Miracle-dz/UniFAR-FTUs huggingface dataset:
Serologic and Virologic Evidence of Influenza a Viruses in Wild Boars (Sus scrofa) from Two Different Locations in Italy

Abstract: Swine influenza viruses (SIVs) have been repeatedly demonstrated to circulate in wild boar (Sus scrofa) populations, whereas no evidence of exposure to avian influenza viruses (AIVs) has been described in wild boar. To better understand how different environments may influence the ecology of influenza A viruses (IAVs) in wild suid populations, we examined biologic samples of wild boars from two study areas represented by an upland (UL) and a wetland (WL) in northern and central Italy, respectively. Serum samples were collected from 388 wild boars sampled in the UL, whereas both a serum sample and a nasal swab were obtained from each of 35 wild boars sampled in the WL. Twenty of 388 (5.2%) sera from the UL were positive by enzyme-linked immunosorbent assay for the presence of antibodies against influenza A nucleoprotein and some of these samples showed antibodies by hemagglutination inhibition to SIVs of H1N1 (1/20), H1N2 (10/20), and H3N2 (1/20) antigenic subtypes. No IAV-seropositive wild boar was detected in the WL, although one of 35 animals was found to be IAV-positive by both a reverse transcriptase PCR and a real-time reverse transcriptase PCR. We hypothesize an SIV exposure for IAV-seropositive wild boars occupying the UL, whereas a possible AIV spillover from aquatic bird species—natural reservoirs of IAVs— to wild boars in the WL cannot be ruled out. Further research is needed to better understand the role played by wild boars in IAV ecology in Mediterranean habitats.
Modeling Cornelia de Lange syndrome in vitro and in vivo reveals a role for cohesin complex in neuronal survival and differentiation

Abstract Cornelia de Lange syndrome (CdLS), which is reported to affect ˜1 in 10 000 to 30 000 newborns, is a multisystem organ developmental disorder with relatively mild to severe effects. Among others, intellectual disability represents an important feature of this condition. CdLS can result from mutations in at least five genes: nipped‐B‐like protein, structural maintenance of chromosomes 1A, structural maintenance of chromosomes 3, RAD21 cohesin complex component and histone deacetylase 8 (HDAC8). It is believed that mutations in these genes cause CdLS by impairing the function of the cohesin complex (to which all the aforementioned genes contribute to the structure or function), disrupting gene regulation during critical stages of early development. Since intellectual disorder might result from alterations in neural development, in this work, we studied the role of Hdac8 gene in mouse neural stem cells (NSCs) and in vertebrate (Danio rerio) brain development by knockdown and chemical inhibition experiments. Underlying features of Hdac8 deficiency is an increased cell death in the developing neural tissues, either in mouse NSCs or in zebrafish embryos.
Asymptomatic Visceral Leishmania infantum Infection in US Soldiers Deployed to Iraq.

BACKGROUND Visceral leishmaniasis (VL), due to Leishmania infantum, is a persistent intracellular parasitic infection transmitted by the bite of infected sand flies. Symptomatic VL has been reported in U.S. soldiers with Iraq deployment. Untreated symptomatic VL can be fatal; asymptomatic VL (AVL) may establish a lifelong risk of reactivation. We report prevalence and AVL risk factors in Operation Iraqi Freedom (OIF) deployers during 2002-11. METHODS Healthy soldiers exposed to VL endemic areas in Iraq and 50 controls who never traveled to endemic regions were recruited through military healthcare facilities (2015-17). Responses to a risk factor survey and blood samples were obtained. Leishmania research diagnostics utilized included enzyme-linked immunosorbent assay (ELISA), rk39 test strips, quantitative polymerase chain reaction (PCR), and interferon gamma release (IGRA) assays. Statistical analyses included Fisher exact test, Pearson χ2 test, Mann-Whitney U test, and logistic regression. RESULTS 200 deployed subjects were enrolled, mostly males (84.0%), of white ethnicity (79.0%), and median age 41 (range 24-61) years. 64% were seropositive for Phlebotomus alexandri saliva antibodies. Prevalence of AVL (any positive test result) was 39/200 (19.5%, 95% confidence interval 14.4%-25.8%). Two (1.0%) PCR, 10 (5%) ELISA, and 28 (14%) IGRA samples were positive. Travel to Ninewa governorate increased risk for AVL (P = .01). CONCLUSION AVL was identified in 19.5% of OIF deployers; travel to northwest Iraq correlated with infection. Further studies are needed to inform risk for reactivation VL in US veterans and to target additional blood safety and surveillance measures.
Non-thermal plasma induces immunogenic cell death in vivo in murine CT26 colorectal tumors

ABSTRACT Immunogenic cell death is characterized by the emission of danger signals that facilitate activation of an adaptive immune response against dead-cell antigens. In the case of cancer therapy, tumor cells undergoing immunogenic death promote cancer-specific immunity. Identification, characterization, and optimization of stimuli that induce immunogenic cancer cell death has tremendous potential to improve the outcomes of cancer therapy. In this study, we show that non-thermal, atmospheric pressure plasma can be operated to induce immunogenic cell death in an animal model of colorectal cancer. In vitro, plasma treatment of CT26 colorectal cancer cells induced the release of classic danger signals. Treated cells were used to create a whole-cell vaccine which elicited protective immunity in the CT26 tumor mouse model. Moreover, plasma treatment of subcutaneous tumors elicited emission of danger signals and recruitment of antigen presenting cells into tumors. An increase in T cell responses targeting the colorectal cancer-specific antigen guanylyl cyclase C (GUCY2C) were also observed. This study provides the first evidence that non-thermal plasma is a bone fide inducer of immunogenic cell death and highlights its potential for clinical translation for cancer immunotherapy.
A systematic review of active case-finding strategies for tuberculosis in homeless populations.

SETTING Tuberculosis (TB) is prevalent in the homeless population, and can create health inequalities and challenges for eradication. Evidence-based approaches to active case finding (ACF) are needed. OBJECTIVES To determine the effectiveness of ACF for TB control, and identify strategies to improve uptake of screening and the diagnostic pathway in homeless populations in low- and medium-burden settings. Secondary objectives were to assess the yield of screening and participant characteristics. DESIGN A systematic search of electronic databases and grey literature sources identified ACF studies that reported population measures (prevalence or incidence) of TB control, and/or uptake and/or yield of screening for latent tuberculous infection (LTBI) or active TB affecting any site. Studies were described using narrative synthesis. RESULTS Twenty studies met the inclusion criteria. Studies were heterogeneous across multiple elements, including programme design, which likely contributed to variability in outcomes. ACF was associated with reductions in TB rates in three time-trend analyses. The strongest evidence for improving uptake of screening was for incentives, with mixed evidence for peer educators. At the observational level, professional support and mandatory screening may also improve uptake, and additional community support enhanced completion of the diagnostic pathway. Those most likely to be diagnosed with TB appeared less likely to accept screening. Yield of screening was 1.5-57% (41 684 participants) for LTBI, and 0-3.1% (91 771 participants) for active TB. CONCLUSION Observational evidence suggests that ACF is effective. Strategies to improve screening uptake were identified. Variability in uptake and yield necessitates programmes tailored to local populations; areas for further research were identified.
Lesional and perilesional tissue characterization by automated image processing in a novel gyrencephalic animal model of peracute intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is an important stroke subtype, but preclinical research is limited by a lack of translational animal models. Large animal models are useful to comparatively investigate key pathophysiological parameters in human ICH. To (i) establish an acute model of moderate ICH in adult sheep and (ii) an advanced neuroimage processing pipeline for automatic brain tissue and hemorrhagic lesion determination; 14 adult sheep were assigned for stereotactically induced ICH into cerebral white matter under physiological monitoring. Six hours after ICH neuroimaging using 1.5T MRI including structural as well as perfusion and diffusion, weighted imaging was performed before scarification and subsequent neuropathological investigation including immunohistological staining. Controlled, stereotactic application of autologous blood caused a space-occupying intracerebral hematoma of moderate severity, predominantly affecting white matter at 5 h post-injection. Neuroimage post-processing including lesion probability maps enabled automatic quantification of structural alterations including perilesional diffusion and perfusion restrictions. Neuropathological and immunohistological investigation confirmed perilesional vacuolation, axonal damage, and perivascular blood as seen after human ICH. The model and imaging platform reflects key aspects of human ICH and enables future translational research on hematoma expansion/evacuation, white matter changes, hematoma evacuation, and other aspects.
Gray Matter Structural Alterations in Social Anxiety Disorder: A Voxel-Based Meta-Analysis

The current insight into the neurobiological pathogenesis underlying social anxiety disorder (SAD) is still rather limited. We implemented a meta-analysis to explore the neuroanatomical basis of SAD. We undertook a systematic search of studies comparing gray matter volume (GMV) differences between SAD patients and healthy controls (HC) using a whole-brain voxel-based morphometry (VBM) approach. The anisotropic effect size version of seed-based d mapping (AES-SDM) meta-analysis was conducted to explore the GMV differences of SAD patients compared with HC. We included eleven studies with 470 SAD patients and 522 HC in the current meta-analysis. In the main meta-analysis, relative to HC, SAD patients showed larger GMVs in the left precuneus, right middle occipital gyrus (MOG) and supplementary motor area (SMA), as well as smaller GMV in the left putamen. In the subgroup analyses, compared with controls, adult patients (age ≥ 18 years) with SAD exhibited larger GMVs in the left precuneus, right superior frontal gyrus (SFG), angular gyrus, middle temporal gyrus (MTG), MOG and SMA, as well as a smaller GMV in the left thalamus; SAD patients without comorbid depressive disorder exhibited larger GMVs in the left superior parietal gyrus and precuneus, right inferior temporal gyrus, fusiform gyrus, MTG and superior temporal gyrus (STG), as well as a smaller GMV in the bilateral thalami; and currently drug-free patients with SAD exhibited a smaller GMV in the left thalamus compared with HC while no larger GMVs were found. For SAD patients with different clinical features, our study revealed directionally consistent larger cortical GMVs and smaller subcortical GMVs, including locationally consistent larger precuneus and thalamic deficits in the left brain. Age, comorbid depressive disorder and concomitant medication use of the patients might be potential confounders of SAD at the neuroanatomical level.
AtROP6 is involved in reactive oxygen species signaling in response to iron‐deficiency stress in Arabidopsis thaliana

Understanding the mechanism of iron (Fe)‐deficiency responses is crucial for improving plant Fe bioavailability. Here, we found that the Arabidopsis Rho‐like GTPase 6 mutant (rop6) is less sensitive to Fe‐deficiency responses and has reduced levels of reactive oxygen species (ROS) compared to wild‐type (WT), while AtROP6‐overexpressing seedlings exhibit more sensitivity to Fe‐deficiency responses and has higher levels of ROS compared to WT. Moreover, treatment with H2O2 improves the sensitivity to Fe‐deficiency responses in rop6 mutants. By using the yeast two‐hybrid system, we further demonstrate the direct interaction between AtROP6 and Arabidopsis respiratory burst oxidase homolog D (AtRBOHD), which controls the generation of ROS. Overall, we suggest that AtROP6 is involved in AtRBOHD‐mediated ROS signaling to modulate Fe‐deficiency responses in Arabidopsis thaliana.
Ertugliflozin: a sodium-glucose cotransporter-2 (SGLT-2) inhibitor for glycemic control in type 2 diabetes

Recently, a new class of anti-diabetic drugs has found its way into the market: sodium-glucose cotransporters (SGLT) inhibitors. Two major SGLT isoforms have been identified: SGLT-2, mainly expressed in proximal renal tubules, and SGLT-1, mainly expressed in the small intestine, the proximal renal tubule, and the myocardium. SGLT-2 inhibitors increase urinary glucose excretion, lowering glycemia without inducing excessive insulin secretion. Marketed SGLT-2 inhibitors actually include dapagliflozin, canagliflozin, and empagliflozin; a new SGLT-2 inhibitor is being studied: ertugliflozin. Ertugliflozin is a potent inhibitor of SGLT-2 and possesses a high selectivity over glucose transport via SGLT-1 and several other glucose transporters GLUT-1–4. Ertugliflozin inhibits renal glucose reabsorption resulting in urinary glucose excretion and thereby reduces plasma glucose and glycated hemoglobin in subjects with type 2 diabetes mellitus. Ertugliflozin is being developed as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. The aim of this review is to evaluate the preliminary published data about this new molecule.
Transdisziplinarität und Partizipativität bei der Entwicklung einer Kampagne zur Reduktion der Passivrauchbelastung bei Kindern

Eine gute Gesundheitskampagne berücksichtigt die spezifischen Bedürfnisse, Motivatoren aber auch Barrieren für das erwünschte Gesundheitsverhalten der Zielgruppe (Fishbein & Yzer, 2003). Trotzdem bleibt eine Kampagne erfolglos, wenn sie die Zielgruppe über die gewählten Kommunikationswege nicht erreicht (Snyder & Hamilton, 2002). Unser Beitrag adressiert und reflektiert diese beiden Erfolgsfaktoren – Botschaften und Kommunikationswege – im Kontext einer Studie zur Entwicklung von Aufklärungskampagnen zur Reduktion der Passivrauchbelastung bei Kindern in Familien mit niedrigem sozioökonomischem Status1. Über die transdisziplinäre Zusammenarbeit mit Medizinern hinaus, beziehen wir auch die schwer erreichbare Zielgruppe der rauchenden Eltern mit niedrigem sozioökonomischem Status partizpativ in unsere Studie mit ein.
A unique intra-molecular fidelity-modulating mechanism identified in a viral RNA-dependent RNA polymerase

Abstract Typically not assisted by proofreading, the RNA-dependent RNA polymerases (RdRPs) encoded by the RNA viruses may need to independently control its fidelity to fulfill virus viability and fitness. However, the precise mechanism by which the RdRP maintains its optimal fidelity level remains largely elusive. By solving 2.1–2.5 Å resolution crystal structures of the classical swine fever virus (CSFV) NS5B, an RdRP with a unique naturally fused N-terminal domain (NTD), we identified high-resolution intra-molecular interactions between the NTD and the RdRP palm domain. In order to dissect possible regulatory functions of NTD, we designed mutations at residues Y471 and E472 to perturb key interactions at the NTD–RdRP interface. When crystallized, some of these NS5B interface mutants maintained the interface, while the others adopted an ‘open’ conformation that no longer retained the intra-molecular interactions. Data from multiple in vitro RdRP assays indicated that the perturbation of the NTD–RdRP interactions clearly reduced the fidelity level of the RNA synthesis, while the processivity of the NS5B elongation complex was not affected. Collectively, our work demonstrates an explicit and unique mode of polymerase fidelity modulation and provides a vivid example of co-evolution in multi-domain enzymes.
Laminar shear stress‐provoked cytoskeletal changes are mediated by epigenetic reprogramming of TIMP1 in human primary smooth muscle cells

Whereas endothelial responses to shear stress are well‐characterized, the cell physiological effects of shear stress in smooth muscle cells (SMCs) remain largely obscure. As SMCs are directly challenged by shear stress after endothelial denuding injury following procedures such as angioplasty or endarterectomy, characterization of these responses represents an important scientific question. Hence we decided to contrast cytoskeletal reorganization, epigenetic reprogramming, signaling transduction, and changes in miRNA (miRs) profiles in primary human aortic smooth muscle cells (AoSMCs) between unstressed cells and cells exposed to shear stress. We observed that shear stress‐provoked reorganization of the actin cytoskeleton in an apparently Cofilin‐dependent fashion and which related to altered integrin signaling, apparently caused by remodeling of the extracellular matrix. The latter appeared a downstream effect of increased expression of matrix metalloproteinases and downregulation of tissue metalloproteinase inhibitor 1 (TIMP1) protein levels. In turn, these effects related to shear stress‐provoked changes in expression and nuclear localization of the epigenetic regulators demethylases TET1, TET2, DNMT1, DNMT3A and DNMT3B, HDAC6, and SIRT1. Accordingly, TIMP1 promotor CpG hypomethylation was a prominent effect, and resulted in a significant increase in TIMP1 transcription, which may also have related increased expression of miRs involved in modulating TIMP1 translation. Thus epigenetic‐reprogramming of TIMP1 emerges as critical element in smooth muscle responses to mechanical signals and as epigenetic machinery is amendable to pharmacological manipulation, this pathway may have important clinical consequences.
Multi-Robot Cyber Physical System for Sensing Environmental Variables of Transmission Line

The normal operation of a power grid largely depends on the effective monitoring and maintenance of transmission lines, which is a process that has many challenges. The traditional method of the manual or remote inspection of transmission lines is time-consuming, laborious, and inefficient. To address this problem, a novel method has been proposed for the Multi-Robot Cyber Physical System (MRCPS) of a power grid based on inspection robots, a wireless sensor network (WSN), and multi-agent theory to achieve a low-cost, efficient, fault-tolerant, and remote monitoring of power grids. For the sake of an effective monitoring system for smart grids, the very research is conducted focusing on designing a methodology that will realize the efficient, fault-tolerant, and financial balance of a multi-robot team for monitoring transmission lines. Multiple testing scenarios are performed, in which various aspects are explored so as to determine the optimal parameters balancing team performance and financial cost. Furthermore, multi-robot team communication and navigation control in smart grid environments are introduced.
Instability of nocturnal parasympathetic nerve function in patients with chronic lung disease with or without nocturnal desaturation

Objective/background This study was performed to evaluate the association of nocturnal autonomic nerve (AN) dysfunction, especially parasympathetic nerve (PN) function instability, and nocturnal oxygen desaturation (NOD) in patients with chronic lung diseases (CLD). Patients and methods Twenty-nine stable CLD patients with irreversible pulmonary dysfunction and mild-to-moderate daytime hypoxemia, 13 CLD patients receiving long-term oxygen therapy (LTOT) with maintained SpO2 >90%, and 17 senior healthy volunteers underwent two-night examinations of nocturnal AN function by pulse rate variability (PRV) instead of heart rate variation using a photoelectrical plethysmograph simultaneously monitoring SpO2 and the presence of sleep disordered breathing at home. AN function was examined by instantaneous time–frequency analysis of PRV using a complex demodulation method. Results There were no significant differences in mean low frequency/high frequency (HF) ratio (index of sympathetic nerve activity) or mean HF amplitude (index of PN activity) among controls and CLD patients with and without NOD (defined as SpO2 <90% for at least 3% of total recording time at night). However, the relative times over which the same main HF peak was sustained for at least 20 seconds (%HF20sec) and 5 minutes in total recording time, indexes of PN function stability, were significantly reduced in CLD patients compared with controls, and further decreased in CLD patients with NOD compared with non-NOD. %HF20sec was significantly higher in the LTOT group than the NOD group. Furthermore, PaO2 at rest and nocturnal hypoxia were significantly correlated with PN function instability in CLD patients. Conclusion PN function is unstable at night associated with nocturnal hypoxemia in CLD patients, which may reflect poor quality of sleep.
Long term follow‐up of titanium implants installed in block‐grafted areas: A systematic review

BACKGROUND An enduring clinical question concerns the outcome (ie, success) of implants placed in areas grafted with block-grafts. OBJECTIVE To undertake a systematic review of the literature on the long term results (≥5 years) of implants placed in maxillofacial areas grafted with any type of osseous block-grafts in two-stage surgeries. Further, the review addresses how available success criteria were used within the studies. MATERIALS AND METHODS The MEDLINE (PubMed) and EMBASE bibliographic databases were searched up to March 2017 for studies evaluating the long term results of implants placed in grafted areas. The search strategy was restricted to English language publications using combined terms which referred to the treatment method (implants placed in areas grafted with bone blocks), and follow-up characteristics (≥5 years and assessment of at least one parameter related to implant success criteria). To qualify for inclusion, studies should present outcome measurements indicating the success (or at least the survival) of the implants. RESULTS The search strategy yielded 17 studies, which were included in this systematic review. These studies presented survival rates ranging from 88.7% (after 15 years follow-up) to 98.7% (after 5 years follow-up). Five studies presented data based on predefined success criteria with success rates ranging from 86.8% to 100%. In these studies, the term "success" was often not properly defined. CONCLUSION The long term survival (≥5 years) of implants placed into block-grafted areas in two-stage surgeries was not lower than 75%, while success rates ranged from 86.8% to 100%. Although it was possible to identify published success criteria for implant follow-up, there is no broad consensus on how to report implant success in a consistent manner.