tbuckley/cabot-search huggingface dataset:
CTL019 Therapy Appears Safe and Effective in Pediatric Patients with Down Syndrome with Relapsed/ Refractory (r/r) Acute Lymphoblastic Leukemia
Authors: Theodore W Laetsch, Shannon L Maude, Stephan A Grupp, Michael W Boyer, Andrew C Harris, Muna Qayed, Christine L Phillips, Michael A Pulsipher, Henrique Bittencourt, Patricia A Wood, Karen Thudium Mueller, Yanqui Weng, Carl H June, Bruce L Levine, Hidefumi Hiramatsu
Journal: Blood (2017)
MO13-3 Dabrafenib and trametinib treatment for patients with anaplastic thyroid cancer
Authors: Tokiko Ito, Masatsugu Amitani, Tadafumi Shimizu, Mayu Ono, Takaaki Ohba, Koichi Ohno, Toshiharu Kanai, Kazuma Maeno, Ken-ichi Ito
Journal: Annals of Oncology (2021)
Use of the typhoid conjugate vaccine in endemic settings
Authors: Farhana Khanam, Firdausi Qadri
Journal: The Lancet Global Health (2021)

Multidrug-resistant and extensively drug-resistant (XDR) strains of Salmonella enterica serotype Typhi (S Typhi) are increasingly creating serious clinical and economic challenges for patients with typhoid fever in south Asia.1 There is a high disease burden of typhoid fever, mostly among children in urban slums, where safe water and a proper sanitation infrastructure are lacking.2,3 The provision of these facilities requires large financial investments and the political will to eliminate the spread of infectious diseases.
Direct characterization of cis-regulatory elements and functional dissection of complex genetic associations using HCR–FlowFISH
Authors: Steven K. Reilly, Sager J. Gosai, Alan Gutierrez, Ava Mackay-Smith, Jacob C. Ulirsch, Masahiro Kanai, Kousuke Mouri, Daniel Berenzy, Susan Kales, Gina M. Butler, Adrianne Gladden-Young, Redwan M. Bhuiyan, Michael L. Stitzel, Hilary K. Finucane, Pardis C. Sabeti, Ryan Tewhey
Journal: Nature Genetics (2021)
Abstract 11470: Effect of Sarpogrelate, a 5-HT2A Antagonist, on Platelet Aggregation in Patients With Stable Atherosclerotic Cardiovascular Disease: Potential for Practical Use at Preoperative Period
Authors: Yeong-Min Lee, Young-Ah Park, Han-Young Jin, Jeong-Sook Seo, Jae-sik Jang, Dae-Kyeong Kim, Dong-Soo Kim, Tae-Hyun Yang
Journal: Circulation (2019)

Introduction: Clopidogrel is a principal antiplatelet agent in patients with atherosclerotic cardiovascular disease (ASCVD). However, patients need to stop clopidogrel at least 5 days before surger...
Nitro-oleic acid reduces thoracic aortic aneurysm progression in a mouse model of Marfan syndrome
Authors: Felix Sebastian Nettersheim, Julian Lemties, Simon Braumann, Simon Geißen, Senai Bokredenghel, Richard Nies, Alexander Hof, Holger Winkels, Bruce A Freeman, Anna Klinke, Volker Rudolph, Stephan Baldus, Dennis Mehrkens, Martin Mollenhauer, Matti Adam
Journal: Cardiovascular Research (2021)

Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the Fibrillin-1 gene. It is associated with formation of thoracic aortic aneurysms that can potentially be a life-threatening condition due to aortic rupture or dissection. Excessive non-canonical transforming growth factor beta signalling, mediated by activation of extracellular signal-regulated kinases 1/2 (ERK1/2), as well as inducible nitric oxide synthase (NOS2)-dependent nitric oxide production, have been identified to drive aortic pathology in MFS through induction of elastin fragmentation and smooth muscle cell apoptosis. Despite promising results in animal studies, specific pharmacological interventions approved for clinical use in patients with MFS-related aortic disease are rare. Nitro-oleic acid (NO2-OA) is an endogenously generated signalling modulator, which is available as an oral compound and has been shown to inhibit ERK1/2 activation and NOS2 expression in different disease models, thereby exerting promising therapeutic effects. In this study, we investigated whether NO2-OA decreases aortic dilation in MFS.Eight-week-old MFS (Fbn1C1041G/+) mice were treated with NO2-OA or vehicle for 4 weeks via subcutaneously implanted osmotic minipumps. Echocardiography indicated progressive ascending aortic dilation and wall stiffening in MFS mice, which was significantly attenuated by NO2-OA treatment. This protective effect was mediated by inhibition of aortic ERK1/2, Smad2 as well as nuclear factor kappa B overactivation and consequent attenuation of elastin fragmentation by matrix metalloproteinase 2, apoptosis, and collagen deposition. Critically, the therapeutic efficacy of NO2-OA in MFS was further emphasized by demonstrating its capability to reduce lethal aortic complications in Fbn1C1041G/+ mice challenged with Angiotensin II.NO2-OA distinctly attenuates progression of aortic dilation in MFS via modulation of well-established disease-mediating pathways, thereby meriting further investigation into its application as a therapeutic agent for the treatment of this condition.
A STAT5B–CD9 axis determines self-renewal in hematopoietic and leukemic stem cells
Authors: Sebastian Kollmann, Reinhard Grausenburger, Thorsten Klampfl, Michaela Prchal-Murphy, Klavdija Bastl, Hanja Pisa, Vanessa M. Knab, Tania Brandstoetter, Eszter Doma, Wolfgang R. Sperr, Sabine Lagger, Matthias Farlik, Richard Moriggl, Peter Valent, Florian Halbritter, Karoline Kollmann, Gerwin Heller, Barbara Maurer, Veronika Sexl
Journal: Blood (2021)
Safety and efficacy of itepekimab in patients with moderate-to-severe COPD: a genetic association study and randomised, double-blind, phase 2a trial
Authors: Klaus F Rabe, Bartolome R Celli, Michael E Wechsler, Raolat M Abdulai, Xiaodong Luo, Maarten M Boomsma, Heribert Staudinger, Julie E Horowitz, Aris Baras, Manuel A Ferreira, Marcella K Ruddy, Michael C Nivens, Nikhil Amin, David M Weinreich, George D Yancopoulos, Helene Goulaouic
Journal: The Lancet Respiratory Medicine (2021)
Abstract 9628: Krüppel-like Factor-10 Serves as a T cell Anti-Aging Factor in Organ Transplantation
Authors: Koichi Shimizu, Peter Libby, Eduardo Folco, Richard Mitchell, Mark Feinberg
Journal: Circulation (2011)

The response of T cells to mitogens wanes with normal aging. Previous work has implicated cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) in the hyporesponsiveness of T cells in the elderly; such reduced activation could impact allograft survival. Conversely, Krüppel-like factor 10 (KLF10) is a transcription factor involved in T-cell activation. This study investigated whether KLF10 participates in age-related diminution in cardiac allograft rejection, using KLF10-deficient mice (KLF10-/-). Methods and Results: Major histocompatibility complex class II (MHC II)-mismatched cardiac allografts showed similar survival when transplanted into young recipients (8-12 week old) of either wild-type (WT) or KLF10-/- strains. In contrast, allografts in older KLF10-/- recipients (20-24 week old) survived an average of only 4.4±2.1 weeks (n=8), compared to &gt;12 weeks (n = 6, p&lt;0.0001) in older WT hosts. At 4 weeks post-transplantation, allografts in older KLF10-/- recipients had significantly higher parenchymal rejection scores (3±0.8, n=6) than did older WT recipients (1.4±0.5, n=7, p &lt;0.005); allografts in older KLF10-/- hosts also had significantly increased allograft accumulation of T cells and macrophages, and significantly increased mRNA levels of IL-6, IFN-γ, TNF-α, MCP-1, IP-10, Mig, and I-TAC compared to WT recipient allografts. Mixed lymphocyte reactions using older KLF10-/- responder cells showed significantly higher reactions compared to WT responders (20-fold), while younger WT and KLF10-/- responders were comparable. WT T cells in older animals expressed significantly higher CTLA-4 levels (4-fold) than did those in young mice, while old KLF10-/- mice expressed lower CTLA-4 levels and higher levels of CD28 expression compared to young KLF10-/- mice. Cardiac allografts of KLF10-/- young host adoptively receiving older KLF10-/- T cells significantly augmented parenchymal rejection with increased inflammatory cell infiltration compared to young KLF10-/- T cell transferred recipient allografts. Conclusion: The absence of KLF10 in older recipient T cells markedly increased effector T-cell activation and exacerbated allograft rejection. Thus, KLF10 regulates age-dependent immune responses in cardiac transplantation.
MiR-143 Targets ERK5 in Granulopoiesis and Predicts Outcome of Patients with Acute Myeloid Leukemia
Authors: Jens-Uwe Hartmann, Daniela Bräuer-Hartmann, Miroslava Kardosova, Franziska Wilke, Alexander Arthur Wurm, Cindy Schoedel, Dennis Gerloff, Christiane Katzerke, Rosanna H.E. Krakowsky, Carolina Yaeko Namasu, Marius Bill, Sebastian Schwind, Carsten Müller-Tidow, Dietger W. Niederwieser, Meritxell Alberich-Jorda, Gerhard Behre
Journal: Blood (2017)
Abstract 17873: Identification of High-Risk Patients Requiring Permanent Pacemaker After Transcatheter Aortic Valve Replacement Using Novel 3D Reconstruction and Tissue Characterization of the Aortic Valve Apparatus: A Pilot Clinical Study
Authors: Guangming Zhang, Rong Liu, Xiaobo Zhou, David Zhao, Robert Applegate, Sanjay Gandhi, Karl Richardson, Min Pu
Journal: Circulation (2017)

Introduction: Conduction system injury requiring permanent pacemaker implantation (PPM) becomes increasingly clinically relevant as transcatheter aortic valve replacement (TAVR) is employed in inte...
P17-9 Absolute white blood cell counts profile as metastatic predictive factors in premenopausal breast cancer
Authors: Ni Putu Sri Indrani Remitha, I Gede Wikania Wira Wiguna, I Gusti Ayu Stiti Sadvika, I Wayan Sudharta Putra, Desak Wihandani, Putu Anda Adiputra, I Gede Supadmanaba
Journal: Annals of Oncology (2021)
Preemptive donor-derived anti-CD19 CAR T-cell infusion showed a promising anti-leukemia effect against relapse in MRD-positive B-ALL after allogeneic hematopoietic stem cell transplantation
Authors: Xiang-Yu Zhao, Zheng-Li Xu, Xiao-Dong Mo, Yu-Hong Chen, Meng Lv, Yi-Fei Cheng, Huan Chen, Ying-Jun Chang, Lan-Ping Xu, Yu Wang, Xiao-Hui Zhang, Kai-Yan Liu, Xiao-Jun Huang
Journal: Leukemia (2021)
A telerehabilitation programme in post-discharge COVID-19 patients (TERECO): a randomised controlled trial
Authors: Jian'an Li, Wenguang Xia, Chao Zhan, Shouguo Liu, Zhifei Yin, Jiayue Wang, Yufei Chong, Chanjuan Zheng, Xiaoming Fang, Wei Cheng, Jan D Reinhardt
Journal: Thorax (2021)

Objectives To investigate superiority of a telerehabilitation programme for COVID-19 (TERECO) over no rehabilitation with regard to exercise capacity, lower limb muscle strength (LMS), pulmonary function, health-related quality of life (HRQOL) and dyspnoea. Design Parallel-group randomised controlled trial with 1:1 block randomisation. Setting Three major hospitals from Jiangsu and Hubei provinces, China. Participants 120 formerly hospitalised COVID-19 survivors with remaining dyspnoea complaints were randomised with 61 allocated to control and 59 to TERECO. Intervention Unsupervised home-based 6-week exercise programme comprising breathing control and thoracic expansion, aerobic exercise and LMS exercise, delivered via smartphone, and remotely monitored with heart rate telemetry. Outcomes Primary outcome was 6 min walking distance (6MWD) in metres. Secondary outcomes were squat time in seconds; pulmonary function assessed by spirometry; HRQOL measured with Short Form Health Survey-12 (SF-12) and mMRC-dyspnoea. Outcomes were assessed at 6 weeks (post-treatment) and 28 weeks (follow-up). Results Adjusted between-group difference in change in 6MWD was 65.45 m (95% CI 43.8 to 87.1; p&lt;0.001) at post-treatment and 68.62 m (95% CI 46.39 to 90.85; p&lt;0.001) at follow-up. Treatment effects for LMS were 20.12 s (95% CI 12.34 to 27.9; p&lt;0.001) post-treatment and 22.23 s (95% CI 14.24 to 30.21; p&lt;0.001) at follow-up. No group differences were found for lung function except post-treatment maximum voluntary ventilation. Increase in SF-12 physical component was greater in the TERECO group with treatment effects estimated as 3.79 (95% CI 1.24 to 6.35; p=0.004) at post-treatment and 2.69 (95% CI 0.06 to 5.32; p=0.045) at follow-up. Conclusions This trial demonstrated superiority of TERECO over no rehabilitation for 6MWD, LMS, and physical HRQOL. Trial registration number ChiCTR2000031834.
IRE1 and PERK signaling regulates inflammatory responses in a murine model of contact hypersensitivity
Authors: Fabian Gendrisch, Lukas Völkel, Melanie Fluck, Petya Apostolova, Robert Zeiser, Thilo Jakob, Stefan F. Martin, Philipp R. Esser
Journal: Allergy (2021)

Abstract Background Contact sensitizers may interfere with correct protein folding. Generation of un‐/misfolded proteins can activate the IRE‐1 or PERK signaling pathways initiating the unfolded protein response (UPR) and thereby determine inflammatory immune responses. We have analyzed the effect of sensitizers with different potencies on the induction of UPR activation/inhibition and the subsequent generation of a pro‐inflammatory micromilieu in vitro as well as the effect of UPR modulation on the inflammatory response in the murine contact hypersensitivity (CHS) in vivo. Methods Semi‐quantitative and quantitative PCR, fluorescence microscopy, ELISA, NF‐κB activation and translocation assays, DC/keratinocyte co‐culture assay, FACS, and in vivo CHS experiments were performed. Results Sensitizers and irritants activate IRE‐1 and PERK in murine and human keratinocytes. Synergistic effects occur after combination of different weak sensitizers / addition of irritants. Moreover, tolerogenic dinitrothiocyanobenzene can be converted into a strong sensitizer by pre‐activation of the UPR. Blocking UPR signaling results in decreased NF‐κB activation and cytokine production in keratinocytes and in activation marker downregulation in a HaCaT/THP‐1 co‐culture. Interestingly, not only s ystemic but also topical application of UPR inhibitors abrogates CHS responses in vivo. Conclusion These observations highlight an important role of the UPR in determination of the inflammatory response in vitro and in vivo further underlining the importance of tissue stress and damage responses in the development of ACD and provide mechanistically based concepts as a basis for the development of new therapeutic approaches to treat allergic contact dermatitis.
MO13-4 Case series of cancer of unknown primary site in Toyama University Hospital
Authors: Takeshi Kaihara, Ryuji Hayashi, Shinya Kajiura, Masahiro Matsumoto, Kazuki Ogawa, Genki Satou, Kouhei Takagi, Momoka Nakatani, Masaya Kinjou, Sora Watanabe, Toshiro Miwa
Journal: Annals of Oncology (2021)
弾性線維溶解性カテプシン誘発/活性化系はラットとヒトの心筋に存在し,高血圧性心不全において上方制御する
Authors: Cheng Xian Wu, Nagata Kohzo, Kuzuya Masafumi, Nishizawa Takao, Nakamura Kae, Obata Koji, Izawa Hideo, Kondo Takahisa, Iguchi Akihisa, Okumura Kenji, Yokota Mitsuhiro, Murohara Toyoaki
Journal: Circulation (2007)
Abstract 8772: Clinical Correlates of Pulmonary Artery Pulse Wave Velocity in Normal Subjects
Authors: Kenji Harada, Yukiko Harada, Manatomo Toyono
Journal: Circulation (2011)

Background: In contrast to systemic artery, much less is known about age-related change in pulmonary artery stiffness. Pulse wave velocity (PWV) is an index for vascular stiffness. The purpose of this study is to assess pulmonary artery PWV and investigate their relations to age, body mass index (BMI), pulmonary artery systolic pressure, left ventricular (LV) diastolic pressure, and systemic artery PWV in normal subjects. Methods: Echocardiography with tissue Doppler imaging was performed in 92 normal subjects from 6 to 80 years. To measure pulmonary artery PWV, pulsed Doppler flow wave transmission time (T) between main pulmonary artery proximal (pulmonary valve) and distal point (pulmonary artery bifurcation) were measured. The distance (D) from the pulsed Doppler sample volume in the pulmonary valve to the pulmonary artery bifurcation was measured. The pulmonary artery PWV was defined as T/D. Pulmonary artery systolic pressure was calculated by use of the modified Bernoulli equation, with right atrial pressure assumed to be 10 mmHg. The ratio of early transmitral flow velocity (E) to early mitral annular myocardial velocity (Em) was used as an echocardiography-derived estimate of LV diastolic pressure. Results: Average value of pulmonary artery PWV was 179±58 cm/sec (range: 78 to 450cm/sec), in good agreement with literature values measured using invasive means. Pulmonary artery PWV did not correlate with heart rate. There were significant relationships between pulmonary artery PWV and age (r = 0.69, p &lt; 0.01), body mass index (r = 0.46, p &lt; 0.01), and pulmonary artery systolic pressure (r = 0.54, p &lt; 0.01). A weak but significant relationship between systemic arterial PWV and pulmonary artery PWV was observed (r = 0.38, p &lt; 0.01). There was no significant relationship between pulmonary artery PWV and mitral E/Em. Conclusions: We provide the first evidence of age-related increase in pulmonary artery pulse wave velocity, its association with increasing pulmonary artery systolic pressure and systemic vascular stiffening, and its negative impact on body mass index. Pulmonary artery pulse wave velocity may serve as a novel cardiovascular risk factor.
Experiences and Perspectives of Transgender Youths in Accessing Health Care
Authors: Lauren S. H. Chong, Jasmijn Kerklaan, Simon Clarke, Michael Kohn, Amanda Baumgart, Chandana Guha, David J. Tunnicliffe, Camilla S. Hanson, Jonathan C. Craig, Allison Tong
Journal: JAMA Pediatrics (2021)

Transgender and nonbinary youths have a higher incidence of a range of health conditions and may paradoxically face limited access to health care.To describe the perspectives and needs of transgender youths in accessing health care.MEDLINE, Embase, PsycInfo, and the Cumulative Index to Nursing and Allied Health Literature were searched from inception to January 2021. Qualitative studies of transgender youths' perspectives on accessing health care were selected. Results from primary studies were extracted. Data were analyzed using thematic synthesis.Ninety-one studies involving 884 participants aged 9 to 24 years across 17 countries were included. We identified 6 themes: experiencing pervasive stigma and discrimination in health care, feeling vulnerable and uncertain in decision-making, traversing risks to overcome systemic barriers to transitioning, internalizing intense fear of consequences, experiencing prejudice undermining help-seeking efforts, and experiencing strengthened gender identity and finding allies. Each theme encapsulated multiple subthemes.This review found that transgender youths contend with feelings of gender incongruence, fear, and vulnerability in accessing health care, which are compounded by legal, economic, and social barriers. This can lead to disengagement from care and resorting to high-risk and unsafe interventions. Improving access to gender-affirming care services with a cultural humility lens and addressing sociolegal stressors may improve outcomes in transgender and nonbinary youths.
Decline of influenza and respiratory syncytial virus detection in facility-based surveillance during the COVID-19 pandemic, South Africa, January to October 2020
Authors: Stefano Tempia, Sibongile Walaza, Jinal N Bhiman, Meredith L McMorrow, Jocelyn Moyes, Thulisa Mkhencele, Susan Meiring, Vanessa Quan, Kate Bishop, Johanna M McAnerney, Anne von Gottberg, Nicole Wolter, Mignon Du Plessis, Florette K Treurnicht, Orienka Hellferscee, Halima Dawood, Fathima Naby, Ebrahim Variava, Comfort Siwele, Neydis Baute, Jeremy Nel, Gary Reubenson, Heather J Zar, Cheryl Cohen
Journal: Eurosurveillance (2021)

Background In South Africa, COVID-19 control measures to prevent SARS-CoV-2 spread were initiated on 16 March 2020. Such measures may also impact the spread of other pathogens, including influenza virus and respiratory syncytial virus (RSV) with implications for future annual epidemics and expectations for the subsequent northern hemisphere winter. Methods We assessed the detection of influenza and RSV through facility-based syndromic surveillance of adults and children with mild or severe respiratory illness in South Africa from January to October 2020, and compared this with surveillance data from 2013 to 2019. Results Facility-based surveillance revealed a decline in influenza virus detection during the regular season compared with previous years. This was observed throughout the implementation of COVID-19 control measures. RSV detection decreased soon after the most stringent COVID-19 control measures commenced; however, an increase in RSV detection was observed after the typical season, following the re-opening of schools and the easing of measures. Conclusion COVID-19 non-pharmaceutical interventions led to reduced circulation of influenza and RSV in South Africa. This has limited the country’s ability to provide influenza virus strains for the selection of the annual influenza vaccine. Delayed increases in RSV case numbers may reflect the easing of COVID-19 control measures. An increase in influenza virus detection was not observed, suggesting that the measures may have impacted the two pathogens differently. The impact that lowered and/or delayed influenza and RSV circulation in 2020 will have on the intensity and severity of subsequent annual epidemics is unknown and warrants close monitoring.
Single cell analysis of <i>M. tuberculosis</i> phenotype and macrophage lineages in the infected lung
Authors: Davide Pisu, Lu Huang, Vipin Narang, Monique Theriault, Gabrielle Lê-Bury, Bernett Lee, Agnes E. Lakudzala, David T. Mzinza, David V. Mhango, Steven C. Mitini-Nkhoma, Kondwani C. Jambo, Amit Singhal, Henry C. Mwandumba, David G. Russell
Journal: The Journal of Experimental Medicine (2021)

In this study, we detail a novel approach that combines bacterial fitness fluorescent reporter strains with scRNA-seq to simultaneously acquire the host transcriptome, surface marker expression, and bacterial phenotype for each infected cell. This approach facilitates the dissection of the functional heterogeneity of M. tuberculosis–infected alveolar (AMs) and interstitial macrophages (IMs) in vivo. We identify clusters of pro-inflammatory AMs associated with stressed bacteria, in addition to three different populations of IMs with heterogeneous bacterial phenotypes. Finally, we show that the main macrophage populations in the lung are epigenetically constrained in their response to infection, while inter-species comparison reveals that most AMs subsets are conserved between mice and humans. This conceptual approach is readily transferable to other infectious disease agents with the potential for an increased understanding of the roles that different host cell populations play during the course of an infection.
Determinants of Adolescent Lung Function in Indians: Race, Nutrition, and Systemic Inflammation
Authors: Mohit Aggarwal, Anubhuti Bansal, Bapu Koundinya Desiraju, Shailendra Singh, Anurag Agrawal
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Determinants of Adolescent Lung Function in Indians: Race, Nutrition, and Systemic Inflammation." American Journal of Respiratory and Critical Care Medicine, 204(9), pp. 1109–1111