestive of alternative diagnoses included nonpontine origin, <50% pontine involvement, focally exophytic morphology, sharply defined margins, and/or marked diffusion restriction throughout.Among 286 patients with pathology from biopsy and/or autopsy, 23 (8%) had histologic diagnoses inconsistent with DIPG, most commonly nondiffuse low-grade gliomas and embryonal tumors. Among 569 patients with centrally-reviewed diagnostic MRIs, 40 (7%) were classified as non-DIPG, alternative diagnosis suspected. The combined analysis included 151 patients with both histopathology and centrally-reviewed MRI. Of 77 patients with imaging classified as characteristic of DIPG, 76 (99%) had histopathologic diagnoses consistent with DIPG (infiltrating grade II-IV gliomas). Of 57 patients classified as likely DIPG with some unusual imaging features, 55 (96%) had histopathologic diagnoses consistent with DIPG. Of 17 patients with imaging features suggestive of an alternative diagnosis, eight (47%) had histopathologic diagnoses inconsistent with DIPG (remaining patients were excluded due to nonpontine tumor origin). Association between central neuro-imaging review impression and histopathology was significant (p < 0.001), and central neuro-imaging impression was prognostic of overall survival.The accuracy and important role of central neuro-imaging review in confirming the diagnosis of DIPG is demonstrated.
Profound alterations in brain tissue linked to hypoxic episode after device implantation
Authors: Lucas S. Kumosa, Jens Schouenborg
Journal: Biomaterials (2021)

To enable authentic interfacing with neuronal structures in the brain, preventing alterations of tissue during implantation of devices is critical. By transiently implanting oxygen microsensors into rat cortex cerebri for 2 h, substantial and long lasting (>1 h) hypoxia is routinely generated in surrounding tissues; this hypoxia is linked to implantation generated compressive forces. Preferential loss of larger neurons and reduced metabolic components in surviving neurons indicates decreased viability one week after such hypoxic, compressive implantations. By devising an implantation method that relaxes compressive forces; magnitude and duration of hypoxia generated following such an implantation are ameliorated and neurons appear similar to naïve tissues. In line with these observations, astrocyte proliferation was significantly more pronounced for more hypoxic, compressive implantations. Surprisingly, astrocyte processes were frequently found to traverse cellular boundaries into nearby neuronal nuclei, indicating injury induction of a previously not described astrocyte-neuron interaction. Found more frequently in less hypoxic, force-relaxed insertions and thus correlating to a more beneficial outcome, this finding may suggest a novel protective mechanism. In conclusion, substantial and long lasting insertion induced hypoxia around brain implants, a previously overlooked factor, is linked to significant adverse alterations in nervous tissue.
Effects of Combined Varenicline With Nicotine Patch and of Extended Treatment Duration on Smoking Cessation
Authors: Timothy B. Baker, Megan E. Piper, Stevens S. Smith, Daniel M. Bolt, James H. Stein, Michael C. Fiore
Journal: JAMA (2021)

<h3>Importance</h3> Smoking cessation medications are routinely used in health care. Research suggests that combining varenicline with the nicotine patch, extending the duration of varenicline treatment, or both, may increase cessation effectiveness. <h3>Objective</h3> To compare combinations of varenicline plus the nicotine or placebo patch vs combinations used for either 12 weeks (standard duration) or 24 weeks (extended duration). <h3>Design, Settings, and Participants</h3> Double-blind, 2 × 2 factorial randomized clinical trial conducted from November 11, 2017, to July 9, 2020, at 1 research clinic in Madison, Wisconsin, and at 1 clinic in Milwaukee, Wisconsin. Of the 5836 adults asked to participate in the study, 1251 who smoked 5 cigarettes/d or more were randomized. <h3>Interventions</h3> All participants received cessation counseling and were randomized to 1 of 4 medication groups: varenicline monotherapy for 12 weeks (n = 315), varenicline plus nicotine patch for 12 weeks (n = 314), varenicline monotherapy for 24 weeks (n = 311), or varenicline plus nicotine patch for 24 weeks (n = 311). <h3>Main Outcomes and Measures</h3> The primary outcome was carbon monoxide–confirmed self-reported 7-day point prevalence abstinence at 52 weeks. <h3>Results</h3> Among 1251 patients who were randomized (mean [SD] age, 49.1 [11.9] years; 675 [54.0%] women), 751 (60.0%) completed treatment and 881 (70.4%) provided final follow-up. For the primary outcome, there was no significant interaction between the 2 treatment factors of medication type and medication duration (odds ratio [OR], 1.03 [95% CI, 0.91 to 1.17];<i>P</i> = .66). For patients randomized to 24-week vs 12-week treatment duration, the primary outcome occurred in 24.8% (154/622) vs 24.3% (153/629), respectively (risk difference, −0.4% [95% CI, −5.2% to 4.3%]; OR, 1.01 [95% CI, 0.89 to 1.15]). For patients randomized to varenicline combination therapy vs varenicline monotherapy, the primary outcome occurred in 24.3% (152/625) vs 24.8% (155/626), respectively (risk difference, 0.4% [95% CI, −4.3% to 5.2%]; OR, 0.99 [95% CI, 0.87 to 1.12]). Nausea occurrence ranged from 24.0% to 30.9% and insomnia occurrence ranged from 24.4% to 30.5% across the 4 groups. <h3>Conclusions and Relevance</h3> Among adults smoking 5 cigarettes/d or more, there were no significant differences in 7-day point prevalence abstinence at 52 weeks among those treated with combined varenicline plus nicotine patch therapy vs varenicline monotherapy, or among those treated for 24 weeks vs 12 weeks. These findings do not support the use of combined therapy or of extended treatment duration. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03176784
Episymbiotic Saccharibacteria suppresses gingival inflammation and bone loss in mice through host bacterial modulation
Authors: Otari Chipashvili, Daniel R. Utter, Joseph K. Bedree, Yansong Ma, Fabian Schulte, Gabrielle Mascarin, Yasmin Alayyoubi, Deepak Chouhan, Markus Hardt, Felicitas Bidlack, Hatice Hasturk, Xuesong He, Jeffrey S. McLean, Batbileg Bor
Journal: Cell Host & Microbe (2021)
Mortality trends in pulmonary arterial hypertension in Canada: a temporal analysis of survival per ESC/ERS guideline era
Authors: Jason G.E. Zelt, Jordan Sugarman, Jason Weatherald, Arun C.R. Partridge, Jiaming (Calvin) Liang, John Swiston, Nathan Brunner, George Chandy, Duncan J. Stewart, Vladimir Contreras-Dominguez, Mitesh Thakrar, Doug Helmersen, Rhea Varughese, Naushad Hirani, Fraz Umar, Rosemary Dunne, Caroyln Doyle-Cox, Julia Foxall, Lisa Mielniczuk
Journal: European Respiratory Journal (2021)

Background The evolution in pulmonary arterial hypertension (PAH) management has been summarised in three iterations of the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. No study has assessed whether changes in management, as reflected in the changing guidelines, has translated to improved long-term survival in PAH. Methods We performed a mixed retrospective/prospective analysis of treatment-naïve, incident PAH patients (n=392) diagnosed at three major centres in Canada from 2009 to 2021. Patients were divided into two groups based on their diagnosis date and in accordance with the 2009 and 2015 ESC/ERS guideline iterations. Overall survival was assessed based on date of diagnosis and initial treatment strategy ( i.e. monotherapy versus combination therapy). Results There was a shift towards more aggressive upfront management with combination therapy in Canada after the publication of the 2015 ESC/ERS guidelines (10.4% and 30.8% in patients from 2009 to 2015 and 36.0% and 57.4% in patients diagnosed after 2015 for baseline and 2-year follow-up, respectively). A key factor associated with combination therapy after 2015 was higher pulmonary vascular resistance (p=0.009). The 1-, 3- and 5-year survival rates in Canada were 89.2%, 75.6% and 56.0%, respectively. Despite changes in management, there was no improvement in long-term survival before and after publication of the 2015 ESC/ERS guidelines (p=0.53). Conclusions There was an increase in the use of initial and sequential combination therapy in Canada after publication of the 2015 ESC/ERS guidelines, which was not associated with improved long-term survival. These data highlight the continued difficulties of managing this aggressive pulmonary disease in an era without a cure.
5-IP7 is a GPCR messenger mediating neural control of synaptotagmin-dependent insulin exocytosis and glucose homeostasis
Authors: Xiaozhe Zhang, Na Li, Jun Zhang, Yanshen Zhang, Xiaoli Yang, Yifan Luo, Bobo Zhang, Zhixue Xu, Zhenhua Zhu, Xiuyan Yang, Yuan Yan, Biao Lin, Shen Wang, Da Chen, Caichao Ye, Yan Ding, Mingliang Lou, Qingcui Wu, Zhanfeng Hou, Keren Zhang, Ziming Liang, Anqi Wei, Bianbian Wang, Changhe Wang, Nan Jiang, Wenqing Zhang, Guozhi Xiao, Cong Ma, Yan Ren, Xiangbing Qi, Weiping Han, Chao Wang, Feng Rao
Journal: Nature Metabolism (2021)
P60.02 Polymorphisms of APE1(T444G), hOGG1(C977G), XRCC1(G839A), XPD(T2251G), XPG(G3310C), XPC(A2815C) Genes in Lung Cancer Patients
Authors: M. Bakanova, V. Minina, Y. Savchenko, A. Glushkov
Journal: Journal of Thoracic Oncology (2021)
Mobile Health (mHealth) in Low- and Middle-Income Countries
Authors: Judith McCool, Rosie Dobson, Robyn Whittaker, Chris Paton
Journal: Annual Review of Public Health (2021)

This article reflects on current trends and proposes new considerations for the future of mobile technologies for health (mHealth). Our focus is predominantly on the value of and concerns with regard to the application of digital health within low- and middle-income countries (LMICs). It is in LMICs and marginalized communities that mHealth (within the wider scope of digital health) could be most useful and valuable. Peer-reviewed literature on mHealth in LMICs provides reassurance of this potential, often reflecting on the ubiquity of mobile phones and ever-increasing connectivity globally, reaching remote or otherwise disengaged populations. Efforts to adapt successful programs for LMIC contexts and populations are only just starting to reap rewards. Private-sector investment in mHealth offers value through enhanced capacity and advances in technology as well as the ability to meet increasing consumer demand for real-time, accessible, convenient, and choice-driven health care options. We examine some of the potential considerations associated with a private-sector investment, questioning whether a core of transparency, local ownership, equity, and safety is likely to be upheld in the current environment of health entrepreneurship.
2MO XPO1 inhibition strongly sensitizes to first-line and second-line therapy in small cell lung cancer
Authors: Á. Quintanal-Villalonga, H. Taniguchi, Y. Hao, A. Chow, Y.A. Zhan, F. Uddin, V. Allaj, P. Manoj, N. Shah, J.M. Chan, M. Offin, M. Ciampricotti, J. Egger, J. Qiu, E. De Stanchina, T.J. Hollmann, R.P. Koche, T. Sen, J.T. Poirier, C.M. Rudin
Journal: Annals of Oncology (2021)
Adherence to CF treatment can be improved with the right approach!
Authors: André Schultz
Journal: Thorax (2021)

The burden of routine, daily therapies prescribed for people with cystic fibrosis (CF) is large. Maintaining adherence to such chronic therapies can be challenging, especially when the financial costs are considerable and they are time consuming, though non-adherence is associated with poor health outcomes.1 Therefore, efforts to improve adherence in people with CF are important, as reflected by the recent global James Lind Alliance Priority Setting Partnership exercise where finding ways to help people with CF to ‘improve and sustain adherence to treatment’ was identified as a priority for the CF community.2

Factors influencing adherence are complex. Non-adherence can be intentional or non-intentional. Patient-related factors include individuals’ understanding of their disease, beliefs about the effectiveness of specific treatments and side effects,3 and the presence or absence of good medication routines.4 External factors that affect adherence include complexity of dosing regimens, cultural factors and the cost of treatments. For people with CF, the reality of living with a chronic disease and having to adhere to complicated treatment regimens inevitably competes with other …
Polycystic Ovary Syndrome, Combined Oral Contraceptives, and the Risk of Dysglycemia: A Population-Based Cohort Study With a Nested Pharmacoepidemiological Case-Control Study
Authors: Balachandran Kumarendran, Michael W. O'Reilly, Anuradhaa Subramanian, Dana Šumilo, Konstantinos Toulis, Krishna M. Gokhale, Chandrika N. Wijeratne, Arri Coomarasamy, Abd A. Tahrani, Laurent Azoulay, Wiebke Arlt, Krishnarajah Nirantharakumar
Journal: Diabetes Care (2021)

Irregular menstrual cycles are associated with increased cardiovascular mortality. Polycystic ovary syndrome (PCOS) is characterized by androgen excess and irregular menses; androgens are drivers of increased metabolic risk in women with PCOS. Combined oral contraceptive pills (COCPs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction. We examined COCP use and risk of dysglycemia (prediabetes and type 2 diabetes) in women with PCOS.Using a large U.K. primary care database (The Health Improvement Network [THIN]; 3.7 million patients from 787 practices), we carried out a retrospective population-based cohort study to determine dysglycemia risk (64,051 women with PCOS and 123,545 matched control subjects), as well as a nested pharmacoepidemiological case-control study to investigate COCP use in relation to dysglycemia risk (2,407 women with PCOS with [case subjects] and without [control subjects] a diagnosis of dysglycemia during follow-up). Cox models were used to estimate the unadjusted and adjusted hazard ratio, and conditional logistic regression was used to obtain adjusted odds ratios (aORs).The adjusted hazard ratio for dysglycemia in women with PCOS was 1.87 (95% CI 1.78-1.97, P < 0.001; adjustment for age, social deprivation, BMI, ethnicity, and smoking), with increased rates of dysglycemia in all BMI subgroups. Women with PCOS and COCP use had a reduced dysglycemia risk (aOR 0.72, 95% CI 0.59-0.87).In this study, limited by its retrospective nature and the use of routinely collected electronic general practice record data, which does not allow for exclusion of the impact of prescription-by-indication bias, women with PCOS exposed to COCPs had a reduced risk of dysglycemia across all BMI subgroups. Future prospective studies should be considered for further understanding of these observations and potential causality.
36P Plasma levels of hsa_circ_0001445 and hsa_circ_0007915 may indicate the presence of metastatic disease in patients with colorectal cancer
Authors: M. Radanova, G. Mihaylova, O. Tasinov, D. Ivanova, N. Nazifova-Tasinova, R. Manev, A. Salim, M. Nikolova, D. Ivanova, N. Conev, Z. Mihaylova, I. Donev
Journal: Annals of Oncology (2021)
P21.02 Real-World Concordance Between Tumor Mutational Burden From Blood and Tissue in Lung Cancer and Other Cancers
Authors: J. Park, I. Park, J.Y. Hwang, W. Bae, G. Lee, L. Kim, Y. Choi, H. Jung, M.J. Kim, S.P. Hong, H. Lee, E. Yu, A. Lee, Y. Park, Y.K. Chae
Journal: Journal of Thoracic Oncology (2021)
P21.01 Selected ctDNA Panel Gene Sequencing for Neoantigen Discovery and Survival Prediction in Patients With Stage IV Non-Small Cell Lung Cancer
Authors: Y. Zhang, W. Dai, L. Xu, L. Ma, Z. Liang, C. Zhao, W. Xu, W. Chen, Z. Chen, L. Yang, F.M. Kong
Journal: Journal of Thoracic Oncology (2021)
Characterization of patients with advanced basal cell carcinoma progressing while receiving Hedgehog pathway inhibitors
Authors: P. Monnet, F. Herms, M. Djermane, S. Dalac, O. Dereure, B. Dréno, M. Beylot‐Barry, L. Mortier, N. Basset‐Seguin
Journal: British Journal of Dermatology (2021)
P57.06 EGFR Mutational Status and PD-L1 in Early-Stage Brazilian Non-Small-Cell Lung Cancer
Authors: R. De Oliveira Cavagna, I. Alves Pinto, A.L. Virginio Da Silva, I. Santana, J. Mourão Dias, L.C. Souza, F.A. Ferreira Da Silva, M.F. Biazotto Fernandes, G. Dix Junqueira Pinto, I. Santos Negreiros, F. Escremim De Paula, G. Noriz Berardinelli, G.M. Stanfoca Casagrande, M.F. Santiago Gonçalves, E.C. Albino Da Silva, V. Duval Da Silva, P. De Marchi, R.M. Vieira Reis, L. Ferro Leal
Journal: Journal of Thoracic Oncology (2021)
Climate change and global issues in allergy and immunology
Authors: Susan E. Pacheco, Guillermo Guidos-Fogelbach, Isabella Annesi-Maesano, Ruby Pawankar, Gennaro D' Amato, Patricia Latour-Staffeld, Marylin Urrutia-Pereira, Matthew J. Kesic, Michelle L. Hernandez
Journal: Journal of Allergy and Clinical Immunology (2021)
An Allogeneic Multiple Myeloma GM-CSF–Secreting Vaccine with Lenalidomide Induces Long-term Immunity and Durable Clinical Responses in Patients in Near Complete Remission
Authors: Luca Biavati, Carol Ann Huff, Anna Ferguson, Amy Sidorski, M. Amanda Stevens, Lakshmi Rudraraju, Cristina Zucchinetti, Syed Abbas Ali, Philip Imus, Christian B. Gocke, Rachel M. Gittelman, Sarah Johnson, Catherine Sanders, Marissa Vignali, Anita Gandhi, Xiaobu Ye, Kimberly A. Noonan, Ivan Borrello
Journal: Clinical Cancer Research (2021)

This proof-of-principle clinical trial evaluated whether an allogeneic multiple myeloma GM-CSF-secreting vaccine (MM-GVAX) in combination with lenalidomide could deepen the clinical response in patients with multiple myeloma in sustained near complete remission (nCR).Fifteen patients on lenalidomide were treated with MM-GVAX and pneumococcal conjugate vaccine (PCV; Prevnar) at 1, 2, 3, and 6 months.Eight patients (53.3%) achieved a true CR. With a median follow-up of 5 years, the median progression-free survival had not been reached, and the median overall survival was 7.8 years from enrollment. MM-GVAX induced clonal T-cell expansion and measurable cytokine responses that persisted up to 7 years in all patients. At baseline, a higher minimal residual disease was predictive of early relapse. After vaccination, a lack of both CD27-DNAM1-CD8+ T cells and antigen-presenting cells was associated with disease progression.MM-GVAX, along with lenalidomide, effectively primed durable immunity and resulted in long-term disease control, as suggested by the reappearance of a detectable, fluctuating M-spike without meeting the criteria for clinical relapse. For patients in a nCR, MM-GVAX administration was safe and resulted in prolonged clinical responses.
Abstract 15454: Identification of ADORA1- PDE10A Complex Formation and Its Bidirectional Regulation of Intracellular Cyclic AMP Levels as a Novel Therapeutic Target for Treating Pulmonary Hypertension
Authors: Chanil Valasarajan, Julio C Laria, Nahomi C Laria, Astrid Wietelmann, Friedrich Grimminger, Werner Seeger, Soni Pullamsetti
Journal: Circulation (2019)

Introduction: Despite substantial advancements in the treatment of pulmonary arterial hypertension (PAH), obstacles still remain in achieving the optimal outcomes. Various treatments have been deve...
P35.01 YB-1 is a Key Player in Aggressive Behaviour and Chemoresistance in Mesothelioma
Authors: K. Schelch, D. Emminger, B. Zitta, M. Phimmachanh, A. Ries, A. Wenninger-Weinzierl, M. Distel, M. Grusch
Journal: Journal of Thoracic Oncology (2021)
Air pollution and development in Africa: impacts on health, the economy, and human capital
Authors: Samantha Fisher, David C Bellinger, Maureen L Cropper, Pushpam Kumar, Agnes Binagwaho, Juliette Biao Koudenoukpo, Yongjoon Park, Gabriella Taghian, Philip J Landrigan
Journal: The Lancet Planetary Health (2021)

<h2>Summary</h2><h3>Background</h3> Africa is undergoing both an environmental and an epidemiological transition. Household air pollution is the predominant form of air pollution, but it is declining, whereas ambient air pollution is increasing. We aimed to quantify how air pollution is affecting health, human capital, and the economy across Africa, with a particular focus on Ethiopia, Ghana, and Rwanda. <h3>Methods</h3> Data on household and ambient air pollution were from WHO Global Health Observatory, and data on morbidity and mortality were from the 2019 Global Burden of Disease Study. We estimated economic output lost due to air pollution-related disease by country, with use of labour income per worker, adjusted by the probability that a person (of a given age) was working. Losses were expressed in 2019 international dollars and as a proportion of gross domestic product (GDP). We also quantified the contribution of particulate matter (PM)<sub>2·5</sub> pollution to intelligence quotient (IQ) loss in children younger than 10 years, with use of an exposure–response coefficient based on previously published data. <h3>Findings</h3> Air pollution was responsible for 1·1 million deaths across Africa in 2019. Household air pollution accounted for 697 000 deaths and ambient air pollution for 394 000. Ambient air pollution-related deaths increased from 361 000 in 2015, to 383 000 in 2019, with the greatest increases in the most highly developed countries. The majority of deaths due to ambient air pollution are caused by non-communicable diseases. The loss in economic output in 2019 due to air pollution-related morbidity and mortality was $3·02 billion in Ethiopia (1·16% of GDP), $1·63 billion in Ghana (0·95% of GDP), and $349 million in Rwanda (1·19% of GDP). PM<sub>2·5</sub> pollution was estimated to be responsible for 1·96 billion lost IQ points in African children in 2019. <h3>Interpretation</h3> Ambient air pollution is increasing across Africa. In the absence of deliberate intervention, it will increase morbidity and mortality, diminish economic productivity, impair human capital formation, and undercut development. Because most African countries are still early in development, they have opportunities to transition rapidly to wind and solar energy, avoiding a reliance on fossil fuel-based economies and minimising pollution. <h3>Funding</h3> UN Environment Programme.
OA04.03 Feasibility of Prospective Dietetic Assessment and Intervention of Patients Receiving Chemo-Radiotherapy for Lung Cancer
Authors: C. Samuelson, M. Brown, I. Phillips, D. Finn, S. Campbell, T. Evans, K. Maclennan, A. Tufail, M. Mackean, C. Barrie, F. Little
Journal: Journal of Thoracic Oncology (2021)
P47.04 TROPION-Lung02: Datopotamab Deruxtecan (Dato-DXd) Plus Pembrolizumab and Platinum-Based Chemotherapy in Advanced NSCLC
Authors: B. Levy, K. Leventakos, Y. Lou, P. Savvides, O. Rixe, A. Tolcher, J. Yin, J. Xie, F. Guevara, Y. Goto
Journal: Journal of Thoracic Oncology (2021)