Miracle-dz/UniFAR-FTUs huggingface dataset:
From Qualitative to Quantitative Analysis of Activity and Property Landscapes

Activity or, more generally, property landscapes (PLs) have been considered as an attractive way to visualize and explore structure-property relationships (SPRs) contained in large data sets of chemical compounds. For graphical analysis, three-dimensional representations reminiscent of natural landscapes are particularly intuitive. So far, the use of such landscape models has essentially been confined to qualitative assessment. We describe recent efforts to analyze PLs in a more quantitative manner, which make it possible to calculate topographical similarity values for comparison of landscape models as a measure of relative SPR information content.
Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells

Coxsackie B (CVB) viruses have been associated with type 1 diabetes. We have recently observed that CVB1 was linked to the initiation of the autoimmune process leading to type 1 diabetes in Finnish children. Viral persistency in the pancreas is currently considered as one possible mechanism. In the current study persistent infection was established in pancreatic ductal and beta cell lines (PANC-1 and 1.1B4) using four different CVB1 strains, including the prototype strain and three clinical isolates. We sequenced 5′ untranslated region (UTR) and regions coding for structural and non-structural proteins and the second single open reading frame (ORF) protein of all persisting CVB1 strains using next generation sequencing to identify mutations that are common for all of these strains. One mutation, K257R in VP1, was found from all persisting CVB1 strains. The mutations were mainly accumulated in viral structural proteins, especially at BC, DE, EF loops and C-terminus of viral capsid protein 1 (VP1), the puff region of VP2, the knob region of VP3 and infection-enhancing epitope of VP4. This showed that the capsid region of the viruses sustains various changes during persistency some of which could be hallmark(s) of persistency.
Wet lung leading to RDS: the lung ultrasound findings and possible mechanisms - a pilot study from an animal mode

Abstract Background Clinically, the lung ultrasound (LUS) showed wet lung could cause respiratory distress syndrome (RDS) in newborns. This work aimed to investigate LUS changes over time and its potential mechanism as alveolar fluid increase in a rabbit model. Methods A total of 35 New Zealand Rabbits were randomly assigned to seven groups. Models of various alveolar fluid levels were induced by infusion of different volumes of normal saline (NS) via the endotracheal tube. LUS was performed before NS infusion, immediately after NS infusion and 4 h after NS infusion. To appraise LUS changes and its potential mechanism as alveolar fluid increase, histopathological examination, the mRNA and protein expression of surfactant protein (SP), and immunohistochemistry (IHC) were performed. The expression levels of SP-B and SP-C proteins were detected using western blotting, and the relative expression levels of SP-B and SP-C mRNA were detected using qRT-PCR. Results The results showed that LUS changed from B-line to lung consolidations accompanied by air-bronchograms in some locations of lungs at 4 h when the injection volume ≥ 6 ml/kg. Histopathological examination showed alveoli collapse, inflammatory cell infiltration and alveolar wall thickened. SP-B and SP-C mRNA and protein expression were statistically significantly reduced when the injection volume ≥6 ml/kg (p < .05). IHC staining displayed the same findings. Conclusions As alveolar fluid increase, LUS changed from wet lung to RDS after 4 h. The possible mechanism was that the SP protein expression was significantly reduced. LUS can be used to guide the administration of exogenous surfactant in this situation.
Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial

Introduction: Aging is characterized by the progressive loss of physiological capacity. At the cellular level, two key hallmarks of the aging process include telomere length (TL) shortening and cellular senescence. Repeated intermittent hyperoxic exposures, using certain hyperbaric oxygen therapy (HBOT) protocols, can induce regenerative effects which normally occur during hypoxia. The aim of the current study was to evaluate whether HBOT affects TL and senescent cell concentrations in a normal, non-pathological, aging adult population. Methods: Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th session, and 1-2 weeks following the last HBOT session. Peripheral blood mononuclear cells (PBMCs) telomeres length and senescence were assessed. Results: Telomeres length of T helper, T cytotoxic, natural killer and B cells increased significantly by over 20% following HBOT. The most significant change was noticed in B cells which increased at the 30th session, 60th session and post HBOT by 25.68%±40.42 (p=0.007), 29.39%±23.39 (p=0.0001) and 37.63%±52.73 (p=0.007), respectively. There was a significant decrease in the number of senescent T helpers by -37.30%±33.04 post-HBOT (P<0.0001). T-cytotoxic senescent cell percentages decreased significantly by -10.96%±12.59 (p=0.0004) post-HBOT. In conclusion, the study indicates that HBOT may induce significant senolytic effects including significantly increasing telomere length and clearance of senescent cells in the aging populations.
Ablation of NPFFR2 in Mice Reduces Response to Single Prolonged Stress Model

Mental stress is highly related to many clinical symptoms and disorders, as it activates the hypothalamic-pituitary-adrenocortical (HPA) axis to affect a wide variety of physiological functions. Furthermore, stress leads to the aberrations in HPA axis activity and disruptions of body homeostasis. It was previously shown that neuropeptide FF (NPFF) regulates the HPA axis through the activation of hypothalamus paraventricular nucleus (PVN), and genetic overexpression or pharmacological stimulation of NPFF receptor 2 (NPFFR2) triggers hyperactivity of HPA axis and suppresses behavioral correlates of emotion in mice. In this study, we further examined the role of NPFFR2 in stress response in mice by utilizing a single prolonged stress (SPS). SPS is considered a model of post-traumatic stress disorder (PTSD), and mice undergo physical restraint, forced swimming, and ether anesthesia within a day followed by social isolation for one week. NPFFR2 knockout B6 mice were generated by CRISPR/Cas9 technology and exposed to SPS. The NPFFR2 knockouts showed resistance to stress exposure-induced anxiety-like behaviors and HPA axis hyperactivity. Additionally, the hippocampal mRNA levels of glucocorticoid receptor and mineralocorticoid receptor were reduced in wild-type (WT) mice but not in NPFFR2 knockouts after stress exposure. Our data also suggested that NPFFR2 knockout mice have stronger negative feedback on the HPA axis after exposure to SPS. Mice with intra-PVN Npffr2 shRNA injection displayed trends toward resistance to SPS exposure in both behavioral and molecular assays. Together, our findings suggest that NPFFR2 may be a potential therapeutic target for disorders relating to stress/anxiety and HPA dysregulation.
The tellurium‐based immunomodulator, AS101 ameliorates adjuvant‐induced arthritis in rats

Despite undeniable improvement in the management of rheumatoid arthritis (RA), the discovery of more effective, less toxic and, ideally, less immune suppressive drugs are much needed. In the current study, we set to explore the potential anti‐rheumatic activity of the non‐toxic, tellurium‐based immunomodulator, AS101 in an experimental animal model of RA. The effect of AS101 was assessed on adjuvant‐induced arthritis (AIA) rats. Clinical signs of arthritis were assessed. Histopathological examination was used to assess inflammation, synovial changes and tissue lesions. Very late antigen‐4 (VLA‐4)+ cellular infiltration was detected using immunohistochemical staining. Enzyme‐linked immunosorbent assay (ELISA) was used to measure circulating anti‐cyclic citrullinated‐peptide autoantibody (ACPA) and real‐time polymerase chain reaction (PCR) was used to measure the in‐vitro effect of AS101 on interleukin (IL)‐6 and IL‐1β expression in activated primary human fibroblasts. Prophylactic treatment with intraperitoneal AS101 reduced clinical arthritis scores in AIA rats (P < 0·01). AS101 abrogated the migration of active chronic inflammatory immune cells, particularly VLA‐4+ cells, into joint cartilage and synovium, reduced the extent of joint damage and preserved joint architecture. Compared to phosphate‐buffered saline (PBS)‐treated AIA rats, histopathological inflammatory scores were significantly reduced (P < 0·05). Furthermore, AS101 resulted in a marked reduction of circulating ACPA in comparison to PBS‐treated rats (P < 0·05). Importantly, AS101 significantly reduced mRNA levels of proinflammatory mediators such as IL‐6 (P < 0·05) and IL‐1β (P < 0·01) in activated primary human fibroblasts. Taken together, we report the first demonstration of the anti‐rheumatic/inflammatory activity of AS101 in experimental RA model, thereby supporting an alternative early therapeutic intervention and identifying a promising agent for therapeutic intervention.
Sleep quality and risk of coronary heart disease - a prospective cohort study from the English longitudinal study of ageing

Background: The association between sleep quality and risk of coronary heart disease (CHD) remains unclear in the elderly. Results: At eight-year follow up, a total of 411 (4.29%) participants developed CHD. Compared with good quality group, the multivariable hazard ratio [HR] (95% confidence interval [CI]) for CHD was 1.393 (1.005, 1.931) for intermediate quality group and 1.913 (1.206, 3.035) for poor quality group. Consistent results were observed in participants with normal sleep duration. Conclusions: Poor sleep quality may be a novel modifiable risk factor for CHD in the elderly independent of conventional cardiovascular risk factors, even when sleep duration was normal. Methods: The current study included 9570 CHD-free participants in the English Longitudinal Study of Ageing (ELSA) from wave 4 (2008 to 2009). Incident CHD included new onset angina or myocardial infarction. Sleep quality was measured by a four-item questionnaire. Score ranged from 1 (best) to 4 (poorest). Participants were divided into three groups: good quality (1 ≤ score <2), intermediate quality (2 ≤ score <3) and poor quality (3 ≤ score ≤4). Cox regression model was used to calculate HR for CHD risk according to sleep quality, adjusted for conventional CHD risk factors and sleep duration.
Spontaneous Remission and Concomitant Progression in a Patient with DLBCL

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. Although DLBCL can be cured in more than half of all patients, up to 50% of patients become refractory to initial treatment or relapse after complete remission. We present a case of complete spontaneous remission of some tumors and concomitant newly developed tumors observed in a patient with relapsed DLBCL. Spontaneous remission of lymphoma without treatment is a rare phenomenon and can occur at baseline as well as in relapsed DLBCL. However, most patients who initially experience spontaneous remission later develop relapse. Thus, careful follow-up is required, and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) allows monitoring of multiple lesions.
Role of Adiponectin and Tumor Necrosis Factor-Alpha in the Pathogenesis and Evolution of Type 1 Diabetes Mellitus in Children and Adolescents

Type 1 diabetes mellitus (T1DM) is a complex condition caused by the destruction of pancreatic beta cells by autoimmune mechanisms. As a result, insulin deficiency and subsequent hyperglycemia occur. The aim of the present study is to investigate the role of adiponectin and tumor necrosis factor alpha (TNF-α) in the development of T1DM. The study is designed as an observational case-control study, involving 52 diabetic patients and 66 controls. Z scores for Body Mass Index (BMI), weight, height, and adiponectin and TNF-α serum levels were assessed in both groups. The T1DM group had significantly higher TNF-α levels and a significantly higher proportion of high-risk patients for inflammation based on TNF-α values as compared to the control group, while both groups had statistically similar adiponectin levels and a similar proportion of high/medium-risk patients based on adiponectin values. TNF-α plays a significant role in the pathogenesis and evolution of T1DM and it may represent an additional marker of disease progression, as well as a potential target of immunotherapeutic strategies. In the present study, no statistically significant differences were recorded in adiponectin levels neither in diabetic patients and controls, nor in high/medium severity risk diabetic patients.
Radiation-induced skin injury: pathogenesis, treatment, and management

Radiation-induced skin injury (RSI) refers to a frequently occurring complication of radiation therapy. Nearly 90% of patients having received radiation therapy underwent moderate-to-severe skin reactions, severely reducing patients' quality of life and adversely affecting their disease treatment. No gold standard has been formulated for RSIs. In the present study, the mechanism of RSI and topical medications was discussed. Besides, this study can be referenced for clinicians to treat RSIs to guide subsequent clinical medicine.
Nano-Bio Interaction between Blood Plasma Proteins and Water-Soluble Silicon Quantum Dots with Enabled Cellular Uptake and Minimal Cytotoxicity

A better understanding of the compatibility of water-soluble semiconductor quantum dots (QDs) upon contact with the bloodstream is important for biological applications, including biomarkers working in the first therapeutic spectral window for deep tissue imaging. Herein, we investigated the conformational changes of blood plasma proteins during the interaction with near-infrared light-emitting nanoparticles, consisting of Pluronic F127 shells and cores comprised of assembled silicon QDs terminated with decane monolayers. Albumin and transferrin have high quenching constants and form a hard protein corona on the nanoparticle. In contrast, fibrinogen has low quenching constants and forms a soft protein corona. A circular dichroism (CD) spectrometric study investigates changes in the protein’s secondary and tertiary structures with incremental changes in the nanoparticle concentrations. As expected, the addition of nanoparticles causes the denaturation of the plasma proteins. However, it is noteworthy that the conformational recovery phenomena are observed for fibrinogen and transferrin, suggesting that the nanoparticle does not influence the ordered structure of proteins in the bloodstream. In addition, we observed enabled cellular uptake (NIH3T3 Fibroblasts) and minimal cytotoxicity using different cell lines (HeLa, A549, and NIH3T3). This study offers a basis to design QDs without altering the biomacromolecule’s original conformation with enabled cellular uptake with minimal cytotoxicity.
Cerebral Ovine Herpesvirus 2 Infection of Cattle Is Associated With a Variable Neuropathological Phenotype

Cross-species infection with ovine herpesvirus 2 (OvHV-2) in cattle causes malignant catarrhal fever (MCF). MCF may involve the central nervous system (CNS) with necrotizing arteritis and/or vasculitis described to be unique to MCF and discriminatory compared to other viral CNS infections. However, a systematic histopathological characterization of the neural form of MCF in cattle is lacking. We examined medulla oblongata (n = 9) or the entire brain (n = 9) of 18 cattle in which OvHV-2 was identified by quantitative polymerase chain reaction (qPCR), in order to pinpoint potential variations in neuropathology. In 2/18 animals (11%) no lesions were identified, while 16/18 cattle (89%) had brain lesions of varying severity. Presence and quantities of OvHV-2 nucleic acid were determined by in situ hybridization and qPCR, respectively, and were related to the severity of lesions. Fifteen of 18 animals (83%) showed vasculitis, which was mainly of the lymphohistiocytic type, while pathognomonic necrotizing arteritis was only rarely present. Neuroparenchymal lesions included gliosis and/or neuronal changes in 7/16 brains with lesions (44%). The number of CD3+ lymphocytes was highest in animals with simultaneous vascular and neuroparenchymal lesions and high viral genome load. In one animal, OvHV-2 was exclusively observed in CD3+ lymphocytes but not in neurons or microglia. In conclusion, the neuropathological phenotype of bovine MCF in the brain was variable. In some cases, lesions mimicked neurotropic viral encephalitis, while pathognomonic necrotizing arteritis was not a consistent feature of neural MCF. Therefore, molecular detection of OvHV-2 is warranted in the presence of nonsuppurative encephalitis and in the absence of necrotizing arteritis.
Perioperative Blood Pressure Management.

Submitted for publication June 12, 2020. Accepted for publication October 5, 2020. Published online first on November 18, 2020. From the Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (B.S.); Outcomes Research Consortium, Cleveland, Ohio (B.S.); and Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio (D.I.S.).
Intégration hétérogène III-V sur silicium de microlasers à émission par la surface à base de cristaux photoniques

La croissance continue et rapide du trafic de donnees dans les infrastructures de telecommunications, impose des niveaux de debit de transmission ainsi que de puissance de traitement de l'information, que les capacites intrinseques des systemes et microcircuits electroniques ne seront plus en mesure d'assurer a breve echeance : le developpement de nouveaux scenarii technologiques s'avere indispensable pour repondre a la demande de bande passante imposee notamment par la revolution de l'internet, tout en preservant une consommation energetique raisonnable. Dans ce contexte, l'integration heterogene fonctionnelle sur silicium de dispositifs photoniques a emission par la surface de type VCSEL utilisant des miroirs large-bandes ultra-compacts a cristaux photoniques constitue une strategie prometteuse pour surmonter l'impasse technologique actuelle, tout en ouvrant la voie a un developpement rapide d'architectures et de systemes de communications innovants dans le cadre du mariage entre photonique et micro-nano-electronique.
Probing the hierarchy of evidence to identify the best strategy for placing class II dental composite restorations using current materials.

OBJECTIVE The objective of this review is to present a synopsis of the existing clinical and in vitro evidence regarding placement of direct class II restorations with dental composites of varying viscosities, focusing on the marginal integrity achievable. OVERVIEW The literature on class II composites placed with various techniques was searched through PubMed, Scopus, and the citations of identified articles, focusing on aspects related to adaptation and clinical performance. Studies comparing layering of conventional composite to layering with a flowable liner, including the "snow plow technique," use of warmed composite, flowable bulk-fill liners with a conventional composite capping layer, and bulk-fill restorative in a single or incremental fill (including placement with sonic energy and dual-curing) CONCLUSIONS: In vitro and clinical evidence does not support any one specific method or material type for achieving optimal performance when restoring class II cavity preparations with current dental composites. CLINICAL SIGNIFICANCE Although there are many available placement methods and types of composite materials on the market for use in class II restorations, the reasonable success presented in the clinical and laboratory literature for the various approaches suggests that the most important factor for achieving success is likely careful and proper placement and light-curing technique, independent of the approach.
Predicting Resolvin D1 Pharmacokinetics in Humans with Physiologically‐Based Pharmacokinetic Modeling

Sjögren’s syndrome (SS) is an autoimmune disease with no effective treatment options. Resolvin D1 (RvD1) belongs to a class of lipid‐based specialized pro‐resolving mediators that showed efficacy in preclinical models of SS. We developed a physiologically‐based pharmacokinetic (PBPK) model of RvD1 in mice and optimized the model using plasma and salivary gland pharmacokinetic (PK) studies performed in NOD/ShiLtJ mice with SS‐like features. The predictive performance of the PBPK model was also evaluated with two external datasets from the literature reporting RvD1 PKs. The PBPK model adequately captured the observed concentrations of RvD1 administered at different doses and in different species. The PKs of RvD1 in virtual humans were predicted using the verified PBPK model at various doses (0.01–10 mg/kg). The first‐in‐human predictions of RvD1 will be useful for the clinical trial design and translation of RvD1 as an effective treatment strategy for SS.
THE EFFECT OF 10 VIBRO-TACTILE P300 BCI SESSIONS IN PATIENTS WITH MINIMALLY CONSCIOUS STATE

It has been shown that brain-computer interface (BCI) technology can help in assessing the cognitive abilities of patients with minimally conscious state (MCS) and can provide a platform for communication. In this study the effects of a vibro-tactile BCI oddball paradigm with three different stimulation location (VT3) were investigated. Seven MCS patients performed 10 VT3 P300 BCI sessions over 10 days with 8-12 runs each day. Changes in the classification accuracies over the 10 days were investigated. Coma Recovery Scale – Revised (CRS-R) was assessed before and after the 10 sessions. The average classification accuracy in the best sessions was 80±15%. Four out of seven patients showed an improvement in the CRS-R score of 2 to 7 points. This study shows the importance of repeated BCI measures in assessing MCS patients. The improvement in the CRS-R score is an important fact which should be considered in future studies.