tbuckley/cabot-search huggingface dataset:
Neuro-regenerative imidazole-functionalized GelMA hydrogel loaded with hAMSC and SDF-1α promote stem cell differentiation and repair focal brain injury
Authors: Yantao Zheng, Gang Wu, Limei Chen, Ying Zhang, Yuwei Luo, Yong Zheng, Fengjun Hu, Tymor Forouzanfar, Haiyan Lin, Bin Liu
Journal: Bioactive Materials (2020)

Brain tissues that are severely damaged by traumatic brain injury (TBI) is hardly regenerated, which leads to a cavity or a repair with glial scarring. Stem-cell therapy is one viable option to treat TBI-caused brain tissue damage, whose use is, whereas, limited by the low survival rate and differentiation efficiency of stem cells. To approach this problem, we developed an injectable hydrogel using imidazole groups-modified gelatin methacrylate (GelMA-imid). In addition, polydopamine (PDA) nanoparticles were used as carrier for stromal-cell derived factor-1 (SDF-1α). GelMA-imid hydrogel loaded with PDA@SDF-1α nanoparticles and human amniotic mesenchymal stromal cells (hAMSCs) were injected into the damaged area in an in-vivo cryogenic injury model in rats. The hydrogel had low module and its average pore size was 204.61 ± 41.41 nm, which were suitable for the migration, proliferation and differentiation of stem cells. In-vitro cell scratch and differentiation assays showed that the imidazole groups and SDF-1α could promote the migration of hAMSCs to injury site and their differentiation into nerve cells. The highest amount of nissl body was detected in the group of GelMA-imid/SDF-1α/hAMSCs hydrogel in the in-vivo model. Additionally, histological analysis showed that GelMA-imid/SDF-1α/hAMSCs hydrogel could facilitate the regeneration of regenerate endogenous nerve cells. In summary, the GelMA-imid/SDF-1α/hAMSCs hydrogel promoted homing and differentiation of hAMSCs into nerve cells, and showed great application potential for the physiological recovery of TBI.
Stressed erythrophagocytosis induces immunosuppression during sepsis through heme-mediated STAT1 dysregulation
Authors: Tolani F. Olonisakin, Tomeka Suber, Shekina Gonzalez-Ferrer, Zeyu Xiong, Hernán F. Peñaloza, Rick van der Geest, Yuting Xiong, David O. Osei-Hwedieh, Jesús Tejero, Matthew R. Rosengart, Wendy M. Mars, Daria Van Tyne, Andreas Perlegas, Samuel Brashears, Daniel B. Kim-Shapiro, Mark T. Gladwin, Michael A. Bachman, Eldad A. Hod, Claudette St. Croix, Yulia Y. Tyurina, Valerian E. Kagan, Rama K. Mallampalli, Anuradha Ray, Prabir Ray, Janet S. Lee
Journal: Journal of Clinical Investigation (2020)

Macrophages are main effectors of heme metabolism, increasing transiently in the liver during heightened disposal of damaged or senescent RBCs (sRBCs). Macrophages are also essential in defense against microbial threats, but pathological states of heme excess may be immunosuppressive. Herein, we uncovered a mechanism whereby an acute rise in sRBC disposal by macrophages led to an immunosuppressive phenotype after intrapulmonary Klebsiella pneumoniae infection characterized by increased extrapulmonary bacterial proliferation and reduced survival from sepsis in mice. The impaired immunity to K. pneumoniae during heightened sRBC disposal was independent of iron acquisition by bacterial siderophores, in that K. pneumoniae mutants lacking siderophore function recapitulated the findings observed with the WT strain. Rather, sRBC disposal induced a liver transcriptomic profile notable for suppression of Stat1 and IFN-related responses during K. pneumoniae sepsis. Excess heme handling by macrophages recapitulated STAT1 suppression during infection that required synergistic NRF1 and NRF2 activation but was independent of heme oxygenase-1 induction. Whereas iron was dispensable, the porphyrin moiety of heme was sufficient to mediate suppression of STAT1-dependent responses in human and mouse macrophages and promoted liver dissemination of K. pneumoniae in vivo. Thus, cellular heme metabolism dysfunction negatively regulated the STAT1 pathway, with implications in severe infection.
Amphiregulin Expression Is a Predictive Biomarker for <i>EGFR</i> Inhibition in Metastatic Colorectal Cancer: Combined Analysis of Three Randomized Trials
Authors: Arndt Stahler, Sebastian Stintzing, Dominik P. Modest, Ingrid Ricard, Clemens Giessen-Jung, Christine Kapaun, Boryana Ivanova, Florian Kaiser, Ludwig Fischer von Weikersthal, Nicolas Moosmann, Andreas Schalhorn, Martina Stauch, Alexander Kiani, Swantje Held, Thomas Decker, Markus Moehler, Jens Neumann, Thomas Kirchner, Andreas Jung, Volker Heinemann
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Amphiregulin (AREG) and epiregulin (EREG) are ligands of EGFR. Predictive information for anti-EGFR treatment in metastatic colorectal cancer (mCRC) was observed, but data for other agents is limited. Experimental Design: Ligand mRNA expression; RAS, BRAF, PIK3CA mutations; and EGFR expression were assessed by qRT-PCR, pyrosequencing, and IHC, respectively, in mCRC tumor tissue of patients participating in the randomized controlled trials FIRE-1, CIOX, and FIRE-3. Normalized mRNA expression was dichotomized using median and third quartile. Overall (OS) and progression-free survival (PFS) were estimated by Kaplan–Meier method including univariate and multivariate Cox regression analyses. Penalized spline regression analysis tested interaction of mRNA expression and outcome. Results: Of 688 patients with available material, high AREG expression was detected in 343 (&amp;gt;median) and 172 (&amp;gt;3rd quartile) patients. High AREG expression was associated with significantly higher OS [26.2 vs. 21.5 months, HR = 0.80; 95% confidence interval (CI), 0.68–0.94; P = 0.007], PFS (10.0 vs. 8.1 months, HR = 0.74; 95% CI, 0.63–0.86; P = 0.001), and objective response rate (63.1% vs. 51.6%, P = 0.004) compared to low expression at both threshold values. This effect remained significant in multivariate Cox regression analysis (OS: P = 0.01, PFS: P = 0.002). High AREG mRNA expression interacted significantly with the efficacy of cetuximab compared with bevacizumab (OS: P = 0.02, PFS: P = 0.04) in RAS WT mCRC. Conclusions: High AREG mRNA expression is a favorable prognostic biomarker for mCRC which interacted significantly with efficacy of anti-EGFR treatment.
A Decision-Making Algorithm for Children With Suspected Coronavirus Disease 2019—Reply
Authors: Lindsay A. Thompson, Sonja A. Rasmussen
Journal: JAMA Pediatrics (2020)

weight across the life span certainly warrant exploration.However, the focus of our study was specifically to investigate the role of energy-balance behaviors in mediating the association between video game use and BMI in childhood.Inclusion of aggression, or other emotional drivers of weight, was therefore beyond the scope of the study.Additionally, while we agree that previous research suggests there is an association between aggression and BMI, 2 we also note that the evidence for an association between aggression and video game use in childhood is more mixed.For example, a meta-analysis of 101 video game studies in children found minimal associations between video game use and childhood aggression. 3Furthermore, a previous longitudinal study using the same data set as our study (the UK-based Millenium Cohort) found no association between video game use at age 5 years and conduct problems at age 7 years (the only measure of aggression available in this data set). 4This suggests it is unlikely that conduct problems (as an indicator of aggression) would have been considered for inclusion as a mediator within our final model had we explored this association.It is also important to highlight that in the United Kingdom, children are restricted in their ability to buy violent video games by the Pan-European Game Information age rating system. 5This means video game use in our sample of 5-year-old children is unlikely to have included violent games, which are of particular concern in relation to aggressive behaviors. 6 We therefore feel that the inclusion of aggression as a potential mediator was not appropriate for this study.However, this is certainly an interesting area of research and future studies could consider exploring these associations further in cohorts of older teenagers and young adults, using appropriate measures of aggression and stress.
Asthma medication use in obese and healthy weight asthma: systematic review/meta-analysis
Authors: Cherry A. Thompson, Shaun R. Eslick, Bronwyn S. Berthon, Lisa G. Wood
Journal: European Respiratory Journal (2020)

Obesity is a common comorbidity in asthma and associated with poorer asthma control, more frequent/severe exacerbations, and reduced response to asthma pharmacotherapy.This review aims to compare use of all classes of asthma medications in obese (body mass index (BMI) ≤30 kg·m-2) versus healthy-weight (BMI <25 kg·m-2) subjects with asthma.Databases including CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane, Embase and MEDLINE were searched up to July 2019 for English-language studies that recorded medication use or dose in obese and healthy-weight adults with asthma. A critical appraisal checklist was utilised for scrutinising methodological quality of eligible studies. Meta-analysis was performed and heterogeneity was examined with the use of the Chi-squared test. This review was conducted based on a published protocol (www.crd.york.ac.uk/PROSPERO CRD42020148671).Meta-analysis showed that obese subjects are more likely to use asthma medications, including short-acting β2-agonists (OR 1.75, 95% CI 1.17-2.60; p=0.006, I2=41%) and maintenance oral corticosteroids (OR 1.86, 95% CI 1.49-2.31; p<0.001, I2=0%) compared to healthy-weight subjects. Inhaled corticosteroid (ICS) dose (µg·day-1) was significantly higher in obese subjects (mean difference 208.14, 95% CI 107.01-309.27; p<0.001, I2=74%). Forced expiratory volume in 1 s (FEV1) % predicted was significantly lower in obese subjects (mean difference -5.32%, 95% CI -6.75--3.89; p<0.001, I2=42%); however, no significant differences were observed in FEV1/forced vital capacity (FVC) ratio between groups.We found that obese subjects with asthma have higher use of all included asthma medication classes and higher ICS doses than healthy-weight asthma subjects, despite lower FEV1 and a similar FEV1/FVC %. A better understanding of the factors driving increased medication use is required to improve outcomes in this subgroup of asthmatics.
Comparative functional survival and equivalent annual cost of 3 long-lasting insecticidal net (LLIN) products in Tanzania: A randomised trial with 3-year follow up
Authors: Lena M. Lorenz, John Bradley, Joshua Yukich, Dennis J. Massue, Zawadi Mageni Mboma, Olivier Pigeon, Jason Moore, Albert Kilian, Jo Lines, William Kisinza, Hans J. Overgaard, Sarah J. Moore
Journal: PLoS Medicine (2020)

Two billion long-lasting insecticidal nets (LLINs) have been procured for malaria control. A functional LLIN is one that is present, is in good physical condition, and remains insecticidal, thereby providing protection against vector-borne diseases through preventing bites and killing disease vectors. The World Health Organization (WHO) prequalifies LLINs that remain adequately insecticidal 3 years after deployment. Therefore, institutional buyers often assume that prequalified LLINs are functionally identical with a 3-year lifespan. We measured the lifespans of 3 LLIN products, and calculated their cost per year of functional life, to demonstrate the economic and public health importance of procuring the most cost-effective LLIN product based on its lifespan.A randomised double-blinded trial of 3 pyrethroid LLIN products (10,571 nets in total) was conducted at 3 follow-up points: 10 months (August-October 2014), 22 months (August-October 2015), and 36 months (October-December 2016) among 3,393 households in Tanzania using WHO-recommended methods. Primary outcome was LLIN functional survival (LLIN present and in serviceable condition). Secondary outcomes were (1) bioefficacy and chemical content (residual insecticidal activity) and (2) protective efficacy for volunteers sleeping under the LLINs (bite reduction and mosquitoes killed). Median LLIN functional survival was significantly different between the 3 net products (p = 0.001): 2.0 years (95% CI 1.7-2.3) for Olyset, 2.5 years (95% CI 2.2-2.8) for PermaNet 2.0 (hazard ratio [HR] 0.73 [95% CI 0.64-0.85], p = 0.001), and 2.6 years (95% CI 2.3-2.8) for NetProtect (HR = 0.70 [95% CI 0.62-0.77], p < 0.001). Functional survival was affected by accumulation of holes, leading to users discarding nets. Protective efficacy also significantly differed between products as they aged. Equivalent annual cost varied between US$1.2 (95% CI $1.1-$1.4) and US$1.5 (95% CI $1.3-$1.7), assuming that each net was priced identically at US$3. The 2 longer-lived nets (PermaNet and NetProtect) were 20% cheaper than the shorter-lived product (Olyset). The trial was limited to only the most widely sold LLINs in Tanzania. Functional survival varies by country, so the single country setting is a limitation.These results suggest that LLIN functional survival is less than 3 years and differs substantially between products, and these differences strongly influence LLIN value for money. LLIN tendering processes should consider local expectations of cost per year of functional life and not unit price. As new LLIN products come on the market, especially those with new insecticides, it will be imperative to monitor their comparative durability to ensure that the most cost-effective products are procured for malaria control.
Mental health status in veterans residing in rural versus non-rural areas: results from the veterans’ health study
Authors: Joseph J. Boscarino, Charles R. Figley, Richard E. Adams, Thomas G. Urosevich, H. Lester Kirchner, Joseph A. Boscarino
Journal: Military Medical Research (2020)

Abstract Background The majority of Veterans Affair (VA) hospitals are in urban areas. We examined whether veterans residing in rural areas have lower mental health service use and poorer mental health status. Methods Veterans with at least 1 warzone deployment in central and northeastern Pennsylvania were randomly selected for an interview. Mental health status, including PTSD, major depression, alcohol abuse and mental health global severity, were assessed using structured interviews. Psychiatric service use was based on self-reported utilization in the past 12 months. Results were compared between veterans residing in rural and non-rural areas. Data were also analyzed using multivariate logistic regression to minimize the influence by confounding factors. Results A total of 1730 subjects (55% of the eligible veterans) responded to the survey and 1692 of them had complete geocode information. Those that did not have this information ( n = 38), were excluded from some analyses. Veterans residing in rural areas were older, more often of the white race, married, and experienced fewer stressful events. In comparison to those residing in non-rural areas, veterans residing in rural areas had lower global mental health severity scores; they also had fewer mental health visits. In multivariate logistic regression, rural residence was associated with lower service use, but not with PTSD, major depression, alcohol abuse, and global mental health severity score after adjusting confounding factors (e.g., age, gender, marital status and education). Conclusions Rural residence is associated with lower mental health service use, but not with poor mental health in veterans with former warzone deployment, suggesting rural residence is possibly protective.
A Potent Anti-Malarial Human Monoclonal Antibody Targets Circumsporozoite Protein Minor Repeats and Neutralizes Sporozoites in the Liver
Authors: Lawrence T. Wang, Lais S. Pereira, Yevel Flores-Garcia, James O’Connor, Barbara J. Flynn, Arne Schön, Nicholas K. Hurlburt, Marlon Dillon, Annie S.P. Yang, Amanda Fabra-García, Azza H. Idris, Bryan T. Mayer, Monica W. Gerber, Raphael Gottardo, Rosemarie D. Mason, Nicole Cavett, Reid B. Ballard, Neville K. Kisalu, Alvaro Molina-Cruz, Jorgen Nelson, Rachel Vistein, Carolina Barillas-Mury, Rogerio Amino, David Baker, Neil P. King, Robert W. Sauerwein, Marie Pancera, Ian A. Cockburn, Fidel Zavala, Joseph R. Francica, Robert A. Seder
Journal: Immunity (2020)
The SickleGenAfrica Network
Authors: Solomon F Ofori-Acquah
Journal: The Lancet Global Health (2020)

In 2012, the US National Institutes of Health and the UK-based Wellcome Trust funded a US$76 million initiative called Human Heredity and Health in Africa (H3Africa), in partnership with the African Society of Human Genetics. Grants were awarded directly to African institutions to support their faculties in directing their own research, fostering collaborations, and building infrastructure in bioinformatics and genomics.1 H3Africa was founded on the belief that researchers and research participants in Africa are best positioned to work together to study diseases that exact a heavy burden on the continent.
Exploring the regulatory roles of circular RNAs in Alzheimer’s disease
Authors: Yuan Zhang, Yanfang Zhao, Ying Liu, Man Wang, Wanpeng Yu, Lei Zhang
Journal: Translational Neurodegeneration (2020)

Abstract Circular RNAs (circRNAs) are a type of covalently closed, single-stranded circular noncoding RNA that can affect the expression of many protein-coding genes. Growing evidence has shown that circRNAs play critical roles in Alzheimer’s disease (AD) and may have therapeutic potentials for this disease. CircRNAs play regulatory roles in neural functions and neurological disorders through diverse mechanisms, including acting as microRNA sponges or interacting with proteins to regulate selective splicing or transcription, as well as through epigenetic modification. In this review, we discuss the biogenesis and functions of circRNAs and the research progress on circRNAs in AD to advance the understanding of how circRNAs contribute to this neurological disorder.
Abstract 14474: Electronic Medical Record-Based Machine Learning Approach to Predict the Risk of 30-Day Major Adverse Cardiac Event After Invasive Coronary Treatment
Authors: Osung Kwon, Wonjun Na, Hyeonkyeong Yang, Jihoon Kweon, Dong Hyun Yang, Jungwoo Chae, Cinyoung Hur, Yonghyun Cho, Young-Hak Kim
Journal: Circulation (2019)

Introduction: There is increasing interest of prediction models to identify patients at risk of major adverse cardiac event (MACE) following invasive coronary treatment using electronic medical rec...
Comment on Chen et al. Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication. Diabetes Care 2020;43:1399–1407
Authors: Bertrand Cariou, Samy Hadjadj, Matthieu Wargny, Matthieu Pichelin, Pierre Gourdy
Journal: Diabetes Care (2020)

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, people with diabetes have been rapidly identified as having more vulnerable profiles. Therefore, as highlighted by Riddle et al. (1), specific data providing a better understanding of the relationship between diabetes and COVID-19 are urgently needed. In this context, the retrospective data of Chen et al. (2), published online 14 May 2020, provided important insights that we would like to comment on in light of the results from our CORONADO (CORONAvirus SARS-CoV-2 and Diabetes Outcomes) study that was published online almost simultaneously on 29 May 2020 (3).

Specifically conducted in patients with diabetes and hospitalized for COVID-19 (>90% with positive PCR for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), the CORONADO study is an observational, multicenter (67 centers), nationwide (France) study with a prespecified protocol (reg. no. NCT04324736, ClinicalTrials.gov) and standardized data collection. The primary end point combines mortality and tracheal intubation on day 7 (D7) after hospital admission. The …
Distinct Cardiac Transcriptomic Clustering in Titin and Lamin A/C-Associated Dilated Cardiomyopathy Patients
Authors: Job A.J. Verdonschot, Kasper W.J. Derks, Mark R. Hazebroek, Ping Wang, Emma Louise Robinson, Michiel E. Adriaens, Ingrid P.C. Krapels, Arthur van den Wijngaard, Han G. Brunner, Stephane R.B. Heymans
Journal: Circulation (2020)
Assessment of Placebo Response in Objective and Subjective Outcome Measures in Rheumatoid Arthritis Clinical Trials
Authors: Jan Vollert, Nancy R. Cook, Ted J. Kaptchuk, Shiv T. Sehra, Deirdre K. Tobias, Kathryn T. Hall
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Large placebo responses in randomized clinical trials may keep effective medication from reaching the market. Primary outcome measures of clinical trials have shifted from patient-reported to objective outcomes, partly because response to randomized placebo treatment is thought to be greater in subjective compared with objective outcomes. However, a direct comparison of placebo response in subjective and objective outcomes in the same patient population is missing. <h3>Objective</h3> To assess whether subjective patient-reported (pain severity) and objective inflammation (C-reactive protein [CRP] level and erythrocyte sedimentation rate [ESR]) outcomes differ in placebo response. <h3>Design, Setting, and Participants</h3> The placebo arms of 5 double-blind, randomized, placebo-controlled clinical trials were included in this cross-sectional study. These trials were conducted internationally for 24 weeks or longer between 2005 and 2009. All patients with rheumatoid arthritis randomized to placebo (N = 788) were included. Analysis of data from these trials was conducted from March 27 to December 31, 2019. <h3>Intervention</h3> Placebo injection. <h3>Main Outcomes and Measures</h3> The difference (with 95% CIs) from baseline at week 12 and week 24 on a 0- to 100-mm visual analog scale to evaluate the severity of pain, CRP level, and ESR. <h3>Results</h3> Of the 788 patients included in the analysis, 644 were women (82%); mean (SD) age was 51 (13) years. There was a statistically significant decrease in patient-reported pain intensity (week 12: −14 mm; 95% CI, −12 to −16 mm and week 24: −20 mm; 95% CI, −16 to −22 mm). Similarly, significant decreases were noted in the CRP level (week 12: −0.51 mg/dL; 95% CI, −0.47 to −0.56 mg/dL and week 24: −1.16 mg/dL; 95% CI, −1.03 to −1.30 mg/dL) and ESR (week 12: −11 mm/h; 95% CI, −10 to 12 mm/h and week 24: −25 mm/h; 95% CI, −12 to −26 mm/h) (all<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> The findings of this study suggest that improvements in clinical outcomes among participants randomized to placebo were not limited to subjective outcomes. Even if these findings could largely demonstrate a regression to the mean, they should be considered for future trial design, as unexpected favorable placebo responses may result in a well-designed trial becoming underpowered to detect the treatment difference needed in clinical drug development.
Warthin Tumor Incidentally Detected on PET/CT Showing Both 68Ga-DOTANOC and 18F-FDG Uptake
Authors: Sofia C. Vaz, Andreia Marques, João Lourenço, Antonio Galzerano
Journal: Clinical Nuclear Medicine (2020)

A patient with moderately differentiated pancreatic neuroendocrine tumor with synchronous multifocal liver metastases was referred for further staging with PET/CT. The examinations were performed on 2 consecutive days and showed mild 68Ga-DOTANOC and intense 18F-FDG uptake in an incidental right parotid nodule. Differential diagnoses include primary or metastatic neuroendocrine tumor, malignant or benign primary parotid tumor, and intraparotid lymph node. Histology revealed characteristics of a Warthin tumor. While focal FDG uptake in Warthin tumor is frequently described, the somatostatin expression was rarely reported. This clinical case describes 68Ga-DOTANOC and 18F-FDG uptake in a parotid Warthin tumor histologically confirmed.