Miracle-dz/UniFAR-FTUs huggingface dataset:
Older Adults’ Perceptions toward Walking: A Qualitative Study Using a Social-Ecological Model

Objectives: In this study, we aimed to investigate older adults’ perceptions of their walking experiences, using the social-ecological model as a guiding framework and to propose future walking intervention content. Methods: Thirty-eight participants (19 women; 47% from private elderly centers; mean age = 72.8 (SD = 7.4 years) took part in semi-structured interviews. Qualitative data analysis software QSR-NVivo was used for thematic coding. Results: Thematic deductive analysis revealed pertinent themes at the individual level (health benefits and barriers, fall risk, perseverance, and walking as a suitable activity for older adults), social environment level (social support and social interaction), physical environment level (density, land-use mix, and connectivity; perceived safety, pedestrian facilities (benches, quality of walking paths and sidewalks, and aesthetics), other pedestrian behaviors, and weather, and policy level (lack of walking programs in the community, and supportive culture for an active lifestyle). Discussion: Our findings provide insights for the planning of future multilevel walking intervention programs for older adults in Hong Kong. It is suggested that future walking intervention should include professionals (e.g., physiotherapist or coach) in a group setting, practical walking recommendations such as proper walking posture, and additional fun activities for older adults.
Toll-Like Receptor 9-Mediated Neuronal Innate Immune Reaction Is Associated with Initiating a Pro-Regenerative State in Neurons of the Dorsal Root Ganglia Non-Associated with Sciatic Nerve Lesion

One of the changes brought about by Wallerian degeneration distal to nerve injury is disintegration of axonal mitochondria and consequent leakage of mitochondrial DNA (mtDNA)—the natural ligand for the toll-like receptor 9 (TLR9). RT-PCR and immunohistochemical or Western blot analyses were used to detect TLR9 mRNA and protein respectively in the lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) ipsilateral and contralateral to a sterile unilateral sciatic nerve compression or transection. The unilateral sciatic nerve lesions led to bilateral increases in levels of both TLR9 mRNA and protein not only in the lumbar but also in the remote cervical DRG compared with naive or sham-operated controls. This upregulation of TLR9 was linked to activation of the Nuclear Factor kappa B (NFκB) and nuclear translocation of the Signal Transducer and Activator of Transcription 3 (STAT3), implying innate neuronal immune reaction and a pro-regenerative state in uninjured primary sensory neurons of the cervical DRG. The relationship of TLR9 to the induction of a pro-regenerative state in the cervical DRG neurons was confirmed by the shorter lengths of regenerated axons distal to ulnar nerve crush following a previous sciatic nerve lesion and intrathecal chloroquine injection compared with control rats. The results suggest that a systemic innate immune reaction not only triggers the regenerative state of axotomized DRG neurons but also induces a pro-regenerative state further along the neural axis after unilateral nerve injury.
Driving Behaviour Analysis Using Machine and Deep Learning Methods for Continuous Streams of Vehicular Data

In the last few decades, vehicles are equipped with a plethora of sensors which can provide useful measurements and diagnostics for both the vehicle’s condition as well as the driver’s behaviour. Furthermore, the rapid increase for transportation needs of people and goods together with the evolution of Information and Communication Technologies (ICT) push the transportation domain towards a new more intelligent and efficient era. The reduction of CO2 emissions and the minimization of the environmental footprint is, undeniably, of utmost importance for the protection of the environment. In this light, it is widely acceptable that the driving behaviour is directly associated with the vehicle’s fuel consumption and gas emissions. Thus, given the fact that, nowadays, vehicles are equipped with sensors that can collect a variety of data, such as speed, acceleration, fuel consumption, direction, etc. is more feasible than ever to put forward solutions which aim not only to monitor but also improve the drivers’ behaviour from an environmental point of view. The approach presented in this paper describes a holistic integrated platform which combines well-known machine and deep learning algorithms together with open-source-based tools in order to gather, store, process, analyze and correlate different data flows originating from vehicles. Particularly, data streamed from different vehicles are processed and analyzed with the utilization of clustering techniques in order to classify the driver’s behaviour as eco-friendly or not, followed by a comparative analysis of supervised machine and deep learning algorithms in the given labelled dataset.
Developmental Inhibition of Long Intergenic Non-Coding RNA, HOTAIRM1, Impairs Dopamine Neuron Differentiation and Maturation

The dopaminergic (DA) system is important for a range of brain functions and subcortical DA development precedes many cortical maturational processes. The dysfunction of DA systems has been associated with neuropsychiatric disorders such as schizophrenia, depression, and addiction. DA neuron cell fate is controlled by a complex web of transcriptional factors that dictate DA neuron specification, differentiation, and maturation. A growing body of evidence suggests that these transcriptional factors are under the regulation of newly discovered non-coding RNAs. However, with regard to DA neuron development, little is known of the roles of non-coding RNAs. The long non-coding RNA (lncRNA) HOX-antisense intergenic RNA myeloid 1 (HOTAIRM1) is present in adult DA neurons, suggesting it may have a modulatory role in DA systems. Moreover, HOTAIRM1 is involved in the neuronal differentiation in human stem cells suggesting it may also play a role in early DA neuron development. To determine its role in early DA neuron development, we knocked down HOTAIRM1 using RNAi in vitro in a human neuroblastoma cell line, and in vivo in mouse DA progenitors using a novel in utero electroporation technique. HOTAIRM1 inhibition decreased the expression of a range of key DA neuron specification factors and impaired DA neuron differentiation and maturation. These results provide evidence of a functional role for HOTAIRM1 in DA neuron development and differentiation. Understanding of the role of lncRNAs in the development of DA systems may have broader implications for brain development and neurodevelopmental disorders such as schizophrenia.
Insights into the mechanism by which atropine inhibits myopia: evidence against cholinergic hyperactivity and modulation of dopamine release

The ability of the muscarinic cholinergic antagonist atropine to inhibit myopia development in humans and animal models would suggest that cholinergic hyperactivity may underlie myopic growth. To test this, we investigated whether cholinergic agonists accelerate ocular growth rates in chickens. Furthermore, we investigated whether atropine alters ocular growth by downstream modulation of dopamine levels, a mechanism postulated to underlie its antimyopic effects.
Postoperative Radiochemotherapy Using Modern Radiotherapy Techniques in Elderly Patients with Head and Neck Squamous Cell Carcinoma: The Challenge of Weighing Up Benefits and Harms of Treatment Modalities in Clinical Practice

Simple Summary Locally advanced head and neck squamous cell carcinomas (HNSCC) are often managed with surgery and postoperative radiochemotherapy (RCT). Until now, a deeper understanding of specific management strategies for elderly patients was lacking. In the present study, we compared patients ≥70 years of age and younger patients treated with postoperative RCT for HNSCC. All patients were treated with modern radiotherapy techniques (IMRT/VMAT). Elderly patients had more comorbidities. In addition, they less frequently received concomitant systemic treatment. The rates of mucositis and dermatitis were lower in patients ≥70 years. Elderly patients had significantly worse overall survival and progression-free survival. Locoregional and distant control were comparable in elderly and younger patients. In conclusion, postoperative radiochemotherapy is a safe and effective treatment option in patients ≥70 years. In light of comorbidities and poor survival rates, potential benefits and harms of radiotherapy and concomitant systemic treatment should be weighed carefully for this age group. Abstract Locally advanced head and neck squamous cell carcinomas (HNSCC) are often managed with surgery followed by postoperative radiochemotherapy (RCT). With the general increase in life expectancy, the proportion of elderly patients with HNSCC is expected to grow rapidly. Until now, a deeper understanding of specific management strategies for these patients in clinical routine was lacking. In the present study, we compared elderly patients (≥70 years, n = 52) and younger patients (n = 245) treated with postoperative RCT for HNSCC at our tertiary cancer center. All patients were irradiated with modern radiotherapy techniques (IMRT/VMAT). Patients ≥70 years of age had more comorbidities. Additionally, elderly patients less frequently received concomitant systemic treatment. The rates of mucositis and dermatitis were lower in patients ≥70 years. Elderly patients had significantly worse overall and progression-free survival. Locoregional and distant control were comparable in elderly and younger patients. In conclusion, postoperative RCT is a safe and effective treatment option in patients ≥70 years. In light of comorbidities and poor overall survival rates, benefits and harms of radiotherapy and concomitant systemic treatment should be weighed carefully. When exclusively applying up-to-date radiotherapy techniques with, at the same time, careful use of concomitant systemic therapy, favorable acute toxicity profiles are achieved.
In Silico Prediction, Molecular Docking and Dynamics Studies of Steroidal Alkaloids of Holarrhena pubescens Wall. ex G. Don to Guanylyl Cyclase C: Implications in Designing of Novel Antidiarrheal Therapeutic Strategies

The binding of heat stable enterotoxin (STa) secreted by enterotoxigenic Escherichia coli (ETEC) to the extracellular domain of guanylyl cyclase c (ECDGC-C) causes activation of a signaling cascade, which ultimately results in watery diarrhea. We carried out this study with the objective of finding ligands that would interfere with the binding of STa on ECDGC-C. With this view in mind, we tested the biological activity of a alkaloid rich fraction of Holarrhena pubescens against ETEC under in vitro conditions. Since this fraction showed significant antibacterial activity against ETEC, we decided to test the screen binding affinity of nine compounds of steroidal alkaloid type from Holarrhena pubescens against extracellular domain (ECD) by molecular docking and identified three compounds with significant binding energy. Molecular dynamics simulations were performed for all the three lead compounds to establish the stability of their interaction with the target protein. Pharmacokinetics and toxicity profiling of these leads demonstrated that they possessed good drug-like properties. Furthermore, the ability of these leads to inhibit the binding of STa to ECD was evaluated. This was first done by identifying amino acid residues of ECDGC-C binding to STa by protein–protein docking. The results were matched with our molecular docking results. We report here that holadysenterine, one of the lead compounds that showed a strong affinity for the amino acid residues on ECDGC-C, also binds to STa. This suggests that holadysenterine has the potential to inhibit binding of STa on ECD and can be considered for future study, involving its validation through in vitro assays and animal model studies.
Phase Stability of Iron Nitride Fe4N at High Pressure—Pressure-Dependent Evolution of Phase Equilibria in the Fe–N System

Although the general instability of the iron nitride γ′-Fe4N with respect to other phases at high pressure is well established, the actual type of phase transitions and equilibrium conditions of their occurrence are, as of yet, poorly investigated. In the present study, samples of γ′-Fe4N and mixtures of α Fe and γ′-Fe4N powders have been heat-treated at temperatures between 250 and 1000 °C and pressures between 2 and 8 GPa in a multi-anvil press, in order to investigate phase equilibria involving the γ′ phase. Samples heat-treated at high-pressure conditions, were quenched, subsequently decompressed, and then analysed ex situ. Microstructure analysis is used to derive implications on the phase transformations during the heat treatments. Further, it is confirmed that the Fe–N phases in the target composition range are quenchable. Thus, phase proportions and chemical composition of the phases, determined from ex situ X-ray diffraction data, allowed conclusions about the phase equilibria at high-pressure conditions. Further, evidence for the low-temperature eutectoid decomposition γ′→α+ε′ is presented for the first time. From the observed equilibria, a P–T projection of the univariant equilibria in the Fe-rich portion of the Fe–N system is derived, which features a quadruple point at 5 GPa and 375 °C, above which γ′-Fe4N is thermodynamically unstable. The experimental work is supplemented by ab initio calculations in order to discuss the relative phase stability and energy landscape in the Fe–N system, from the ground state to conditions accessible in the multi-anvil experiments. It is concluded that γ′-Fe4N, which is unstable with respect to other phases at 0 K (at any pressure), has to be entropically stabilised in order to occur as stable phase in the system. In view of the frequently reported metastable retention of the γ′ phase during room temperature compression experiments, energetic and kinetic aspects of the polymorphic transition γ′⇌ε′ are discussed.
Functional Specialization within the EXO70 Gene Family in Arabidopsis

Localized delivery of plasma-membrane and cell-wall components is a crucial process for plant cell growth. One of the regulators of secretory-vesicle targeting is the exocyst tethering complex. The exocyst mediates first interaction between transport vesicles and the target membrane before their fusion is performed by SNARE proteins. In land plants, genes encoding the EXO70 exocyst subunit underwent an extreme proliferation with 23 paralogs present in the Arabidopsis (Arabidopsis thaliana) genome. These paralogs often acquired specialized functions during evolution. Here, we analyzed functional divergence of selected EXO70 paralogs in Arabidopsis. Performing a systematic cross-complementation analysis of exo70a1 and exo70b1 mutants, we found that EXO70A1 was functionally substituted only by its closest paralog, EXO70A2. In contrast, none of the EXO70 isoforms tested were able to substitute EXO70B1, including its closest relative, EXO70B2, pointing to a unique function of this isoform. The presented results document a high degree of functional specialization within the EXO70 gene family in land plants.
Accuracy of Dental Implant Placement by a Novel In-House Model-Free and Zero-Setup Fully Guided Surgical Template Made of a Light-Cured Composite Resin (VARO Guide®): A Comparative In Vitro Study

Background: This in vitro study mainly aimed to compare VARO Guide® to the surgical guide fabricated by CAD/CAM (NAVI Guide®) in terms of accuracy and efficacy of the implant surgery held in the dentiform model. Methods: Twenty surgeons, 10 dentists in the beginner group and 10 dentists in the expert group, participated in the study. Each surgeon conducted fully guided surgery in dentiform models twice, once with VARO Guide® (VG surgery) and the other time with a conventional type of templates, NAVI Guide® (NG surgery). Based on the superimposition of presurgical and postsurgical STL files, the positional deviations between the virtually planned and actually placed implants and the time spent on presurgical preparation and surgical procedures were estimated and compared. Results: All dimensional deviations were similar between the two groups (p > 0.05), and there was no significant difference between the expert and beginner groups regardless of the guide system. The total procedure time (mean (median)) of the VG surgery (26.33 (28.58) min) was significantly shorter than that of the NG surgery (378.83 (379.35) min; p < 0.05). While the time spent only for the fully guided implant surgery (from the start of the surgical guide sitting onto the dentiform model to the final installation of the implant fixture) was comparable (p > 0.05), the presurgical preparation time spent on virtual implant planning and surgical guide fabrication in the VG surgery (19.63 (20.93) min) was significantly shorter compared to the NG surgery (372.93 (372.95) min; p < 0.05). Conclusions: Regardless of experience, both VG and NG surgery showed reliable positional accuracy; however, the total procedure time and the preparation time were much shorter in the VG surgery compared to the NG surgery.
Preeclampsia and Cardiovascular Risk for Offspring

There is growing evidence of long-term cardiovascular sequelae in children after in utero exposure to preeclampsia. Maternal hypertension and/or placental ischaemia during pregnancy increase the risk of hypertension, stroke, diabetes, and cardiovascular disease (CVD) in the offspring later in life. The mechanisms associated with CVD seem to be a combination of genetic, molecular, and environmental factors which can be defined as fetal and postnatal programming. The aim of this paper is to discuss the relationship between pregnancy complicated by preeclampsia and possibility of CVD in the offspring. Unfortunately, due to its multifactorial nature, a clear dependency mechanism between preeclampsia and CVD is difficult to establish.
Knee joint loadings are related to tibial torsional alignments in people with radiographic medial knee osteoarthritis

Torsional malalignment was detected in subjects with medial knee osteoarthritis (KOA) but few studies have reported the effect of torsional deformity on knee joint loads during walking. Therefore, this study examined the relationships between lower limb torsional alignments and knee joint loads during gait in people with symptomatic medial KOA using cross-sectional study design. Lower limb alignments including tibial torsion, tibiofemoral rotation and varus/valgus alignments in standing were measured by EOS low-dose bi-planar x-ray system in 47 subjects with mild or moderate KOA. The external knee adduction moment (KAM), flexion moment (KFM) and the KAM index which was defined as (KAM/ (KAM+KFM)*100) during walking were analyzed using a motion analysis system so as to estimate the knee loads. Results revealed externaltibial torsion was positively associated with KAM in subjects with moderate KOA (r = 0.59, p = 0.02) but not in subjects with mild KOA. On the contrary, significant association was found between knee varus/valgus alignment and KAM in the mild KOA group (r = 0.58, p<0.001) and a sign of association in the moderate KOA group (r = 0.47, p = 0.08). We concluded tibial torsion and knee varus/valgus mal-alignments would be associated with joint loading in subjects with moderate medial KOA during walking. Radiographic severity might need to be considered when using gait modification as a rehabilitation strategy for this condition.
Reduced Order Multiscale Simulation of Diffuse Damage in Concrete

Damage in concrete structures initiates as the growth of diffuse microcracks that is followed by damage localisation and eventually leads to structural failure. Weak changes such as diffuse microcracking processes are failure precursors. Identification and characterisation of these failure precursors at an early stage of concrete degradation and application of suitable precautionary measures will considerably reduce the costs of repair and maintenance. To this end, a reduced order multiscale model for simulating microcracking-induced damage in concrete at the mesoscale level is proposed. The model simulates the propagation of microcracks in concrete using a two-scale computational methodology. First, a realistic concrete specimen that explicitly resolves the coarse aggregates in a mortar matrix was generated at the mesoscale. Microcrack growth in the mortar matrix is modelled using a synthesis of continuum micromechanics and fracture mechanics. Model order reduction of the two-scale model is achieved using a clustering technique. Model predictions are calibrated and validated using uniaxial compression tests performed in the laboratory.
[68Ga]Ga-DFO-c(RGDyK): Synthesis and Evaluation of Its Potential for Tumor Imaging in Mice

Angiogenesis has a pivotal role in tumor growth and the metastatic process. Molecular imaging was shown to be useful for imaging of tumor-induced angiogenesis. A great variety of radiolabeled peptides have been developed to target αvβ3 integrin, a target structure involved in the tumor-induced angiogenic process. The presented study aimed to synthesize deferoxamine (DFO)-based c(RGD) peptide conjugate for radiolabeling with gallium-68 and perform its basic preclinical characterization including testing of its tumor-imaging potential. DFO-c(RGDyK) was labeled with gallium-68 with high radiochemical purity. In vitro characterization including stability, partition coefficient, protein binding determination, tumor cell uptake assays, and ex vivo biodistribution as well as PET/CT imaging was performed. [68Ga]Ga-DFO-c(RGDyK) showed hydrophilic properties, high stability in PBS and human serum, and specific uptake in U-87 MG and M21 tumor cell lines in vitro and in vivo. We have shown here that [68Ga]Ga-DFO-c(RGDyK) can be used for αvβ3 integrin targeting, allowing imaging of tumor-induced angiogenesis by positron emission tomography.