Miracle-dz/UniFAR-FTUs huggingface dataset:
Improvement of Attention, Executive Functions, and Processing Speed in Elderly Women as a Result of Involvement in the Nordic Walking Training Program and Vitamin D Supplementation

Research indicates that life satisfaction declines with age, and cognitive abilities are gradually reduced—mainly attentional functioning and cognitive processing speed. Therefore, scientists seek to find protective factors and test possible intervention programs; moderately intensive physical activity stands out as particularly promising. In this context, we evaluated the influence of Nordic Walking training supported by vitamin D supplementation (as this nutrient is especially deficient in older people in Poland) on the cognitive and psychological functioning of elderly women. A total of 52 healthy elderly women took part in a Nordic Walking training program complemented by vitamin D supplementation. Cognitive functioning was assessed with the Trail Making Test and the D2 Test of Attention. Quality of life and severity of depressive symptoms were measured with the Short Form Health Survey and the Beck Depression Inventory 2. Significant improvements in all aspects of cognitive functioning was observed (p = 0.01–0.47). The study also showed a decrease in depressive symptoms (p = 0.026). Physical activity and adequate levels of vitamin D can be the key factors in maintaining self-reliance in old age. Involvement in Nordic Walking training, supported by vitamin D supplementation, can strengthen the cognitive functioning of older people—reflected in higher attentional capabilities, better executive functions, and improved cognitive processing speed.
An Advanced in Silico Modelling of the Interaction between FSCPX, an Irreversible A1 Adenosine Receptor Antagonist, and NBTI, a Nucleoside Transport Inhibitor, in the Guinea Pig Atrium

In earlier studies, we generated concentration-response (E/c) curves with CPA (N6-cyclopentyladenosine; a selective A1 adenosine receptor agonist) or adenosine, in the presence or absence of S-(2-hydroxy-5-nitrobenzyl)-6-thioinosine (NBTI, a selective nucleoside transport inhibitor), and with or without a pretreatment with 8-cyclopentyl-N3-[3-(4-(fluorosulfonyl)-benzoyloxy)propyl]-N1-propylxanthine (FSCPX, a chemical known as a selective, irreversible A1 adenosine receptor antagonist), in isolated, paced guinea pig left atria. Meanwhile, we observed a paradoxical phenomenon, i.e., the co-treatment with FSCPX and NBTI appeared to enhance the direct negative inotropic response to adenosine. In the present in silico study, we aimed to reproduce eight of these E/c curves. Four models (and two additional variants of the last model) were constructed, each one representing a set of assumptions, in order to find the model exhibiting the best fit to the ex vivo data, and to gain insight into the paradoxical phenomenon in question. We have obtained in silico evidence for an interference between effects of FSCPX and NBTI upon our ex vivo experimental setting. Regarding the mechanism of this interference, in silico evidence has been gained for the assumption that FSCPX inhibits the effect of NBTI on the level of endogenous (but not exogenous) adenosine. As an explanation, it may be hypothesized that FSCPX inhibits an enzyme participating in the interstitial adenosine formation. In addition, our results suggest that NBTI does not stop the inward adenosine flux in the guinea pig atrium completely.
What does computational fluid dynamics tell us about intracranial aneurysms? A meta-analysis and critical review

Despite the plethora of published studies on intracranial aneurysms (IAs) hemodynamic using computational fluid dynamics (CFD), limited progress has been made towards understanding the complex physics and biology underlying IA pathophysiology. Guided by 1733 published papers, we review and discuss the contemporary IA hemodynamics paradigm established through two decades of IA CFD simulations. We have traced the historical origins of simplified CFD models which impede the progress of comprehending IA pathology. We also delve into the debate concerning the Newtonian fluid assumption used to represent blood flow computationally. We evidently demonstrate that the Newtonian assumption, used in almost 90% of studies, might be insufficient to describe IA hemodynamics. In addition, some fundamental properties of the Navier–Stokes equation are revisited in supplementary material to highlight some widely spread misconceptions regarding wall shear stress (WSS) and its derivatives. Conclusively, our study draws a roadmap for next-generation IA CFD models to help researchers investigate the pathophysiology of IAs.
Identification and Characterization of microRNAs and Their Predicted Functions in Biomineralization in the Pearl Oyster (Pinctada fucata)

The biological process of pearl formation is an ongoing research topic, and a number of genes associated with this process have been identified. However, the involvement of microRNAs (miRNAs) in biomineralization in the pearl oyster, Pinctada fucata, is not well understood. In order to investigate the divergence and function of miRNAs in P. fucata, we performed a transcriptome analysis of small RNA libraries prepared from adductor muscle, gill, ovary, and mantle tissues. We identified 186 known and 42 novel miRNAs in these tissues. Clustering analysis showed that the expression patterns of miRNAs were similar among the somatic tissues, but they differed significantly between the somatic and ovary tissues. To validate the existence of the identified miRNAs, nine known and three novel miRNAs were verified by stem-loop qRT-PCR using U6 snRNA as an internal reference. The expression abundance and target prediction between miRNAs and biomineralization-related genes indicated that miR-1990c-3p, miR-876, miR-9a-3p, and novel-3 may be key factors in the regulatory network that act by controlling the formation of matrix proteins or the differentiation of mineralogenic cells during shell formation in mantle tissue. Our findings serve to further clarify the processes underlying biomineralization in P. fucata.
Optimizing Genetic Workup in Pheochromocytoma and Paraganglioma by Integrating Diagnostic and Research Approaches

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors with a strong hereditary background and a large genetic heterogeneity. Identification of the underlying genetic cause is crucial for the management of patients and their families as it aids differentiation between hereditary and sporadic cases. To improve diagnostics and clinical management we tailored an enrichment based comprehensive multi-gene next generation sequencing panel applicable to both analyses of tumor tissue and blood samples. We applied this panel to tumor samples and compared its performance to our current routine diagnostic approach. Routine diagnostic sequencing of 11 PPGL susceptibility genes was applied to blood samples of 65 unselected PPGL patients at a single center in Dresden, Germany. Predisposing germline mutations were identified in 19 (29.2%) patients. Analyses of 28 PPGL tumor tissues using the dedicated PPGL panel revealed pathogenic or likely pathogenic variants in known PPGL susceptibility genes in 21 (75%) cases, including mutations in IDH2, ATRX and HRAS. These mutations suggest sporadic tumor development. Our results imply a diagnostic benefit from extended molecular tumor testing of PPGLs and consequent improvement of patient management. The approach is promising for determination of prognostic biomarkers that support therapeutic decision-making.
Interactivity and Persuasion

ABSTRACT The recent arrival of interactive messaging/marketing units (IMUs) begs the question: Does interacting with an advertisement enhance its persuasive appeal? How does interactivity compare with other structural features of online ads such as animation and ad shape? A 3 (Interactivity: Low, Medium, High) × 2 (Animation: Animated, Static) × 2 (Ad Shape: Banner, Square) fully-crossed factorial within-participants experiment was conducted to explore these questions. All participants (N = 48) were exposed to 12 news-article Web pages, with one ad in each of them. Results show not only that the level of interactivity is positively associated with ad and product attitudes, but also that it interacts with animation and ad shape in complex ways to influence the persuasion process.
Influence of Fixation Methods on Prosthetic Joint Infection Following Primary Total Knee Replacement: Meta-Analysis of Observational Cohort and Randomised Intervention Studies

The type of fixation used in primary total knee replacement (TKR) may influence the risk of prosthetic joint infection (PJI). We conducted a systematic review and meta-analysis to assess published evidence linking type of fixation (cemented, uncemented, or hybrid) with the risk of PJI following primary TKR. Randomised controlled trials (RCTs) and observational cohort studies comparing fixation methods and reporting PJI incidence following primary TKR were identified in MEDLINE, Embase, Web of Science, and Cochrane Library up until November 2018. Summary measures were relative risks (RR) with 95% confidence intervals (CIs). We identified 32 eligible articles (24 observational studies and 8 RCTs) involving 1,161,292 TKRs. In pooled analysis of observational studies, uncemented fixation was associated with a decreased overall PJI risk when compared with cemented fixation at 0.76 (0.64–0.89). Comparing antibiotic-loaded cemented fixation with plain cement, there was no significant difference in overall PJI risk at 0.95 (0.69–1.31), but PJI risk was increased in the first 6-month postoperative period to 1.65 (1.12–2.43). Limited data from RCTs showed no differences in PJI risk among the fixation types. Observational evidence suggests uncemented fixation may be associated with lower PJI risk in primary TKR when compared with cemented fixation. In the early postoperative period, antibiotic-loaded cemented fixation may be associated with increased PJI risk when compared with plain cement. This may either reflect appropriate selection of higher risk patients for the development of PJI to cemented and antibiotic-loaded cement or may reflect a lower PJI risk in uncemented TKR due to factors such as shorter operative time.
Structural Characterization of Arabidopsis thaliana NAP1-Related Protein 2 (AtNRP2) and Comparison with Its Homolog AtNRP1

Nucleosome Assembly Protein (NAP) is a highly conserved family of histone chaperones present in yeast, animals, and plants. Unlike other organisms, plants possess an additional class of proteins in its NAP family, known as the NAP1-related proteins or NRP. Arabidopsis thaliana possesses two NRP isoforms, namely AtNRP1 and AtNRP2, that share 87% sequence identity. Both AtNRP1 and AtNRP2 get expressed in all the plant tissues. Most works in the past, including structural studies, have focused on AtNRP1. We wanted to do a comparative study of the two proteins to find why the plant would have two very similar proteins and whether there is any difference between the two for their structure and function as histone chaperones. Here we report the crystal structure of AtNRP2 and a comparative analysis of its structural architecture with other NAP family proteins. The crystal structure of AtNRP2 shows it to be a homodimer, with its fold similar to that of other structurally characterized NAP family proteins. Although AtNRP1 and AtNRP2 have a similar fold, upon structural superposition, we find an offset in the dimerization helix of the two proteins. We evaluated the stability, oligomerization status, and histone chaperoning properties of the two proteins, for a comparison. The thermal melting experiments suggest that AtNRP2 is more stable than AtNRP1 at higher temperatures. In addition, electrophoretic mobility shift assay and isothermal titration calorimetry experiments suggest histone binding ability of AtNRP2 is higher than that of AtNRP1. Overall, these results provide insights about the specific function and relevance of AtNRP2 in plants through structural and biophysical studies.
Perspectives on microRNAs and Phased Small Interfering RNAs in Maize (Zea mays L.): Functions and Big Impact on Agronomic Traits Enhancement

Small RNA (sRNA) population in plants comprises of primarily micro RNAs (miRNAs) and small interfering RNAs (siRNAs). MiRNAs play important roles in plant growth and development. The miRNA-derived secondary siRNAs are usually known as phased siRNAs, including phasiRNAs and tasiRNAs. The miRNA and phased siRNA biogenesis mechanisms are highly conserved in plants. However, their functional conservation and diversification may differ in maize. In the past two decades, lots of miRNAs and phased siRNAs have been functionally identified for curbing important maize agronomic traits, such as those related to developmental timing, plant architecture, sex determination, reproductive development, leaf morphogenesis, root development and nutrition, kernel development and tolerance to abiotic stresses. In contrast to Arabidopsis and rice, studies on maize miRNA and phased siRNA biogenesis and functions are limited, which restricts the small RNA-based fundamental and applied studies in maize. This review updates the current status of maize miRNA and phased siRNA mechanisms and provides a survey of our knowledge on miRNA and phased siRNA functions in controlling agronomic traits. Furthermore, improvement of those traits through manipulating the expression of sRNAs or their targets is discussed.
Fine printing method of silver nanowire electrodes with alignment and accumulation

One-dimensional metal nanowires offer great potential in printing transparent electrodes for next-generation optoelectronic devices such as flexible displays and flexible solar cells. Printing fine patterns of metal nanowires with widths <100 μm is critical for their practical use in the devices. However, the fine printing of metal nanowires onto polymer substrates remains a major challenge owing to their unintended alignment. This paper reports on a fine-printing method for transparent silver nanowires (AgNWs) electrodes miniaturized to a width of 50 μm on ultrathin (1 μm) polymer substrate, giving a high yield of >90%. In this method, the AgNW dispersion, which is swept by a glass rod, is spontaneously deposited to the hydrophilic areas patterned on a hydrophobic-coated substrate. The alignment and accumulation of AgNWs at the pattern periphery are enhanced by employing a high sweeping rate of >3.2 mm s−1, improving electrical conductivity and pattern definition. The more aligned and more accumulated AgNWs lower the sheet resistance by a factor of up to 6.8. In addition, a high pattern accuracy ≤ 3.6 μm, which is the deviation from the pattern designs, is achieved. Quantitative analyses are implemented on the nanowire alignment to understand the nanowire geometry. This fine-printing method of the AgNW electrodes will provide great opportunities for realizing flexible and high-performance optoelectronic devices.
Effects of a training programme of functional electrical stimulation (FES) powered cycling, recreational cycling and goal-directed exercise training on children with cerebral palsy: a randomised controlled trial protocol

Introduction Children with cerebral palsy (CP) experience declines in gross motor ability as they transition from childhood to adolescence, which can result in the loss of ability to perform sit-to-stand transfers, ambulate or participate in leisure activities such as cycling. Functional electrical stimulation (FES) cycling is a novel technology that may provide opportunities for children with CP to strengthen their lower limbs, improve functional independence and increase physical activity participation. The proposed randomised controlled trial will test the efficacy of a training package of FES cycling, adapted cycling and goal-directed functional training to usual care in children with CP who are susceptible to functional declines. Methods and analysis Forty children with CP (20 per group), aged 6–8 years and classified as Gross Motor Function Classification System (GMFCS) levels II–IV will be recruited across South East Queensland. Participants will be randomised to either an immediate intervention group, who will undertake 8 weeks of training, or a waitlist control group. The training group will attend two 1 hour sessions per week with a physiotherapist, consisting of FES cycling and goal-directed, functional exercises and a 1 hour home exercise programme per week, consisting of recreational cycling. Primary outcomes will be the gross motor function measure and Canadian occupational performance measure, and secondary outcomes will include the five times sit-to-stand test, habitual physical activity (accelerometry), power output during cycling and Participation and Environment Measure-Children and Youth. Outcomes will be assessed at baseline, postintervention (8 weeks) and 8 weeks following the intervention (retention). Ethics and dissemination Ethical approval has been obtained from Griffith University (2018/037) and the Children’s Health Queensland Hospital and Health Service (CHQHHS) Human Research Ethics Committee (HREC/17/QRCH/88). Site-specific approval was obtained from CHQHHS research governance (SSA/17/QRCH/145). Results from this trial will be disseminated via publication in relevant peer-reviewed journals. Trial registration number ACTRN12617000644369p.
Managing supply chain uncertainty and risk in the pharmaceutical industry

The purpose of the conceptual paper is to present a framework for managing pharmaceutical supply chain uncertainty and risk. The supply chain risk management strategy is critical and significant to strategically support the firms to success in the long run. However, very little research has been conducted in the pharmaceutical firms so far. Based on literature review, the supply chain integration capability is considered as effective risk management tools for mitigating the supply chain uncertainty and risk. The authors identified main types of pharmaceutical supply chain uncertainty and risk. The conceptual framework focuses on the relationships among the supply chain integration capability and pharmaceutical supply chain uncertainty and risk. This provides insights into the pharmaceutical supply chain risk management. The study focuses on the pharmaceutical industry. However, the proposed framework can be validated with an empirical work in different sectors. Moreover, this contributes to the pharmaceutical supply chain management literature.
Perforin and Granzyme B Expressed by Murine Myeloid-Derived Suppressor Cells: A Study on Their Role in Outgrowth of Cancer Cells

A wide-range of myeloid-derived suppressor cell (MDSC)-mediated immune suppressive functions has previously been described. Nevertheless, potential novel mechanisms by which MDSCs aid tumor progression are, in all likelihood, still unrecognized. Next to its well-known expression in natural killer cells and cytotoxic T lymphocytes (CTLs), granzyme B (GzmB) expression has been found in different cell types. In an MDSC culture model, we demonstrated perforin and GzmB expression. Furthermore, similar observations were made in MDSCs isolated from tumor-bearing mice. Even in MDSCs from humans, GzmB expression was demonstrated. Of note, B16F10 melanoma cells co-cultured with perforin/GzmB knock out mice (KO) MDSCs displayed a remarkable decrease in invasive potential. B16F10 melanoma cells co-injected with KO MDSCs, displayed a significant slower growth curve compared to tumor cells co-injected with wild type (WT) MDSCs. In vivo absence of perforin/GzmB in MDSCs resulted in a higher number of CD8+ T-cells. Despite this change in favor of CD8+ T-cell infiltration, we observed low interferon-γ (IFN-γ) and high programmed death-ligand 1 (PD-L1) expression, suggesting that other immunosuppressive mechanisms render these CD8+ T-cells dysfunctional. Taken together, our results suggest that GzmB expression in MDSCs is another means to promote tumor growth and warrants further investigation to unravel the exact underlying mechanism.
Amyloid Beta-Related Alterations to Glutamate Signaling Dynamics During Alzheimer’s Disease Progression

Alzheimer’s disease (AD) ranks sixth on the Centers for Disease Control and Prevention Top 10 Leading Causes of Death list for 2016, and the Alzheimer’s Association attributes 60% to 80% of dementia cases as AD related. AD pathology hallmarks include accumulation of senile plaques and neurofibrillary tangles; however, evidence supports that soluble amyloid beta (Aβ), rather than insoluble plaques, may instigate synaptic failure. Soluble Aβ accumulation results in depression of long-term potentiation leading to cognitive deficits commonly characterized in AD. The mechanisms through which Aβ incites cognitive decline have been extensively explored, with a growing body of evidence pointing to modulation of the glutamatergic system. The period of glutamatergic hypoactivation observed alongside long-term potentiation depression and cognitive deficits in later disease stages may be the consequence of a preceding period of increased glutamatergic activity. This review will explore the Aβ-related changes to the tripartite glutamate synapse resulting in altered cell signaling throughout disease progression, ultimately culminating in oxidative stress, synaptic dysfunction, and neuronal loss.
Longitudinal associations between depression and diabetes complications: a systematic review and meta‐analysis

To conduct a systematic review and meta‐analysis of longitudinal studies assessing the bi‐directional association between depression and diabetes macrovascular and microvascular complications. Embase, Medline and PsycINFO databases were searched from inception through 27 November 2017. A total of 4592 abstracts were screened for eligibility. Meta‐analyses used multilevel random/mixed‐effects models. Quality was assessed using the Newcastle‐Ottawa scale. Twenty‐two studies were included in the systematic review. Sixteen studies examined the relationship between baseline depression and incident diabetes complications, of which nine studies involving over one million participants were suitable for meta‐analysis. Depression was associated with an increased risk of incident macrovascular (HR = 1.38; 95% CI: 1.30–1.47) and microvascular disease (HR = 1.33; 95% CI: 1.25–1.41). Six studies examined the association between baseline diabetes complications and subsequent depression, of which two studies involving over 230 000 participants were suitable for meta‐analysis. The results showed that diabetes complications increased the risk of incident depressive disorder (HR = 1.14; 95% CI: 1.07–1.21). The quality analysis showed increased risk of bias notably in the representativeness of selected cohorts and ascertainment of exposure and outcome. Depression in people with diabetes is associated with an increased risk of incident macrovascular and microvascular complications. The relationship between depression and diabetes complications appears bi‐directional. However, the risk of developing diabetes complications in depressed people is higher than the risk of developing depression in people with diabetes complications. The underlying mechanisms warrant further research.