Miracle-dz/UniFAR-FTUs huggingface dataset:
Ecological Design: The Role of Extended Producer Responsibility System

ABSTRACT Dong, Y. ; Zhang, F. , and Fu, L. , 2019. Ecological design: The role of extended producer responsibility system. In: Guido-Aldana, P.A. and Mulahasan, S. (eds.), Advances in Water Resources and Exploration. Journal of Coastal Research, Special Issue No. 93, pp. 354–361. Coconut Creek (Florida), ISSN 0749-0208. With the development of the society, terrestrial and marine ecosystems are destroyed seriously. To protect the ecosystems, ecological design is the key factor to implement the extended producer responsibility system (EPR), which can effectively improve the nature resource utilization, and reduce the waste of resources and environmental destruction during the production, circulation, use and processing stages for products. Firstly, this paper studies the driving factors of producer extended responsibility system, which includes government regulation and incentive, consumer demand pressure, the internal environment of the enterprise management and so on. After analyzing these factors, this paper studies the driving factors on ecological design. Through interviews and questionnaires on the production enterprises, and combined with the current research literatures in china and abroad, this paper verified and developed the scale for ecological design, extended producer responsibility, the driving force of ecological performance factors. The results show that as key elements of EPR, government regulation and incentives, corporate internal environment management can effectively promote the concept and behavior of ecological design of manufacturing enterprises; but consumer demand pressure cannot significantly affect the implementation of ecological design.
Hairpin coiling of central line catheter: Pinch-off syndrome?

Central line insertion is a commonly performed procedure in the intensive care unit. Although technical difficulty is moderate, experience decreases the failure rate. Central vein catheter (CVC) insertion is associated with various complications such as pneumothorax and arterial puncture, but rare possibilities such as coiling of catheter can still occur and every intensivist should be cautious about it. Chest X-ray remains the gold standard to confirm the course and position of CVC and should be correlated with clinical findings. We report a case where CVC insertion was associated with coiling and led to occlusion of the proximal port.
Myocardial Perfusion Imaging: A Brief Review of Nuclear and Nonnuclear Techniques and Comparative Evaluation of Recent Advances

Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Invasive coronary angiography (ICA) is the gold standard for the evaluation of epicardial CAD. In the pathogenesis of the CAD, myocardial perfusion abnormalities are the first changes that appear followed by wall motion abnormalities, electrocardiogram changes, and angina. Myocardial perfusion imaging (MPI) demonstrates the cumulative effect of pathology at epicardial coronary arteries, small vessels, and endothelium. Thus, it evaluates the overall burden of ischemic heart disease (IHD). MPI is used noninvasively to diagnose early asymptomatic CAD or to know the functional significance of known CAD. There are evidence that early detection of myocardial perfusion abnormalities followed by aggressive intervention against cardiovascular risk factors may restore myocardial perfusion. This may lead to reduce morbidity and mortality. Various MPI modalities have been used to diagnose and define the severity of CAD. Cardiac myocardial perfusion single-photon emission computed tomography (myocardial perfusion scintigraphy [MPS]) has been in use since decades. Several newer modalities such as positron emission tomography, cardiac magnetic resonance imaging, computed tomography perfusion, and myocardial contrast echocardiography are developing utilizing the similar principle of MPS. We shall be reviewing briefly these modalities, their performance, comparison to each other, and with ICA.
Rehabilitation with robotic glove (Gloreha) in poststroke patients

Background and Objectives: Stroke is a leading cause of long-term disability. Rehabilitation involving repetitive, high-intensity, and task-specific exercise is the pathway to restore motor skills. Robotic assistive devices such as Gloreha are increasingly being used in upper limb rehabilitation. The aim of this study is to explore the efficacy of robotic therapy for upper limb rehabilitation using robotic glove (Gloreha) in patients with stroke. Materials and Methods: The patients affected by stroke who were admitted to our rehabilitation unit were studied. Patients were exposed to Gloreha device rehabilitation (30 min/die), physiotherapy (1,5 hours/die), and occupational therapy (30 min/die). We measured the impairment in motor function and muscle tone using the modified Ashworth scale (MAS), the activities of daily living functional independence measure (FIM), and the finger dexterity Nine-Hole Peg test (NHPT). Results: Twelve patients (mean age = 64.5 years; male/female: 8:4) were admitted at the rehabilitation training. We found statistically significant differences between admission and discharged in terms of functional recovery using the FIM scale (pre/M = 88.33; post/M = 117.25,P = 0.01); hand training showed a better outcome using the NHPT (pre/M = 51.8; post/M = 36.33, P = 0.01). No significant changes were observed in terms of spasticity with the MAS (pre/M = 1.25; post/M = 1.08;P > 0.05). Conclusions: Rehabilitation with robotic glove (Gloreha) can positively promote functional recovery of arm function in a patient with stroke.
Towards discovery of novel scaffold with potent antiangiogenic activity; design, synthesis of pyridazine based compounds, impact of hinge interaction, and accessibility of their bioactive conformation on VEGFR-2 activities

Abstract Pyridazine scaffolds are considered privileged structures pertaining to its novelty, chemical stability, and synthetic feasibility. In our quest towards the development of novel scaffolds for effective vascular endothelial growth 2 (VEGFR-2) inhibition with antiangiogenic activity, four novel series of pyridazines were designed and synthesised. Five of the synthesised compounds; namely (8c, 8f, 15, 18b, and 18c) exhibited potent VEGFR-2 inhibitory potency (>80%); with IC50 values ranging from low micromolar to nanomolar range; namely compounds 8c, 8f, 15, 18c with (1.8 µM, 1.3 µM, 1.4 µM, 107 nM), respectively. Moreover, 3-[4-{(6-oxo-1,6-dihydropyridazin-3-yl)oxy}phenyl]urea derivative (18b) exhibited nanomolar potency towards VEGFR-2 (60.7 nM). In cellular assay, the above compounds showed excellent inhibition of VEGF-stimulated proliferation of human umbilical vein endothelial cells at 10 μM concentration. Finally, an extensive molecular simulation study was performed to investigate the probable interaction with VEGFR-2.
Ontogenetic Variation in Movements and Depth Use, and Evidence of Partial Migration in a Benthopelagic Elasmobranch

Tope (Galeorhinus galeus) is a highly mobile elasmobranch in the temperate to subtropical northeast Atlantic. It is highly migratory and has been shown to display complex movement patterns, such as partial migration, in the southern hemisphere. In the northeast Atlantic, previous mark-recapture studies have struggled to identify movement patterns and the species behaviour is poorly described, yet identification of migratory behaviors and habitats of importance for the species is of paramount importance for effective management. Here, we combined fisheries independent survey data with mark-recapture (MR) data to investigate the distribution of different age classes of tope across the northeast Atlantic. We further investigated depth use in detail with archival electronic tags and a pop-up satellite archival tag (PSAT). We suggest previous studies struggling to find consistent movement patterns using MR data were confounded by a combination of site fidelity, partial migration by females and increasing depth and home range of juveniles. Survey and MR data showed immature tope less than 40 cm were caught exclusively in continental shelf waters less than 45 m deep, showing a significant relationship between habitat depth and total length. Immature individuals seemed to remain on the continental shelf, while mature tope of both genders were caught in both shelf and offshore waters. This use of deeper water habitats by mature tope was further supported by archival tags, which indicated individuals use both shallow (<200 m depth) and deep-water habitats, diving to depths of 826 m; the deepest record for this species. The PSAT tag tracked the horizontal movements of an adult male, which confirmed utilisation of both shallow inshore and deep offshore habitats. Most tope remained within 500 km of their tagging site, although some mature females had a larger, more southerly range, including connectivity with the Mediterranean. This study clearly demonstrates the highly migratory habits of tope, and suggests larger individuals divide their time between shallow and deep-water habitats. It shows the northeast Atlantic tope population should benefit from consistent management throughout its range.
Antimicrobial Activity of Cinnamaldehyde on Streptococcus mutans Biofilms

Streptococcus mutans is considered the most relevant bacteria in the transition of non-pathogenic commensal oral microbiota to biofilms which contribute to the dental caries process. The present study aimed to evaluate the antimicrobial activity of a natural plant product, cinnamaldehyde against S. mutans biofilms. Minimum inhibitory concentrations (MIC), minimal bactericidal concentration (MBC), and growth curves were determined to assess its antimicrobial effect against planktonic S. mutans. The biofilm biomass and metabolism with different concentrations of cinnamaldehyde and different incubation time points were assessed using the crystal violet and MTT assays. The biofilms were visualized using confocal laser scanning microscopy (CLSM). Bacterial cell surface hydrophobicity, aggregation, acid production, and acid tolerance were evaluated after cinnamaldehyde treatment. The gene expression of virulence-related factors (gtfB, gtfC, gtfD, gbpB, comDE, vicR, ciaH, ldh and relA) was investigated by real-time PCR. The MIC and MBC of cinnamaldehyde against planktonic S. mutans were 1000 and 2000 μg/mL, respectively. The results showed that cinnamaldehyde can decrease biofilm biomass and metabolism at sub-MIC concentrations. CLSM images revealed that the biofilm-covered surface areas decreased with increasing concentrations of cinnamaldehyde. Cinnamaldehyde increased cell surface hydrophobicity, reduced S. mutans aggregation, inhibited acid production, and acid tolerance. Genes expressions in the biofilms were down-regulated in the presence of cinnamaldehyde. Therefore, our data demonstrated that cinnamaldehyde at sub-MIC level suppressed the microbial activity on S. mutans biofilm by modulating hydrophobicity, aggregation, acid production, acid tolerance, and virulence gene expression.
Staphylococcus aureus Internalized by Skin Keratinocytes Evade Antibiotic Killing

Staphylococcus aureus causes the majority of skin and soft tissue infections. Half of patients treated for primary skin infections suffer recurrences within 6 months despite appropriate antibiotic sensitivities and infection control measures. We investigated whether S. aureus internalized by human skin keratinocytes are effectively eradicated by standard anti-staphylococcal antibiotics. S. aureus, but not S. epidermidis, were internalized and survive within keratinocytes without inducing cytotoxicity or releasing the IL-33 danger signal. Except for rifampicin, anti-staphylococcal antibiotics in regular clinical use, including flucloxacillin, teicoplanin, clindamycin, and linezolid, did not kill internalized S. aureus, even at 20-fold their standard minimal inhibitory concentration. We conclude that internalization of S. aureus by human skin keratinocytes allows the bacteria to evade killing by most anti-staphylococcal antibiotics. Antimicrobial strategies, including antibiotic combinations better able to penetrate into mammalian cells are required if intracellular S. aureus are to be effectively eradicated and recurrent infections prevented.
Structural Analysis of PfSec62-Autophagy Interacting Motifs (AIM) and PfAtg8 Interactions for Its Implications in RecovER-phagy in Plasmodium falciparum

Autophagy is a degradative pathway associated with many pathological and physiological processes crucial for cell survival. During ER stress, while selective autophagy occurs via ER-phagy, the re-establishment of physiologic ER homeostasis upon resolution of a transient ER stress is mediated by recovER-phagy. Recent studies demonstrated that recovER-phagy is governed via association of Sec62 as an ER-resident autophagy receptor through its autophagy interacting motifs (AIM)/LC3-interacting region (LIR) toAtg8/LC3. Atg8 is an autophagy protein, which is central to autophagosome formation and maturation. Plasmodium falciparum Atg8 (PfAtg8) has both autophagic and non-autophagic functions critical for parasite survival. Since Plasmodium also has Sec62 in the ER membrane and is prone to ER stress due to drastic transformation during their complex intraerythrocytic cycle; hence, we initiated the studies to check whether recovER-phagy occurs in the parasite. To achieve this, a comprehensive study based on the computational approaches was carried out. This study embarks upon identification of AIM sequences in PfSec62 by carrying out peptide-protein docking simulations and comparing the interactions of these AIMs with PfAtg8, based on the molecular dynamic simulations. Detailed analysis is based on electrostatic surface complementarity, peptide-protein interaction strength, mapping of non-covalent bond interactions and rupture force calculated from steered MD simulations. Potential mean forces and unbinding free energies (ΔGdissociation) using Jarzynski's equality were also computed for the AIM/LIR motif complexes with PfAtg8/HsLC3 autophagy proteins to understand their dissociation free energy profiles and thereby their binding affinities and stability of the peptide-protein complexes. Through this study, we predict Sec62 mediated recovER-phagy in Plasmodium falciparum, which might open new avenues to explore novel drug targets for antimalarial drug discovery.
Mechanical Properties of Magnetron Sputtered Free Standing Mg-Ag Alloy Films

Magnesium based alloys gained great interest for medical biodegradable applications. Limitations arise from high corrosion rates and mechanical properties of the Mg based alloys. In recent work it was shown that the corrosion rate of a precipitate free Mg-6Ag thin film can be reduced by a factor of three compared to pure sputtered Mg. As Mg-6Ag combines the very promising corrosion results with a potential therapeutically use of Ag ions, the investigation of their mechanical properties is needed for a full characterization of Mg-Ag alloys as biodegradable material. In this work the Ag content was varied from 2 wt% to 10 wt%. The investigated thin film samples were dog-bone shaped samples with a thickness of 20 µm. The samples were fabricated by a combination of UV lithography, sacrificial layer technique and magnetron sputtering. The mechanical properties were determined using uniaxial tensile test. Compared to pure Mg samples fabricated by the same processing route the yield strength is approximately doubled for Ag containing samples. For films with a Ag concentration up to 8 wt% the elongation at fracture reaches a value of 7%. Further increase of the Ag concentration leads to lower elongation at fracture. Thus, especially due to the low corrosion rate, Mg-6Ag shows the optimum of all investigated alloys, with a yield strength of 310 MPa and an elongation at fracture of 6%.
Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention

Aging is accompanied by remodeling of the immune system. With time, this leads to a decline in immune efficacy, resulting in increased vulnerability to infectious diseases, diminished responses to vaccination, and a susceptibility to age-related inflammatory diseases. An age-associated immune alteration, extensively reported in previous studies, is the reduction in the number of peripheral blood naïve cells, with a relative increase in the frequency of memory cells. These two alterations, together with inflamm-aging, are considered the hallmarks of immunosenescence. Because aging is a plastic process, it is influenced by both nutritional and pharmacological interventions. Therefore, the role of nutrition and of immunomodulation in immunosenescence is discussed, due to the multifactorial influence on these hallmarks. The close connection between nutrition, intake of bioactive nutrients and supplements, immune function, and inflammation demonstrate the key role of dietary strategies as regulators of immune response and inflammatory status, hence as possible modulators of the rate of immunosenescence. In addition, potential options for therapeutic intervention are clarified. In particular, the use of interleukin-7 as growth factor for naïve T cells, the function of checkpoint inhibitors in improving T cell responses during aging and, the potential of drugs that inhibit mitogen-activated protein kinases and their interaction with nutrient signaling pathways are discussed. Finally, it is suggested that the inclusion of appropriate combinations of toll-like receptor agonists may enhance the efficacy of vaccination in older adults.
Association Between Endothelial Cell Stabilizing Medication and Small Vessel Disease Stroke: A Case-Control Study

Increasing evidence suggests a role for endothelial cell (EC) dysfunction in pathogenesis of cerebral small vessel disease. Commonly used medications including certain antihypertensives and statins have EC-stabilizing effects. We used individual patient data from completed acute stroke trials to assess whether prior exposure to EC-stabilizing medications was associated with lacunar stroke, using lacunar stroke as a clinical proxy for cerebral small vessel disease. Across 12,002 patients with relevant data, 2,855 (24%) had a lacunar stroke presentation. Univariable analyses suggested potential confounding from vascular diseases treated with EC-stabilizing medications. Initial multivariable logistic regression gave conflicting results when describing the independent association of exposure to EC-stabilizing medication and lacunar stroke in the complete population (O.R. 0.87, 95% C.I.: 0.77– 0.98) and limited to those taking any antihypertensive (O.R. 1.51, 95% C.I.: 1.21–1.88). Re-running the analyses including statins in the EC-stabilizing category suggested a beneficial effect of EC-stabilizing medication exposure on lacunar stroke incidence (O.R. 0.83, 95% C.I.: 0.73–0.93). These results align with recent pre-clinical data and would support interventional trials of EC-stabilizing medication for preventing cerebral small vessel disease. Our results also suggest that analyses of EC-stabilizing interventions need to adjust for potential endothelial effects of other co-prescribed medication.
Fibulin-4 exerts a dual role in LTBP-4L–mediated matrix assembly and function

Significance Soft tissues such as blood vessels, lung, and skin require various extracellular proteins, including tropoelastin, fibrillins, fibulin-4, and latent TGF-β binding protein-4 (LTBP-4) to synthesize functional elastic fibers in a highly hierarchical fashion. Mutations in these proteins cause heritable diseases, resulting in deficient elastic fibers and function. We provide evidence for a dual role of fibulin-4 in this context. Our results demonstrate how physical interactions between these elastogenic proteins play key roles in inducing conformational and functional changes, which then impacts self-assembly and elastic fiber formation. This fundamental finding is essential to understand the pathogenesis of diseases associated with mutations in elastogenic proteins. Elastogenesis is a hierarchical process by which cells form functional elastic fibers, providing elasticity and the ability to regulate growth factor bioavailability in tissues, including blood vessels, lung, and skin. This process requires accessory proteins, including fibulin-4 and -5, and latent TGF binding protein (LTBP)-4. Our data demonstrate mechanisms in elastogenesis, focusing on the interaction and functional interdependence between fibulin-4 and LTBP-4L and its impact on matrix deposition and function. We show that LTBP-4L is not secreted in the expected extended structure based on its domain composition, but instead adopts a compact conformation. Interaction with fibulin-4 surprisingly induced a conformational switch from the compact to an elongated LTBP-4L structure. This conversion was only induced by fibulin-4 multimers associated with increased avidity for LTBP-4L; fibulin-4 monomers were inactive. The fibulin-4–induced conformational change caused functional consequences in LTBP-4L in terms of binding to other elastogenic proteins, including fibronectin and fibrillin-1, and of LTBP-4L assembly. A transient exposure of LTBP-4L with fibulin-4 was sufficient to stably induce conformational and functional changes; a stable complex was not required. These data define fibulin-4 as a molecular extracellular chaperone for LTBP-4L. The altered LTBP-4L conformation also promoted elastogenesis, but only in the presence of fibulin-4, which is required to escort tropoelastin onto the extended LTBP-4L molecule. Altogether, this study provides a dual mechanism for fibulin-4 in 1) inducing a stable conformational and functional change in LTBP-4L, and 2) promoting deposition of tropoelastin onto the elongated LTBP-4L.
Early Efficacy Analysis of Cluster and Conventional Immunotherapy in Patients With Allergic Rhinitis

Background: Specific immunotherapy is an important immune-modifying treatment for patients with allergic rhinitis (AR). We compared the early efficacy and safety of cluster and conventional immunotherapies for patients with AR. Methods: One hundred forty-nine patients with persistent AR were enrolled in a randomized and open-label trial and were divided into the following 4 groups: 60 children treated conventionally, 33 children treated using the cluster schedule, 23 adults treated conventionally, and 33 adults treated using the cluster schedule. Patients in the cluster groups reached the maintenance dose within 6 weeks, while those receiving conventional therapy reached the maintenance dose within 14 weeks. Symptom scores and skin prick test scores (SPTs) were used to evaluate clinical efficacy and adverse reactions. Results: After buildup phase of treatment, symptom scores, and SPTs were significantly lower than those prior to treatment in each group (P < .05). No significant differences were found in the efficacy of nasal symptoms scores among four groups (P > .05). However, the efficacy of SPTs using conventional schedule was higher than cluster schedule in children groups (group A and B, 57.7 vs 30.2%, P = .001). Besides, the efficacy of SPTs in adults was higher than children when using the cluster treatment (group D and B, 53.0 vs 30.2%, P = .008). No severe adverse reaction occurred. Conclusions: Conventional and cluster immunotherapy schedules have similar efficacies, which do not vary with age; both schedules are safe and reliable. Also, SPT facilitate evaluation of clinical efficacy.