Developing sensor materials for screening intestinal diseases

Intestinal diseases have always been the focus of clinicians and scientific researchers, which have high mortality and morbidity rates, and bring huge encumbrance on the public medical system and economy worldwide. In the progression of many intestinal diseases, early diagnosis and intervention are valuable. Fortunately, the emergence of sensor materials can effectively assist clinical early diagnosis and health monitoring. By accurately locating the lesion and sensitively analyzing the level of disease markers, these sensor materials can help to precisely diagnose the stage and state of lesions, thereby avoiding delaying the treatment. In this review, we provide a comprehensive and in-depth knowledge into diagnosing and monitoring intestinal diseases with the assistance of sensor materials, particularly emphasizing the design and application of them in bioimaging and biodetection. This review is dedicated to conveying the practical applications of sensor materials in the intestine, a critical analysis of their mechanisms and applications, and discussion of their future roles in medicine. We believe that this review would promote the multidisciplinary communication between material science, medicine, and the relevant engineering fields, thus improving the clinical translation of sensor materials

A Mixture of Pure, Isolated Polyphenols Worsens the Insulin Resistance and Induces Kidney and Liver Fibrosis Markers in Diet-Induced Obese Mice

Obesity is a worldwide epidemic with severe metabolic consequences. Polyphenols are secondary metabolites in plants and the most abundant dietary antioxidants, which possess a wide range of health effects. The most relevant food sources are fruit and vegetables, red wine, black and green tea, coffee, virgin olive oil, and chocolate, as well as nuts, seeds, herbs, and spices. The aim of this work was to evaluate the ability of a pure, isolated polyphenol supplementation to counteract the pernicious metabolic effects of a high-fat diet (HFD). Our results indicated that the administration of pure, isolated polyphenols under HFD conditions for 26 weeks worsened the glucose metabolism in diet-induced obese mice. The data showed that the main target organ for these undesirable effects were the kidneys, where we observed fibrotic, oxidative, and kidney-disease markers. This work led us to conclude that the administration of pure polyphenols as a food supplement would not be advisable. Instead, the ingestion of complete “whole” foods would be the best way to get the health effects of bioactive compounds such as polyphenols.

Estimation of the journal distance of Genomics & Informatics from other bioinformatics journals, 2003-2018

This study explored the trends of Genomics & Informatics during the period of 2003-2018 in comparison with 11 other scholarly journals: BMC Bioinformatics, Algorithms for Molecular Biology: AMB, BMC Systems Biology, Journal of Computational Biology, Briefings in Bioinformatics, BMC Genomics, Nucleic Acids Research, American Journal of Human Genetics, Oncogenesis, Disease Markers, and Microarrays. In total, 22,423 research articles were reviewed. Content analysis was the main method employed in the current research. The results were interpreted using descriptive analysis, a clustering analysis, word embedding, and deep learning techniques. Trends are discussed for the 12 journals, both individually and collectively. This is an extension of our previous study (PMCID: PMC6808643).

Differences Between Anticoagulated Patients With Ischemic Stroke Versus Intracerebral Hemorrhage

Background Data on the relative contribution of clinical and neuroimaging risk factors to acute ischemic stroke (AIS) versus intracerebral hemorrhage (ICH) occurring on oral anticoagulant treatment are scarce. Methods and Results Cross‐sectional study was done on consecutive oral anticoagulant–treated patients presenting with AIS, transient ischemic attack (TIA), or ICH from the prospective observational NOACISP (Novel‐Oral‐Anticoagulants‐In‐Stroke‐Patients)‐Acute registry. We compared clinical and neuroimaging characteristics (small vessel disease markers and atherosclerosis) in ICH versus AIS/TIA (reference) using logistic regression. Among 734 patients presenting with stroke on oral anticoagulant treatment (404 [55%] direct oral anticoagulants, 330 [45%] vitamin K antagonists), 605 patients (82%) had AIS/TIA and 129 (18%) had ICH. Prior AIS/TIA, coronary artery disease, dyslipidemia, and worse renal function were associated with AIS/TIA (adjusted odds ratio [aOR] [95% CI] 0.51 [0.32–0.82], 0.48 [0.26–0.86], 0.55 [0.34–0.89], and 0.82 [0.75–0.90] per 10 mL/min). Prior ICH, older age, higher admission blood pressure, and statin treatment were associated with ICH (aOR [95% CI] 6.33 [2.87–14.04], 1.37 [1.04–1.81] per 10 years, 1.19 [1.10–1.29] per 10 mm Hg, and 1.81 [1.09–3.03]). Cerebral microbleeds and moderate‐to‐severe white matter hyperintensities contributed more to ICH (aOR [95% CI] 2.77 [1.34–6.18], and 2.62 [1.28–5.63]). Aortic arch, common and internal carotid artery atherosclerosis, and internal carotid artery stenosis ≥50% contributed more to AIS/TIA (aOR [95% CI] 0.54 [0.31–0.90], 0.29 [0.05–0.97], 0.48 [0.30–0.76], and 0.32 [0.13–0.67]). Conclusions In patients presenting with stroke on oral anticoagulant, AIS/TIA was 5 times more common than ICH. A high atherosclerotic burden (indicated by cardiovascular comorbidities and extracranial atherosclerosis) and prior AIS/TIA contributed more to AIS/TIA, while small vessel disease markers and prior ICH were stronger determinants for ICH. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02353585.

Pre-operative Cerebral Small Vessel Disease on MR Imaging Is Associated With Cerebral Hyperperfusion After Carotid Endarterectomy

Objectives: To determine whether pre-operative cerebral small vessel disease is associated with cerebral hyperperfusion (CH) after carotid endarterectomy (CEA).Methods: Seventy-seven patients (mean age of 66 years and 58% male) undergoing CEA for carotid stenosis were investigated using brain MRI before and after surgery. CH was defined as an increase in cerebral blood flow > 100% compared with pre-operative values on arterial spin labeling MR images. The grade or the number of four cerebral small vessel disease markers (white matter hyperintensities, lacunes, perivascular spaces, and cerebral microbleeds) were evaluated based on pre-operative MRI. Cerebral small vessel disease markers were correlated with CH by using multivariate logistic regression analysis. The cutoff values of cerebral small vessel disease markers for predicting CH were assessed by receiver-operating characteristic curve analysis.Results: CH after CEA was observed in 16 patients (20.78%). Logistic regression analysis revealed that white matter hyperintensities (OR 3.09, 95% CI 1.72–5.54; p < 0.001) and lacunes (OR 1.37, 95% CI 1.06–1.76; p = 0.014) were independently associated with post-operative CH. Receiver-operating characteristic curve analysis showed that Fazekas score of white matter hyperintensities ≥3 points [area under the curve (AUC) = 0.84, sensitivity = 81.3%, specificity = 73.8%, positive predictive value (PPV) = 44.8% and negative predictive value (NPV) = 93.8%] and number of lacunes ≥ 2 (AUC = 0.73, sensitivity = 68.8%, specificity = 78.7%, PPV = 45.8% and NPV = 90.6%) were the optimal cutoff values for predicting CH.Conclusion: In patients with carotid stenosis, white matter hyperintensities and lacunes adversely affect CH after CEA. Based on the NPVs, pre-operative MR imaging can help identify patients who are not at risk of CH.

Immune Profiles of Myeloma Tumor Microenvironment May Predict Sensitivity or Resistance to Elotuzumab

Background: Elotuzumab (ELO), an immunobiologic therapy targeting SLAMF7/CD319, is effective in the treatment of multiple myeloma (MM) with clinical indications in relapsed/refractory disease in combination with lenalidomide or pomalidomide. ELO binds SLAMF7 on the surface of MM cells to increase immune recognition while also binding SLAMF7 on NK cells resulting in the activation of an effector cell population capable of readily killing via antibody-dependent cellular cytotoxicity (ADCC) mechanisms. ELO efficacy has also been linked to enhanced antibody-dependent cellular phagocytosis (ADCP). Given the dependence of ELO activity on immune elements of the tumor microenvironment (TME), we hypothesized that characterization of the immunologic constituents of the immune TME (iTME) would provide cues capable of predicting clinical efficacy. Methods: Nineteen patients were enrolled on a single-center clinical trial run at Moffitt Cancer Center comparing clinical activity of ELO in combination with low-dose (10mg) vs high-dose (25mg) lenalidomide and dexamethasone in patients with biochemical relapse while on lenalidomide maintenance after first line therapy. Bone marrow aspirate (BMA) and peripheral blood (PB) samples we collected at baseline, after completion of 2 treatment cycles, and at time of progression. Cells isolated from the BMA were analyzed by multiparameter flow cytometry (MPFC) using 4 panels; 3 panels characterized lymphocytes according to maturation, activation and polarization (T H1, T H2, T H17 or T Reg) and a 4 th panel characterized myeloid elements. Data was acquired on a BD Symphony cytometer and analysis was performed using FlowJo software. Results: Patient samples were categorized according to initial therapeutic response. Responders (n=6) achieved >PR at best response, Progressors (n=5) were identified as patients whose disease markers increased >25% and Stable Disease (n=8) was identified as demonstrating <25% change in serologic disease markers. Here, we present a comparison of phenotypic profiles from the BM samples acquired at baseline before treatment initiation from patients classified as Responders or Progressors (patients demonstrating stable disease as best response were analyzed separately). Sample analysis by MPFC revealed distinct populations uniquely associated with responses as well as with treatment refractoriness. Principal component analysis (PCA) of the myeloid immune compartment shows 2 clusters representing distinct populations detectable only in Responders, while another large cluster, also expressing a granulocytic phenotype consistent with granulocytic myeloid suppressor cells, is prevalent in the Progressor patients but nearly absent from Responder patients, as might be predicted. Similarly, PCA identified monocyte/macrophage clusters uniquely associated with Responder or Progressor samples. Evaluation of lymphoid populations using 3 lymphoid panels also reveals distinctive clustering patters by PCA highlighting populations differentially associated with Responder or Progressor samples. Notably, while NK cells are present in all patient samples, there is a population of immature NK cells enriched in Responder patients that is largely absent from the Progressor population. Conclusion: Immune profiling of the myeloid and lymphoid components of the baseline BM iTME in MM prior to treatment with ELO reveals distinct patterns of cellular constitution associated with responsiveness or refractoriness to subsequent treatment. While NK cells are known to be important to the ELO mechanism of action, our data suggests that ELO activity is compromised in the absence of immature NK cells. This work suggests that measurable characteristics of the cellular components of the iTME may provide important cues to help predict ELO therapeutic efficacy. These observations will need to be confirmed in a larger data set. Disclosures Shain: Amgen Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi Genzyme: Consultancy, Speakers Bureau; Adaptive Biotechnologies Corporation: Consultancy, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithLine, LLC: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen oncology: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm Therapeutics Inc.: Honoraria, Research Funding. Baz: BMS, sanofi, Karyopharm, Janssen, AbbVie: Consultancy, Research Funding; Oncopeptides: Consultancy; GlaxoSmithKline: Consultancy, Honoraria; Merck: Research Funding. Nishihori: Novartis: Research Funding; Karyopharm: Research Funding.

Rehabilitation and In-Hospital Mortality in COVID-19 patients

Background COVID-19 guidelines endorse early rehabilitation to improve outcomes in hospitalized patients, but the evidence-base to support this recommendation is lacking. We examined the association between early rehabilitation and in-hospital deaths in COVID-19 patients. Methods Single center retrospective study involving 990 COVID-19 patients (42·4% women, mean age 67.8 years) admitted between March 1, 2020 and May 31, 2020 to a community hospital. Association of rehabilitation during hospitalization with in-hospital mortality was examined using logistic regression analysis adjusted for demographics, length of stay, body mass index, comorbid illnesses, functional status as well as for COVID-19 presentations, treatments, and complications. Results Over the 3-month study period, 475 (48·0%) in-patients were referred for rehabilitation. Patients who received rehabilitation were older (73·7 ± 14·0 vs. 62·3 ± 17·2). There were 61 hospital deaths (12·8%) in the rehabilitation group and 165 (32·0%) in the non-rehabilitation group. Receiving rehabilitation was associated with an 89% lower in-hospital mortality (OR 0·11, 95% CI 0·06–0·19) after adjusting for multiple confounders and COVID-19 disease markers. In sensitivity analyses, the results were significant in sub-populations defined by age group, sex, race, length of hospitalization, or pulmonary presentations. Each additional rehabilitation session was associated with a 29% lower risk of in-hospital mortality (OR per session 0·71, 95% CI 0·64-0·79) in the fully adjusted model. Conclusion Among hospitalized COVID-19 patients, receiving early rehabilitation was associated with lower in-hospital mortality. Our findings support implementation of rehabilitation services for COVID-19 patients in acute care settings, but further research from randomized clinical trials is needed.

Glycation and Glycosylation in Cardiovascular Remodeling: Focus on Advanced Glycation End Products and O-Linked Glycosylations as Glucose-Related Pathogenetic Factors and Disease Markers

Glycation and glycosylation are non-enzymatic and enzymatic reactions, respectively, of glucose, glucose metabolites, and other reducing sugars with different substrates, such as proteins, lipids, and nucleic acids. Increased availability of glucose is a recognized risk factor for the onset and progression of diabetes-mellitus-associated disorders, among which cardiovascular diseases have a great impact on patient mortality. Both advanced glycation end products, the result of non-enzymatic glycation of substrates, and O-linked-N-Acetylglucosaminylation, a glycosylation reaction that is controlled by O-N-AcetylGlucosamine (GlcNAc) transferase (OGT) and O-GlcNAcase (OGA), have been shown to play a role in cardiovascular remodeling. In this review, we aim (1) to summarize the most recent data regarding the role of glycation and O-linked-N-Acetylglucosaminylation as glucose-related pathogenetic factors and disease markers in cardiovascular remodeling, and (2) to discuss potential common mechanisms linking these pathways to the dysregulation and/or loss of function of different biomolecules involved in this field.