Miracle-dz/UniFAR-FTUs huggingface dataset:
Socially Communicative Eye Contact and Gender Affect Memory

Because of their value as a socially communicative cue, researchers have strived to understand how the gaze of other people influences a variety of cognitive processes. Recent work in social attention suggests that the use of images of people in laboratory studies, as a substitute for real people, may not effectively test socially communicative aspects of eye gaze. As attention affects many other cognitive processes, it is likely that social attention between real individuals could also affect other cognitive processes, such as memory. However, from previous work alone, it is unclear whether, and if so how, socially communicative eye gaze affects memory. The present studies test the assumption that socially communicative aspects of eye gaze may impact memory by manipulating the eye gaze of a live speaker in the context of a traditional recognition paradigm used frequently in the laboratory. A female (Experiment 1) or male (Experiment 2) investigator read words aloud and varied whether eye contact was, or was not, made with a participant. With both female and male investigators, eye contact improved word recognition only for female participants and hindered word recognition in male participants. When a female investigator prolonged their eye contact (Experiment 3) to provide a longer opportunity to both observe and process the investigator’s eye gaze, the results replicated the findings from Experiments 1 and 2. The findings from Experiments 1–3 suggest that females interpret and use the investigator’s eye gaze differently than males. When key aspects from the previous experiments were replicated in a noncommunicative situation (i.e., when a video of a speaker is used instead of a live speaker; Experiment 4), the memory effects observed previously in response to eye gaze were eliminated. Together, these studies suggest that it is the socially communicative aspects of eye gaze from a real person that influence memory. The findings reveal the importance of using social cues that are communicative in nature (e.g., real people) when studying the relationship between social attention and memory.
Cardiac sympathetic innervation network shapes the myocardium by locally controlling cardiomyocyte size through the cellular proteolytic machinery

The heart is innervated by a dense sympathetic neuron network which, in the short term, controls chronotropy and inotropy and, in the long term, regulates cardiomyocyte size. Acute neurogenic control of heart rate is achieved locally through direct neuro‐cardiac coupling at specific junctional sites (neuro‐cardiac junctions). The ventricular sympathetic network topology is well‐defined and characteristic for each mammalian species. In the present study, we used cell size regulation to determine whether long‐term modulation of cardiac structure is achieved via direct sympatho‐cardiac coupling. Local density of cardiac innervation correlated with cell size throughout the myocardial walls in all mammalian species analysed, including humans. The data obtained suggest that constitutive neurogenic control of cardiomyocyte trophism occurs through direct intercellular signalling at neuro‐cardiac junctions.
Strengthening Aboriginal and Torres Strait Islander health policy: lessons from a case study of food and nutrition

Abstract Objective: To examine key factors influencing the prioritisation of food and nutrition in Aboriginal and Torres Strait Islander health policy during 1996–2015. Design: A qualitative policy analysis case study was undertaken, combining document analysis with thematic analysis of key informant interviews. Setting: Australia. Participants: Key actors involved in Aboriginal and Torres Strait Islander health policy between 1996 and 2015 (n 38). Results: Prioritisation of food and nutrition in policy reduced over time. Several factors which may have impeded the prioritisation of nutrition were identified. These included lack of cohesion among the community of nutritionists, Aboriginal and Torres Strait Islander leaders and civil society actors advocating for nutrition; the absence of an institutional home for nutrition policy; and lack of consensus and a compelling policy narrative about how priority nutrition issues should be addressed. Political factors including ideology, dismantling of public health nutrition governance structures and missing the opportunities presented by ‘policy windows’ were also viewed as barriers to nutrition policy change. Finally, the complexity and multifaceted nature of nutrition as a policy problem and perceived lack of evidence-based solutions may also have constrained its prioritisation in Aboriginal and Torres Strait Islander health policy. Conclusions: Future advocacy should focus on embedding nutrition within holistic approaches to health and building a collective voice through advocacy coalitions with Aboriginal and Torres Strait Islander leadership. Strategic communication and seizing political opportunities may be as important as evidence for raising the priority of Aboriginal and Torres Strait Islander health issues.
Fetal Hemoglobin Induction to Treat b-Hemoglobinopathies : From Bench to Bedside

The developmental regulation of the γto β-globin switch has motivated research efforts to establish therapeutic modalities for individuals affected with β-hemoglobinopathies. Fetal Hemoglobin (HbF) synthesis is high at birth but declines to adult levels by one year of ages; since HbF blocks hemoglobin S polymerization in Sickle Cell Disease (SCD) and compensated for anemia in β-Thalassemia, reactivating expression is of great research interest. Naturally occurring mutations in the β-globin locus on chromosome 11, produce elevated HbF expression after birth which ameliorates symptoms in SCD. Genome-wide studies discovered three gene loci including BCL11A that account for the majority of inherited HbF variance but considerable work is required to advance this protein as a therapeutic target. Therefore, efforts to develop chemical inducers of HbF are desirable. Hydroxyurea is a potent HbF inducer with clinical efficacy in adults and children with SCD but it has been underutilized in the clinical setting. Numerous pharmacological agents that reactivate γ-gene transcription have been discovered over the last three decades but few have been translated into clinical therapeutics. We will review the progress made in understanding molecular mechanisms of γ-globin regulation and current efforts to expand the number of chemical HbF inducers available for treatment of patients with β-hemoglobinopathies.
Bioinformatics identification of microRNAs involved in polycystic ovary syndrome based on microarray data

Polycystic ovary syndrome (PCOS) is the most common endocrine disease in women of reproductive age. MicroRNAs (miRNAs or miRs) serve important roles in the physiological and pathological process of PCOS. To identify PCOS-associated miRNAs, the dataset GSE84376 was extracted from the Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) were obtained from Gene-Cloud Biotechnology Information and potential target genes were predicted using TargetScan, DIANA-microT-CDS, miRDB and miRTarBase tools. Gene Ontology enrichment analysis was performed using Metascape and a protein-protein interaction network was constructed using Cytoscape. Transcription factors were obtained from FunRich. DE-miRNAs were verified by reverse transcription-quantitative PCR. At the screening phase, there were seven DE-miRNAs in the PCOS group not present in the control group. In total, 935 target genes were identified, which are involved in the development and maturation of oocytes. Mitogen-activated protein kinase 1, phosphatase and tensin homolog, cAMP responsive element binding protein 1, signal transducer and activator of transcription 3, interferon γ, Fms-related tyrosine kinase 1, transcription factor p65, insulin receptor substrate 1, DnaJ homolog superfamily C member 10 and casein kinase 2 α 1 were identified as the top 10 hub genes in the protein-protein interaction network. Specificity protein 1 was the most enriched transcription factor. At the validation phase, the levels of Homo sapiens (hsa)-miR-3188 and hsa-miR-3135b were significantly higher in the PCOS group than in the control group. In addition, the expression level of hsa-miR-3135b was significantly correlated with the number of oocytes retrieved, the fertilization rate and the cleavage rate (P<0.05). The present bioinformatics study on miRNAs may offer a novel understanding of the mechanism of PCOS, and may serve to identify novel miRNA therapeutic targets.
Coleoptera in the Canopy of the Cloud Forest From Tlanchinol in the State of Hidalgo, Mexico

Abstract We describe the biodiversity, seasonal variation, and the possible edge effect of Coleoptera found in the canopy of the cloud forest inTlanchinol in the state of Hidalgo. The coleopterans were collected by means of three fogging events during the dry season and another three during the rainy season in three sites of the forest: the edge, an intermediate, and an internal site. In total, 3,487 coleopterans were collected, belonging to 325 morphospecies from 52 families. The family with the largest number of morphospecies and abundance was Staphylinidae, followed by Curculionidae and Chrysomelidae. Species richness and abundance were higher in the dry season than in the rainy season. The biodiversity analyses, however, suggest that the rainy season showed the highest biodiversity levels, mainly because of the pronounced dominance of some species in the dry season. Species composition was different between the dry and rainy seasons. The internal site showed the lowest biodiversity compared with the intermediate and edge sites. The main edge effect detected was that species composition in the edge site differed from the intermediate and internal sites. Species composition did not differ significantly between the two latter sites. These results suggest that the study zone had a considerable level of biodiversity of Coleoptera and that it was very likely in a well-preserved condition, which supports the findings of another study previously performed in the same site using flight intercept traps.
Assimilation of Satellite-Based Snow Cover and Freeze/Thaw Observations Over High Mountain Asia

Toward qualifying hydrologic changes in the High Mountain Asia (HMA) region, this study explores the use of a hyper-resolution (1 km) land data assimilation (DA) framework developed within the NASA Land Information System using the Noah Multi-parameterization Land Surface Model (Noah-MP) forced by the meteorological boundary conditions from Modern-Era Retrospective analysis for Research and Applications, Version 2 data. Two different sets of DA experiments are conducted: (1) the assimilation of a satellite-derived snow cover map (MOD10A1) and (2) the assimilation of the NASA MEaSUREs landscape freeze/thaw product from 2007 to 2008. The performance of the snow cover assimilation is evaluated via comparisons with available remote sensing-based snow water equivalent product and ground-based snow depth measurements. For example, in the comparison against ground-based snow depth measurements, the majority of the stations (13 of 14) show slightly improved goodness-of-fit statistics as a result of the snow DA, but only four are statistically significant. In addition, comparisons to the satellite-based land surface temperature products (MOD11A1 and MYD11A1) show that freeze/thaw DA yields improvements (at certain grid cells) of up to 0.58 K in the root-mean-square error (RMSE) and 0.77 K in the absolute bias (relative to model-only simulations). In the comparison against three ground-based soil temperature measurements along the Himalayas, the bias and the RMSE in the 0–10 cm soil temperature are reduced (on average) by 10 and 7%, respectively. The improvements in the top layer of soil estimates also propagate through the deeper soil layers, where the bias and the RMSE in the 10–40 cm soil temperature are reduced (on average) by 9 and 6%, respectively. However, no statistically significant skill differences are observed for the freeze/thaw DA system in the comparisons against ground-based surface temperature measurements at mid-to-low altitude. Therefore, the two proposed DA schemes show the potential of improving the predictability of snow mass, surface temperature, and soil temperature states across HMA, but more ground-based measurements are still required, especially at high-altitudes, in order to document a more statistically significant improvement as a result of the two DA schemes.
Plasma Protein Binding as an Optimizable Parameter for Acidic Drugs

The low volume of distribution associated with acidic molecules means that clearance (CL) must also be very low to achieve an effective half-life commensurate with once or twice daily dosing. Plasma protein binding (PPB) should not usually be considered a parameter for optimization, but in the particular case of acidic molecules, raising the PPB above a certain level can result in distribution volume becoming a constant low value equal to the distribution volume of albumin while acting to reduce CL through restricting hepatic and renal access of unbound drug. Thus effective half-life can be increased. Here we detail the approaches and lessons learned at AstraZeneca during the optimization of acidic CXC chemokine receptor 2 (CXCR2) antagonists for the oral drug treatment of inflammatory diseases, resulting in discovery and clinical testing of N-[2-[(2,3-difluorophenyl)methylsulfanyl]-6-[(2R,3S)-3,4-dihydroxybutan-2-yl]oxypyrimidin-4-yl]azetidine-1-sulfonamide (AZD5069) and AZD4721, orally bioavailable acidic molecules with PPB of <1%, human hepatocyte intrinsic clearance values <5 µl/min per 106 cells and predicted human volume of distribution at steady state (Vss) <0.3 l/kg, resulting in effective half-lives in humans of 4 and 17 hours, respectively. Significance Statement Provided that the pharmacologic potency is high enough, modulation of plasma protein binding can form part of a viable strategy in drug discovery to optimize the effective half-life of drug candidates in humans.
Persistence and Lethality of a Fungal Biopesticide (Aprehend) Applied to Insecticide-impregnated and Encasement-type Box Spring Covers for Bed Bug Management

Abstract The newly developed fungal biopesticide Aprehend, containing spores of Beauveria bassiana, is the first biological control agent to be incorporated into management programs to control the common bed bug (Cimex lectularius L.) (Hemiptera: Cimicidae). Aprehend is sprayed as barriers where bed bugs are likely to walk and pick up spores as they search for a bloodmeal. A key application target for Aprehend is the box spring, which may be covered by encasement-type or insecticide-impregnated covers. Since some insecticides can reduce the persistence of fungal spores, we tested the efficacy and spore germination percentages of Aprehend when applied to the two types of box spring covers. We found that spore germination was about 11% lower on the permethrin-impregnated ActiveGuard cover than on the encasement-type AllerEase cover. However, bed bugs exposed for 15 min to Aprehend on the two box spring covers suffered similarly high levels of mortality irrespective of the cover material. Thus, there was no inhibitory or additive effect of the ActiveGuard cover on bed bug mortality. Lastly, overall mortality was higher if bed bugs were exposed to Aprehend-treated ActiveGuard than the ActiveGuard cover alone. Our findings indicate that if pest managers are using ActiveGuard covers in combination with Aprehend, best practice would be to use ActiveGuard on mattresses and apply Aprehend directly to the box spring or to a box spring covered by an encasement-type cover.
The impact of e-cigarette price changes on vaping and smoking behaviors

Abstract Background: Understanding the relations between e-cigarette prices and e-cigarette/cigarette use may shed light on the possible impact of e-cigarette regulations on public health. Objectives: This study aimed to assess potential impacts of e-cigarette price changes on vaping and smoking behaviors by smoking status (current, former, and never smokers) and e-cigarette type (pre-filled only vs. refillable). Methods: A total of 918 US-based adult e-cigarette users completed an online survey, designed to assess behavioral intention of e-cigarette/cigarette use in hypothetical situations with varying prices of e-cigarettes, in 2017. Results: With reduction in e-cigarette prices, more than 50% of current smokers reported they would reduce or quit smoking, but with greater increases in price, the rates of not only those who would quit (12.5–19.4%), but also those who would increase smoking rose (15.1–25.1%). Current smokers (vs. former/never) were more likely to increase e-cigarette use at reduced e-cigarette prices. Among current smokers, pre-filled users were less likely to quit smoking with reduced prices. At higher prices, pre-filled users were more likely to quit e-cigarettes (former smokers), but also more likely to start smoking (never smokers). Among former smokers, recent quitters were more likely to restart smoking with any e-cigarette price changes, and less likely to reduce or quit e-cigarettes with increased prices. Conclusions: Both smoking and e-cigarette use seem to be sensitive to e-cigarette price changes. Increases in e-cigarette price may have both positive and negative effects on smoking behavior, and e-cigarette price changes may disproportionately affect pre-filled users and recent quitters.
Targeting MAPKs, NF‐κB, and PI3K/AKT pathways by methyl palmitate ameliorates ethanol‐induced gastric mucosal injury in rats

Excessive drinking of alcohol has been frequently associated with gastric injury; however, its underlying molecular mechanisms have been inadequately investigated. Methyl palmitate (MP) has demonstrated marked hepato‐, cardio‐ and pulmonary protective features; however, its effects on ethanol‐induced gastric injury have not been studied. The aim of the present study was to evaluate the potential gastroprotective activity of MP against ethanol‐evoked gastric mucosal damage in rats and associated molecular mechanisms, for example, mitogen‐activated protein kinases (MAPKs), nuclear factor κB (NF‐κB), and phosphoinositide 3 kinase/protein kinase B (PI3K/AKT) pathways. The rat stomachs were examined in terms of the inflammatory, oxidative, and apoptotic perturbations. Current data demonstrated that pretreatment with MP attenuated the gross gastric damage, scores of ulcer index, area of mucosal lesions and histopathology outcomes; actions which were similar to the reference antiulcer omeprazole. MP inhibited NF‐κB expression, its nuclear translocation, and the expression of its downstream signals, for example, tumor necrosis factor‐α and myeloperoxidase besides restoration of interleukin‐10 levels. Western blot analysis revealed that MP counteracted the disruption of MAPKs signaling via lowering p‐c‐Jun N‐terminal kinase 1/2 (p‐JNK1/2) expression and restoring the phospho‐extracellular signal‐regulated kinase 1/2 (p‐ERK1/2) levels without affecting p‐p38MAPK levels. Additionally, MP improved the antioxidant milieu via diminishing lipid peroxides and enhancing glutathione, glutathione peroxidase, total antioxidant capacity and mucosal nitric oxide. In the context of apoptosis, MP inhibited the cleavage of caspase‐3 and poly(ADP‐ribose)polymerase (PARP) and Bax protein expression with upregulating B cell lymphoma‐2 expression (Bcl‐2), thus, promoting gastric cellular survival. This was confirmed by MP activation of the PI3K/AKT pathway manifested by enhanced expression of PI3K p110α and p‐AKT. Together, the present findings report the gastroprotective actions of MP mediated via its anti‐inflammatory, antioxidant, and antiapoptotic actions. The underlying molecular mechanisms involve, at least partly, the modulation of MAPKs, NF‐κB and PI3K/AKT transduction.
A Comparative Solubility Enhancement Study of Cefixime Trihydrate Using Different Dispersion Techniques

This study aimed to investigate the effect of different polymers (polyethylene glycol 4000 and 6000 and Soluplus®) on the enhancement of solubility, dissolution, and stability of cefixime trihydrate as a selected class II model drug. Different solid dispersions have been prepared using conventional methods and supercritical fluid technology. The effect of co-solvent incorporation in supercritical fluid technology was also studied. Physicochemical properties for solid dispersions were investigated using Fourier transform infrared analysis, differential scanning calorimetry, thermogravimetric analysis, powder X-ray diffraction, and scanning electron microscopy. The solubility of the prepared solid dispersions increased except for those prepared with Soluplus® using supercritical fluid technology without co-solvent. The best enhancement in the release profile was recorded by Soluplus®-based solid dispersions prepared using a conventional method. The conventional methods of preparation and the presence of co-solvent in supercritical fluid technology converted cefixime into its amorphous form.
A Translational Quantitative Systems Pharmacology Model for CD3 Bispecific Molecules: Application to Quantify T Cell-Mediated Tumor Cell Killing by P-Cadherin LP DART®

CD3 bispecific antibody constructs recruit cytolytic T cells to kill tumor cells, offering a potent approach to treat cancer. T cell activation is driven by the formation of a trimolecular complex (trimer) between drugs, T cells, and tumor cells, mimicking an immune synapse. A translational quantitative systems pharmacology (QSP) model is proposed for CD3 bispecific molecules capable of predicting trimer concentration and linking it to tumor cell killing. The model was used to quantify the pharmacokinetic (PK)/pharmacodynamic (PD) relationship of a CD3 bispecific targeting P-cadherin (PF-06671008). It describes the disposition of PF-06671008 in the central compartment and tumor in mouse xenograft models, including binding to target and T cells in the tumor to form the trimer. The model incorporates T cell distribution to the tumor, proliferation, and contraction. PK/PD parameters were estimated for PF-06671008 and a tumor stasis concentration (TSC) was calculated as an estimate of minimum efficacious trimer concentration. TSC values ranged from 0.0092 to 0.064 pM across mouse tumor models. The model was translated to the clinic and used to predict the disposition of PF-06671008 in patients, including the impact of binding to soluble P-cadherin. The predicted terminal half-life of PF-06671008 in the clinic was approximately 1 day, and P-cadherin expression and number of T cells in the tumor were shown to be sensitive parameters impacting clinical efficacy. A translational QSP model is presented for CD3 bispecific molecules, which integrates in silico, in vitro and in vivo data in a mechanistic framework, to quantify and predict efficacy across species.