Miracle-dz/UniFAR-FTUs huggingface dataset:
αv-Class integrin binding to fibronectin is solely mediated by RGD and unaffected by an RGE mutation

Fibronectin–integrin interactions through the Arg-Gly-Asp cell binding motif play crucial roles in cellular functions. Benito-Jardón and colleagues, using force spectroscopy and mouse genetics, show that neither α5β1 nor αv-class integrins bind to RGD-deficient fibronectin and that αv-class integrins retain normal binding to a mutated RGE motif.
The Role of the Microbiome in Oral Squamous Cell Carcinoma with Insight into the Microbiome–Treatment Axis

Oral squamous cell carcinoma (OSCC) is one of the leading presentations of head and neck cancer (HNC). The first part of this review will describe the highlights of the oral microbiome in health and normal development while demonstrating how both the oral and gut microbiome can map OSCC development, progression, treatment and the potential side effects associated with its management. We then scope the dynamics of the various microorganisms of the oral cavity, including bacteria, mycoplasma, fungi, archaea and viruses, and describe the characteristic roles they may play in OSCC development. We also highlight how the human immunodeficiency viruses (HIV) may impinge on the host microbiome and increase the burden of oral premalignant lesions and OSCC in patients with HIV. Finally, we summarise current insights into the microbiome–treatment axis pertaining to OSCC, and show how the microbiome is affected by radiotherapy, chemotherapy, immunotherapy and also how these therapies are affected by the state of the microbiome, potentially determining the success or failure of some of these treatments.
Diagnosing colorectal cancer in primary care: cohort study in Sweden of qualitative faecal immunochemical tests, haemoglobin levels, and platelet counts

Background Colorectal cancer (CRC) diagnostics are challenging in primary care and reliable diagnostic aids are desired. Qualitative faecal immunochemical tests (FITs) have been used for suspected CRC in Sweden since the mid-2000s, but evidence regarding their effectiveness is scarce. Anaemia and thrombocytosis are both associated with CRC. Aim To evaluate the usefulness of qualitative FITs requested for symptomatic patients in primary care, alone and combined with findings of anaemia and thrombocytosis, in the diagnosis of CRC. Design and setting A population-based cohort study using electronic health records and data from the Swedish Cancer Register, covering five Swedish regions. Method Patients aged ≥18 years in the five regions who had provided FITs requested by primary care practitioners from 1 January 2015 to 31 December 2015 were identified. FIT and blood-count data were registered and all CRC diagnoses made within 2 years were retrieved. Diagnostic measurements were calculated. Results In total, 15 789 patients provided FITs (four different brands); of these patients, 304 were later diagnosed with CRC. Haemoglobin levels were available for 13 863 patients, and platelet counts for 10 973 patients. Calculated for the different FIT brands only, the sensitivities for CRC were 81.6%–100%; specificities 65.7%–79.5%; positive predictive values 4.7%–8.1%; and negative predictive values 99.5%–100%. Calculated for the finding of either a positive FIT or anaemia, the sensitivities increased to 88.9–100%. Adding thrombocytosis did not further increase the diagnostic performance. Conclusion Qualitative FITs requested in primary care seem to be useful as rule-in tests for referral when CRC is suspected. A negative FIT and no anaemia indicate a low risk of CRC.
Single-Cell Transcriptome Analysis Highlights a Role for Neutrophils and Inflammatory Macrophages in the Pathogenesis of Severe COVID-19

Cumulative data link cytokine storms with coronavirus disease 2019 (COVID-19) severity. The precise identification of immune cell subsets in bronchoalveolar lavage (BAL) and their correlation with COVID-19 disease severity are currently being unraveled. Herein, we employed iterative clustering and guide-gene selection 2 (ICGS2) as well as uniform manifold approximation and projection (UMAP) dimensionality reduction computational algorithms to decipher the complex immune and cellular composition of BAL, using publicly available datasets from a total of 68,873 single cells derived from two healthy subjects, three patients with mild COVID-19, and five patients with severe COVID-19. Our analysis revealed the presence of neutrophils and macrophage cluster-1 as a hallmark of severe COVID-19. Among the identified gene signatures, IFITM2, IFITM1, H3F3B, SAT1, and S100A8 gene signatures were highly associated with neutrophils, while CCL8, CCL3, CCL2, KLF6, and SPP1 were associated with macrophage cluster-1 in severe-COVID-19 patients. Interestingly, although macrophages were also present in healthy subjects and patients with mild COVID-19, they had different gene signatures, indicative of interstitial and cluster-0 macrophage (i.e., FABP4, APOC1, APOE, C1QB, and NURP1). Additionally, MALAT1, NEAT1, and SNGH25 were downregulated in patients with mild and severe COVID-19. Interferon signaling, FCγ receptor-mediated phagocytosis, IL17, and Tec kinase canonical pathways were enriched in patients with severe COVID-19, while PD-1 and PDL-1 pathways were suppressed. A number of upstream regulators (IFNG, PRL, TLR7, PRL, TGM2, TLR9, IL1B, TNF, NFkB, IL1A, STAT3, CCL5, and others) were also enriched in BAL cells from severe COVID-19-affected patients compared to those from patients with mild COVID-19. Further analyses revealed genes associated with the inflammatory response and chemotaxis of myeloid cells, phagocytes, and granulocytes, among the top activated functional categories in BAL from severe COVID-19-affected patients. Transcriptome data from another cohort of COVID-19-derived peripheral blood mononuclear cells (PBMCs) revealed the presence of several genes common to those found in BAL from patients with severe and mild COVID-19 (IFI27, IFITM3, IFI6, IFIT3, MX1, IFIT1, OASL, IFI30, OAS1) or to those seen only in BAL from severe-COVID-19 patients (S100A8, IFI44, IFI44L, CXCL8, CCR1, PLSCR1, EPSTI1, FPR1, OAS2, OAS3, IL1RN, TYMP, BCL2A1). Taken together, our data reveal the presence of neutrophils and macrophage cluster-1 as the main immune cell subsets associated with severe COVID-19 and identify their inflammatory and chemotactic gene signatures, also partially reflected systemically in the circulation, for possible diagnostic and therapeutic interventions.
Limited Diagnostic Utility of Chromogranin A Measurements in Workup of Neuroendocrine Tumors

Background: Plasma chromogranin A (CgA) is related to tumor burden and recommended in the follow-up of patients diagnosed with neuroendocrine tumors (NETs). The use of CgA in the workup of a suspected NET is more questionable. Objective: To assess the positive predictive value (PPV) of CgA plasma concentrations above the upper reference limit (URL) in patients with suspected NET. Method: Patients referred to the NET Centre, Rigshospitalet, Copenhagen from 2015 to 2019 with clinically suspected NET were included if a CgA measurement was performed prior to referral. The utility of CgA was assessed by comparing pre-referral CgA concentrations to the outcome of a thorough workup. In 47 selected cases with continuously unexplained elevated CgA concentrations, a processing-independent analysis (PIA) for CgA was performed. Results: A total of 197 patients were included. NET was ultimately diagnosed in 25 patients. CgA plasma concentrations were above the URL (elevated) in 19/25 patients diagnosed with NET. In total, 167/197 had elevated CgA concentrations at referral. The positive predictive value (PPV) of elevated CgA concentration was 11% (19/167). Proton pump inhibitor (PPI) treatment was identified as the possible cause of CgA elevation in 55/148 patients with falsely elevated CgA. CgA concentration was normal in 28/47 patients when using PIA. Conclusion: Our data do not support using measurement of CgA for screening when NET is suspected since the PPV was rather low. PPI treatment is a common cause of increased CgA concentrations and should always be discontinued before CgA measurement. PIA of CgA could be a way of excluding NET when suspicion is based primarily on elevated CgA.
An Efficient ECG Classification System Using Resource-Saving Architecture and Random Forest

This paper presents a resource-saving system to extract a few important features of electrocardiogram (ECG) signals. In addition, real-time classifiers are proposed as well to classify different types of arrhythmias via these features. The proposed feature extraction system is based on two delta-sigma modulators adopting 250 Hz sampling rate and three wave detection algorithms to analyze outputs of the modulators. It extracts essential details of each heartbeat, and the details are encoded into 68 bits data that is only 1.48% of the other comparable methods. To evaluate our classification, we use a novel patient-specific training protocol in conjunction with the MIT-BIH database and the recommendation of the AAMI to train the classifiers. The classifiers are random forests that are designed to recognize two major types of arrhythmias. They are supraventricular ectopic beats (SVEB) and ventricular ectopic beats (VEB). The performance of the arrhythmia classification reaches to the F1 scores of 81.05% for SVEB and 97.07% for VEB, which are also comparable to the state-of-the-art methods. The method provides a reliable and accurate approach to analyze ECG signals. Additionally, it also possesses time-efficient, low-complexity, and low-memory-usage advantages. Benefiting from these advantages, the method can be applied to practical ECG applications, especially wearable healthcare devices and implanted medical devices, for wave detection and arrhythmia classification.
Treatment Experiences in Adults Born With Cleft Lip and/or Palate: A Whole of Life Survey in the United Kingdom

Objectives: Adults with cleft lip and/or palate (CL/P) may report dissatisfaction with aesthetic and/or functional outcomes and express desire for further treatment. Although medical intervention can improve quality of life, surgical procedures require complex decision-making and can invoke psychological distress. The aim of this study was to gain a better understanding of ongoing treatment-related support needs by examining self-reported treatment experiences of a sample of adults born with CL/P. Design: An online, mixed-methods survey was designed by the Cleft Lip and Palate Association in collaboration with the Centre for Appearance Research at the University of the West of England. A total of 207 eligible responses were received. Qualitative data were analyzed using inductive content analysis, while quantitative data were analyzed using descriptive statistics. Results: Although participants were satisfied with surgical and dental/orthodontic outcomes overall, many reported ongoing difficulties. Some stated they would seek further treatment while others felt conflicted about risks and benefits. Some had refused treatment, citing treatment fatigue, anxiety, and/or concerns that treatment would be unsuccessful. More than 40% of participants were unaware of their entitlement to cleft-related treatment provided by the National Health Service, and many others had experienced difficulties accessing care. Conclusions: Although advances in health care may offer opportunities for adults to improve their quality of life, treatment decisions should be weighed with the support of a clinical psychologist where available. Guidance for young adults considering future treatment is also recommended. Finally, training and resources for local practitioners may improve general awareness of CL/P services and increase access to specialist care for adults with ongoing CL/P-related concerns.
The horse as a natural model to study reproductive aging-induced aneuploidy and weakened centromeric cohesion in oocytes

Aneuploidy of meiotic origin is a major contributor to age-related subfertility and an increased risk of miscarriage in women. Although age-related aneuploidy has been studied in rodents, the mare may be a more appropriate animal model to study reproductive aging. Similar to women, aged mares show reduced fertility and an increased incidence of early pregnancy loss; however, it is not known whether aging predisposes to aneuploidy in equine oocytes. We evaluated the effect of advanced mare age on (1) gene expression for cohesin components, (2) incidence of aneuploidy and (3) chromosome centromere cohesion (measured as the distance between sister kinetochores) in oocytes matured in vitro. Oocytes from aged mares showed reduced gene expression for the centromere cohesion stabilizing protein, Shugoshin 1. Moreover, in vitro matured oocytes from aged mares showed a higher incidence of aneuploidy and premature sister chromatid separation, and weakened centromeric cohesion. We therefore propose the mare as a valid model for studying effects of aging on centromeric cohesion; cohesion loss predisposes to disintegration of bivalents and premature separation of sister chromatids during the first meiotic division, leading to embryonic aneuploidy; this probably contributes to the reduced fertility and increased incidence of pregnancy loss observed in aged mares.
Physical Activity and Cardiac Self-Efficacy Levels During Early Recovery After Acute Myocardial Infarction: A Jordanian Study

ABSTRACT Background Regular physical activity is important for patients with established coronary heart disease as it favorably influences their coronary risk profile. General self-efficacy is a powerful predictor of health behavior change that involves increases in physical activity levels. Few studies have simultaneously measured physical activity and self-efficacy during early recovery after a first acute myocardial infarction (AMI). Purpose The aims of this study were to assess changes in objectively measured physical activity levels at 2 weeks (T2) and 6 weeks (T3) and self-reported cardiac self-efficacy at hospital discharge (T1) and at T2 and T3 in patients recovering from AMI. Methods A repeated-measures design was used to recruit a purposive sample of patients from a single center in Jordan who were diagnosed with first AMI and who did not have access to cardiac rehabilitation. A body-worn activity monitor (activPAL) was used to objectively measure free-living physical activity levels for 7 consecutive days at two time points (T2 and T3). An Arabic version of the cardiac self-efficacy scale was administered at T1, T2, and T3. Paired t tests and analysis of variance were used to examine differences in physical activity levels and cardiac self-efficacy scores, respectively. Results A sample of 100 participants was recruited, of which 62% were male. The mean age of the sample was 54.5 ± 9.9 years. No statistically significant difference in physical activity levels was measured at 2 weeks (T2) and 6 weeks (T3). Cardiac self-efficacy scores improved significantly between T1, T2, and T3 across subscales and global cardiac self-efficacy. Conclusions/Implications for Practice Participants recovering from AMI in Jordan did not increase their physical activity levels during the early recovery phase, although cardiac self-efficacy scores improved. This may be because the increase in cardiac self-efficacy was not matched by the practical skills and knowledge required to translate this positive psychological construct into behavioral change. This study provides a first step toward understanding the complex relationship between cardiac self-efficacy and physical activity in this population. The authors hope that these findings support the design of culturally appropriate interventions to increase physical activity levels in this population.
Indoxyl Sulfate, a Tubular Toxin, Contributes to the Development of Chronic Kidney Disease

Indoxyl sulfate (IS), a uremic toxin, causes chronic kidney disease (CKD) progression via its tubulotoxicity. After cellular uptake, IS directly induces apoptotic and necrotic cell death of tubular cells. Additionally, IS increases oxidative stress and decreases antioxidant capacity, which are associated with tubulointerstitial injury. Injured tubular cells are a major source of transforming growth factor-β1 (TGF-β1), which induces myofibroblast transition from residual renal cells in damaged kidney, recruits inflammatory cells and thereby promotes extracellular matrix deposition in renal fibrosis. Moreover, IS upregulates signal transducers and activators of transcription 3 phosphorylation, followed by increases in TGF-β1, monocyte chemotactic protein-1 and α-smooth muscle actin production, which participate in interstitial inflammation, renal fibrosis and, consequently, CKD progression. Clinically, higher serum IS levels are independently associated with renal function decline and predict all-cause mortality in CKD. The poor removal of serum IS in conventional hemodialysis is also significantly associated with all-cause mortality and heart failure incidence in end-stage renal disease patients. Scavenging the IS precursor by AST-120 can markedly reduce tubular IS staining that attenuates renal tubular injury, ameliorates IS-induced oxidative stress and rescues antioxidant glutathione activity in tubular epithelial cells, thereby providing a protective role against tubular injury and ultimately retarding renal function decline.
Changes in Appetite During the Heart Failure Trajectory and Association With Fatigue, Depressive Symptoms, and Quality of Life

Background Decreased appetite can contribute to malnutrition in patients with heart failure (HF). Little is known about the trajectory of appetite over time in patients with HF and the factors associated with decreased appetite after discharge from the hospital. Objective The aims of this study were to investigate changes in appetite over time and explore how fatigue, depressive symptoms, and quality of life are associated with decreased appetite. Methods Data from the multicenter randomized Coordinating study evaluating Outcomes of Advising and Counseling in Heart Failure were used. Logistic regression and mixed-effects logistic regression were used to investigate changes in appetite over time and to explore the relationship between appetite and fatigue, depressive symptoms, and quality of life. Results A total of 734 patients with HF (mean age, 69 years) were included. Decreased appetite was present at all follow-up measurements; however, decreased appetite was significantly lower at the 1-month (odds ratio [OR], 0.43; confidence interval [CI], 0.29–0.63), 6-month (OR, 0.31; CI, 0.20–0.47), 12-month (OR, 0.22; CI, 0.14–0.34), and 18-month (OR, 0.24; CI, 0.15–0.37) follow-ups compared with baseline. Decreased appetite was associated with fatigue (OR, 3.09; CI, 1.98–4.84), depressive symptoms (OR, 1.76; CI, 1.35–2.29), and low quality of life (OR, 1.01; CI, 1.01–1.02) across all measurement points adjusted for covariates. Conclusions Appetite improved after discharge; however, at all time points, at least 22% of patients reported decreased appetite. Fatigue, depressive symptoms, and low quality of life are factors associated with decreased appetite. Decreased appetite is a long-standing problem in that it does not disappear spontaneously after an acute HF deterioration.
Controllable Fabrication of Percolative Metal Nanoparticle Arrays Applied for Quantum Conductance-Based Strain Sensors

We use gas phase deposition of well-defined nanoparticles (NPs) to fabricate closely-spaced Pd NP arrays on flexible membranes prepatterned with interdigital electrodes (IDEs). The evolution of the morphology and electron conductance of the NP arrays during deposition is analyzed. The growth of two-dimensional percolation clusters of interconnected NPs, which correlate with the percolation pathway for electron conduction in the NP deposits, is demonstrated. The percolative nature of the NP arrays permits us to finely control the percolation geometries and conductance of the NP film by controlling the NP deposition time so as to realize a precise and reproducible fabrication of sensing materials. Electron transport measurements reveal that the electrical conductance of the NP films is dominated by electron tunneling or hopping across the NP percolating networks. Based on the percolative and quantum tunneling nature, the closely-spaced Pd NP films on PET membranes are used as flexible strain sensors. The sensor demonstrates an excellent response ability to distinguish tiny deformations down to 5×10−4 strain and a high sensitivity with a large gauge factor of 200 up to 4% applied strain.
An Overview of the Use of Equine Collagen as Emerging Material for Biomedical Applications

Type I collagen has always aroused great interest in the field of life-science and bioengineering, thanks to its favorable structural properties and bioactivity. For this reason, in the last five decades it has been widely studied and employed as biomaterial for the manufacture of implantable medical devices. Commonly used sources of collagen are represented by bovine and swine but their applications are limited because of the zoonosis transmission risks, the immune response and the religious constrains. Thus, type-I collagen isolated from horse tendon has recently gained increasing interest as an attractive alternative, so that, although bovine and porcine derived collagens still remain the most common ones, more and more companies started to bring to market a various range of equine collagen-based products. In this context, this work aims to overview the properties of equine collagen making it particularly appealing in medicine, cosmetics and pharmaceuticals, as well as its main biomedical applications and the currently approved equine collagen-based medical devices, focusing on experimental studies and clinical trials of the last 15 years. To the best of our knowledge, this is the first review focusing on the use of equine collagen, as well as on equine collagen-based marketed products for healthcare.
In vivo miRNA knockout screening identifies miR-190b as a novel tumor suppressor

MicroRNAs (miRNAs) play important roles in the development of various cancers including lung cancer which is one of the devastating diseases worldwide. How miRNAs function in de novo lung tumorigenesis remains largely unknown. We here developed a CRISPR/Cas9-mediated dual guide RNA (dgRNA) system to knockout miRNAs in genetically engineered mouse model (GEMM). Through bioinformatic analyses of human lung cancer miRNA database, we identified 16 downregulated miRNAs associated with malignant progression and performed individual knockout with dgRNA system in KrasG12D/Trp53L/L (KP) mouse model. Using this in vivo knockout screening, we identified miR-30b and miR-146a, which has been previously reported as tumor suppressors and miR-190b, a new tumor-suppressive miRNA in lung cancer development. Over-expression of miR-190b in KP model as well as human lung cancer cell lines significantly suppressed malignant progression. We further found that miR-190b targeted the Hus1 gene and knockout of Hus1 in KP model dramatically suppressed lung tumorigenesis. Collectively, our study developed an in vivo miRNA knockout platform for functionally screening in GEMM and identified miR-190b as a new tumor suppressor in lung cancer.