tbuckley/cabot-search huggingface dataset:
Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases
Authors: Baoyi Guan, Jinlin Tong, Haiping Hao, Zhixu Yang, Keji Chen, Hao Xu, Anlu Wang
Journal: Acta Pharmaceutica Sinica B (2021)

Cardiometabolic disease (CMD), characterized with metabolic disorder triggered cardiovascular events, is a leading cause of death and disability. Metabolic disorders trigger chronic low-grade inflammation, and actually, a new concept of metaflammation has been proposed to define the state of metabolism connected with immunological adaptations. Amongst the continuously increased list of systemic metabolites in regulation of immune system, bile acids (BAs) represent a distinct class of metabolites implicated in the whole process of CMD development because of its multifaceted roles in shaping systemic immunometabolism. BAs can directly modulate the immune system by either boosting or inhibiting inflammatory responses via diverse mechanisms. Moreover, BAs are key determinants in maintaining the dynamic communication between the host and microbiota. Importantly, BAs via targeting Farnesoid X receptor (FXR) and diverse other nuclear receptors play key roles in regulating metabolic homeostasis of lipids, glucose, and amino acids. Moreover, BAs axis per se is susceptible to inflammatory and metabolic intervention, and thereby BAs axis may constitute a reciprocal regulatory loop in metaflammation. We thus propose that BAs axis represents a core coordinator in integrating systemic immunometabolism implicated in the process of CMD. We provide an updated summary and an intensive discussion about how BAs shape both the innate and adaptive immune system, and how BAs axis function as a core coordinator in integrating metabolic disorder to chronic inflammation in conditions of CMD.
Measuring the success of treatments for congenital melanocytic naevi (birthmarks)
Journal: British Journal of Dermatology (2021)

Congenital melanocytic naevi (CMN) are birthmarks that can have a great impact on the lives of patients because of the unusual appearance of CMN and the risk of developing skin cancer (melanoma) or brain and spine problems. Larger CMN (more than 20 cm) are relatively rare and affect one in every 20,000 newborns. At the moment, different studies looking at CMN often measure different outcomes and this makes it difficult to compare studies.
Leptomeningeal disease and brain control after postoperative stereotactic radiosurgery with or without immunotherapy for resected brain metastases
Authors: Giuseppe Minniti, Gaetano Lanzetta, Luca Capone, Martina Giraffa, Ivana Russo, Francesco Cicone, Alessandro Bozzao, Filippo Alongi, Luca Nicosia, Gioia Fineschi, Luca Marchetti, Tommaso Tufo, Federico Bianciardi, Vincenzo Esposito, PierCarlo Gentile, Sergio Paolini
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immunotherapy has shown activity in patients with brain metastases (BM) and leptomeningeal disease (LMD). We have evaluated LMD and intraparenchymal control rates for patients with resected BM receiving postoperative stereotactic radiosurgery (SRS) and immunotherapy or postoperative SRS alone. We hypothesize that postoperative SRS and immunotherapy will result in a lower rate of LMD with acceptable toxicity compared with postoperative SRS.One hundred and twenty-nine patients with non-small-cell lung cancer (NSCLC) and melanoma BM who received postoperative fractionated SRS (fSRS; 3×9 Gy) in combination with immunotherapy or postoperative fSRS alone for completely resected BM were retrospectively evaluated. The primary endpoint of the study was the rate of LMD after treatments. The secondary endpoints were local failure, distant brain parenchymal failure (DBF), overall survival (OS), and treatment-related toxicity.Sixty-three patients received postoperative SRS and immunotherapy, either nivolumab or pembrolizumab, and 66 patients received postoperative SRS alone to the resection cavity. With a median follow-up of 15 months, LMD occurred in 19 patients: fSRS group, 14; fSRS and immunotherapy, 5. The 12-month LMD cumulative rates were 22% (95% CI 14% to 37%) in the fSRS group and 6% (95% CI 2% to 17%) in the combined treatment group (p=0.007). Resection cavity control was similar between the groups, whereas DBF and OS were significantly different; the 1-year DBF rates were 31% (95% CI 20% to 46%) in the fSRS and immunotherapy group and 52% (95% CI 39% to 68%) in the fSRS group; respective OS rates were 78% (95% CI 67% to 88%) and 58.7% (95% CI 47% to 70%). Twenty-two patients undergoing postoperative fSRS and immunotherapy and nine subjected to postoperative fSRS experienced treatment-related imaging changes suggestive of radiation-induced brain necrosis (p=0.02).Postoperative fSRS in combination with immunotherapy decreases the incidence of LMD and DBF in patients with resected BM from NSCLC and melanoma as compared with fSRS alone, reducing the rate of neurological death and prolonging survival.
Updated Results of a Phase 1/2 Clinical Study of Zinc Finger Nuclease-Mediated Editing of <i>BCL11A</i> in Autologous Hematopoietic Stem Cells for Transfusion-Dependent Beta Thalassemia
Authors: Mark C. Walters, Angela R. Smith, Gary J. Schiller, Erica B. Esrick, David A. Williams, Tatiana Gogoleva, Didier Rouy, Bettina M. Cockroft, Gregory M. Vercellotti
Journal: Blood (2021)
88P Clinical outcomes in patients with metastatic (m+) melanoma treated with immune-checkpoint inhibitors (ICI) with or without radiotherapy (RT): A monocentric retrospective study
Authors: M.S. Grimaudo, M.C. Tronconi, D. Baldaccini, A. Solferino, L. Cozzaglio, R. Borroni, L. Mancini, S. Manara, F. Mrakic-Sposta, A. Veronesi, M. Scorsetti, A. Santoro
Journal: Annals of Oncology (2021)
Prior upregulation of interferon pathways in the nasopharynx impacts viral shedding following live attenuated influenza vaccine challenge in children
Authors: André G. Costa-Martins, Karim Mane, Benjamin B. Lindsey, Rodrigo L.T. Ogava, Ícaro Castro, Ya Jankey Jagne, Hadijatou J. Sallah, Edwin P. Armitage, Sheikh Jarju, Bankole Ahadzie, Rebecca Ellis-Watson, John S. Tregoning, Colin D. Bingle, Debby Bogaert, Ed Clarke, Jose Ordovas-Montanes, David Jeffries, Beate Kampmann, Helder I. Nakaya, Thushan I. de Silva
Journal: Cell Reports Medicine (2021)

In children lacking influenza-specific adaptive immunity, upper respiratory tract innate immune responses may influence viral replication and disease outcome. We use trivalent live attenuated influenza vaccine (LAIV) as a surrogate challenge model in children aged 24–59 months to identify pre-infection mucosal transcriptomic signatures associated with subsequent viral shedding. Upregulation of interferon signaling pathways prior to LAIV is significantly associated with lower strain-specific viral loads (VLs) at days 2 and 7. Several interferon-stimulated genes are differentially expressed in children with pre-LAIV asymptomatic respiratory viral infections and negatively correlated with LAIV VLs. Upregulation of genes enriched in macrophages, neutrophils, and eosinophils is associated with lower VLs and found more commonly in children with asymptomatic viral infections. Variability in pre-infection mucosal interferon gene expression in children may impact the course of subsequent influenza infections. This variability may be due to frequent respiratory viral infections, demonstrating the potential importance of mucosal virus-virus interactions in children.
Enhancement of stratum corneum lipid structure improves skin barrier function and protects against irritation in adults with dry, eczema‐prone skin*
Authors: Simon G. Danby, Paul V. Andrew, Linda J. Kay, Abigail Pinnock, John Chittock, Kirsty Brown, Samuel F. Williams, Michael J. Cork
Journal: British Journal of Dermatology (2021)

The skin of patients with atopic dermatitis is characterized by abnormal stratum corneum lipid levels. Consequently, the lamellar matrices are disrupted and skin barrier function is diminished, increasing skin sensitivity to irritants and allergens.To determine whether a cream containing ceramides, triglycerides and cholesterol in a multivesicular emulsion can reinforce the skin barrier and protect against skin irritation.A randomized observer-blind intrapatient-controlled study in 34 adults with dry, eczema-prone skin was conducted. Each participant underwent 4 weeks of treatment with the test cream on one forearm and lower leg and a reference emollient cream on the other. Skin properties were determined before and after treatment. Lipid structure was assessed by Fourier-transform infrared spectroscopy using a novel interface.Skin barrier integrity was greater at sites treated with the test cream [effect size for area under the transepidermal water loss curve -162, 95% confidence interval (CI) -206 to -118]. Skin sensitivity to sodium lauryl sulfate was reduced (-0·5 points visual redness, 97·57% CI -1·00 to -0·25), as was transepidermal water loss (-15·3 g m-2 h-1 , 95% CI -20·3 to -10·4) compared with the reference. Sites treated with the test cream displayed enhanced lipid chain ordering, which was significantly associated with skin barrier integrity (r = 0·61). Compared with the reference, treatment with the test cream increased hydration (8·61 capacitance units, 95% CI 6·61-10·6) and decreased signs of dryness.The test cream facilitates skin barrier restoration and protects the skin from dryness and irritation. Compared with a commonly prescribed emollient in the UK, the test cream is highly suited to the management of dry, sensitive skin.
Accelerated Epigenetic Aging and Incident Atrial Fibrillation: New Outlook on an Immutable Risk Factor?
Authors: Cavin K. Ward-Caviness
Journal: Circulation (2021)

hronological age might be the most common health predictor, but are measures of aging built on molecular changes better predictors of health than chronological age alone?Epigenetics refers to the biological mechanisms that control gene transcription and cellular state without changing the underlying genetic code.Epigenetic aging biomarkers allow researchers to interrogate the aging process from a biological, as opposed to a chronological, perspective and to understand aging-related health risks using epigenetic features such as DNA methylation.Epigenetic aging biomarkers are associated with a range of health outcomes including cancer, obesity, cardiovascular disease, and lung function. 1,2One of the primary goals of research involving all aging biomarkers is to translate chronological age-related risks (which are unmodifiable) into biological aging-related risks that are grounded in biological processes that may be modifiable or even reversible.In this article, 3 the authors seek to translate the unmodifiable risks of chronological age for incident atrial fibrillation (AF) into modifiable risks using DNA methylation age, ie, biological age as estimated by DNA methylation loci, which may be reversible under certain interventions, 4 giving it significant clinical and public health benefits.
Risk factors for musculoskeletal injuries in the military: a qualitative systematic review of the literature from the past two decades and a new prioritizing injury model
Authors: Stefan Sammito, Vedran Hadzic, Thomas Karakolis, Karen R. Kelly, Susan P. Proctor, Ainars Stepens, Graham White, Wes O. Zimmermann
Journal: Military Medical Research (2021)

Abstract Background Musculoskeletal injuries (MSkIs) are a leading cause of health care utilization, as well as limited duty and disability in the US military and other armed forces. MSkIs affect members of the military during initial training, operational training, and deployment and have a direct negative impact on overall troop readiness. Currently, a systematic overview of all risk factors for MSkIs in the military is not available. Methods A systematic literature search was carried out using the PubMed, Ovid/Medline, and Web of Science databases from January 1, 2000 to September 10, 2019. Additionally, a reference list scan was performed (using the “snowball method”). Thereafter, an international, multidisciplinary expert panel scored the level of evidence per risk factor, and a classification of modifiable/non-modifiable was made. Results In total, 176 original papers and 3 meta-analyses were included in the review. A list of 57 reported potential risk factors was formed. For 21 risk factors, the level of evidence was considered moderate or strong. Based on this literature review and an in-depth analysis, the expert panel developed a model to display the most relevant risk factors identified, introducing the idea of the “order of importance” and including concepts that are modifiable/non-modifiable, as well as extrinsic/intrinsic risk factors. Conclusions This is the qualitative systematic review of studies on risk factors for MSkIs in the military that has attempted to be all-inclusive. A total of 57 different potential risk factors were identified, and a new, prioritizing injury model was developed. This model may help us to understand risk factors that can be addressed, and in which order they should be prioritized when planning intervention strategies within military groups.
Restoring an adequate dietary fiber intake by inulin supplementation: a pilot study showing an impact on gut microbiota and sociability in alcohol use disorder patients
Authors: Camille Amadieu, Valentin Coste, Audrey M. Neyrinck, Victoria Thijssen, Quentin Leyrolle, Laure B. Bindels, Hubert Piessevaux, Peter Stärkel, Philippe de Timary, Nathalie M. Delzenne, Sophie Leclercq
Journal: Gut Microbes (2021)

Alcohol use disorder (AUD) is a chronic relapsing disease associated with malnutrition, metabolic disturbances, and gut microbiota alterations that are correlated with the severity of psychological symptoms. This study aims at supplementing AUD patients with prebiotic fiber during alcohol withdrawal, in order to modulate the gut microbiota composition and to evaluate its effect on gastrointestinal tolerance, metabolism, and patient's behavior. A randomized, double-blind, placebo-controlled study included 50 AUD patients assigned to inulin versus maltodextrin daily supplementation for 17 days. Biological measurements (fecal microbial 16S rDNA sequencing, serum biology), dietary intake, validated psychological questionnaires, and gastrointestinal tolerance assessment were performed before and after the intervention. Inulin significantly decreased the richness and evenness and induced changes of 8 genera (q < 0.1) including Bifidobacterium and Bacteroides. Prebiotic had minor effects on gastrointestinal symptoms and nutritional intakes compared to placebo. All patients showed an improvement in depression, anxiety, and craving scores during alcohol withdrawal regardless of the intervention group. Interestingly, only patients treated with inulin significantly improved the sociability score and had an increased serum level of brain-derived neurotrophic factor. This pilot study shows that inulin is well tolerated and modulates the gut microbiota and the social behavior in AUD patients, without further improving other psychological and biological parameters as compared to placebo. Gut2Brain study, clinicaltrial.gov: NCT03803709, https://clinicaltrials.gov/ct2/show/NCT03803709
Radical Prostatectomy Without Prior Biopsy Following Multiparametric Magnetic Resonance Imaging and Prostate-specific Membrane Antigen Positron Emission Tomography
Authors: Valentin H. Meissner, Isabel Rauscher, Kristina Schwamborn, Jan Neumann, Gregor Miller, Wolfgang Weber, Jürgen E. Gschwend, Matthias Eiber, Matthias M. Heck
Journal: European Urology (2021)
Radiomics for the noninvasive prediction of the BRAF mutation status in patients with melanoma brain metastases
Authors: Anna-Katharina Meißner, Robin Gutsche, Norbert Galldiks, Martin Kocher, Stephanie T Jünger, Marie-Lisa Eich, Manuel Montesinos-Rongen, Anna Brunn, Martina Deckert, Christina Wendl, Wolfgang Dietmaier, Roland Goldbrunner, Maximilian I Ruge, Cornelia Mauch, Nils-Ole Schmidt, Martin Proescholdt, Stefan Grau, Philipp Lohmann
Journal: Neuro-Oncology (2021)

Abstract Background The BRAF V600E mutation is present in approximately 50% of patients with melanoma brain metastases and an important prerequisite for response to targeted therapies, particularly BRAF inhibitors. As heterogeneity in terms of BRAF mutation status may occur in melanoma patients, a wild-type extracranial primary tumor does not necessarily rule out a targetable mutation in brain metastases using BRAF inhibitors. We evaluated the potential of MRI radiomics for a noninvasive prediction of the intracranial BRAF mutation status. Methods Fifty-nine patients with melanoma brain metastases from two university brain tumor centers (group 1, 45 patients; group 2, 14 patients) underwent tumor resection with subsequent genetic analysis of the intracranial BRAF mutation status. Preoperative contrast-enhanced MRI was manually segmented and analyzed. Group 1 was used for model training and validation, group 2 for model testing. After radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. Finally, the best performing radiomics model was applied to the test data. Diagnostic performances were evaluated using receiver operating characteristic (ROC) analyses. Results Twenty-two of 45 patients (49%) in group 1, and 8 of 14 patients (57%) in group 2 had an intracranial BRAF V600E mutation. A linear support vector machine classifier using a six-parameter radiomics signature yielded an area under the ROC curve of 0.92 (sensitivity, 83%; specificity, 88%) in the test data. Conclusions The developed radiomics classifier allows a noninvasive prediction of the intracranial BRAF V600E mutation status in patients with melanoma brain metastases with high diagnostic performance.
Cross-reactive adaptive immunity against coronaviruses in young children
Journal: Nature Immunology (2021)

briefing Cross-reactive adaptive immunity against coronaviruses in young childrenCoronavirus-specific antibody and T cell responses were characterized in young children who had been naturally infected with SARS-CoV-2.Immune responses were focused against the spike protein, strong and stable in magnitude, and showed notable cross-reactivity with other human coronaviruses.
Disparities in Reporting a History of Cardiovascular Disease Among Adults With Limited English Proficiency and Angina
Authors: Brandon M. Herbert, Amber E. Johnson, Michael K. Paasche-Orlow, Maria M. Brooks, Jared W. Magnani
Journal: JAMA Network Open (2021)

Individuals with limited English proficiency (LEP) may be unaware of underlying cardiovascular disease (CVD) owing to a lack of diagnostic testing or poor communication with health care practitioners.To evaluate whether participants with anginal symptoms and LEP would be less likely to report a history of CVD compared with those without LEP.This population-based cross-sectional study combined data from 5 National Health and Nutrition Examination Survey (NHANES) cycles conducted from 2007 to 2016. Each cycle includes an interview that collects demographic, dietary, and health-related data as well as a medical examination component in which physiological measurements are taken. All NHANES participants aged 40 years or older who took the Rose questionnaire were included. Data were analyzed from September 2020 to April 2021.LEP was defined as a participant receiving the survey in a non-English language or by interpreter.The 7-item Rose questionnaire assessed the presence of anginal symptoms. Self-reported CVD was defined as history of heart failure, coronary heart disease, angina pectoris, or myocardial infarction. The association between LEP status and self-reported CVD among those with anginal symptoms was determined in multivariable-adjusted models. All analyses were weighted per NHANES analytic protocols.Among 19 320 participants (mean [SD] age, 57.8 [11.8] years; 9344 [47.2%] male; 4145 [10.6%] Black; 2743 [6.3%] Mexican American; 2111 [4.6%] other Hispanic; 8386 [71.6%] White; and 1935 [6.9%] other race), 583 (3.0%) reported anginal symptoms. Of these, most were non-LEP (484 [96.1%]), women (344 [62.1%]), White (251 [66.8%]), and did not report having CVD (347 [62.8%]). Among those with angina, 73 of 99 respondents with LEP (79.0%) reported not having a history of CVD, compared with 274 of 484 without LEP (61.4%; P = .002). Participants with LEP had 2.8-fold higher odds of not reporting a history of CVD compared with participants without LEP (odds ratio, 2.77; 95% CI, 1.38-5.55; P = .005).Among NHANES participants reporting anginal symptoms, participants with LEP were more likely not to report having CVD. This discrepancy may be because of higher rates of undiagnosed CVD or lower awareness of such diagnoses among individuals with LEP. Our findings highlight the relevance of communication strategies for individuals with LEP to provide effective intervention and treatment for CVD prevention.
Abstract 13811: Cognitive and Psychological Outcomes of Patients 6 Months After Cardiac Arrest or Intensive Care Stay
Authors: Matthew R Potter, Marco Mion, Eleni A Nikolopoulou, Neil Magee, Kelly Farrell, Jean Davis, Daryl Perilla, Ellie Gudde, John R Davies, Thomas R Keeble
Journal: Circulation (2021)

Background: The neuropsychological and cognitive consequences of an ICU stay can cause a large burden on many patients. In this study, we assessed the outcomes of a group of patients attending a newly set up, multi-disciplinary outpatient clinic focused on assessing neuropsychological and cognitive outcomes following a significant (&gt;72 hours) ICU stay, and compared patients whose ICU was post-OHCA (out of hospital cardiac arrest), and those non-OHCA. Methods: Between 2016 and 2019, 152 patients were assessed within the Care after REsuscitation (CARE) / ICU follow up clinic, 6 months following hospital discharge, using the SF-36, HADS, PTSS-14 and MoCA. The OHCA group were compared to other non-OHCA, ICU patients (&gt;72 hour stay). Results: No significant differences (p&lt;0.05) were found between the groups outcomes, however we found that 6 months post-discharge, the non-OHCA group experience significantly more pain, are older, and required a longer length of stay (p&lt;0.05). However, we found compared to normative data of the SF-36, over half of the OHCA group (on 6 out of the 8 subscales) and the non-OHCA (on 7 out of the 8) were below population norms, especially Role-Physical (66.7% OHCA and 71.6% non-OHCA) and Energy/ fatigue (66.7% OHCA and 61.4% non-OHCA). Anxiety was observed in 33.3% of the OHCA group, and 35.2% of the non-OHCA group had an abnormal total HADS score. PTSD was seen in 12.7% of the OHCA group and 10.2% of the non-OHCA group. Cognitive impairment was observed in 61.9% of OHCA and 59.1% of non-OHCA patients. Age and hospital length of stay had no significant effect on outcomes on our OHCA population, however females had significantly worse health related quality of life (HRQoL) on 6 out of the 8 subscales (p&lt;0.05). Conclusion: Despite the OHCA and non-OHCA groups having no significant difference between their outcomes, there is a great disease burden upon many individuals following ICU stay, with many experiencing poor HRQoL, mood disorders, PTSD and cognitive impairment. The factors contributing to poor outcome following both ICU related illness and cardiac arrest should be further studied. The creation and validation of new assessment tools is imperative to ensure we fully appreciate the extent of the morbidity in this group to improve care for all ICU patients.