tbuckley/cabot-search huggingface dataset:
17731 Evolving resolution of clinical, cellular, and transcriptomic inflammatory markers during 1-year IL-17A inhibition by secukinumab
Authors: Mayte Suarez-Farinas, Lewis Tomalin, Frank Kolbinger, Maria Suprun, Martin Letzkus, Nicole Hartmann, Anton Glueck, Marina Milutinovic, James G. Krueger
Journal: Journal of the American Academy of Dermatology (2020)
Cancer risk in individuals with major birth defects: large Nordic population based case-control study among children, adolescents, and adults
Authors: Dagrun Slettebø Daltveit, Kari Klungsøyr, Anders Engeland, Anders Ekbom, Mika Gissler, Ingrid Glimelius, Tom Grotmol, Laura Madanat-Harjuoja, Anne Gulbech Ording, Solbjørg Makalani Myrtveit Sæther, Henrik Toft Sørensen, Rebecca Troisi, Tone Bjørge
Journal: BMJ (2020)

Abstract Objective To examine associations between birth defects and cancer from birth into adulthood. Design Population based nested case-control study. Setting Nationwide health registries in Denmark, Finland, Norway, and Sweden. Participants 62 295 cancer cases (0-46 years) and 724 542 frequency matched controls (matched on country and birth year), born between 1967 and 2014. Main outcome measures Relative risk of cancer in relation to major birth defects, estimated as odds ratios with 99% confidence intervals from logistic regression models. Results Altogether, 3.5% (2160/62 295) of cases and 2.2% (15 826/724 542) of controls were born with major birth defects. The odds ratio of cancer for people with major birth defects compared with those without was 1.74 (99% confidence interval 1.63 to 1.84). For individuals with non-chromosomal birth defects, the odds ratio of cancer was 1.54 (1.44 to 1.64); for those with chromosomal anomalies, the odds ratio was 5.53 (4.67 to 6.54). Many structural birth defects were associated with later cancer in the same organ system or anatomical location, such as defects of the eye, nervous system, and urinary organs. The odds ratio of cancer increased with number of defects and decreased with age, for both non-chromosomal and chromosomal anomalies. The odds ratio of cancer in people with any non-chromosomal birth defect was lower in adults (≥20 years: 1.21, 1.09 to 1.33) than in adolescents (15-19 years: 1.58, 1.31 to 1.90) and children (0-14 years: 2.03, 1.85 to 2.23). The relative overall cancer risk among adults with chromosomal anomalies was markedly reduced from 11.3 (9.35 to 13.8) in children to 1.50 (1.01 to 2.24). Among adults, skeletal dysplasia (odds ratio 3.54, 1.54 to 8.15), nervous system defects (1.76, 1.16 to 2.65), chromosomal anomalies (1.50, 1.01 to 2.24), genital organs defects (1.43, 1.14 to 1.78), and congenital heart defects (1.28, 1.02 to 1.59) were associated with overall cancer risk. Conclusions The increased risk of cancer in individuals with birth defects persisted into adulthood, both for non-chromosomal and chromosomal anomalies. Further studies on the molecular mechanisms involved are warranted.
Pembrolizumab plus GX-188E therapeutic DNA vaccine in patients with HPV-16-positive or HPV-18-positive advanced cervical cancer: interim results of a single-arm, phase 2 trial
Authors: Jin Won Youn, Soo-Young Hur, Jung Won Woo, Yong-Man Kim, Myong Cheol Lim, Sang Yoon Park, Sang Soo Seo, Jae Hong No, Byoung-Gie Kim, Jae-Kwan Lee, So Jin Shin, Kyungun Kim, Marya F Chaney, Yoon-Jeong Choi, You Suk Suh, Jong Sup Park, Young Chul Sung
Journal: The Lancet Oncology (2020)
Partial<i>F8</i>gene duplication (factor VIII Padua) associated with high factor VIII levels and familial thrombophilia
Authors: Paolo Simioni, Stefano Cagnin, Francesca Sartorello, Gabriele Sales, Luca Pagani, Cristiana Bulato, Sabrina Gavasso, Francesca Nuzzo, Francesco Chemello, Claudia M. Radu, Daniela Tormene, Luca Spiezia, Tilman M. Hackeng, Elena Campello, Elisabetta Castoldi
Journal: Blood (2020)
Abstract PO-052: Combinatorial targeting of chromatin and metabolism for synergistic anti-cancer efficacy
Authors: Tahir N. Sheikh, Xiao Chen, Xinjing Xu, Parag P. Patwardhan, Gary K. Schwartz, Chao Lu
Journal: Cancer Research (2020)

Abstract Altered cellular metabolic network and chromatin landscape represent two molecular hallmarks of cancer. Despite considerable interests, targeting metabolic or chromatin regulatory pathways as monotherapy was met with limited success in pre-clinical and clinical studies, in part due to the ability of cancer cells to rewire and adapt to the stress induced by therapeutic intervention. Therefore, there is a critical need to understand resistance programs and to identify strategies for more effective combinatorial therapies. We have previously uncovered that DNA and histone modifications are exquisitely sensitive to perturbations of the metabolic state. During tumor initiation, this metabolism-chromatin “crosstalk” is often hijacked by cancer cells to respond to fluctuations in signaling and nutrient abundance, but the role of such interplay in drug resistance has remained elusive. Here we demonstrated that cancer cells which developed resistance to inhibitor of glutamine catabolism (CB-839) displayed increased ratio of α-ketoglutarate to succinate that acts as a metabolic regulator of TET-family DNA hydroxylases and Jumonji-family histone demethylases. Accordingly, CB-839 resistant cancer cells showed global DNA hypomethylation and decreased levels of H3K9me3 and H3K27me3, which in turn resulted in increases in histone acetylation and a gene expression program that promoted metabolic adaptation to inhibition of glutaminolysis. Importantly, this altered chromatin landscape also represented a therapeutic vulnerability, as CB-839 resistant cells were selectively hyper-sensitive to small-molecule inhibitors of BET domain such as JQ1 and PLX51107. We are currently testing the possible synergistic effects of clinical stage glutaminase and BET inhibitors across various cancer types. Taken together, these results highlight the potential of exploring and therapeutically exploiting metabolic and chromatin interactions for developing rationally designed, precision combinatorial anti-cancer treatment strategies. Citation Format: Tahir N. Sheikh, Xiao Chen, Xinjing Xu, Parag P. Patwardhan, Gary K. Schwartz, Chao Lu. Combinatorial targeting of chromatin and metabolism for synergistic anti-cancer efficacy [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-052.
Abstract 10799: Clinical Implications of Intrarenal Hemodynamic Evaluation by Ultrasonography in Patients With Heart Failure
Authors: Tomofumi Misaka, Akiomi Yoshihisa, Yasuhiro Ichijo, Yusuke Kimishima, Yuki Kanno, Tetsuro Yokokawa, Satoshi Abe, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2019)

Backgrounds: Renal hypoperfusion and congestion are critically involved in the pathophysiology of heart failure (HF). We aimed to 1) compare intrarenal hemodynamics assessed by renal ultrasonograph...
Myeloid cell–targeted STAT3 inhibition sensitizes head and neck cancers to radiotherapy and T cell–mediated immunity
Authors: Dayson Moreira, Sagus Sampath, Haejung Won, Seok Voon White, Yu-Lin Su, Marice Alcantara, Chongkai Wang, Peter Lee, Ellie Maghami, Erminia Massarelli, Marcin Kortylewski
Journal: Journal of Clinical Investigation (2020)

The tumor microenvironment affects the outcome of radiotherapy against head and neck squamous cell carcinoma (HNSCC). We recently found that tolerogenic myeloid cells accumulate in the circulation of HNSCC patients undergoing radiotherapy. Here, we analyzed tumor-containing lymph node biopsies collected from these patients. After 2 weeks of radiotherapy, we found an increase in tumor-associated macrophages (TAMs) with activated STAT3, while CD8+ T cells were reduced as detected using multiplex IHC. Gene expression profiling indicated upregulation of M2 macrophage–related genes (CD163, CD206), immunosuppressive mediators (ARG1, LIF, TGFB1), and Th2 cytokines (IL4, IL5) in irradiated tumors. We next validated STAT3 as a potential target in human HNSCC-associated TAMs, using UM-SCC1 xenotransplants in humanized mice. Local injections of myeloid cell–targeted STAT3 antisense oligonucleotide (CpG-STAT3ASO) activated human DCs/macrophages and promoted CD8+ T cell recruitment, thereby arresting UM-SCC1 tumor growth. Furthermore, CpG-STAT3ASO synergized with tumor irradiation against syngeneic HPV+ mEERL and HPV– MOC2 HNSCC tumors in mice, triggering tumor regression and/or extending animal survival. The antitumor immune responses were CD8+ and CD4+ T cell dependent and associated with the activation of antigen-presenting cells (DCs/M1 macrophages) and increased CD8+ to regulatory T cell ratio. Our observations suggest that targeted inhibition of STAT3 in tumor-associated myeloid cells augments the efficacy of radiotherapy against HNSCC.
How does occupational physical activity influence health? An umbrella review of 23 health outcomes across 158 observational studies
Authors: Bart Cillekens, Matthias Lang, Willem van Mechelen, Evert Verhagen, Maaike A Huysmans, Andreas Holtermann, Allard J van der Beek, Pieter Coenen
Journal: British Journal of Sports Medicine (2020)

Objective Physical activity (PA) has substantial benefits across a range of health outcomes. There is uncertainty about the PA-specific health effects, and in particular, the occupational domain. In this umbrella review, we synthesised available evidence on the associations between occupational PA (OPA) and health-related outcomes (including cancer, all-cause mortality and cardiovascular disease). This work informed the development of WHO’s guidelines on PA and sedentary behaviour (2020). Design Umbrella review of systematic reviews. Data source We performed a literature search in PubMed, Web of Science, Embase, CINAHL and Sportdiscuss from database inception to 2 December 2019. Eligibility criteria for selecting studies We included systematic reviews if they contained a quantitative assessment of OPA and its relationship with at least one health-related outcome. Results We summarised the evidence of 17 reviews covering 23 unique health-related outcomes. We graded most evidence as low or very low, or moderate quality. We found health benefits for those engaging in high versus low OPA for multiple cancer outcomes (including colon and prostate), ischaemic stroke, coronary heart disease and mental health (ie, mental well-being and life satisfaction). High OPA was associated with unfavourable health outcomes for all-cause mortality in men, mental ill health (ie, depression and anxiety), osteoarthritis, and sleep quality and duration. Conclusions We found favourable associations for most health-related outcomes with high OPA levels, but we also found some evidence for unfavourable associations due to high OPA levels. At this point, there is a need for better quality evidence to provide a unequivocal statement on the health effects of OPA.
Ending deaths from HIV-related cryptococcal meningitis by 2030
Authors: Amir Shroufi, Tom Chiller, Alex Jordan, David W Denning, Thomas S Harrison, Nelesh P Govender, Angela Loyse, Solange Baptiste, Radha Rajasingham, David R Boulware, Isabela Ribeiro, Joseph N Jarvis, Gilles Van Cutsem
Journal: The Lancet Infectious Diseases (2020)
17141 Real-world dermatology visit in moderate to severe plaque psoriasis patients treated with biologics or apremilast
Authors: Jashin J. Wu, Jingchuan Zhang, Yang Zhao, Diane Martinez, Lorena Lopez-Gonzalez, Elizabeth H. Marchlewicz, George Shrady, Alan Mendelsohn, Steven Feldman
Journal: Journal of the American Academy of Dermatology (2020)
Pfs230 yields higher malaria transmission–blocking vaccine activity than Pfs25 in humans but not mice
Authors: Sara A. Healy, Charles Anderson, Bruce J. Swihart, Agnes Mwakingwe, Erin E. Gabriel, Hope Decederfelt, Charlotte V. Hobbs, Kelly M. Rausch, Daming Zhu, Olga Muratova, Raul Herrera, Puthupparampil V. Scaria, Nicholas J. MacDonald, Lynn E. Lambert, Irfan Zaidi, Camila H. Coelho, Jonathan P. Renn, Yimin Wu, David L. Narum, Patrick E. Duffy
Journal: Journal of Clinical Investigation (2021)

BACKGROUND. Vaccines that block human-to-mosquito Plasmodium transmission are needed for malaria eradication, and clinical trials have targeted zygote antigen Pfs25 for decades. We reported that a Pfs25 protein-protein conjugate vaccine formulated in alum adjuvant induced serum functional activity in both US and Malian adults. However, antibody levels declined rapidly, and transmission-reducing activity required 4 vaccine doses. Functional immunogenicity and durability must be improved before advancing transmission-blocking vaccines further in clinical development. We hypothesized that the prefertilization protein Pfs230 alone or in combination with Pfs25 would improve functional activity.
EZ-ALBI Score for Predicting Hepatocellular Carcinoma Prognosis
Authors: Kazuya Kariyama, Kazuhiro Nouso, Atsushi Hiraoka, Akiko Wakuta, Ayano Oonishi, Teiji Kuzuya, Hidenori Toyoda, Toshifumi Tada, Kunihiko Tsuji, Ei Itobayashi, Toru Ishikawa, Koichi Takaguchi, Akemi Tsutsui, Noritomo Shimada, Masatoshi Kudo, Takashi Kumada
Journal: Liver Cancer (2020)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; The ALBI score is acknowledged as the gold standard for the assessment of liver function in patients with hepatocellular carcinoma (HCC). Unlike the Child-Pugh score, the ALBI score uses only objective parameters, albumin (Alb) and total bilirubin (T.Bil), enabling a better evaluation. However, the complex calculation of the ALBI score limits its applicability. Therefore, we developed a simplified ALBI score, based on data from a large-scale HCC database.We used the data of 5,249 naïve HCC cases registered in eight collaborating hospitals. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We developed a new score, the EZ (Easy)-ALBI score, based on regression coefficients of Alb and T.Bil for survival risk in a multivariate Cox proportional hazard model. We also developed the EZ-ALBI grade and EZ-ALBI-T grade as alternative options for the ALBI grade and ALBI-T grade and evaluated their stratifying ability. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The equation used to calculate the EZ-ALBI score was simple {[T.Bil (mg/dL)] – [9 × Alb (g/dL)]}; this value highly correlated with the ALBI score (correlation coefficient, 0.981; &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.0001). The correlation was preserved across different Barcelona clinic liver cancer grade scores (regression coefficient, 0.93–0.98) and across different hospitals (regression coefficient, 0.98–0.99), indicating good generalizability. Although a good agreement was observed between ALBI and EZ-ALBI, discrepancies were observed in patients with poor liver function (T.Bil, ≥3 mg/dL; regression coefficient, 0.877). The stratifying ability of EZ-ALBI grade and EZ-ALBI-T grade were good and their Akaike’s information criterion values (35,897 and 34,812, respectively) were comparable with those of ALBI grade and ALBI-T grade (35,914 and 34,816, respectively). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; The EZ-ALBI score, EZ-ALBI grade, and EZ-ALBI-T grade are useful, simple scores, which might replace the conventional ALBI score in the future.
Abstract 17120: Reproducibility of Noninvasive Cardiac Output Monitoring During Exercise in Healthy Volunteers
Authors: Michael Coll Barroso, Matthias Hoppe, Werner Nickl, Christian Kiefer, Thomas Mondritzki, Frank Kramar, Max Fritschka, Hubert Truebel, Hans Dirk Duengen, Thomas Krahn, Wilfried Dinh
Journal: Circulation (2017)

Introduction: Cardiac output (CO) responds to exercise is a key determinant of cardiac performance. Exercise CO is estimated by measuring peak oxygen uptake (VO2) during cardiopulmonary exercise te...
Prolyl isomerase Pin1 interacts with adipose triglyceride lipase and negatively controls both its expression and lipolysis
Authors: Yusuke Nakatsu, Takeshi Yamamotoya, Mizuki Okumura, Tetsuhiro Ishii, Mayu Kanamoto, Miki Naito, Mikako Nakanishi, Shunya Aoyama, Yasuka Matsunaga, Akifumi Kushiyama, Hideyuki Sakoda, Midori Fujishiro, Hiraku Ono, Tomoichiro Asano
Journal: Metabolism (2020)
Targeting PAK4 to reprogram the vascular microenvironment and improve CAR-T immunotherapy for glioblastoma
Authors: Wenjuan Ma, Yanling Wang, Rongxin Zhang, Fan Yang, Duo Zhang, Menggui Huang, Lin Zhang, Jay F. Dorsey, Zev A. Binder, Donald M. O’Rourke, Joseph A. Fraietta, Yanqing Gong, Yi Fan
Journal: Nature Cancer (2020)
Maintaining musculoskeletal health using a behavioural therapy approach: a population-based randomised controlled trial (the MAmMOTH Study)
Authors: Gary J Macfarlane, Marcus Beasley, Neil Scott, Huey Chong, Paul McNamee, John McBeth, Neil Basu, Philip C Hannaford, Gareth T Jones, Phil Keeley, Gordon J Prescott, Karina Lovell
Journal: Annals of the Rheumatic Diseases (2021)

Cognitive-behavioural therapy (CBT) has been shown to be effective in the management of chronic widespread pain (CWP); we now test whether it can prevent onset among adults at high risk.A population-based randomised controlled prevention trial, with recruitment through UK general practices. A mailed screening questionnaire identified adults at high risk of CWP. Participants received either usual care (UC) or a short course of telephone CBT (tCBT). The primary outcome was CWP onset at 12 months assessed by mailed questionnaire. There were seven secondary outcomes including quality of life (EuroQol Questionnaire-five dimensions-five levels/EQ-5D-5L) used as part of a health economic assessment.996 participants were randomised and included in the intention-to-treat analysis of which 825 provided primary outcome data. The median age of participants was 59 years; 59% were women. At 12 months there was no difference in the onset of CWP (tCBT: 18.0% vs UC: 17.5%; OR 1.05; 95% CI 0.75 to 1.48). Participants who received tCBT were more likely to report better quality of life (EQ-5D-5L utility score mean difference 0.024 (95% CI 0.009 to 0.040)); and had 0.023 (95% CI 0.007 to 0.039) more quality-adjusted life-years at an additional cost of £42.30 (95% CI -£451.19 to £597.90), yielding an incremental cost-effectiveness ratio of £1828. Most secondary outcomes showed significant benefit for the intervention.A short course of tCBT did not prevent onset of CWP in adults at high risk, but improved quality of life and was cost-effective. A low-cost, short-duration intervention benefits persons at risk of CWP.ClinicalTrials.gov Registry (NCT02668003).
15182 Population pharmacokinetic modeling and simulations for GBR 830, a first-in-class humanized monoclonal antibody inhibiting OX40, to support clinical development in patients with moderate to severe atopic dermatitis
Authors: Girish Gudi, C.A. Vinu, Sunitha Gn, Christine von Gunten, Yacine Salhi, Andrea J. Acocella, Gerhard Wolff
Journal: Journal of the American Academy of Dermatology (2020)
Vertical Stratification in Urban Green Space Aerobiomes
Authors: Jake M. Robinson, Christian Cando-Dumancela, Craig Liddicoat, Philip Weinstein, Ross Cameron, Martin F. Breed
Journal: Environmental Health Perspectives (2020)

Background: Exposure to a diverse environmental microbiome is thought to play an important role in "educating" the immune system and facilitating competitive exclusion of pathogens to maintain human health. Vegetation and soil are key sources of airborne microbiota––the aerobiome. A limited number of studies have attempted to characterize the dynamics of near surface green space aerobiomes, and no studies to date have investigated these dynamics from a vertical perspective. Vertical stratification in the aerobiome could have important implications for public health and for the design, engineering, and management of urban green spaces. Objectives: The primary objectives of this study were to: a) assess whether significant vertical stratification in bacterial species richness and evenness (alpha diversity) of the aerobiome occurred in a parkland habitat in Adelaide, South Australia; b) assess whether significant compositional differences (beta diversity) between sampling heights occurred; and c) to preliminarily assess whether there were significant altitudinal differences in potentially pathogenic and beneficial bacterial taxa. Methods: We combined an innovative columnar sampling method at soil level, 0.0, 0.5, 1.0, and 2.0m, using passive petri dish sampling to collect airborne bacteria. We used a geographic information system (GIS) to select study sites, and we used high-throughput sequencing of the bacterial 16S rRNA gene to assess whether significant vertical stratification of the aerobiome occurred. Results: Our results provide evidence of vertical stratification in both alpha and beta (compositional) diversity of airborne bacterial communities, with diversity decreasing roughly with height. We also found significant vertical stratification in potentially pathogenic and beneficial bacterial taxa. Discussion: Although additional research is needed, our preliminary findings point to potentially different exposure attributes that may be contingent on human height and activity type. Our results lay the foundations for further research into the vertical characteristics of urban green space aerobiomes and their implications for public health and urban planning. https://doi.org/10.1289/EHP7807