tbuckley/cabot-search huggingface dataset:
Supportive Care in Head and Neck Cancers: Multidisciplinary Management
Authors: Jimmy J. Caudell, David G. Pfister, Randal S. Weber
Journal: Journal of the National Comprehensive Cancer Network (2021)

Patients with head and neck cancer experience a broad array of negative quality-of-life issues, but particularly common are dental complications following radiation therapy, and compromised nutrition with significant weight loss. At the NCCN 2021 Virtual Annual Conference, a panel of experts used a case-based approach to discuss some of these common adverse effects of head and neck cancer and its treatment, as well as optimal supportive care strategies to manage them.
Author Correction: Human plasma proteomic profiles indicative of cardiorespiratory fitness
Authors: Jeremy M. Robbins, Bennet Peterson, Daniela Schranner, Usman A. Tahir, Theresa Rienmüller, Shuliang Deng, Michelle J. Keyes, Daniel H. Katz, Pierre M. Jean Beltran, Jacob L. Barber, Christian Baumgartner, Steven A. Carr, Sujoy Ghosh, Changyu Shen, Lori L. Jennings, Robert Ross, Mark A. Sarzynski, Claude Bouchard, Robert E. Gerszten
Journal: Nature Metabolism (2021)
27945 Biologics-resistant areas in Korean patients with moderate to severe psoriasis
Authors: Sang-Hyeon Won, Bong Seok Shin, Dae-Lyong Ha, Jin-Hwa Son, Jungsoo Lee, Kihyuk Shin, Hoon-Soo Kim, Hyun-Chang Ko, Moon-Bum Kim, Kyunghyung Seo, Byung-Soo Kim
Journal: Journal of the American Academy of Dermatology (2021)
Efficacy and Safety of Adalimumab in Conjunction With Surgery in Moderate to Severe Hidradenitis Suppurativa
Authors: Falk G. Bechara, Maurizio Podda, Errol P. Prens, Barbara Horváth, Evangelos J. Giamarellos-Bourboulis, Afsaneh Alavi, Jacek C. Szepietowski, Joslyn Kirby, Ziqian Geng, Christine Jean, Gregor B. E. Jemec, Christos C. Zouboulis
Journal: JAMA Surgery (2021)

Surgery is a mainstay in the management of hidradenitis suppurativa (HS). Adalimumab is the first drug approved for HS.To investigate the efficacy and safety of adalimumab in combination with wide-excision surgery followed by secondary intention healing.The Safety and Efficacy of Adalimumab for Hidradenitis Suppurativa Peri-Surgically (SHARPS) trial was a phase 4, randomized, double-blind, placebo-controlled study of adalimumab in conjunction with surgery. Patients were enrolled in 45 sites across 20 countries from July 18, 2016, to February 2, 2019, with the last patient visit on October 16, 2019. Eligible patients (aged 18-65 years) had moderate to severe HS that required radical surgery in an axillary or inguinal region and had 2 other anatomical regions affected, with 1 or more regions at Hurley stage II or III. Analysis was conducted in November 2019.Patients were randomized 1:1 to receive continuous adalimumab, 40 mg, or placebo during presurgery (12 weeks), perioperative (2 weeks), and postoperative (10 weeks) periods.The primary end point was the proportion of patients achieving HS clinical response across all body regions at week 12.Overall, 103 patients were randomized to adalimumab and 103 to matching placebo. Among all patients, 51% (n = 106) were women, 94% (n = 193) were White, and the mean (SD) age was 37.6 (11.3) years. At week 12, significantly more patients receiving adalimumab (49 of 103 [48%]) vs placebo (35 of 103 [34%]; P = .049) achieved HS clinical response across all body regions (treatment difference, 14% [95% CI, 0%-27%]). Treatment-emergent adverse events were reported in 74 of 103 patients (72%) and 69 of 103 patients (67%) in the adalimumab and placebo groups, respectively. No increased risk of postoperative wound infection, complication, or hemorrhage was observed with adalimumab vs placebo. Two deaths occurred in the adalimumab group; neither was considered as having a reasonable possibility of relationship to study drug.Adalimumab was efficacious in conjunction with wide-excision surgery followed by secondary intention healing, with no need to interrupt treatment prior to surgery. These data support further investigation of adalimumab as an adjuvant therapy to surgery in patients with moderate to severe HS.ClinicalTrials.gov Identifier: NCT02808975.
Dietary Linoleic Acid: Will Modifying Dietary Fat Quality Reduce the Risk of Type 2 Diabetes?
Authors: Matthias B. Schulze
Journal: Diabetes Care (2021)

Linoleic acid (LA) is the major polyunsaturated fatty acid (PUFA) in Western diets; e.g., it accounts for almost 90% of PUFA intake in the U.S. diet (1). Intake levels as a percentage of total energy have increased over time in the U.S. (2), with mean intake being right within the range recommended by the U.S. Institute of Medicine (5–10%) (3). Although the intake of PUFA has been part of dietary recommendations for cardiovascular risk prevention, usually in the context of reducing intake of saturated fatty acids (SFA) (4), the American Diabetes Association does not clearly emphasize LA as a component of diet quality for diabetes prevention (5). This might be due to the fact that there are no available data from trials designed to investigate diabetes incidence as an outcome. However, prospective observational studies have now accumulated a substantial amount of data on the relation between LA intake or status and diabetes incidence, which helpful for reevaluation of its role for diabetes prevention.

In this issue of Diabetes Care , Mousavi et al. (6) summarize data from such prospective studies. They first systematically identified cohort studies on either dietary intake or tissue biomarkers of LA status and diabetes incidence. This led to nine cohorts on dietary intake, with a total of 22,639 cases of diabetes, and 27 cohorts on LA tissue biomarkers (including a total of 18,458 incident cases). The authors then performed meta-analyses of individual study findings. With regard to dietary intake of LA, results of the meta-analysis suggest an inverse association. This was evident in considering different categories of intake and also from a dose-response analysis, where each additional 5% of energy from LA was associated with a 10% lower risk …
Hybrid material mimics a hypoxic environment to promote regeneration of peripheral nerves
Authors: Qi Quan, Lei Hong, Yu Wang, Rui Li, Xin Yin, Xiaoqing Cheng, Guangbo Liu, He Tang, Haoye Meng, Shuyun Liu, Quanyi Guo, Biqin Lai, Qing Zhao, Min Wei, Jiang Peng, Peifu Tang
Journal: Biomaterials (2021)
Diagnostic accuracy of blood biomarkers for Alzheimer’s disease and amnestic mild cognitive impairment: A meta-analysis
Authors: Ying-Ren Chen, Chih-Sung Liang, Hsin Chu, Joachim Voss, Xiao Linda Kang, Grant O'Connell, Hsiu-Ju Jen, Doresses Liu, Shu-Tai Shen Hsiao, Kuei-Ru Chou
Journal: Ageing Research Reviews (2021)
Use of inhaled corticosteroids and risk of acquiring<i>Pseudomonas aeruginosa</i>in patients with chronic obstructive pulmonary disease
Authors: Josefin Eklöf, Truls Sylvan Ingebrigtsen, Rikke Sørensen, Mohamad Isam Saeed, Imane Achir Alispahic, Pradeesh Sivapalan, Jonas Bredtoft Boel, Jette Bangsborg, Christian Ostergaard, Ram Benny Dessau, Ulrich Stab Jensen, Ejvind Frausing Hansen, Therese Sophie Lapperre, Howraman Meteran, Torgny Wilcke, Niels Seersholm, Jens-Ulrik Stæhr Jensen
Journal: Thorax (2021)

Inhaled corticosteroids (ICS) are commonly used to treat COPD and are associated with increased risk of pneumonia. The aim of this study was to assess if accumulated use of ICS is associated with a dose-dependent risk of a positive airway culture with Pseudomonas aeruginosa in patients with COPD.We conducted a multiregional epidemiological cohort study including Danish COPD patients followed in outpatient clinics during 2010-2017. ICS use was categorised based on accumulated prescriptions redeemed 365 days prior to cohort entry. Cox proportional hazard regression model was used to estimate the risk of acquiring P. aeruginosa. Propensity score matched models were used as sensitivity analyses.A total of 21 408 patients were included in the study, of which 763 (3.6%) acquired P. aeruginosa during follow-up. ICS use was associated with a dose-dependent risk of P. aeruginosa (low ICS dose: HR 1.38, 95% CI 1.03 to 1.84, p=0.03; moderate ICS dose: HR 2.16, 95% CI 1.63 to 2.85, p<0.0001; high ICS dose: HR 3.58, 95% CI 2.75 to 4.65, p<0.0001; reference: no ICS use). A propensity matched model confirmed the results (high ICS dose compared with no/low/moderate ICS dose: HR 2.05, 95% CI 1.76 to 2.39, p p<0.0001).Use of ICS in patients with COPD followed in Danish outpatient clinics was associated with a substantially increased and dose-dependent risk of acquiring P. aeruginosa. Caution should be taken when administering high doses of ICS in severely ill patients with COPD. These results should be confirmed in comparable cohorts and other settings.
27590 Abrocitinib in the treatment of moderate-to-severe atopic dermatitis refractory to dupilumab treatment: An analysis of JADE-EXTEND, a phase 3 long-term extension study
Authors: Vivian Shi, Tina Bhutani, Mette Deleuran, Luz Fonacier, Stephen Shumack, Fan Zhang, Michael C. Cameron, Gary Chan, Hernan Valdez, Natalie Yin
Journal: Journal of the American Academy of Dermatology (2021)
Exosome membrane-modified M2 macrophages targeted nanomedicine: Treatment for allergic asthma
Authors: Weiya Pei, Xueqin Li, Runlei Bi, Xin Zhang, Min Zhong, Hui Yang, Yingying Zhang, Kun Lv
Journal: Journal of Controlled Release (2021)

Exosomes are naturally secreted nanovesicles that have emerged as a promising therapeutic nanodelivery platform due to their specific composition, biological properties, and stability. Modifying synthetic nanoparticles with the intrinsic hallmarks of exosome membrane to create exosome mimetics could lead to safe and efficient smart silencer delivery.The study focuses on exploring the combination of polylactic-co-glycolic acid (PLGA)-based nanoparticles with naturally occurring exosome membrane from M2 macrophages to deliver a Dnmt3aos smart silencer to treat allergic asthma (AA) in mice.Exosome membrane of M2 macrophages and PLGA nanoparticles (PLGA NPs) wrapped with the smart silencer of Dnmt3aos (Dnmt3aossmart silencer) were first synthesized. The resulting exosome membrane coated PLGA@Dnmt3aossmart silencer (EM-PLGA@Dnmt3aossmart silencer) was administered intravenously into Der f1-induced asthma mice, which was followed by the investigation of therapeutic outcomes and the mechanism in vivo.Seven infusions of EM-PLGA@Dnmt3aossmart silencer ameliorated AA with a marked reduction of lung inflammation. After intravenous injection, the EM-PLGA@Dnmt3aossmart silencer was distributed in various organs, including the lungs, with retention over 48 h, and it targeted M2 macrophages. Moreover, the injections of EM-PLGA@Dnmt3aossmart silencer markedly decreased the proportion of M2 macrophages and inflammatory cytokines in the airway. More importantly, the EM-PLGA@Dnmt3aossmart silencer treatment did not obviously suppress the overall immune function of host.To our knowledge, this study provides the first experimental evidence of the ability of EM-PLGA@Dnmt3aossmart silencer to target M2 macrophages in the treatment of AA by combining exosome membrane and biomaterials, thus presenting a novel immunotherapy for the allergic disease.
SPARC-positive macrophages are the superior prognostic factor in the microenvironment of diffuse large B-cell lymphoma and independent of MYC rearrangement and double-/triple-hit status
Authors: G.A. Croci, R.K.H. Au-Yeung, S. Reinke, A.M. Staiger, K. Koch, I. Oschlies, J. Richter, V. Poeschel, G. Held, M. Loeffler, L. Trümper, A. Rosenwald, G. Ott, R. Spang, B. Altmann, M. Ziepert, W. Klapper
Journal: Annals of Oncology (2021)
Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial
Authors: Andrew Blauvelt, Jonathan I. Silverberg, Charles W. Lynde, Thomas Bieber, Samantha Eisman, Jacek Zdybski, Walter Gubelin, Eric L. Simpson, Fernando Valenzuela, Paulo Ricardo Criado, Mark G. Lebwohl, Claire Feeney, Tahira Khan, Pinaki Biswas, Marco DiBonaventura, Hernan Valdez, Michael C. Cameron, Ricardo Rojo
Journal: Journal of the American Academy of Dermatology (2021)
Effects of a large-scale social media advertising campaign on holiday travel and COVID-19 infections: a cluster randomized controlled trial
Authors: Emily Breza, Fatima Cody Stanford, Marcella Alsan, Burak Alsan, Abhijit Banerjee, Arun G. Chandrasekhar, Sarah Eichmeyer, Traci Glushko, Paul Goldsmith-Pinkham, Kelly Holland, Emily Hoppe, Mohit Karnani, Sarah Liegl, Tristan Loisel, Lucy Ogbu-Nwobodo, Benjamin A. Olken, Carlos Torres, Pierre-Luc Vautrey, Erica T. Warner, Susan Wootton, Esther Duflo
Journal: Nature Medicine (2021)

Abstract During the Coronavirus Disease 2019 (COVID-19) epidemic, many health professionals used social media to promote preventative health behaviors. We conducted a randomized controlled trial of the effect of a Facebook advertising campaign consisting of short videos recorded by doctors and nurses to encourage users to stay at home for the Thanksgiving and Christmas holidays ( NCT04644328 and AEARCTR-0006821 ). We randomly assigned counties to high intensity ( n = 410 (386) at Thanksgiving (Christmas)) or low intensity ( n = 410 (381)). The intervention was delivered to a large fraction of Facebook subscribers in 75% and 25% of randomly assigned zip codes in high- and low-intensity counties, respectively. In total, 6,998 (6,716) zip codes were included, and 11,954,109 (23,302,290) users were reached at Thanksgiving (Christmas). The first two primary outcomes were holiday travel and fraction leaving home, both measured using mobile phone location data of Facebook users. Average distance traveled in high-intensity counties decreased by −0.993 percentage points (95% confidence interval (CI): –1.616, −0.371; P = 0.002) for the 3 days before each holiday compared to low-intensity counties. The fraction of people who left home on the holiday was not significantly affected (adjusted difference: 0.030; 95% CI: −0.361, 0.420; P = 0.881). The third primary outcome was COVID-19 infections recorded at the zip code level in the 2-week period starting 5 days after the holiday. Infections declined by 3.5% (adjusted 95% CI: −6.2%, −0.7%; P = 0.013) in intervention compared to control zip codes. Social media messages recorded by health professionals before the winter holidays in the United States led to a significant reduction in holiday travel and subsequent COVID-19 infections.
Health Disparities, Systemic Racism, and Failures of Cultural Competence: Authors’ Response to Commentaries
Authors: Jeffrey Todd Berger, Dana Ribeiro Miller
Journal: The American Journal of Bioethics (2021)

This article refers to:Health Disparities, Systemic Racism, and Failures of Cultural CompetenceCultural Competence as New Racism: Working as Intended?Materializing Systemic Racism, Materializing Health DisparitiesTeaching about Health Disparities: Pedagogy, Curriculum, and Learning TheoryThe Disruptive Power of IntersectionalityTrading Cultural Competency for Trauma Informed CareMaking Culture a Verb: Implications for Health EquityGrounding Medical Education in Health Equity: The Time is NowDisability Cultural Competence for All as a Model
A Phase I Study of LSZ102, an Oral Selective Estrogen Receptor Degrader, with or without Ribociclib or Alpelisib, in Patients with Estrogen Receptor–Positive Breast Cancer
Authors: Komal Jhaveri, Dejan Juric, Yoon-Sim Yap, Sara Cresta, Rachel M. Layman, Francois P. Duhoux, Catherine Terret, Shunji Takahashi, Jens Huober, Nicole Kundamal, Qing Sheng, Alejandro Balbin, Yan Ji, Wei He, Adam Crystal, Serena De Vita, Giuseppe Curigliano
Journal: Clinical Cancer Research (2021)

Data are sparse for oral selective estrogen receptor (ER) degraders (SERD) in cancer treatment. The investigational oral SERD LSZ102 was assessed in monotherapy and combination use in a phase I study.
Characterizing DNA methylation signatures and their potential functional roles in Merkel cell carcinoma
Authors: Hemant Gujar, Arjun Mehta, Hong-Tao Li, Yvonne C. Tsai, Xiangning Qiu, Daniel J. Weisenberger, Miriam Galvonas Jasiulionis, Gino K. In, Gangning Liang
Journal: Genome Medicine (2021)

Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with limited treatment possibilities. Merkel cell tumors display with neuroendocrine features and Merkel cell polyomavirus (MCPyV) infection in the majority (80%) of patients. Although loss of histone H3 lysine 27 trimethylation (H3K27me3) has been shown during MCC tumorigenesis, epigenetic dysregulation has largely been overlooked. We conducted global DNA methylation profiling of clinically annotated MCC primary tumors, metastatic skin tumors, metastatic lymph node tumors, paired normal tissues, and two human MCC cell lines using the Illumina Infinium EPIC DNA methylation BeadArray platform. Significant differential DNA methylation patterns across the genome are revealed between the four tissue types, as well as based on MCPyV status. Furthermore, 964 genes directly regulated by promoter or gene body DNA methylation were identified with high enrichment in neuro-related pathways. Finally, our findings suggest that loss of H3K27me3 occupancy in MCC is attributed to KDM6B and EZHIP overexpression as a consequence of promoter DNA hypomethylation. We have demonstrated specific DNA methylation patterns for primary MCC tumors, metastatic MCCs, and adjacent-normal tissues. We have also identified DNA methylation markers that not only show potential diagnostic or prognostic utility in MCC management, but also correlate with MCC tumorigenesis, MCPyV expression, neuroendocrine features, and H3K27me3 status. The identification of DNA methylation alterations in MCC supports the need for further studies to understand the clinical implications of epigenetic dysregulation and potential therapeutic targets in MCC.
Abstract 8198: Serum Heat Shock Protein 60 Level Predicts Cardiac Events in Chronic Heart Failure Patients with Preserved Left Ventricular Systolic Function
Authors: Takeshi Niizeki, Kazuyoshi Kaneko, Toshiki Sasaki, Koki Omi, Shigeo Sugawara, Isao Kubota
Journal: Circulation (2011)

Background: More than 40% of patients hospitalized with chronic heart failure (CHF) have preserved left ventricular ejection fraction (LVEF) and are at high risk for cardiac events. Heat shock protein 60 (Hsp60) are induced by a variety of stressors including infection, anoxia, oxidative stress, and inflammation and have a protective role against stress-induced cardiomyocyte injury. Recently, it has been reported that Hsp60 exists in the circulation and serum Hsp60 levels are positively associated with serum TNF-α level, interleukin-6 level, and an important proinflammatory cytokines. CHF is characterized by systemic abnormalities and the myocardium is continually exposed to various stressors, such as anoxia, ischemia, inflammation, and free radicals. We have been reported that serum Hsp60 level was related to severity of CHF and associated with a high risk for adverse cardiac events in CHF patients. The purpose of this study was to examine whether Hsp60 is useful to determine the prognosis of CHF patients with preserved LVEF. Methods and Results: Serum Hsp60 level was measured in 141 CHF patients with preserved LVEF and 62 control subjects by the competitive enzyme-linked immunosorbent assay. Patients were prospectively followed with endpoints of cardiac death or re-hospitalization for worsening CHF during a median follow-up period of 786 days. Serum Hsp60 level was increased with advancing NYHA functional class (P &lt; 0.0001). There were 45 cardiac events during follow-up period (31%). Serum Hsp60 level was significantly higher in patients with cardiac events than those in event free patients. Kaplan-Meier analysis clearly demonstrated that the high Hsp60 group had a significantly higher incidence of cardiac events than the low Hsp60 group (P &lt; 0.0001). Patients were divided into 3 groups based upon Hsp60 level, and the highest 3 rd tertile was associated with the highest risk of cardiac events (6.27-fold compared to the 1 st tertile). In the multivariate Cox analysis, Hsp60 level was an independent risk factor for cardiac events (hazard ratio 3.51, 95% confidence interval 1.46-5.01, P = 0.0031). Conclusion: Serum Hsp60 level is an independent and powerful prognostic factor and may be useful for risk stratification of CHF patients with preserved LVEF.
Abstract P193: Prospective Association of Allostatic Load with Incident CVD in American Indians: The Strong Heart Study
Authors: Hao Peng, Fawn Yeh, Shelley A. Cole, Lyle G. Best, Mary J. Roman, Elisa T. Lee, Barbara V. Howard, Jinying Zhao
Journal: Circulation (2016)

Background: Chronic stress increases the risk of CVD. Allostatic load (AL) is a measure of multisystem physiological dysregulation resulting from long-term response to stress. American Indians (AIs) suffer higher rates of chronic stress and CVD, but no study has examined the association of AL with CVD in this high risk population. Objective: To examine whether baseline AL predicts incident CVD in AIs in the Strong Heart Study. Methods: Among 1400 apparently healthy AIs (free of CVD and diabetes at baseline) followed for an average of 7.8 years, we calculated AL score using 10 markers at baseline, including leukocyte telomere length, fasting glucose, total cholesterol, triglycerides, low- and high- density lipoprotein, estimated glomerular filtration rate, body mass index, and systolic and diastolic blood pressure. Each of the 10 markers was categorized as high or low risk according to criteria listed in Table 1. A composite AL score was calculated by summing the number of high-risk markers. CVD events were defined as fatal and nonfatal MI, congestive heart failure, and stroke. The association of baseline AL with incident CVD was examined by Cox proportional hazard model, adjusting for age, sex, study site, socioeconomic status, smoking and drinking at baseline. Results: The mean age at baseline was 55±8 years. Participants with AL scores of 0, 1, 2, 3 and 4+ comprised of 20%, 30%, 28%, 13%, and 9%, respectively, of the study population. A total of 224 participants developed CVD during the follow-up period. Compared to participants with an AL score of 0, those with a score of 1, (HR=1.62 [1.00 - 2.62]), 2 (HR=2.28 [1.42 - 3.66]), 3 (HR=2.25 [1.33 - 3.80]), or 4+ (HR=3.06 [1.77 - 5.30]) had significantly higher risk for developing CVD. Moreover, there was a dose-response relationship between AL and CVD (trend P &lt;0.001). Conclusion: A higher AL score at baseline significantly predicts incident CVD among AIs, independent of sociodemographic and behavioral risk factors. The mechanisms underlying this association warrant further investigation.
TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination
Authors: Garyfallia Gouna, Christian Klose, Mar Bosch-Queralt, Lu Liu, Ozgun Gokce, Martina Schifferer, Ludovico Cantuti-Castelvetri, Mikael Simons
Journal: The Journal of Experimental Medicine (2021)

Upon demyelinating injury, microglia orchestrate a regenerative response that promotes myelin repair, thereby restoring rapid signal propagation and protecting axons from further damage. Whereas the essential phagocytic function of microglia for remyelination is well known, the underlying metabolic pathways required for myelin debris clearance are poorly understood. Here, we show that cholesterol esterification in male mouse microglia/macrophages is a necessary adaptive response to myelin debris uptake and required for the generation of lipid droplets upon demyelinating injury. When lipid droplet biogenesis is defective, innate immune cells do not resolve, and the regenerative response fails. We found that triggering receptor expressed on myeloid cells 2 (TREM2)–deficient mice are unable to adapt to excess cholesterol exposure, form fewer lipid droplets, and build up endoplasmic reticulum (ER) stress. Alleviating ER stress in TREM2-deficient mice restores lipid droplet biogenesis and resolves the innate immune response. Thus, we conclude that TREM2-dependent formation of lipid droplets constitute a protective response required for remyelination to occur.