Miracle-dz/UniFAR-FTUs huggingface dataset:
Feasibility of feeding Aedes aegypti mosquitoes on dengue virus-infected human volunteers for vector competence studies in Iquitos, Peru

Background Transmission of dengue virus (DENV) from humans to mosquitoes represents a critical component of dengue epidemiology. Examinations of this process have generally been hampered by a lack of methods that adequately represent natural acquisition of DENV by mosquitoes from humans. In this study, we assessed artificial and natural blood feeding methods based on rates of DENV infection and dissemination within mosquitoes for use in a field-based epidemiological cohort study in Iquitos, Peru. Methodology/Principal findings Our study was implemented, stepwise, between 2011 and 2015. Participants who were 5 years and older with 5 or fewer days of fever were enrolled from ongoing clinic- and neighborhood-based studies on dengue in Iquitos. Wild type, laboratory-reared Aedes aegypti were fed directly on febrile individuals or on blood collected from participants that was either untreated or treated with EDTA. Mosquitoes were tested after approximately 14 days of extrinsic incubation for DENV infection and dissemination. A total of 58 participants, with viremias ranging from 1.3 × 102 to 2.9 × 106 focus-forming units per mL of serum, participated in one or more feeding methods. DENV infection and dissemination rates were not significantly different following direct and indirect-EDTA feeding; however, they were significantly lower for mosquitoes that fed indirectly on blood with no additive. Relative to direct feeding, infection rates showed greater variation following indirect-EDTA than indirect-no additive feeding. Dissemination rates were similar across all feeding methods. No differences were detected in DENV infection or dissemination rates in mosquitoes fed directly on participants with different dengue illness severity. Conclusions/Significance Our study demonstrates the feasibility of using direct and indirect feeding methods for field-based studies on vector competence. Direct mosquito feeding is preferable in terms of logistical ease, biosecurity, and reliability.
Topical, systemic and biologic therapies in hidradenitis suppurativa: pathogenic insights by examining therapeutic mechanisms

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the skin, manifesting in chronic, recurrent painful pustules, nodules, boils and purulent draining abscesses. Our current understanding of the pathogenesis of the disease is incomplete. This review aims to identify available treatment options in HS and discuss the pharmacological mechanisms through which such agents function. Identifying common pathways may inform our understanding of the pathogenesis of HS as well as identify future therapeutic targets. The pharmacological mechanisms implicated in topical therapies, antibiotic, hormonal, systemic immunomodulatory and biologic therapies for HS are discussed. Significant differences exist between agents and implicated pathways in therapy for mild and severe disease. This is an expression of the possible dichotomy in inflammatory pathways (and treatment responses) in HS. Studies involving monoclonal antibodies provide the greatest insight into what these specific mechanisms may be. Their variable levels of clinical efficacy compared with placebo bolsters the suggestion that differential inflammatory pathways may be involved in different presentations and severity of disease. Nuclear factor kappa B (NF-κB), tumor necrosis factor (TNF)-α and other innate immune mechanisms are strongly represented in treatments which are effective in mild to moderate disease in the absence of scarring or draining fistulae, however complex feed-forward mechanisms in severe disease respond to interleukin (IL)-1 inhibition but are less likely to respond to innate immune inhibition (through NF-κB or TNF-α) alone. It is unclear whether IL-17 inhibition will parallel TNF-α or IL-1 inhibition in effect, however it is plausible that small molecule targets (Janus kinase1 and phosphodiesterase 4) may provide effective new strategies for treatment of HS.
Reduced local immunity in HPV‐related VIN: Expression of chemokines and involvement of immunocompetent cells

Usual type VIN is a premalignant disorder caused by persistent HPV infection. High prevalence of VIN in immuno‐suppressed women suggests that a good innate and adaptive immune response is important for defense against HPV. Here, we explored expression levels of chemokines and related these to the presence or absence of immuno‐competent cells (dendritic and T‐cells) in affected (HPV‐positive VIN) and non‐affected (HPV‐negative) vulvar tissues from the same patients. Combining microarray data with quantitative real‐time RT‐PCR, it was observed that several important chemokines were differentially expressed between VIN and control samples (up‐regulation of IL8, CXCL10, CCL20 and CCL22 and down‐regulation of CXCL12, CCL21 and CCL14). Furthermore, an increased number of mature dendritic cells (CD208+) seemed to be bottled up in the dermis, and although a T‐cell response (increased CD4+ and CD8+ cells) was observed in VIN, a much larger response is required to clear the infection. In summary, it seems that most mature dendritic cells do not receive the proper chemokine signal for migration and will stay in the dermis, not able to present viral antigen to naive T‐cells in the lymph node. Consequently the adaptive immune response diminishes, resulting in a persistent HPV infection with increased risk for neoplasia. © 2008 Wiley‐Liss, Inc.
Fatty Acid Profiles of Cow’s Milk and Cheese as Affected by Mountain Pasture Type and Concentrate Supplementation

Simple Summary It is well-known that milk and cheese derived from grazing animals are beneficial for human health. Grazing dairy cows produce milk with high levels of unsaturated fatty acids and conjugated linoleic acid, which are able to reduce cardiovascular diseases and have some anticancer properties. The aim of this trial was to assess the effect of pasture type and concentrate supplementation levels on the fatty acid composition of milk and cheese obtained during summer grazing on mountain pasture. Seventy-two dairy cows, supplemented with 3.0 kg/head/d or 1.5 kg/head/d of energetic concentrate feed in the diet, grazed on a nutritionally rich Poion alpinae pasture, and subsequently a nutritionally poor Seslerion caeruleae pasture. In milk, the highest concentrate level reduced linolenic acid and total polyunsaturated fatty acids, while the pasture type influenced the monounsaturated fatty acids. In cheeses, these differences were markedly reduced. Abstract The aim of this trial was to assess the effect of pasture type and concentrate supplementation on the fatty acids (FA) composition of milk and cheese obtained during summer grazing on mountain pasture. Seventy-two Italian Simmental dairy cows were assigned to two groups that differed by the amount of concentrate supplementation: 3.0 kg/head/d (HIGH) vs. 1.5 kg/head/d (LOW). The dairy cows grazed on a Poion alpinae alliance pasture (PAST1), and subsequently they grazed on a Seslerion caeruleae alliance pasture (PAST2) for 10 d each. In the last three days of each experimental period, milk samples were collected immediately before each cheese-making event. Cheese samples were collected from each cheese loaf after 60 d of ripening. LOW showed higher isoFA, FA intermediates of the ruminal biohydrogenation, C18:3 c9,c12,c15, and total polyunsaturated fatty acid (PUFA) levels than HIGH. The pasture type had a more limited effect on FA composition of milk than concentrate level and was mainly related to monounsaturated fatty acids (MUFA), which were higher in PAST1 than PAST2 (p < 0.05). In cheeses, these differences were reduced. The phytanic acid and phytanic isomer ratio (SRR/RRR) in milk were not affected either by supplement level (p > 0.05) or by type of pasture (p > 0.05). Increasing the concentrate offered to dairy cows from 1.5 to 3.0 kg/d did not markedly influence the level of PUFA in cheeses produced during summer grazing on high mountain pasture.
Volterra-series-based equivalent nonlinear system method for subharmonic vibration systems

ABSTRACT Subharmonics generation in the nonlinear system, directly using the traditional finite Volterra series, cannot generally represent the aimed system. In this paper, a new approach is presented, which is an extension of single finite Volterra series for representation and analysis of the subharmonic vibration system based on equivalent nonlinear system. The equivalent nonlinear system, which is constructed by pre-compensating the subharmonic vibration system with the super-harmonic nonlinear model, yields the input–output relation between the virtual source and the response of the aimed nonlinear system. Orthogonal least square method is employed to identify the truncated order of Volterra series and predominant Volterra kernels of the equivalent nonlinear system. The MGFRFs (modified generalised frequency response functions) of the equivalent nonlinear system is obtained from the data of the virtual source and response, and verified by comparing the response estimated by the MGFRFs with its true value. Therefore, the aimed subharmonic vibration system can be analysed by taking advantage of a truncated Volterra series based on the equivalent nonlinear system. Numerical simulations were carried out, whose results have shown that the proposed method is valid and feasible, and suitable to apply on representation and analysis of subharmonic vibration systems.
Control of fibrinolytic drug injection via real-time ultrasonic monitoring of blood coagulation

In the present study, we investigated the capabilities of a novel ultrasonic approach for real-time control of fibrinolysis under flow conditions. Ultrasonic monitoring was performed in a specially designed experimental in vitro system. Fibrinolytic agents were automatically injected at ultrasonically determined stages of the blood clotting. The following clots dissolution in the system was investigated by means of ultrasonic monitoring. It was shown, that clots resistance to fibrinolysis significantly increases during the first 5 minutes since the formation of primary micro-clots. The efficiency of clot lysis strongly depends on the concentration of the fibrinolytic agent as well as the delay of its injection moment. The ultrasonic method was able to detect the coagulation at early stages, when timely pharmacological intervention can still prevent the formation of macroscopic clots in the experimental system. This result serves as evidence that ultrasonic methods may provide new opportunities for real-time monitoring and the early pharmacological correction of thrombotic complications in clinical practice.
Bias in PET Images of Solid Phantoms Due to CT-Based Attenuation Correction

The use of computed tomography (CT) images to correct for photon attenuation in positron emission tomography (PET) produces unbiased patient images, but it is not optimal for synthetic materials. For test objects made from epoxy, image bias and artifacts have been observed in well-calibrated PET/CT scanners. An epoxy used in commercially available sources was infused with long-lived 68Ge/68Ga nuclide and measured on several PET/CT scanners as well as on older PET scanners that measured attenuation with 511-keV photons. Bias in attenuation maps and PET images of phantoms was measured as imaging parameters and methods varied. Changes were made to the PET reconstruction to show the influence of CT-based attenuation correction. Additional attenuation measurements were made with a new epoxy intended for use in radiology and radiation treatment whose photonic properties mimic water. PET images of solid phantoms were biased by between 3% and 24% across variations in CT X-ray energy and scanner manufacturer. Modification of the reconstruction software reduced bias, but object-dependent changes were required to generate accurate attenuation maps. The water-mimicking epoxy formulation showed behavior similar to water in limited testing. For some solid phantoms, transformation of CT data to attenuation maps is a major source of PET image bias. The transformation can be modified to accommodate synthetic materials, but our data suggest that the problem may also be addressed by using epoxy formulations that are more compatible with PET/CT imaging.
Investigating the Impact of Indemnity Waivers on the Length of Stay of Cats at an Australian Shelter

Simple Summary The practice of adopting animals from shelters with ‘indemnity waivers’ is becoming increasingly common. Indemnity waivers serve to limit the ongoing responsibility of a shelter to an animal with a pre-existing condition likely to involve veterinary treatment in the future, thereby allowing shelters to adopt out animals that may have been previously considered unsuitable for adoption and instead euthanased. However, there has been concern from some sectors of the sheltering community that indemnity waivers can lead to animals staying in shelters longer than necessary because with a waiver they become less desirable to the public. This research sought to examine if there was a link between the presence of indemnity waivers and increased lengths of stay (LOS) of cats at an Australian animal shelter. It examined data for 249 cats adopted from the Royal Society for the Prevention of Cruelty to Animals (RSPCA) Weston shelter located in the Australian Capital Territory (ACT), Australia over a period of six months in 2017. The results demonstrated that cats adopted with indemnity waivers were found to have a longer LOS than those adopted without waivers, however no particular waiver type was found to be responsible for this effect. This finding should encourage shelters to use indemnity waivers judiciously due to the impact on LOS. Abstract Due to resource limitations, animal shelters in Australia historically have focused on rehoming animals considered ‘highly adoptable’. Increasingly, animal shelters in Australia are rehoming animals with pre-existing medical and/or behavioural issues. These animals are often rehomed with an ‘indemnity waiver’ to transfer the responsibility of ongoing financial costs associated with these conditions from the shelter to the new owner. However, it is unknown what effect these indemnity waivers have on the length of stay (LOS) of animals prior to adoption. The current study used data collected from the Royal Society for the Prevention of Cruelty to Animals (RSPCA) Weston shelter located in the Australian Capital Territory (ACT), Australia in 2017 to investigate the effect of indemnity waivers on the LOS of cats. A restricted maximum likelihood model (REML) was used to determine the effect of breed, age, coat colour, presence of a waiver, waiver type (categorised into seven groups) and waiver number (no waiver, single waiver or multiple waivers) on LOS. In the final multivariate model, age, breed and waiver number were found to influence LOS. Young cats, purebred cats and cats adopted without a waiver were adopted fastest. This study is the first to report the effect of indemnity waivers on the adoptability of cats from shelters.
Potential Role of Flavonoids in Treating Chronic Inflammatory Diseases with a Special Focus on the Anti-Inflammatory Activity of Apigenin

Inflammation has been reported to be intimately linked to the development or worsening of several non-infectious diseases. A number of chronic conditions such as cancer, diabetes, cardiovascular disorders, autoimmune diseases, and neurodegenerative disorders emerge as a result of tissue injury and genomic changes induced by constant low-grade inflammation in and around the affected tissue or organ. The existing therapies for most of these chronic conditions sometimes leave more debilitating effects than the disease itself, warranting the advent of safer, less toxic, and more cost-effective therapeutic alternatives for the patients. For centuries, flavonoids and their preparations have been used to treat various human illnesses, and their continual use has persevered throughout the ages. This review focuses on the anti-inflammatory actions of flavonoids against chronic illnesses such as cancer, diabetes, cardiovascular diseases, and neuroinflammation with a special focus on apigenin, a relatively less toxic and non-mutagenic flavonoid with remarkable pharmacodynamics. Additionally, inflammation in the central nervous system (CNS) due to diseases such as multiple sclerosis (MS) gives ready access to circulating lymphocytes, monocytes/macrophages, and dendritic cells (DCs), causing edema, further inflammation, and demyelination. As the dearth of safe anti-inflammatory therapies is dire in the case of CNS-related disorders, we reviewed the neuroprotective actions of apigenin and other flavonoids. Existing epidemiological and pre-clinical studies present considerable evidence in favor of developing apigenin as a natural alternative therapy against chronic inflammatory conditions.
Task constraints and stepping movement of fast-pitch softball hitting

This study aims to clarify the relationship between task constraints and the preparatory movement of fast-pitch softball batters in Japan for three different competition categories, namely high school, college, and league. As task constraints, we focused on the temporal and tool constraints and evaluated preparatory movements using initiation time and step duration of the stepping movement in a striking action. First, we confirmed the temporal constraints in each category and then examined the relationship between the temporal constraints and the stepping movements. The results demonstrated that the temporal constraints affected both initiation time and step duration of the stepping movements. Hierarchical cluster analysis was applied to the two variables. Consequently, the stepping movement of the softball players was classified into three types: “late initiation–short duration” (LS), “early initiation–short duration” (ES), and “early initiation–long duration” (EL) corresponding to the task constraints. Finally, the relationship between the task constraints of each category and the stepping movements was examined. The results revealed that high school players exhibited mostly the LS- or EL-type stepping movement; college players exhibited mostly the EL-type stepping movement; and league players exhibited all types. These results depict that the players in each category with each temporal and tool constraint exhibited particular types of stepping movements as a preparatory movement corresponding to each task constraint, thereby arguing that players use a not-to-lose strategy exploiting the redundancy in solutions under various task constraints.
Recommendations for Methodology of Virtual Reality Clinical Trials in Health Care by an International Working Group: Iterative Study

Background Therapeutic virtual reality (VR) has emerged as an efficacious treatment modality for a wide range of health conditions. However, despite encouraging outcomes from early stage research, a consensus for the best way to develop and evaluate VR treatments within a scientific framework is needed. Objective We aimed to develop a methodological framework with input from an international working group in order to guide the design, implementation, analysis, interpretation, and communication of trials that develop and test VR treatments. Methods A group of 21 international experts was recruited based on their contributions to the VR literature. The resulting Virtual Reality Clinical Outcomes Research Experts held iterative meetings to seek consensus on best practices for the development and testing of VR treatments. Results The interactions were transcribed, and key themes were identified to develop a scientific framework in order to support best practices in methodology of clinical VR trials. Using the Food and Drug Administration Phase I-III pharmacotherapy model as guidance, a framework emerged to support three phases of VR clinical study designs—VR1, VR2, and VR3. VR1 studies focus on content development by working with patients and providers through the principles of human-centered design. VR2 trials conduct early testing with a focus on feasibility, acceptability, tolerability, and initial clinical efficacy. VR3 trials are randomized, controlled studies that evaluate efficacy against a control condition. Best practice recommendations for each trial were provided. Conclusions Patients, providers, payers, and regulators should consider this best practice framework when assessing the validity of VR treatments.
B2 Adrenergic Receptor Polymorphisms and Treatment- Outcomes in CardiovascularDiseases

B2 Adrenergic Receptor Polymorphisms and Treatment- Outcomes in Cardiovascular Diseases Cardiovascular diseases (CVD) represent the major health problem in the western world and heavy social and economic burden. Under this name an eterogenous group of multifactorial conditions is included. There is appreciable inter-individual variability in the susceptibility to cardiovascular disease and in the response to the associated pharmacological treatments. Genetic polymorphism may be, at least in part, responsible for both susceptibility to disease and inter-individual variability in response to pharmacological treatments.
Benthic community succession on artificial and natural coral reefs in the northern Gulf of Aqaba, Red Sea

Evaluating the efficacy of artificial structures in enhancing or sustaining biodiversity on tropical coral reefs is key to assessing their role in reef conservation or management. Here, we compare spatial and temporal patterns of colonization and succession of the benthic assemblage on settlement collectors (ceramic tiles) in a 13-mo mensurative experiment on a suspended artificial reef, a seafloor artificial reef, and two nearby natural reefs at Eilat, Gulf of Aqaba. We also conducted a concurrent 7-mo manipulative experiment on the suspended reef and one of the natural reefs, and monitored fish feeding behaviour on experimental collectors, to examine effects of large mobile consumers on these patterns. In both experiments, taxonomic composition as percent planar cover for the whole community or biomass for the invertebrate component differed between collector topsides, dominated by a filamentous algal matrix, and shaded undersides with a profuse assemblage of suspension- or filter-feeding invertebrates. In the mensurative experiment, we found differences in final community and invertebrate composition between sites, which clustered according to reef type (artificial vs. natural) for collector undersides. Invertebrate biomass was greater at both artificial reefs than at one (undersides) or both (topsides) natural reefs. In the manipulative experiment, we found similar differences in composition between sites/reef types as well as between treatments (exclusion vs. control), and the invertebrate biomass was greater on the artificial reef. Invertebrate biomass was greater in the exclusion treatment than the control on collector undersides, suggesting mobile consumers can affect community composition and abundance. Predominant fish species observed interacting with collectors differed between artificial and natural reefs, likely contributing to differences in patterns of colonization and succession between sites and reef types. Our findings suggest artificial reefs have the potential to enhance cover and biomass of certain reef-associated assemblages, particularly those occupying sheltered microhabitats.