tbuckley/cabot-search huggingface dataset:
JWA, a functional molecule to control cancer cells migration via MAPK cascades and F-actin cytoskeleton
Authors: Hairong Chen, Jin Bai, Jian Ye, Zulong Liu, Rui Chen, Wenge Mao, Aiping Li, Jianwei Zhou
Journal: Cancer Research (2007)

1351  JWA, a functional molecule to control cancer cells migration via MAPK cascades and F-actin cytoskeleton  Hairong Chen, Jin Bai, Jian Ye, Zulong Liu, Rui Chen, Wenge Mao, Aiping Li, Jianwei Zhou†  Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, People’s Republic of China  †To whom correspondence should be addressed; E-mail: jwzhou@njmu.edu.cn  Tel: +86-25-8686-2746; Fax: +86-25-8652-7613.  Running Title: JWA regulates cell migration  Abstract   Cell migration is a process that is critical at many stages of embryonic development, and essential for wound healing and tumor cell invasion. Cell migration is regulated by coordinated changes in the actin cytoskeleton and by cell adhesion. Mitogen activated protein kinase (MAPK) cascades are thought to mediate diverse biological functions such as cell growth, differentiation and migration. In the present study, we successfully established series normal and mutant target gene rescue transfecting cell culture models, combined with cell migration assays and MAPK signal transduction pathway activation assays, and investigated the potential function of JWA on tumor cell migration and the behind mechanisms. Data showed that JWA, a newly identified novel microtubule-associated protein (MAP) was indispensable for the rearrangement of F-actin cytoskeleton and activation of MAPK cascades induced by arsenic trioxide (As2O3) and phorbol ester (PMA). Knock down JWA expression alone in HeLa, B16 and HCCLM3 cancer cells obviously induced intracellular F-actin rearrangement, and companied with accelerated cellular migration. In contrast, over express JWA alone in these cell lines inhibited their migration. The expression of JWA was also enhanced PMA and inhibited As2O3 decreased cell migration in HeLa cells. Further analysis indicated that JWA was necessary for both PMA and As2O3 regulated cell migration via activating of MEK-ERK phosphorylation, especially, the SDR-SLR PKC activating motifs of JWA protein were critical in this process. The function of JWA differentially regulated PMA and As2O3 induced cell migration was found to associate with regulating ERK downstream effectors focal adhesion kinase (FAK) and cyclooxygenase-2 (COX-2), respectively. In conclusion, our study provided unexpected role of JWA at first time that JWA regulates tumor cellular migration via controlling of MEK-ERK phosophorylation and F-actin cytoskeleton rearrangement two distinct mechanisms. JWA might be a potential useful molecule target for tumor metastasis.
Fine Particulate Matter and Poor Cognitive Function among Chinese Older Adults: Evidence from a Community-Based, 12-Year Prospective Cohort Study
Authors: Jiaonan Wang, Tiantian Li, Yuebin Lv, Virginia Byers Kraus, Yi Zhang, Chen Mao, Zhaoxue Yin, Wanying Shi, Jinhui Zhou, Tongzhang Zheng, Patrick L. Kinney, John Ji, Song Tang, Xiaoming Shi
Journal: Environmental Health Perspectives (2020)

Background: Research on the relationship between long-term exposure to particulate matter with aerodynamic diameter ≤2.5μm (PM2.5) and poor cognitive function is lacking in developing countries, especially in highly polluted areas. Objectives: We evaluated associations of long-term exposure to PM2.5 with poor cognitive function in a diverse, national sample of older adults in China. Methods: This analysis included data on 13,324 older adults (5,879 who were 65–79 years of age, 3,052 who were 80–89 years of age, 2,634 who were 90–99 years of age, and 1,759 who were ≥100 years of age) with normal cognitive function at baseline from March 2002 to September 2014, with 64,648 person-years of follow-up. We used a geographic information system analysis to estimate the annual average satellite-derived PM2.5 concentration for the geocoded location of the participants' baseline residences. Poor cognitive function was defined as a score of less than 18 on the Chinese version of the Mini-Mental State Examination (MMSE). Competing risk models were performed to explore the association of PM2.5 with poor cognitive function. Results: Each 10-μg/m3 increase in PM2.5 was associated with a 5.1% increased risk of poor cognitive function [adjusted hazard ratio (HR): 1.051; 95% confidence interval (CI): 1.023, 1.079]. Compared to the lowest quartile of PM2.5 (<41.4 μg/m3), adjusted HR values were 1.20 (95% CI: 1.09, 1.33), 1.27 (95% CI: 1.15, 1.41), and 1.21 (95% CI: 1.09, 1.34) for the second (≥41.4–50.3 ug/m3), third (≥50.3–60.7μg/m3), and fourth (≥60.7 μg/m3) quartiles of PM2.5, respectively (p for trend <0.001). Subgroup analyses suggested stronger associations between PM2.5 and poor cognitive impairment in men than women. The association was positive in the 65- to 79- and ≥100-y age group but not significant and positive in the other two age groups with similar results. Conclusion: PM2.5 was identified as a risk factor for poor cognitive function in Chinese older adults. Improving air quality may reduce the future population burden of poor cognitive function, especially in areas with high air pollution. https://doi.org/10.1289/EHP5304
Tislelizumab Plus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma
Authors: Jianming Xu, Yuxian Bai, Nong Xu, Enxiao Li, Buhai Wang, Jin Wang, Xiang Li, Xin Wang, Xianglin Yuan
Journal: Clinical Cancer Research (2020)

This phase II study (NCT03469557) assessed safety/tolerability and antitumor activity of first-line tislelizumab, a monoclonal antibody against programmed cell death-1, plus chemotherapy in patients with locally advanced/metastatic esophageal squamous cell carcinoma (ESCC) or gastric/gastroesophageal junction (G/GEJ) adenocarcinoma.Patients with ESCC received tislelizumab [200 mg i.v. every 3 weeks (Q3W)] plus cisplatin (80 mg/m² i.v. Q3W for ≤6 cycles) and fluorouracil (800 mg/m²/day i.v., Days 1-5 Q3W for ≤6 cycles); patients with G/GEJ adenocarcinoma received tislelizumab (200 mg i.v. Q3W) plus oxaliplatin (130 mg/m² i.v. Q3W for up to six cycles) and oral capecitabine (1,000 mg/m² twice daily, Days 1-14 Q3W). The safety/tolerability profile of combination therapy was the primary endpoint; secondary endpoints included objective response rate (ORR), duration of response (DoR), disease control rate (DCR), and progression-free survival per RECIST v1.1. Exploratory endpoints included overall survival and potential predictive biomarkers.As of March 31, 2019, 30 patients (n = 15 per cohort) were enrolled. Most common adverse events considered related to tislelizumab and/or chemotherapy were anemia (n = 18), decreased appetite (n = 17), nausea (n = 16), and asthenia (n = 15). One patient experienced fatal hepatic dysfunction, confounded by progressive disease and underlying hepatitis, attributed to treatment by the investigator. Confirmed ORRs and DCRs were 46.7% and 80%, respectively, for both ESCC and G/GEJ adenocarcinoma. In ESCC, median DoR was 12.8 months (95% confidence interval, 3.5-12.8); DoR was not yet mature for the G/GEJ cohort.Tislelizumab plus chemotherapy demonstrated durable responses with manageable tolerability in patients with advanced ESCC or G/GEJ adenocarcinoma.
Morbidity and Mortality From COVID‐19 Are Not Increased Among Children or Patients With Autoimmune Rheumatic Disease—Possible Immunologic Rationale: Comment on the Article by Henderson et al
Authors: Edoardo Sean Ferraccioli, Elisa Gremese, Gianfranco Ferraccioli
Journal: Arthritis & Rheumatology (2020)

receiving biologic DMARDs is well known, and patients have probably been informed of this risk at the time of treatment initiation (6,7).Reduced physical activity resulting from home confinement could be another explanation for worsening symptoms.In SpA patients, exercise can reduce disease activity and, consequently, is recommended for optimal treatment (8).In this patient population, COVID-19 occurrence was associated with SpA treatment modification.We did not find a link between NSAID or biologic treatment and COVID-19.When considering both the confirmed and the clinically suspected cases of COVID-19, we found 31 cases (13 clinically suspicious and 18 selfreported as being confirmed), which is more substantial than the 8 cases in a cohort of 320 patients with chronic arthritis (4 confirmed and 4 highly suggestive) reported by Monti et al ( 9).However, it is impossible to compare prevalence as the population, methodology, and period are different (9).It is important to emphasize that a majority of our patients were treated with NSAIDs.Our results are interesting because they provide data from a real-life setting.Our findings should be interpreted within the limitations of the study.The most important limitation is that our results are based on self-reported data.For patients who reported having confirmed COVID-19, we could not verify that this was in fact confirmed via a positive test result.However, this is the first study providing information on therapy compliance during home confinement and reporting the frequency of COVID-19 in SpA patients.The size of our cohort reinforces the importance of our results.Thus, our survey results show that in SPA patients, home confinement linked to the COVID-19 pandemic is associated with worsening of the disease and reduction or suspension of medication intake, in particular NSAIDs.These findings have considerable clinical implications, given that home confinement is likely to recur in the future.Patients need to be educated about the current evidence regarding NSAID treatment and ways to stay physically active at home.
Is time to remove parabens from standard patch test batteries? Retrospective study of 10 461 patients
Authors: María Macarena Giácaman‐von der Weth, Blanca Ferrer‐Guillén, Jose María Ortiz‐Salvador, Ana Victoria‐Martínez, Joan Sanfeliu‐García, Jorge Magadaleno‐Tapial, Concepción Sierra‐Talamantes, Violeta Zaragoza‐Ninet
Journal: Allergy (2020)
Reply
Authors: John Denis Ryan, Sandro Altamura, Martina Muckenthaler, John Crowe
Journal: Hepatology (2013)

We appreciate the interest of Strnad et al. in our recent article.1 Similar to our study, Strnad et al. demonstrate a significant increase in serum hepcidin levels in HCV genotype 1 patients soon after commencing pegylated interferon-α/ribavirin (PEG/RBV) therapy. However, the hepcidin assay used and the timepoints studied were different from ours, limiting comparisons between studies. Importantly, neither study found a significant association between baseline or dynamic changes in serum hepcidin levels and treatment outcomes. Specifically, in our study we did not find any significant differences between baseline serum hepcidin levels according to gender, but male subjects experienced a greater increase in serum hepcidin following the first PEG/RBV dose than females (P = 0.052). The cause of this difference is unclear but could relate to gender-specific influences on expression of interferon stimulated genes before and after IFN-α treatment.2 Indeed, anemia was commonly seen during PEG/RBV treatment and although no gender difference was noted, we agree that hepcidin induction is likely to contribute at least in part to this important adverse effect. As noted elsewhere, significantly higher hepcidin levels 6 months following the end of treatment in those achieving a sustained virological response (SVR) may reflect a direct role for the hepatitis C virus in hepcidin dysregulation, which is ameliorated upon viral eradication.3 Finally, the authors speculate as to the cause of the observed rise in hepcidin during treatment. Our study demonstrates a positive correlation between serum hepcidin and serum IFN-α levels in HCV patients and a clear induction of hepcidin by interferon-α treatment of cultured cells, suggesting a direct effect of IFN-α on hepcidin levels in hepatocytes during HCV therapy. John Denis Ryan, M.B., B.Ch. Sandro Altamura, Ph.D. Martina Muckenthaler, Ph.D. John Crowe, Ph.D., PRCPI Center for Liver Disease Mater Misericordiae University Hospital Dublin, Ireland
Successful simulation requires bridging levels of abstraction
Authors: Zidong Zhao, Judith N. Mildner, Diana I. Tamir
Journal: Behavioral and Brain Sciences (2020)

Abstract Although many simulations draw upon only one level of abstraction, the process for generating rich simulations requires a dynamic interplay between abstract and concrete knowledge. A complete model of simulation must account for a mind and brain that can bridge the perceptual with the conceptual, the episodic with the semantic, and the concrete with the abstract.
Association of Azithromycin Use With Cardiovascular Mortality
Authors: Jonathan G. Zaroff, T. Craig Cheetham, Niki Palmetto, Lucy Almers, Charles Quesenberry, Jennifer Schneider, Nicolle Gatto, Douglas A. Corley
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Azithromycin is one of the most commonly prescribed antibiotics in the US. It has been associated with an increased risk of cardiovascular death in some observational studies. <h3>Objective</h3> To estimate the relative and absolute risks of cardiovascular and sudden cardiac death after an outpatient azithromycin prescription compared with amoxicillin, an antibiotic not known to increase cardiovascular events. <h3>Design, Setting, and Participants</h3> This retrospective cohort study included 2 large, diverse, community-based integrated care delivery systems with comprehensive capture of encounters and prescriptions from January 1, 1998, to December 31, 2014. The cohort included patients aged 30 to 74 years who had at least 12 months of health-plan enrollment prior to antibiotic exposure. The exclusion criteria were absence of prescription benefits, prescription for more than 1 type of study antibiotic within 10 days, hospitalization or nursing home residence, and serious medical conditions. Risk of cardiovascular death associated with azithromycin vs amoxicillin exposure was calculated after controlling for confounding factors using a propensity score. Data were analyzed from December 1, 2016, to March 30, 2020. <h3>Exposures</h3> Outpatient prescription of azithromycin or amoxicillin. <h3>Main Outcomes and Measures</h3> The primary outcomes were cardiovascular death and sudden cardiac death. An a priori subgroup analysis quantified the effects of azithromycin exposure among patients with increased baseline cardiovascular risk. The secondary outcomes were noncardiovascular death and all-cause mortality. <h3>Results</h3> The study included 7 824 681 antibiotic exposures, including 1 736 976 azithromycin exposures (22.2%) and 6 087 705 amoxicillin exposures (77.8%), among 2 929 008 unique individuals (mean [SD] age, 50.7 [12.3] years; 1 810 127 [61.8%] women). Azithromycin was associated with a significantly increased hazard of cardiovascular death (hazard ratio [HR], 1.82; 95% CI, 1.23-2.67) but not sudden cardiac death (HR, 1.59; 95% CI, 0.90-2.81) within 5 days of exposure. No increases in risk were found 6 to 10 days after exposure. Similar results were observed in patients within the top decile of cardiovascular risk (HR, 1.71; 95% CI, 1.06-2.76). Azithromycin was also associated with an increased risk of noncardiovascular death (HR, 2.17; 95% CI, 1.44-3.26) and all-cause mortality (HR, 2.00; 95% CI, 1.51-2.63) within 5 days of exposure. <h3>Conclusions and Relevance</h3> These findings suggest that outpatient azithromycin use was associated with an increased risk of cardiovascular death and noncardiovascular death. Causality cannot be established, particularly for noncardiovascular death, owing to the likelihood of residual confounding.
Khalid Musa Hussain
Authors: M Al-Sudani
Journal: BMJ (2020)

Khalid Musa Hussain was born in Baghdad, Iraq, and graduated from the medical college of the University of Baghdad in 1967. On completing his military service in the summer of 1969, he took up a post as senior house officer at Al-Fallujah Teaching Hospital. In November 1970 he returned to Baghdad medical college and joined the department of forensic medicine as a demonstrator and junior lecturer. He went on to obtain the higher diploma in forensic medicine from the college in 1973. …
Reconsidering the Trade-offs of Prostate Cancer Screening
Authors: Jonathan E. Shoag, Yaw A. Nyame, Roman Gulati, Ruth Etzioni, Jim C. Hu
Journal: New England Journal of Medicine (2020)

Shoag and colleagues review the long-term results of PSA screening from randomized trials and raise questions about whether the risk–benefit ratio is as strongly in favor of risk over benefit as currently gauged. The decline in PSA screening appears to have been precipitated in part by misinterpretations of data from randomized trials.
Quantitative proteomics reveals specific metabolic features of acute myeloid leukemia stem cells
Authors: Simon Raffel, Daniel Klimmeck, Mattia Falcone, Aykut Demir, Alireza Pouya, Petra Zeisberger, Christoph Lutz, Marco Tinelli, Oliver Bischel, Lars Bullinger, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Anthony D. Ho, Carsten Müller-Tidow, Zuguang Gu, Carl Herrmann, Jeroen Krijgsveld, Andreas Trumpp, Jenny Hansson
Journal: Blood (2020)
Immunoglobulin light chain toxicity in a mouse model of monoclonal immunoglobulin light-chain deposition disease
Authors: Sébastien Bender, Maria Victoria Ayala, Amélie Bonaud, Vincent Javaugue, Claire Carrion, Christelle Oblet, Alexia Rinsant, Sihem Kaaki, Zeliha Oruc, François Boyer, Agnes Paquet, Nicolas Pons, Bastien Herve, Mohamad Omar Ashi, Arnaud Jaccard, Laurent Delpy, Guy Touchard, Michel Cogne, Frank Bridoux, Christophe Sirac
Journal: Blood (2020)
Inflammasomes and Proteostasis Novel Molecular Mechanisms Associated With Atrial Fibrillation
Authors: Na Li, Bianca J.J.M. Brundel
Journal: Circulation Research (2020)

Atrial fibrillation (AF), the most common progressive and age-related cardiac arrhythmia, affects millions of people worldwide. AF is associated with common risk factors, including hypertension, diabetes mellitus, and obesity, and serious complications such as stroke and heart failure. Notably, AF is progressive in nature, and because current treatment options are mainly symptomatic, they have only a moderate effect on prevention of arrhythmia progression. Hereto, there is an urgent unmet need to develop mechanistic treatments directed at root causes of AF. Recent research findings indicate a key role for inflammasomes and derailed proteostasis as root causes of AF. Here, we elaborate on the molecular mechanisms of these 2 emerging key pathways driving the pathogenesis of AF. First the role of NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome on AF pathogenesis and cardiomyocyte remodeling is discussed. Then we highlight pathways of proteostasis derailment, including exhaustion of cardioprotective heat shock proteins, disruption of cytoskeletal proteins via histone deacetylases, and the recently discovered DNA damage-induced nicotinamide adenine dinucleotide + depletion to underlie AF. Moreover, potential interactions between the inflammasomes and proteostasis pathways are discussed and possible therapeutic targets within these pathways indicated.
Gut Bacteria have a novel sweet tooth: ribose sensing and scavenging from fiber
Authors: Vivekanudeep Karri, Kendal D. Hirschi
Journal: Gut Microbes (2020)

Dietary fiber is known to influence symbiotic gut microbiota community structure and physiology; however, how and if dietary fiber can induce further exogenous nutrient uptake within gut microbes is ill-defined. Recent findings highlight how during periods of high-fiber consumption, a prevalent gut bacteria senses and scavenges the ubiquitous sugar ribose. This molecular adaptation exemplifies how particular gut microbes have developed a sophisticated system to scavenge nutrients in a diet-dependent manner.
Gadolinium-hyaluronic acid nanoparticles as an efficient and safe magnetic resonance imaging contrast agent for articular cartilage injury detection
Authors: Rong Lu, Yuyang Zhang, Hongyue Tao, Lu Zhou, Huidi Li, Tianwu Chen, Peng Zhang, Yao Lu, Shuang Chen
Journal: Bioactive Materials (2020)

Accurate detection of cartilage injuries is critical for their proper treatment because these injuries lack the self-healing ability and lead to joint dysfunction. However, the low longitudinal T1 relaxivity (
Short-term Treatment of Migraine in Children and Adolescents
Authors: Irene Patniyot, William Qubty
Journal: JAMA Pediatrics (2020)

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Human–computer collaboration for skin cancer recognition
Authors: Philipp Tschandl, Christoph Rinner, Zoe Apalla, Giuseppe Argenziano, Noel Codella, Allan Halpern, Monika Janda, Aimilios Lallas, Caterina Longo, Josep Malvehy, John Paoli, Susana Puig, Cliff Rosendahl, H. Peter Soyer, Iris Zalaudek, Harald Kittler
Journal: Nature Medicine (2020)