tbuckley/cabot-search huggingface dataset:
Knowledge Gaps and Research Priorities in Immune Checkpoint Inhibitor–related Pneumonitis. An Official American Thoracic Society Research Statement
Authors: Catherine R. Sears, Tobias Peikert, Jennifer D. Possick, Jarushka Naidoo, Mizuki Nishino, Sandip P. Patel, Philippe Camus, Mina Gaga, Edward B. Garon, Michael K. Gould, Andrew H. Limper, Philippe R. Montgrain, William D. Travis, M. Patricia Rivera
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Section:ChooseTop of pageAbstract <<ContentsOverviewIntroductionMethodsResultsConclusionsReferencesCITING ARTICLES
Inhibition of IL-2 responsiveness by IL-6 is required for the generation of GC-T <sub>FH</sub> cells
Authors: Amber Papillion, Michael D. Powell, Danielle A. Chisolm, Holly Bachus, Michael J. Fuller, Amy S. Weinmann, Alejandro Villarino, John J. O’Shea, Beatriz León, Kenneth J. Oestreich, André Ballesteros-Tato
Journal: Science Immunology (2019)

IL-6–mediated inhibition of CD122 allows T FH cells to receive TCR signaling without initiating an inhibitory TCR/IL-2 loop (see the related Focus by Zhou and Yu )..
Baselines for human morality should include species typicality, inheritances, culture, practice, and ecological attachment
Authors: Darcia Narvaez
Journal: Behavioral and Brain Sciences (2019)

Empirical studies involve WEIRD (Western, European, industrialized, rich, democratic) but also un-nested (raised outside humanity's evolved nest) and underdeveloped participants. Assessing human moral potential needs to integrate a transdisciplinary approach to understanding species typicality and baselines, relevant evolutionary inheritances beyond genes, assessment of cultures and practices that foster (or not) virtue, and ecological morality. Human moral reason (nous) emerges from all of these.
Association Between Recalled Exposure to Gender Identity Conversion Efforts and Psychological Distress and Suicide Attempts Among Transgender Adults
Authors: Jack L. Turban, Noor Beckwith, Sari L. Reisner, Alex S. Keuroghlian
Journal: JAMA Psychiatry (2019)

Gender identity conversion efforts (GICE) have been widely debated as potentially damaging treatment approaches for transgender persons. The association of GICE with mental health outcomes, however, remains largely unknown.To evaluate associations between recalled exposure to GICE (by a secular or religious professional) and adult mental health outcomes.In this cross-sectional study, a survey was distributed through community-based outreach to transgender adults residing in the United States, with representation from all 50 states, the District of Columbia, American Samoa, Guam, Puerto Rico, and US military bases overseas. Data collection occurred during 34 days between August 19 and September 21, 2015. Data analysis was performed from June 8, 2018, to January 2, 2019.Recalled exposure to GICE.Severe psychological distress during the previous month, measured by the Kessler Psychological Distress Scale (defined as a score ≥13). Measures of suicidality during the previous year and lifetime, including ideation, attempts, and attempts requiring inpatient hospitalization.Of 27 715 transgender survey respondents (mean [SD] age, 31.2 [13.5] years), 11 857 (42.8%) were assigned male sex at birth. Among the 19 741 (71.3%) who had ever spoken to a professional about their gender identity, 3869 (19.6%; 95% CI, 18.7%-20.5%) reported exposure to GICE in their lifetime. Recalled lifetime exposure was associated with severe psychological distress during the previous month (adjusted odds ratio [aOR], 1.56; 95% CI, 1.09-2.24; P < .001) compared with non-GICE therapy. Associations were found between recalled lifetime exposure and higher odds of lifetime suicide attempts (aOR, 2.27; 95% CI, 1.60-3.24; P < .001) and recalled exposure before the age of 10 years and increased odds of lifetime suicide attempts (aOR, 4.15; 95% CI, 2.44-7.69; P < .001). No significant differences were found when comparing exposure to GICE by secular professionals vs religious advisors.The findings suggest that lifetime and childhood exposure to GICE are associated with adverse mental health outcomes in adulthood. These results support policy statements from several professional organizations that have discouraged this practice.
Transcriptional inhibition by CDK7/9 inhibitor SNS-032 abrogates oncogene addiction and reduces liver metastasis in uveal melanoma
Authors: Jing Zhang, Shenglan Liu, Qianyun Ye, Jingxuan Pan
Journal: Molecular Cancer (2019)

Life of patients with uveal melanoma (UM) is largely threatened by liver metastasis. Little is known about the drivers of liver organotropic metastasis in UM. The elevated activity of transcription of oncogenes is presumably to drive aspects of tumors. We hypothesized that inhibition of transcription by cyclin-dependent kinase 7/9 (CDK7/9) inhibitor SNS-032 diminished liver metastasis by abrogating the putative oncogenes in charge of colonization, stemness, cell motility of UM cells in host liver microenvironment.The effects of SNS-032 on the expression of the relevant oncogenes were examined by qRT-PCR and Western blotting analysis. Proliferative activity, frequency of CSCs and liver metastasis were evaluated by using NOD-SCID mouse xenograft model and NOG mouse model, respectively.The results showed that CDK7/9 were highly expressed in UM cells, and SNS-032 significantly suppressed the cellular proliferation, induced apoptosis, and inhibited the outgrowth of xenografted UM cells and PDX tumors in NOD-SCID mice, repressed the cancer stem-like cell (CSC) properties through transcriptional inhibition of stemness-related protein Krüppel-like factor 4 (KLF4), inhibited the invasive phonotypes of UM cells through matrix metalloproteinase 9 (MMP9). Mechanistically, SNS-032 repressed the c-Myc-dependent transcription of RhoA gene, and thereby lowered the RhoA GTPase activity and actin polymerization, and subsequently inhibited cell motility and liver metastasis.In conclusion, we validate a set of transcription factors which confer metastatic traits (e.g., KLF4 for CSCs, c-Myc for cell motility) in UM cells. Our results identify SNS-032 as a promising therapeutic agent, and warrant a clinical trial in patients with metastatic UM.
Homotypic Cell Membrane-Cloaked Biomimetic Nanocarrier for the Targeted Chemotherapy of Hepatocellular Carcinoma
Authors: Xiaojun Liu, Yingxue Sun, Shushen Xu, Xiaonan Gao, Fanpeng Kong, Kehua Xu, Bo Tang
Journal: Theranostics (2019)

Goals: Hepatocellular carcinoma (HCC) has been reported to be the third most common malignant tumor and has the highest rate of mortality.To increase the chemotherapy efficacy of HCC, a drug delivery system featured with desirable active targeting ability, delivery efficiency and immune evasion is in high demand.Methods: We have developed a drug nanocarrier by utilizing a homotypic cancer cell membrane for targeted chemotherapy of HCC.Structurally, the homotypic HepG2 cell membrane was used as the cloak, and a poly (lactic-co-glycolic acid) (PLGA) nanoparticle as the core, resulting in the nanocarrier HepM-PLGA.Results: The HepM-PLGA nanoparticles exhibit excellent targeting ability toward HepG2 cells.Doxorubicin (Dox) carried by HepM-PLGA possesses high delivery efficiency and a remarkable in vitro therapeutic effect.In in vivo experiments, HepM-PLGA delivers Dox directly to the tumor lesion of nude mice, and tumor volume decreases by approximately 90% after treatment. Conclusion:We have developed a drug nanocarrier by utilizing a homotypic cancer cell membrane for targeted chemotherapy of HCC with excellent active targeting ability.This biomimetic platform not only effectively treats HCC but also provides a sound strategy for the treatment of other cancers via changes in the corresponding homotypic cancer cell membrane.
Emergence of dominant toxigenic M1T1 Streptococcus pyogenes clone during increased scarlet fever activity in England: a population-based molecular epidemiological study
Authors: Nicola N Lynskey, Elita Jauneikaite, Ho Kwong Li, Xiangyun Zhi, Claire E Turner, Mia Mosavie, Max Pearson, Masanori Asai, Ludmila Lobkowicz, J Yimmy Chow, Julian Parkhill, Theresa Lamagni, Victoria J Chalker, Shiranee Sriskandan
Journal: The Lancet Infectious Diseases (2019)

BackgroundSince 2014, England has seen increased scarlet fever activity unprecedented in modern times. In 2016, England's scarlet fever seasonal rise coincided with an unexpected elevation in invasive Streptococcus pyogenes infections. We describe the molecular epidemiological investigation of these events.MethodsWe analysed changes in S pyogenes emm genotypes, and notifications of scarlet fever and invasive disease in 2014–16 using regional (northwest London) and national (England and Wales) data. Genomes of 135 non-invasive and 552 invasive emm1 isolates from 2009–16 were analysed and compared with 2800 global emm1 sequences. Transcript and protein expression of streptococcal pyrogenic exotoxin A (SpeA; also known as scarlet fever or erythrogenic toxin A) in sequenced, non-invasive emm1 isolates was quantified by real-time PCR and western blot analyses.FindingsCoincident with national increases in scarlet fever and invasive disease notifications, emm1 S pyogenes upper respiratory tract isolates increased significantly in northwest London in the March to May period, from five (5%) of 96 isolates in 2014, to 28 (19%) of 147 isolates in 2015 (p=0·0021 vs 2014 values), to 47 (33%) of 144 in 2016 (p=0·0080 vs 2015 values). Similarly, invasive emm1 isolates collected nationally in the same period increased from 183 (31%) of 587 in 2015 to 267 (42%) of 637 in 2016 (p<0·0001). Sequences of emm1 isolates from 2009–16 showed emergence of a new emm1 lineage (designated M1UK)—with overlap of pharyngitis, scarlet fever, and invasive M1UK strains—which could be genotypically distinguished from pandemic emm1 isolates (M1global) by 27 single-nucleotide polymorphisms. Median SpeA protein concentration in supernatant was nine-times higher among M1UK isolates (190·2 ng/mL [IQR 168·9–200·4]; n=10) than M1global isolates (20·9 ng/mL [0·0–27·3]; n=10; p<0·0001). M1UK expanded nationally to represent 252 (84%) of all 299 emm1 genomes in 2016. Phylogenetic analysis of published datasets identified single M1UK isolates in Denmark and the USA.InterpretationA dominant new emm1 S pyogenes lineage characterised by increased SpeA production has emerged during increased S pyogenes activity in England. The expanded reservoir of M1UK and recognised invasive potential of emm1 S pyogenes provide plausible explanation for the increased incidence of invasive disease, and rationale for global surveillance.FundingUK Medical Research Council, UK National Institute for Health Research, Wellcome Trust, Rosetrees Trust, Stoneygate Trust.
Effect of bariatric surgery on asthma: 3 months follow-up
Authors: Astrid van Huisstede, Manuel Castro Cabezas, Hans Zengerink, Ronald Luitwieler, Christiaan Taube, Pieter S. Hiemstra, Gert-Jan Braunstahl
Journal: European Respiratory Journal (2012)

Background: Asthma in obese subjects is poorly understood and the effect of weight loss on asthma control is not well described.  Aim: To investigate the effects of bariatric surgery on asthma control, quality of life and lung function.  Methods: We performed a prospective study in patients with confirmed diagnosis asthma (GINA guidelines) and non asthmatic patients undergoing bariatric surgery with 12M FU.  Results: 28 asthma patients (BS+A) and 40 non-asthmatics (BS-A) underwent bariatric surgery, 14 obese asthma patients served as controls (NBS+A). Following bariatric surgery, BMI decreased to 31.5 kg/m 2  (p 2  (p 2 , p=0.387). At 12 months FU, ACQ and AQLQ significantly improved in BS+A group (1.4 to 0.4, p 1  improved significantly in BS+A (from 94 to 99%pred, p=0.004) and BS-A (from 102 to 110%pred, p 1 /FVC only improved in the BS-A group (mean 81 to 82%pred, p=0.015), TLC improved in both surgery groups (BS+A 94 to 100%pred, p=0.012; BS-A 96 to 102%pred, p  Conclusion: Bariatric surgery improves lung function, asthma control and quality of life in patients with asthma and morbid obesity after 12 months. Demonstrating that weight loss is an important component of asthma management in obese asthmatics.
Impaired right ventricular lusitropy is associated with ventilatory inefficiency in pulmonary arterial hypertension
Authors: Khodr Tello, Antonia Dalmer, Rebecca Vanderpool, Hossein A. Ghofrani, Robert Naeije, Fritz Roller, Werner Seeger, Daniel Dumitrescu, Natascha Sommer, Anne Brunst, Henning Gall, Manuel J. Richter
Journal: European Respiratory Journal (2019)

Cardiopulmonary exercise testing (CPET) is an important tool for assessing functional capacity and prognosis in pulmonary arterial hypertension (PAH). However, the associations of CPET parameters with the adaptation of right ventricular (RV) function to afterload remain incompletely understood. In this study, 37 patients with PAH (idiopathic in 31 cases) underwent single-beat pressure–volume loop measurements of RV end-systolic elastance (Ees), arterial elastance (Ea) and diastolic elastance (Eed). Pulmonary arterial stiffness was assessed by magnetic resonance imaging. The results were correlated to CPET variables. The predictive relevance of RV function parameters for clinically relevant ventilatory inefficiency, defined as minute ventilation/carbon dioxide production ( V′ E / V′ CO 2 ) slope &gt;48, was evaluated using logistic regression analysis. The median (interquartile range) of the V′ E / V′ CO 2 slope was 42 (32–52) and the V′ E / V′ CO 2 nadir was 40 (31–44). The mean± sd of peak end-tidal carbon dioxide tension ( P ETCO 2 ) was 23±8 mmHg. Ea, Eed and parameters reflecting pulmonary arterial stiffness (capacitance and distensibility) correlated with the V′ E / V′ CO 2 slope, V′ E / V′ CO 2 nadir, P ETCO 2 and peak oxygen pulse. RV Ees and RV–arterial coupling as assessed by the Ees/Ea ratio showed no correlations with CPET parameters. Ea (univariate OR 7.28, 95% CI 1.20–44.04) and Eed (univariate OR 2.21, 95% CI 0.93–5.26) were significantly associated with ventilatory inefficiency (p&lt;0.10). Our data suggest that impaired RV lusitropy and increased afterload are associated with ventilatory inefficiency in PAH.
Neurocognitive outcomes in adult survivors of neuroblastoma: A report from the Childhood Cancer Survivor Study.
Authors: Caroline Hesko, Wei Liu, Deokumar Srivastava, Tara M. Brinkman, Lisa Diller, Todd M. Gibson, Kevin C. Oeffinger, Wendy Leisenring, Rebecca M. Howell, Gregory T. Armstrong, Kevin R. Krull, Tara O. Henderson
Journal: Journal of Clinical Oncology (2019)

11563 Background: Long-term survivors of neuroblastoma may be at risk for neurocognitive impairment due to young age at diagnosis and intensive multimodal therapies. Methods: 837 survivors of neuroblastoma (57% female; median [range] age 25 [17-58] years, age at diagnosis 1 [0-21] years) and 728 siblings (56% female; age 32[16-43] years) self-reported neurocognitive problems using a neurocognitive questionnaire. Impairment was defined as scores ≥90th percentile of siblings in emotional regulation (ER), organization, task efficiency (TE), and memory. Multivariable log-binomial models evaluated associations with treatment exposures, era and chronic conditions (Grade 2-4 CTCAE v5) adjusting for sex, age, and race. Analyses were stratified by age at diagnosis (≤1 and &gt; 1 year) as proxy for risk group. Results: Rates of impairment were 19.7% (ER), 25.3% organization, 21.9% TE and 19.4% for memory. Survivors had 50% higher risk of impaired TE (≤1 year relative risk [RR] 1.48, 95% confidence interval [CI] 1.08-2.03; &gt; 1 year: RR 1.58, CI 1.22-2.06) and ER (≤1 year RR 1.51, CI 1.07-2.12; &gt; 1 year RR 1.44, CI 1.06-1.95) versussiblings. Among survivors ≤1 year at diagnosis, treatment with platinum (RR 1.74, CI 1.01-2.97), hearing loss (RR 1.95, CI 1.26-3.00), cardiovascular (RR 1.83, CI 1.15-2.89) and neurologic (RR 2.00, CI 1.32-3.03) conditions were associated with higher risk of impaired TE. Female sex (RR = 1.54, CI, 1.02-2.33), cardiovascular (RR 1.71, CI 1.08-2.70) and respiratory (RR 1.99, CI 1.14-3.49) conditions were associated with higher risk of impaired ER. Among survivors &gt; 1 year at diagnosis those treated in 1970-79 vs. 1990-99 had 80% higher risk of impaired ER (RR 1.77, CI 1.02-3.06). Hearing loss (RR 1.56 (1.09-2.24), respiratory (RR 2.35, CI 1.60-3.45) and cardiovascular (RR 1.74, CI 1.12-2.69) conditions were associated with higher risk of impaired TE. Conclusions: Adult survivors of neuroblastoma are at-risk for neurocognitive impairment. Differences associated with age at diagnosis, chronic disease and treatment exposures may inform risk-stratified inventions to improve neurocognitive outcomes. Reduced risk in later eras may reflect improved supportive care and knowledge of late effects.
Cisplatin Facilitates Radiation-Induced Abscopal Effects in Conjunction with PD-1 Checkpoint Blockade Through CXCR3/CXCL10-Mediated T-cell Recruitment
Authors: Ren Luo, Elke Firat, Simone Gaedicke, Elena Guffart, Tsubasa Watanabe, Gabriele Niedermann
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Localized radiotherapy can cause T-cell–mediated abscopal effects on nonirradiated metastases, particularly in combination with immune checkpoint blockade (ICB). However, results of prospective clinical trials have not met the expectations. We therefore investigated whether additional chemotherapy can enhance radiotherapy-induced abscopal effects in conjunction with ICB. Experimental Design: In three different two-tumor mouse models, triple therapy with radiotherapy, anti–PD-1, and cisplatin (one of the most widely used antineoplastic agents) was compared with double or single therapies. Results: In these mouse models, the response of the nonirradiated tumor and the survival of the mice were much better upon triple therapy than upon radiotherapy + anti–PD-1 or cisplatin + anti–PD-1 or the monotherapies; complete regression of the nonirradiated tumor was usually only observed in triple-treated mice. Mechanistically, the enhanced abscopal effect required CD8+T cells and relied on the CXCR3/CXCL10 axis. Moreover, CXCL10 was found to be directly induced by cisplatin in the tumor cells. Furthermore, cisplatin-induced CD8+T cells and direct cytoreductive effects of cisplatin also seem to contribute to the enhanced systemic effect. Finally, the results show that the abscopal effect is not precluded by the observed transient radiotherapy-induced lymphopenia. Conclusions: This is the first report showing that chemotherapy can enhance radiotherapy-induced abscopal effects in conjunction with ICB. This even applies to cisplatin, which is not classically immunogenic. Whereas previous studies have focused on how to effectively induce tumor-specific T cells, this study highlights that successful attraction of the induced T cells to nonirradiated tumors is also crucial for potent abscopal effects.
Abstract P034: The Effectiveness of 12-week Tai Chi Training on the Migraine Attack Days, Body Composition, and Blood Pressure in Chinese Women With Episodic Migraine: A Randomized Controlled Trial
Authors: Yao Jie Xie, Stanley Sai-chuen Hui, Suzanne C. Ho, Lorna Kwai Ping Suen
Journal: Circulation (2018)

Background: Tai Chi is a body-mind exercise. It’s prophylactic efficacy on migraine attack remains largely unknown. The purpose of this study was to examine the effect of a 12-week Tai Chi training on the migraine attack days per month, body composition, and blood pressure (BP) in a sample of Chinese women with episodic migraine. Method: A two-arm randomized controlled trial was designed. Eighty-two local women aged 18 to 65 years and diagnosed with episodic migraine were randomized to the Tai Chi group or the waiting list control group. A modified 32-short form Yang-style Tai Chi training with 1 hour per day, 5 days per week for 12 weeks was adopted as intervention. An additional 12 weeks follow was conducted. The control group received a “delayed” Tai Chi training at the end of the trial. The difference in migraine days between 1 month before baseline, 3rd month (12nd week) and 6th month (24th week) after the randomization were examined. The changes in weight, body fat, and BP before and after the intervention were also analyzed. Results: Of 189 women screened, 82 eligible women completed the baseline assessment. After randomization, 9 women withdrew immediately, finally 40 in Tai Chi group and 33 in control group were involved in the analysis. On average, women in Tai Chi group had 3.6 (95% CI: -4.7 to -2.5, P&lt;0.01) days reduction of migraine attack. Compared with control group, the difference was statistically significant (P&lt;0.001). Tai Chi group also lost 0.6 kg of body weight and 0.6% of body fat at the 3rd month, and 10.8 mmHg systolic BP at the 6th month, respectively (all p&lt;0.001). The between-group difference of systolic BP was -6.9 mmHg (95% CI: -11.6 mmHg to -2.1mmHg, p&lt;0.05), whereas no significant differences were observed regarding weight and body fat at the 3rd month (all p&gt;0.05). Among Tai Chi group, change in systolic BP was significantly correlated to the change in migraine days (P&lt;0.05). Conclusion: The 12-week Tai Chi training significantly decreased the frequency of migraine attack and improved the systolic BP. The association between migraine attack reduction and BP improvement needs further investigations.
Anti‐β<sub>c</sub> mAb CSL311 inhibits human nasal polyp pathophysiology in a humanized mouse xenograft model
Authors: Kwok Ho Yip, Nicholas J. Wilson, Harshita Pant, Christopher L. Brown, Samantha Busfield, Milica Ng, Monther Alhamdoosh, Naomi Woodman, Mark Schembri, Damon J. Tumes, Gino Vairo, Angel F. Lopez, Andrew D. Nash, Michael J. Wilson, Michele A. Grimbaldeston, Catherine M. Owczarek
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Analyzing debunking arguments in moral psychology: Beyond the counterfactual analysis of influence by irrelevant factors
Authors: Joanna Demaree-Cotton
Journal: Behavioral and Brain Sciences (2019)

Abstract May assumes that if moral beliefs are counterfactually dependent on irrelevant factors, then those moral beliefs are based on defective belief-forming processes. This assumption is false. Whether influence by irrelevant factors is debunking depends on the mechanisms through which this influence occurs. This raises the empirical bar for debunkers and helps May avoid an objection to his Debunker's Dilemma.
Clinician Experience of Electronic Health Record Configurations Displaying 1 vs 4 Records at a Time
Authors: William N. Southern, Jo R. Applebaum, Hojjat Salmasian, Jerard Kneifati-Hayek, Eileen J. Carter, Jennifer A. Sumner, Jason S. Adelman
Journal: JAMA Internal Medicine (2019)

This survey study of more than 1200 clinicians from several large urban medical centers highlights clinicians’ experiences with restrictions on the number of electronic health records that can be opened and displayed concurrently.