In recent years, the widespread introduction of bike-sharing systems in China has had a profound impact on the daily lives of Chinese citizens and the development of the urban transport system. This article attempts to analyse the impact of this phenomenon on sustainability. The gradual improvement of related monitoring measures has facilitated the maturation of the bike-sharing industry from the initial stage of uncontrolled growth to the current stage of standardised management. By tracing the global development of bike-sharing systems with a special focus on China, this study sheds light on the platformisation of bicycles and its multiple impacts on technical, environmental, cultural, economic and social sustainability. Furthermore, the study provides a comprehensive analysis of the transformation of bicycles in China and highlights the diverse impacts of platform-based bike sharing on various facets of Chinese society. The development of different bike-sharing systems in China is a unique and crucial case to interpret the current situation of bike-sharing and imagine future scenarios. In contrast to the prevailing and uniform approach derived from the experiences of Northern European countries, the massive and widespread experimentation with different bike-sharing schemes in China reveals not only potentials and aspects of sustainability, innovation and urban and social regeneration, but also some hidden shadows similar to those in small-scale contexts such as Northern Europe. Furthermore, the study emphasises the crucial role of sustainable development principles in addressing urban challenges specific to China.

Input noise causes inescapable bias to the weight vectors of the adaptive filters during the adaptation processes. Moreover, the impulse noise at the output of the unknown systems can prevent bias compensation from converging. This paper presents a robust bias compensation method for a sparse normalized quasi-Newton least-mean (BC-SNQNLM) adaptive filtering algorithm to address this issue. We have mathematically derived the biased-compensation terms in an impulse noisy environment. Inspired by the convex combination of adaptive filters' step sizes, we propose a novel variable-mixing-norm method to accelerate the convergence for our BC-SNQNLM algorithm, which is referred to as BC-SNQNLM-VMN. Simulation results confirm that the proposed method significantly outperforms other comparative works regarding normalized mean-squared deviation (NMSD) in the steady state.

Lower limb exoskeletons have the potential to reduce the prevalence of work-related musculoskeletal disorders; however, they often lack user-oriented control strategies. Human-in-the-loop (HITL) controls can adapt an exoskeleton’s assistance in real-time, to optimize the user-exoskeleton interaction. This study presents a HITL control for a knee exoskeleton to minimize the users’ physical effort, a parameter innovatively evaluated by their interaction torque with the exoskeleton (a muscular effort indicator) and metabolic cost. This work innovates by estimating the user’s metabolic cost within the HITL control through a machine-learning model. The regression model was able to estimate the metabolic cost, in real-time, with a root-mean-squared error of 0.66 W/kg and a mean absolute percentage error of 26%, making faster (10s) and less noisy estimations than a respirometer (K5, Cosmed) device. The HITL reduced the user’s metabolic cost and interaction torque by 7.3% and 32.3%, respectively, when compared to a zero-torque control. The developed HITL control surpassed both a non-exoskeleton and a zero-torque condition regarding the user’s physical effort, even for a simple task such as slow walking. Furthermore, the user-specific control enabled a lower metabolic cost than the non-user-specific assistance. This proof-of-concept demonstrated the potential for HITL controls in assisted working.

Infections caused by KPC-producing K. pneumoniae continue to pose a significant clinical challenge due to emerging resistance to new antimicrobials. We investigated the association between two drugs whose roles have been repurposed against multidrug-resistant bacteria: fosfomycin and temocillin. Temocillin exhibits unusual stability against KPC enzymes, while fosfomycin acts as a potent “synergizer”. We conducted in vitro antimicrobial activity studies on 100 clinical isolates of KPC-producing K. pneumoniae using a combination of fosfomycin and temocillin. The results demonstrated synergistic activity in 91% of the isolates. Subsequently, we assessed the effect on Galleria mellonella larvae using 5 different KPC-Kp isolates. The addition of fosfomycin to temocillin increased larvae survival from 73 to 97% (+Δ 32%; isolate 1), from 93 to 100% (+Δ 7%; isolate 2), from 63 to 86% (+Δ 36%; isolate 3), from 63 to 90% (+Δ 42%; isolate 4), and from 93 to 97% (+Δ 4%; isolate 10), respectively. Among the temocillin-resistant KPC-producing K. pneumoniae isolates (24 isolates), the addition of fosfomycin reduced temocillin MIC values below the resistance breakpoint in all isolated except one. Temocillin combined with fosfomycin emerges as a promising combination against KPC-producing K. pneumoniae, warranting further clinical evaluation.

Despite past efforts towards therapeutical innovation, cancer remains a highly incident and lethal disease, with current treatments many times lacking efficiency and leading to severe side-effects. Hence, it is imperative to develop new, more efficient, and safer therapies. Bee venom has proven to have multiple and synergistic bioactivities, including antitumor effects. Nevertheless, some toxic effects have been associated with its administration. To tackle these issues, in this work, bee venom-loaded niosomes were developed, for cancer treatment. The vesicles had a small (150.4 ± 3.7 nm) and homogeneous (PDI of 0.162 ± 0.008) particle size, and revealed good therapeutic efficacy in in vitro gastric, colorectal, breast, lung, and cervical cancer models, with GI50 values between 12.37 ng/mL and 14.72 ng/mL. Additionally, they also revealed substantial anti-inflammatory activity, with an IC50 of 28.98 ng/mL, effects that have been reported to be complementary to direct antitumor activity. Finally, the niosomes' safety was assessed, both in vitro, on skin, liver and kidney cells, and ex vivo, in a HET-CAM assay, and results showed that compound encapsulation increased its safety. Hence, small and homogeneous bee venom-loaded niosomes were successfully developed, with substantial anticancer and anti-inflammatory effects, making them potentially promising primary or adjuvant cancer therapies.

The feeling of beauty is one of the positive human feelings. In architecture and design, it is associated with forms appropriate to their purpose. The usefulness of products to meet needs is also important. They are well received by users. The task of designers is to achieve perfection in their work. The rational design and use of artificial living environments are expressions of concern for natural resources (sustainable environment). These issues are addressed, i.e., by an interdisciplinary initiative of the New European Bauhaus. The aim of the paper is to expand knowledge about beauty and utility. They are important when choosing mass-produced goods. The article uses research methods: interpretive research, analyses, comparisons, logical argumentation, etc. Experimental qualitative research using a checklist was used. The results expand the knowledge on the selected topic and research scope of the research of the paper. The survey can be used to rationally evaluate architecture, interiors, and design facilities. It can be helpful for various aesthetic and functional strategies dedicated to different users. The paper demonstrates the role of beauty and functionality in the built environment. They are analyzed in the context of social and technical conditions, as well as contemporary sustainable design

Abstract: The objective of these studies was to determine the dependence of the distribution of the microwave field into a grain layer and the efficiency of energy transfer from the magnetron into the grain layer, via a waveguide, on the moisture content. The subject of the research was a semicircular waveguide with slot radiators that supply a microwave field to the grain surrounding the waveguide. The change in the directional diagram of the microwave field in the longitudinal direction of the waveguide was studied using CST Microwave Studio 2019 software. It was found that the change in the moisture content of the processed grain leads to a significant change in both the radiation and total efficiency values of the waveguide. For instance, the radiation efficiency of the waveguide decreases by 15.1% (from 68.729 dB to 58.294 dB) when the moisture content of the processed grain increases from 14% to 26%. The total radiation efficiency also decreases (from 11.27 dB to 21.7 dB). In this case, not only the value of the radiation efficiency but also the shape of its dependence on the magnetron radiation frequency change. Data were obtained on the change in the Q-factor for resonators in which grain layers are processed, depending on the variation in grain moisture content.

This study investigates the impact of experienced contact on prejudiced attitudes toward individuals with intellectual disabilities (ID), examining beliefs in a just world (BJW) and social dominance orientation (SDO) as potential serial mediators. Data were collected from 224 university students (M = 23.02, SD = 2.48). Path analysis modeling assessed the structural relationships between the study variables. The findings revealed that experienced contact was negatively and significantly associated with BJW and SDO. Additionally, BJW and SDO fully mediated the relationship between experienced contact and overt prejudice. These findings underscore the influence of individual differences on attitudes toward individuals with ID, establishing a crucial foundation for future research and the development of interventions aimed at reducing prejudice and discrimination.

In drilling small holes with diameters of 1 mm or less, minute clogging and twining of chips or adhesion of the workpiece material can become factors in causing breakages of the drill bit; moreover, it can be difficult to identify the machining state. Acoustic emission (AE) sensing is a nondestructive inspection technique that measures the elastic-stress waves that are generated when a material is deformed and fractured. AE sensing permits highly sensitive measurements to be made without changing the rigidity of the experimental system, unlike force sensing of cutting resistance, etc. In the present study, attempts were made to identify the machining state and tool wear, and to predict abnormalities in small-diameter drilling by using the change in the frequency of AE signal waveforms arising from deformation and fracture. It was shown that it is possible to predict the breakage of the drill bit by detecting the high-frequency AE signals caused by adhesion. In addition, a correlation map of the AE frequency spectrum for identifying the machining state in a drilling operation is suggested.

Hypertension is one of the most common primary cardiometabolic diseases and is a major contributor to cardiac mortality and morbidity. Furthermore, cardiac risk factors such as obesity and sedentary lifestyle are often seen in hypertensive patients. Regular exercise acts against these risk factors and improves the overall health of an individual. High-intensity interval training appears to do so in a more efficient way. We used a systematic literature review (SLR) approach to provide an overview of the present literature highlighting the cardiovascular advantages of HIIT in hypertensive individuals. We reviewed 4004 articles from reputable journals published between 2013 and August 14, 2023, focusing on 7 selected papers for in-depth analysis. This systematic review revealed the protective effects of HIIT against cardiac complications in hypertension. All the reviewed articles showed a decrease in blood pressure and many other risk variables of cardiovascular diseases. However, guidelines for this exercise are needed for maximum benefits. Therefore, further research on HIIT is necessary to fully harness its potential.

The study of angular correlations of heavy-flavor particles in hadronic collisions can provide crucial insight into the heavy-quark production, showering and hadronization processes. The comparison with model predictions allows us to discriminate among different approaches for heavy-quark production and hadronization, as well as different treatments of the underlying event employed by the models to reproduce correlation observables. In ultra-relativistic heavy-ion collisions, where a deconfined state of matter, the quark-gluon plasma (QGP), is created, heavy-flavor correlations can shed light on the modification of the heavy-quark fragmentation due to interaction of charm and beauty quarks with the QGP constituents, as well as characterize their energy loss processes while traversing the medium. Insight into possible emergence of collective-like mechanisms in smaller systems, resembling those observed in heavy-ion collisions, can also be obtained by performing correlation studies in high-multiplicity proton-proton and proton-nucleus collisions. In this review, the most recent and relevant measurements of heavy-flavor correlations performed in all collision systems at the LHC and RHIC will be presented, and the new understandings that they provide will be discussed.

The Ames/quantitative structure-activity relationship (QSAR) International Challenge Projects held during 2014–2017 and 2020–2022, evaluated the performance of various predictive models. Despite the significant insights gained, the rules allowing participants to select prediction targets introduced ambiguity in model performance evaluation. This reanalysis identified the highest-performing prediction model, assuming a 100% coverage rate (COV) for all prediction target compounds and an estimated performance variation due to changes in COV. All models from both projects were evaluated using balance accuracy (BA), Matthews correlation coefficient (MCC), F1 Score (F1), and the first principal component (PC1). After normalizing the COV, a correlation analysis with these indicators was conducted, and the evaluation index for all prediction models in terms of the COV was estimated. In total, 109 models, the highest estimated BA (76.9) at 100% COV was MMI-VOTE1, reported by Meiji Pharmaceutical University (MPU). The best models for MCC, F1, and PC1 were all MMI-STK1, also reported by MPU. All models reported by MPU ranked in the top four. MMI-STK1 was estimated to have F1 scores of 59.2, 61.5, and 63.1 at COV levels of 90%, 60%, and 30%, respectively. These findings highlight the current state and potential of the Ames prediction technology.

Accurate determination of protein localization, levels, or protein-protein interactions is pivotal for the study of their function, and in situ protein labeling via homologous recombination has emerged as a critical tool in many organisms. While this approach has been refined in various model fungi, the study of protein function in most plant pathogens has predominantly relied on ex-situ or overexpression manipulations. To dissect the molecular mechanisms of development and infection for Verticillium dahliae, a formidable plant pathogen responsible for vascular wilt diseases, we have established a robust, homologous recombination-based in situ protein labeling strategy in this organism. Utilizing Agrobacterium tumefaciens-mediated transformation (ATMT), this methodology facilitates the precise tagging of specific proteins at their C-termini with epitopes, such as GFP and Flag, within the native context of V. dahliae. We demonstrate the efficacy of our approach through the in situ labeling of VdCf2 and VdDMM2, followed by subsequent confirmation via subcellular localization and protein-level analyses. Our findings confirm the applicability of homologous recombination for in situ protein labeling in V. dahliae and suggest its potential utility across a broad spectrum of filamentous fungi. This labeling method stands to significantly advance the field of functional genomics in plant pathogenic fungi, offering a versatile and powerful tool for the elucidation of protein function.

Recruitment is a fundamental aspect of Human Resource Management to drive organizational performance. Traditional recruitment processes, with manual stages, are time-consuming and inefficient. Artificial Intelligence (AI), which demonstrates its potential in various sectors such as healthcare, education and notable cases of ChatGPT, is currently reshaping recruitment by automating tasks to improve efficiency. However, in Thailand, where there is a growing demand for talents, the application of AI in recruitment remains relatively limited. This research focuses on human resources (HR) and recruitment professionals in Thailand, aiming to understand their perspectives on the integration of AI in recruitment. It extended the Unified Theory for Acceptance and Use of Technology (UTAUT) model, customized to suit the specific requirements of Thai recruitment practices. The study explores the factors influencing users' intention to adopt AI in recruitment. Survey questionnaire items were created based on prior literatures and refined with insights from HR and recruitment experts to ensure applicability in the context of recruitment in Thailand. A survey involving 364 HR and recruiting professionals in Bangkok metropolitan area supplied comprehensive responses. The research reveals that several factors, including Perceived Value, Perceived Autonomy, Effort Expectancy, and Facilitating Conditions, significantly impact the intention to adopt AI for recruitment. While Social Influence and Trust in AI Technology do not have a direct influence on intention, Social Influence directly affects Perceived Value. Trust in AI Technology positively influences Effort Expectancy. This study provides valuable benefits for HR and recruitment professionals, organizations and AI developers by offering insights into AI adoption and sustainability, enhancing recruitment processes and promoting the effective use of AI tools in this sector.

Based on the multiple coordination framework of “promising government-effective market-ordered society”, this paper takes 68 cases of adding elevators to old buildings as samples, and selects six conditional variables: approval optimization, financial subsidies, financing innovation, technological innovation, capable people leading and neighborhood committee guidance. Using Crisp-Set Qualitative Comparative Analysis (csQCA), this paper discusses the combination of conditions that affect the success or failure. It is found that: approval optimization and neighborhood committee guidance are sufficient conditions for the success; successful cases can be divided into three types: “political and social dual-drive type”, “market and social dual-drive type” and “ternary co-drive type”; lack of approval optimization, lack of financing innovation, and the existence of capable people leading are necessary conditions for the failure. The failure cases can be divided into “government and market double failure type” and “market failure type”.

Background and Objective: Intimate relationships hold significant importance during emerging adulthood. This study aimed to investigate the critical determinants of perceived well-being in friendship relationships during emerging adulthood.Method: Using a quantitative approach, a sample of 726 undergraduate students from the Ferdowsi University of Mashhad were selected through convenience sampling. They completed the Interpersonal Behaviors Questionnaire (IBQ), the Compassionate and self-image goals scale (CSIGS), the Basic Need Satisfaction in Relationships Scale (BNS-RS), the Interpersonal Needs Questionnaire (INQ-10), Friendship Self-Regulation Questionnaire (SRQ-F), Interpersonal Behaviors Questionnaire-Self (IBQ-self), State Level Subjective Vitality Scale (SVS-SL), the Perceived Relationship Quality Component (PRQC), and the Basic Empathy Scale (BES). Data analysis was conducted using Partial Least Squares Structural Equation Modeling (PLS-SEM).Results: The results indicated that the critical determinants in predicting perceived well-being in friendship relationships were, in order, goals in friendship relationships, friendship self-regulation, perceived support of basic psychological needs by friends, satisfied basic psychological needs, frustrated psychological needs, and supporting the basic psychological needs of friends.Conclusion: The findings demonstrate that self-determination theory (SDT) provides a coherent framework for explaining perceived well-being in friendships.

An all-dielectric metasurface composed of orthogonal-slit silicon disks is proposed in this study. By modifying the unit structure of the metasurface with the bound states in the continuum (BIC) theory, a sharp Fano resonance can be generated. The resonance properties of the metasurface are investigated by analyzing the effects of the structural parameters on the resonance using the eigenmode analysis method. The Q factor and the resonance wavelength can be adjusted by varying the slit width, the disk thickness, and the disk radius. The electromagnetic characteristics and mechanism of the toroidal dipole-BIC (TD-BIC) are explored in depth through an analysis of the multipole expansion of the scattered power, along with the electromagnetic field and the current distribution at resonance. This research provides a novel approach for excitation of a strong TD-BIC resonance and proposes potential applications in optical switches, high-sensitivity optical sensors, and related areas.

: This article reports on polymer (PLLA, poly(L-lactic acid)) nanosheets incorporated with Fe-ion nanoparticles, aiming at using the latter nanoparticles as source to release Fe ions to facilitate burn wound healing when such nanosheets are applied on skin as biomedical tissue. Laser ablation in liquid phase was used to produce Fe-containing nanoparticles that after incorporation into PLLA nanosheets would release Fe ions when in immersed in water. Such nanoparticles prepared in chloroform are shown by XPS to be based on iron chloride and oxide phases. After incorporation into PLLA nanosheets, the ion –release test demonstrated that Fe ions could be released successfully into water at pH 7.4, which implies that such polymer nanosheets show promise for biomedical applications as potential patches for healing burn wounds. Incorporation with two different metal ions (Fe and Zn) is shown to be efficient and both types of ions were demonstrated to be released simultaneously and with comparable release rates.

Uncontrolled chronic inflammation results in cardiovascular disease and early death. In this review, we studied the impact of rheumatoid arthritis on the cardiovascular system, including the early and accelerated development of atherosclerosis, and its clinical manifestations, focusing on the inflammatory mechanisms leading to arterial wall damage, rapid atherosclerotic plaque formation, and thrombosis. Furthermore, the influence of medications used to treat rheumatoid arthritis on the cardiovascular system. The influence of chronic inflammation and medicaments on traditional cardiovascular risk factors is not the main subject of this review. We found that uncontrolled chronic inflammation and some medications directly impact all stages of atherosclerosis. In conclusion, reducing inflammation and maintaining long-term remission in rheumatoid arthritis may pre-vent early atherosclerosis. We believe that this review will encourage a better interdisciplinary approach for these patients and further research in this field.

This paper aims to stress the nexus between sustainable development, economic freedom and local participatory democracy in 21 European smart cities. The development of smart cities is strongly correlated with technological advancements and improved access to pub-lic services for all residents. Furthermore, smart cities are characterized by efficient man-agement of social, economic and environmental resources and a strong partnership be-tween the public and private sectors. The paper aims to map the dynamics of local partic-ipatory democracy in European smart cities and to identify several relevant predictors of local participatory democracy. The sample is represented by 21 European capitals (20 EU countries plus UK), which are included in the Smart City Index (SCI). Using the quantita-tive design based on both statistical regressions and structural equations modelling (SEM), the paper shows positive statistical correlation between economic factors, sustainable de-velopment, political culture, education and the level of local participatory democracy. Be-sides the exogenous variables, the study emphasized the main priority areas, which might be seen as urgent issues for local governments. The conclusion of the paper underlines the fact that economic freedom, sustainable development, upper secondary education, afford-able housing and an increased level of citizens’ engagement could predict further evolu-tions of the local participatory democracy in 21 European capitals.

This study examined the status of Education for Sustainable Development (ESD) practices and the understanding of Sustainable Development (SD) among Saudi kindergarten teachers in a specific governorate. Two hundred twenty-seven kindergarten teachers participated, and data was collected through a questionnaire. The results indicated that most kindergarten teachers (89.9%) were unaware of SD. The overall status of ESD practices among the participating teachers was weak, with an average score of 2.60 out of 4. Among the different dimensions, values (2.74), competencies (2.69), and practice (2.65) obtained relatively higher scores, while the content dimension (2.49) received the lowest score. Significant differences were found in the mean scores of ESD practices based on teachers’ qualifications and the type of school. However, no differences were observed based on experience. The lack of awareness regarding SD emerged as the primary barrier to implementing ESD in kindergarten institutions. Expanding teacher training was identified as the most crucial step in promoting ESD in kindergartens. The findings highlight the importance of raising awareness among Saudi kindergarten teachers about SD, providing professional development opportunities to enhance ESD implementation in classrooms, and creating teaching materials aligned with ESD principles.

Forest education is pivotal for achieving the Sustainable Development Goals and promoting sustainable forest management in the face of global challenges. However, existing programs struggle to keep up with rapidly changing crises and uncertainties that contribute to deforestation and forest degradation. To address these challenges, integrating innovative approaches into forest education is crucial. This paper demonstrates the transformative use of a role-playing game as an innovative teaching method for integrated forest management. The game provides students with practical experience and a comprehensive understanding of landscape approaches, using the Congo Basin as a case study. Our research focuses on sustainable forest governance, stakeholder roles, and valuing natural assets and ecosystem services, supporting the transformation of economic, political, and social/cultural relationships at various scales. We highlight the potential of innovative forest education to foster sustainability, trigger critical thinking, resolve conflicts, and prevent costly forest losses.

Abstract: Background. The newer wireless portable scanners seem to permit a quicker bedside ultrasound (US) assessment, shortening the transfer times of the portable US unit and without the hindering of connection cables. However, no substantial evidence is currently available regarding of the clinical effectiveness of such new generation devices. Objective. The aim of the current study was to evaluate the efficacy of a wireless US system with respect to a high-end US unit in a cohort of consecutive respiratory patients. Materials and Methods. This prospective observational study included a total of 72 respiratory patients admitted in the department of Internal Medicine. The US examination were independently performed by two experienced blinded examiners with a high-end Esaote MyLab-Twice scanner and a wireless double-head linear and convex probe OTE-L/C501CD. The findings resulting from the high-end US assessment and the wireless US examination were then compared each other. All the patients had a confirmation chest CT scan. Results. The high-end US machine identified 64 positive cases for pleuro-pulmonary alterations, in comparison to which the wireless US unit resulted in 13 false negative results. The respective overall sensitivity and specificity for the portable wireless US unit were of 79.69% and 100.00%, respectively. The resolution of the portable wireless US device was judged as good in 22 (31%) cases, affected by minor diagnostic limitations in 26 (36%) cases and affected by major diagnostic limitations in 24 (33%). The main diagnostic strength of the wireless probe was in the detection of pleural effusion (sensitivity 100%). The diagnostic sensitivity of the wireless probe in assessing abnormalities of the pleural line (67%), pulmonary subpleural consolidations (65%), pleural lesions (33%) and pericardial effusion (0%) was reduced. Conclusions. The newer wireless US probes may have clinical roles for the detection and management of pleural effusion when used by experienced examiners. However, sensitivity in detecting other pleuro-pulmonary pathologies is not comparable to high-end ultrasound machines.

Dubermatinib (DMB, TP-0903), a benzenesulfonamide, is an inhibitor of the tyrosine kinase AXL, which is a member of the TAM family, and can prevent GAS6-mediated activation of AXL in cancer cells. Patients with previously treated chronic lymphocytic leukemia are being studied in phase I/II clinical trials to determine its antineoplastic potential (CLL). In the current work, the reactive intermediates of DMB were studied using liquid chromatography-mass spectrometry (LC-MS). Human liver microsomes (HLMs) were exposed to dimethylbenzene in a laboratory setting, and the resulting metabolites were collected through protein precipitation. Intense reactivity toward nucleophilic macromolecules was seen in the metabolites of the piperazine and pyrimidine rings in DMB, iminium and 2,5-quinone-imine, respectively. To assess the toxicities of the possibly reactive metabolites, DMB was incubated with HLMs in the presence of 1.0 mM KCN and 1.0 mM glutathione. The DMB metabolites found by LC-MS/MS were seven in vitro phase I metabolites, three cyano adducts, and two GSH conjugates. Phase I in vitro metabolic reactions included N-demethylation, hydroxylation, and dechlorination. The in vitro metabolism of DMB and the metabolites it produces have not been studied before.

Background. In the last decade, it was concluded that glaucomatous optic neuropathy is part of the neurodegenerative diseases in which destructive neuronal lesions are located not only in the structure of the retina, but they are also present at the level of the central visual and nervous pathways. Patients with Primitive Open Angle Glaucoma may have experienced changes such as sensorineural hearing loss as well as balance changes. The purpose of this study is to evaluate the degree of involvement of the auditory system in patients with glaucoma, the structural changes in the optic nerve and, to establish correlation between the hearing loss and structural changes in the optic nerve. The subjects included in the study are grouped as follows: a group of patients with glaucoma that will be compared to a group of patients without glaucoma only as well as identi-fy-ing the evolution of structural changes in optic nerve to patients with glaucoma and to normal patients. Material and methods. It is a prospective, cross-sectional study on 32 eyes of 16 subjects with Primitive Open Angle Glaucoma in a study group and 24 eyes of 12 healthy subjects in con-trol group with a mean age of 62 years in both groups. Both groups underwent ophthalmo-logical, audiological and radio imaging evaluation: Pure-tone audiometry (PTA) were recorded, oph-thalmologic evaluations according to a standardized protocol and MRI cerebral examination was performed. Results: In the Study group patients, compared to the Control group, the average lev-els of the left PTA, the cup/disc (C/D) area in both eyes, the C/D ratio in both eyes are in-creased. The mean level of Retinal nerve fiber layer (RNFL) mean thickness was slightly lower in patients with glaucoma. Multivariate analysis demonstrates that gender can be a good predictor of C/D area, gender and age can be good predictors of PTA both eyes and C/D ratio in the right eye, and gender, age and background can be good predictors of disc area in the left eye. Conclu-sions: Pa-tients with Primitive Open Angle Glaucoma show changes in audiometry test in correla-tion with ophthalmological parameters demonstrating that the auditory system can be affected in Primitive Open Angle Glaucoma. This study emphasizes the problem of interdisciplinarity in medicine with the aim of ensuring the quality of life of patients with glaucoma. A good collabora-tion between ophthalmologist and otolaryngologist will be very useful for these patients.

Migraine is a debilitating neurovascular disorder characterized by recurrent headache attacks of moderate to severe intensity. Calcitonin gene-related peptide (GGRP), which is abundantly expressed in trigeminal ganglion (TG) neurons, plays a crucial role in migraine pathogenesis. Cortical spreading depolarization (CSD), the biological correlate of migraine aura, activates the trigeminovascular system. In the present study, we investigated CGRP mRNA expression in TG neurons in a CSD-based mouse migraine model. Our in situ hybridization analysis showed that CGRP mRNA expression was observed in smaller neuronal populations. CSD did not significantly change the density of CGRP mRNA-synthesizing neurons in the ipsilateral TG. However, the cell sizes of CGRP mRNA-synthesizing TG neurons were significantly larger in the 48 h and 72 h post-CSD groups than in the control group. The proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters less than 14 μm became significantly less at several time points after CSD. In contrast, we found significantly greater proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters of 14–18 μm at 24 h, 48, and 72 h post-CSD. We deduce that the CSD-induced upward cell size shift in CGRP mRNA-synthesizing TG neurons might be causative of greater disease activity and/or less responsiveness to CGRP-based therapy.

Metal-organic frameworks (MOFs), composed of metal nodes and inorganic linkers are promising for a wide range of applications due to their unique periodic frameworks that can be flexibly tuned. Understanding of the structure-activity relationships can facilitate the development and application of MOFs nanomaterials. Transmission electron microscopy (TEM) is a one-of-a-kind technique capable of characterizing MOFs microstructures at the atomic scale. Besides, in-situ TEM set-ups make it possible to direct visualize the microstructural evolution of MOFs in real time, which enables monitoring transitions of MOFs during growth as well as under working conditions. However, MOFs are so sensitive to the high-energy electron beam which makes TEM-based characterizing methods challenging. In this review, we first introduce the main damage mechanisms for MOFs under electron beam irradiation and two strategies to minimize the damages: low-dose TEM and cryo-TEM. Then, we discuss the techniques combined with the two strategies to analyze the MOFs’ microstructure, including three-dimensional electron diffraction, direct detection electron counting camera, and iDPC-STEM. Groundbreaking milestones and research advances with respect to static characterization of MOFs structures are highlighted. In-situ TEM studies are exemplary reviewed to provide insights into MOFs dynamics induced by various stimuli. Additionally, perspectives on promising techniques that may further facilitate the MOFs study using TEM are analyzed.

Antarctic krill protein-iron complex and peptide-iron complex were obtained to investigate their iron bioavailability, expression of iron-regulated genes, and in vivo antioxidant capacity. Results indicated that Antarctic krill peptide-iron complex increased significantly the hemoglobin (Hb), serum iron (SI) and iron content in the liver and spleen in iron-deficiency anemia (IDA) mice (P < 0.05) compared with those of Antarctic krill protein-iron complex. Despite the gene expressions of divalent metal transporter 1(DMT1), transferrin (Tf) and transferrin receptor (TfR) could be better regulated by both Antarctic krill peptide-iron complex and protein-iron complex, the relative iron bioavailability of the Antarctic krill peptide-iron complex group (152.53±21.05%) was significantly higher than that of the protein-iron complex group (112.75±9.60%) (P<0.05). Moreover, Antarctic krill peptide-iron complex could enhance the antioxidant enzyme activities of superoxidase dismutase (SOD) and glutathione peroxidase (GSH-Px), reduce the malondialdehyde (MDA) level in IDA mice compared with the protein-iron complex, reducing the cell damage caused by IDA. Therefore, these results demonstrated that Antarctic krill peptide-iron complex could be used as a highly efficient and multifunctional iron supplement.

Background Community health workers (CHWs) drawn from the general population are an important human resource in health care systems, preventing non-communicable diseases (NCDs) and contributing to an increase in healthy life expectancy in Japan. Thus, we have developed the COmmunity health workers perceptual and behavioral Competency Scale for preventing Non-communicable diseases (COCS-N) to measure CHWs’ competence in preventing NCDs. The purpose of this study is to examine individual and community factors affecting CHWs’ COCS-N scores. Methods Municipal public health nurses and other public health professionals are responsible for training and supporting CHWs in Japan. Therefore, the existence of CHWs and their willingness to participate in the study were confirmed with the municipalities, who were asked to distribute the self-administered questionnaire to CHWs where consent was obtained (N = 6,480). Variables used included demographic characteristics, COCS-N scores, and individual- and community-related factors. Logistic regression analysis was used to assess associations between variables. Results A total of 3,120 people completed the questionnaire, a valid response rate of 48.1%. The respondents’ mean age was 67.0 years (standard deviation = 9.0), and 88.0% were female. Comparison of the high- and low- competence groups in terms of NCD prevention based on COCS-N scores identified 13 factors associated with significant differences, including years spent working as a CHW (p < 0.001), subjective sense of health (p = 0.005), European Health Literacy Survey Questionnaire (HLS-EU-Q47) scores (p < 0.001), and community commitment scale (CCS) scores (p < 0.001). Logistic regression analysis revealed that HLS-EU-Q47 scores (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.02–1.03) were a significant individual factor, while CCS scores (OR: 1.14, 95% CI: 1.11–1.16) were a significant community factor. Conclusions We found that the COCS-N score was associated with the individual factors overall health literacy (HL), perceptions of HL, and subjective sense of health, and with the community factor CCS scores. These results suggest that strengthening individual factors such as HL and subjective sense of health, and community factors such as sense of community is an effective strategy for increasing CHWs’ competence in preventing NCDs.

We report the isolation of two novel degrading bacterial strains active against the potential environmental pollutant acetamino-phen/paracetamol. Streptomyces Chrestomyceticus (RS2) and Streptomyces Flavofuscus (M33) collected from El-Natrun Valley, Egypt, water, sediment, and sand samples were taxonomically characterized via conidiophores morphologic characterization under Trans-mission Electron Microscope (TEM). Genotypic identification, done based on their 16S rRNA gene sequence analysis followed by BLAST alignment and deposited on the NCBI as 2 novel strains. The phylogenetic tree was constructed using an appropriate software. Acetaminophen degradation-products chemical structure was identified by GC/LC MS. The biological antimicrobial activity of some selected acetaminophen degradation-products extracts and derived compounds was examined against panel of test micro-organisms and found to be have high anti-microbial effect. In addition, in silico cheminformatics Swiss ADMET evaluation of these selected deg-radation extract for gastric absorption, distribution, hepatic metabolism, renal excretion as well as distribution to CNS and finally not mutagenic/teratogenic or genotoxic virtually. In vitro cytotoxic activity of these selected bio-degradation products was performed against HepG2 and MCF7 cancer cell lines, revealing that M33 and RS2 extract effect on acetaminophen/paracetamol bio-degradation products are potentially safe with higher IC50 on HepG2 and MCF7, in comparison to acetaminophen/paracetamol with IC50 of 108.5 μg/ml. Moreover, the in vivo acute oral single dose toxicity experiment was conducted, being compared with acetamino-phen/paracetamol to confirm that the bio-degradation products have lower toxicity than acetaminophen in vivo and in silico.

Embryoid bodies (EBs) are multicellular three-dimensional (3D) aggregates generated from induced pluripotent stem cells (iPSCs) in suspension and serve as useful biological sources for many downstream applications. Imaging of live EBs has been hampered mainly due to the inherent limitations of the imaging techniques applied to date. This study aimed to image human iPSC (hiPSC) derived EBs to obtain their 3D volume, determining size, morphology, and cell viability from day 7 to 14 using Light Sheet Fluorescence Microscopy (LSFM). Furthermore, chromosomal stability was assessed using Multicolor fluorescence in situ hybridization (M-FISH) from day 8 to 14. EB volume increased from day 7 to 13 which, decreased at day 14. From day 7 to 11, the EBs mainly appeared spherical and morphed into an ellipsoidal shape by day 13. All EBs showed varied external morphologies and larger cavities at day 14. The EB karyotype was diploid 46XY at day 8 and exhibited a low level of aneuploidy from day 10 to 14. This study shows that an increase in cell death affects the morphology and chromosomal stability in EBs derived from hiPSC. We demonstrate that the combination of LSFM and M-FISH helps characterize EBs that will assist future stem cell therapies.

This article develops a duality principle and a related convex dual formulation suitable for a large class of models in physics and engineering. The results are based on standard tools of functional analysis, calculus of variations and duality theory. In particular, we develop applications to a model in non-linear elasticity.

This study was aimed to highlight the trends of antibiotic resistance (AR) prevalence in two annualities, 2021 and 2022, for a major bacterial pathogen, Staphylococcus aureus, that causes mastitis infections necessitating antibiotic therapy in milk producing animals. Fiftyfour isolates, 27 for each year, were obtained from routine tests for the identification of clinical mastitis agents carried out in the author institution for four provinces of Abruzzo and Molise regions, Italy. These were analyzed for phenotypic resistance to eight antibiotics used in human therapy suggested for testing by the European guidelines and for the presence of 14 transferable AR genes by qPCR tests developed in this study. The prevalence of AR genes was lower than reported in studies carried out in other countries, except for blaZ detected in 59.2% 2021 isolates and in 48.1 % 2022 isolates. However, some iso-lates with blaZ were not resistant to cefoxitin. One methicillin resistant (MRSA) strain, carrying the mecA gene, was isolated in 2022 and two multidrug resistant (MDR) isolates were identified in 2021. Other AR genes occurring were aph3’-III (two 2021 isolates), ant6-Ia (one 2021 isolate), ermB (one 2022 isolate), ermC/T (two 2021 isolates) and mph (one 2022 isolate). An interview to the veterinarians who conferred the samples indicated a good management of antibiotic therapies in farms that could explain why AR prevalence was stable in the time inter-val considered, thus underlining the effectiveness of controlled antibiotic usage in containing the AR threat.

This paper estimates the effect of trust in government on rural residents’ contributions in China’s rural pension program using the Propensity Score Matching (PSM) method. We construct an analytical framework for rural residents' decision-making in pension program and provide analysis using data from China Family Panel Studies (CFPS) and 25 provincial Departments of the Human Resources and Social Security (DOHRSS) in China. Our analysis shows that rural residents’ trust in government will influence their contributions to the pension programs by affecting their expected return of the investments. Our results suggest that the government should improve rural residents’ trust in government in order to develop a successful and sustainable rural pension program.

The calculation of the exact value of the square root of 2 is requested. In order to obtain its infinite value, A new concept is proposed where the accumulations of the infinitely many of finity is indicated by the change in direction which means that there is a jump from finity to infinity .The meaningless for an infinite number with a decimal point is indicated by this jump because any decimal number only have meanings within a finite range values and there is only an infinite integer quantity that can not be operated by algorithms like operations of multiplication，division,addition, and subtraction . The final result of the change in direction is two quantity where the second quantity and the first quantity extend in parallel line and never intersect and the second quantity represent the size of the first quantity. The first quantity is the infinitely great that can't be talked about anything outside of it and can compress any quantities outside of it to nothing and it is the exact value of the square root of 2 .

Acute kidney injury (AKI) is a complication that can occur after cardiac surgery and requires ongoing research in light of the exponential expansion of technological advancements and knowledge in medicine. In this study, we aim to evaluate the outcomes of treated electives of emergency aortic disease with high serum creatinine levels (SCr). Methods: The cohort includes 183 patients, all of whom have an aortic disease and whose SCr levels were checked upon admission on the first day in the intensive care unit (ICU) and upon discharge from the hospital. We examined the correlation of SCr levels with in-hospital mortality and immediate mortality at least six months after discharge as well as with cross-clamp time and bypass time.Results: A high SCr level upon admission is a significant predictive factor of n-hospital mortality (p = 0.001) but not immediate mortality (p = 0.409). A statistically significant correlation was also observed between elevated SCr level on the first day of ICU and aortic disease (p = 0.041) but not immediate mortality (p = 0.119). We observed a significant correlation between aortic disease and in-hospital mortality (p < 0.001), but no correlation was found between high SCr level on the first day of ICU and immediate mortality (p = 0.119). The cross-clamp time is statistically significant correlated with elevated SCr level (p = 0.013) and in-hospital mortality (p = 0.001) but not immediate mortality (p = 0.847). Furthermore, the bypass time is negatively correlated with a high SCr level on the first day of ICU (p = 0.090), in-hospital mortality (p = 0.410), and immediate mortality (p = 0.625). We also found that aortic disease is not correlated with elevated creatinine levels at ICU discharge (p = 0.152) or long-term mortality (p = 0.106). Conclusions: Although this study only included a small portion of the elaborate aspects of surgical and medical management developed around cardiac patients who received invasive treatment, the conclusions reached are nevertheless clearly relevant, as evidenced by the significantly correlations uncovered. In order to manage AKI after AAS and improve the outcome, the SCr level could be used as a marker for renoprotective strategy. Moving forward, these results serve as a first step in motivating us to expand the range of our research, collect newly relevant data, and use it to benefit patients.

Background: Sexualized substance use (SSU) is the practice of psychotropic substance usage, before or during sexual intercourse in order to increase sexual pleasure and arousal. It has a strong association with sexually transmitted infections (STIs). The present study aimed to assess the knowledge gaps regarding SSUs among the community health mobilizers by interviewing them regarding their knowledge, attitudes, and practices through qualitative approach. Methodology: In-depth interviews (IDIs) were conducted with a total of nineteen community health mobilizers engaged in counselling of sexualized substance users. A semi-structured open-ended questionnaire with socio-demographic information and probes related to SSU was administered. Informed consent was taken from each participant prior to data collection. Results: Gender-wise distribution indicated that 47% of the community mobilizers are men, followed by transgender persons (32%), and women (21%). Responses of participants highlighted that alcohol consumption was the most observed form of SSU. The findings indicated that drug administration through injection was most common, followed by sniffing and swallowing. Sources of drug pro-curement enlisted by participants included peddlers, peer groups, sexual parties, medical and liquor stores. Only 63% of participants had fair knowledge about STIs such as HIV, viral hepatitis, syphilis, and gonorrhoea. All were familiar with the administration of naloxone injections and the locations of nearby hospitals where patients could be transported in the event of an overdose. Conclusions: The in-depth interviews among the study participants reflected substantial know-ledge gaps related to various areas associated with SSU, which highlights the need for periodic workshops and training for upgradation of existing knowledge and practices among community health mobilizers. This will help to broaden their knowledge of different types of SSUs, the latest substances of abuse, the diseases caused by high-risk sexual practices, and additional health and psychological issues associated with SSUs, which would ultimately help in better counseling and management of sexualized substance users. It may also play a crucial role in the strengthening of capacity-building systems and engagements at the community level. This study may be used as formative research by researchers and policy makers to develop study protocols for multi-centric community-based studies among community health mobilizers and sexualized substance users across the country for further validation and exploration.

Noisy data is always encountered in real applications, such as bioinformatics, neuroimage and remote sensing. Existing methods mainly consider linear or generalized linear errors-in-variables regression, while relatively little attention is paid for the multivariate response case, and how to evaluate the estimation performance under perturbed covariates is still an open question. In this paper, we consider the information-theoretic limitations of estimating a low-rank matrix in the multi-response errors-in-variables regression model. By application of the information theory and statistical techniques on concentration inequalities, the minimax lower bound is provided in terms of the squared Frobenius loss, which recaptures the rate provided under the clean covariate assumption in previous literatures. Hence our result further indicates that though under the more realistic errors-in-variables situation, no more samples are required so as to achieve a rate-optimal estimation.

Endotoxins are toxic substances that widely exist in the environment and can enter the intestine with food and other substances. Intestinal epithelial cells are protected by a mucus layer that contains MUC2 as its main structural component. However, a detailed understanding of the mechanisms involved in the function of the mucus barrier in endotoxin penetration is lacking. Here, we established the most suitable proportion of Caco-2/HT-29 co-culture cells as a powerful tool to evaluate the intestinal mucus layer. Our findings significantly advance current knowledge as focal adhesion and ECM-receptor interaction were identified as the two most significantly implicated pathways in MUC2 small interfering RNA (siRNA)-transfected Caco-2/HT-29 co-culture cells after 24 h of LPS stimulation. When the mucus layer was not intact, LPS was found to damage the tight junctions of Caco-2/HT29 co-cultured cells. Furthermore, LPS was demonstrated to inhibit the integrin-mediated focal adhesion structure and damage the matrix network structure of the extracellular and actin microfilament skeletons. Ultimately, LPS inhibited the interactive communication between the extracellular matrix and the cytoskeleton for 24 h in the siMUC2 group compared with the LPS(+) and LPS(-) groups. Overall, we recognized the potential of MUC2 as a tool for barrier function in several intestinal bacterial diseases.

The presented results of simulations take into account the optical parameters of the selected sea region (from literature data on the southern Baltic Sea) and two optically extreme types of crude oil (from historical data) which exist in the form of a highly diluted oil-in-water emulsion (10 ppm). The spectral index was analyzed based on the results of modelling the radiance reflectance distribution for almost an entire hemisphere of the sky (zenith angle from 0 to 80o). The spectral index was selected and is universal for all optically different types of oil (wavelengths 650 and 412 nm). The possibility of detecting pollution in the conditions of the wavy sea surface (as a result of wind of up to 10 m/s) was studied. It has been also shown that if the viewing direction is close to a direction perpendicular to the sea surface, observations aimed at determining the spectral index are less effective than observation under the zenith angle of incidence of sunlight for all azimuths excluding the direction of sunlight specular reflection.

With this article, impact of effluent mixed water with the quality of the Mansagar Lake has been established by evaluating the physico-chemical parameters and the heavy-metal contents experimentally. The process of calculating water quality and the metal pollution quality indices is also explained in brief with respect to selected sample locations and varied environmental conditions (Pre- and Post-Monsoon season). Distribution trends of Pearson‘s correlation factor have also been discussed to establish their relation among the physico-chemical parameters and the heavy-metal contents for varied environmental conditions. In the end, detailed discussion on observations made during this study and useful recommendations are also elaborated in details. With this article, we intend to present a document for better understanding of the water quality of this lake in view of futuristic management strategies to be adopted to maintain it heritage values.

The deep neural network - BERT model (Bidirectional Encoder Representations from Transformers) and the stocks cumulative abnormal return is used in this article to analyze the sentiment of financial texts. The proposed approach, unlike those used so far, does not require the creation of dictionaries, takes into account the broad context of words and their meaning in financial texts, eliminates the problem of ambiguity of words in various contexts, does not require manual labelling of data and is free from the subjective assessment of the researcher. The sentiment of financial texts in the meaning presented in this paper is directly related to the market reaction to the information contained in these texts. For texts belonging to one of the two classes (positive or negative) with the highest probability the BERT model gives the results of predictions with a precision level of 62.38% for the positive class and 55% for the negative class. The results at this level can be used in event study, market efficiency research, investment strategy development or support of investment analysts using fundamental analysis.

Nociceptive innervation of the thoracolumbar fascia (TLF) has been investigated over decades, however these studies have not been compiled or collectively appraised. The purpose of this scoping review was to assess current knowledge regarding nociceptive innervation of the TLF to better inform future mechanistic and clinical TLF research targeting low back pain (LBP) treatment. PubMed, ScienceDirect, Cochrane and Embase databases were searched in January 2021 using relevant descriptors encompassing fascia and pain. Eligible studies were: (a) published in English; (b) preclinical and clinical (in vivo and ex vivo) studies; (c) original data; (d) included quantification of at least one TLF nociceptive component. Two-phase screening procedures were conducted by a pair of independent reviewers, data were extracted and summarized from eligible studies. The search resulted in 257 articles of which 10 met inclusion criteria. Studies showed histological evidence of nociceptive nerve fibers terminating in low back fascia, suggesting a TLF contribution to LBP. Noxious chemical injection or electrical stimulation into fascia resulted in longer pain duration and higher pain intensities than injections into subcutaneous tissue or muscle. Pre-clinical and clinical research provides histological and functional evidence of nociceptive innervation of TLF. Greater knowledge of fascial neurological components could impact LBP treatment.

Since HIV was first identified, and in a relatively short period of time, AIDS has become one of the most devastating infectious diseases of the 21st century. Classical antiretroviral therapies were a major step forward in disease treatment options, significantly improving the survival rates of HIV-infected individuals. Even though these therapies have greatly improved HIV clinical outcomes, antiretrovirals (ARV) feature biopharmaceutic and pharmacokinetic problems such as poor aqueous solubility, short half-life and poor penetration into HIV reservoir sites, which contribute to the sub-optimal efficacy of these regimens. To overcome some of these issues, novel nanotechnology-based strategies for ARV delivery towards HIV viral reservoirs have been proposed. The current review focus on the benefits of using lipid-based nanocarriers for tuning the physicochemical properties of ARVs to overcome biological barriers upon administration. Furthermore, a correlation of these properties and the potential therapeutic outcomes has been established. Biotechnological advancements using lipid nanocarriers for RNA interference delivery for the treatment of HIV infections were also discussed.

Theories of reading comprehension emphasize decoding and listening comprehension as two essential components. The current study aimed to investigate how Chinese character decoding and context-driven auditory semantic integration contribute to reading comprehension in Chinese middle school students. Seventy-five middle school students were tested. Context-driven auditory semantic integration was assessed with speech-in-noise tests in which the fundamental frequency (F0) contours of spoken sentences were either kept natural or acoustically flattened with the latter requiring a higher degree of contextual information. Statistical modelling with hierarchical regression was conducted to examine the contributions of Chinese character decoding and context-driven auditory semantic integration to reading comprehension. Performance on Chinese character decoding and auditory semantic integration scores with the flattened (but not natural) F0 sentences significantly predicted reading comprehension. Furthermore, the contributions of these two factors to reading comprehension were better fitted with an additive model instead of a multiplicative model. These findings indicate that reading comprehension in middle schoolers is associated with not only character decoding but also the listening ability to make better use of the sentential context for semantic integration in a severely degraded speech-in-noise condition. The results add to our better understanding of the multi-faceted reading comprehension in children. Future research could further address the age-dependent development and maturation of reading skills by examining and controlling other important cognitive variables, and apply neuroimaging techniques such as functional magmatic resonance imaging to reveal the neural substrates for the contribution of auditory semantic integration and the observed additive model to reading comprehension.

Authors such as Schnoebelen (2012: 12) suggest that in some languages (cf. Navajo) certain dependent clauses are frequently used independently to “mark emotional evaluation and background information”. Evans (2007) uses the term insubordination to refer to this phenomenon. Our study focuses on a particular insubordinate construction introduced by the sequence ni que in Spanish, as in the example [¡Una carta cada día!] Ni que yo fuese Umbral. (CORPES 100), used as an independent clause with a sociopragmatic meaning which is different from that of its subordinate counterpart (cf. No escribiría una carta cada día ni que yo fuese Umbral). Our research questions ask about the potential for ni que to be used as a discourse marker fulfilling an expressive function when it introduces this type of construction, and the derived hypothesis is then oriented to test whether Schnoebelen's (2012) observation about insubordinate constructions applies also to this Spanish construction. In order to test this hypothesis, we performed a functional-discourse analysis of more than 2000 concordances (and their extended contexts) in Mark Davies' Corpus del Español and the Real Academia CORPES XXI. Our findings show that the insubordinate construction differs in function and meaning from its subordinate counterpart, the former fulfilling a stronger emotive function, often combined with other discourse-pragmatic functions, such as evaluation or the organization of discourse.

Temporary pavilions play an important role as experimental fields for architects, designers and engineers, apart from providing exhibition spaces. Novel structural and formal solutions applied in pavilions also can give them unusual appearance that attracts eyesight of spectators. In this article authors explore the possibility of combination of structural novelty, visual attractiveness and low-cost by a design and construction of a temporary pavilion. For that purpose, an innovative structural system and design approach was applied, i.e. membrane structure designed in Rhino and Grasshopper environments with the use of Kiwi!3D IsoGeometric analysis tool. The designed pavilion, named Obverse/Reverse, was built in Opole, Poland, for the occasion of World Architecture Day in July 2019. Design and construction was performed by the authors in cooperation with students’ organisation Humanisation of Urban Environment from the Faculty of Architecture Wroclaw University of Science and Technology. The Rresultant pavilion proved the possibility of obtaining a low-budgets but visually attractive architectural solution with the adaption of parametrical design tools and some scientific background with innovative structural systems.

A new approach to fabricate TiNi surfaces combining the advantages of both monolithic and porous materials for implants is used in this work. New materials were obtained by depositing a porous TiNi powder onto monolithic TiNi plates followed by sintering at 1200°C. Then, further modification of the material surface with a high-current-pulsed electron beam (HCPEB) was carried out. Three materials obtained (one after sintering and two after subsequent beam treatment by 20 and 30 pulses, respectively) were studied by XRD, SEM, EDX, EIS methods, profilometry and OCP measurements. Structural and compositional changes caused by HCPEB treatment were investigated. Surface properties of the samples during their storage in saline for 10 days were studied and a model experiment with cell growth (MCF-7) was carried out for the sample unmodified with electron beam to detect cell appearance on different surface locations.

An extension of the models used to generate fractal traffic flows is presented by means of the formulation of a model that considers the use of one-dimensional chaotic maps. Based on the disaggregation of the temporal series generated by the model, a valid explanation of behavior of the values of Hurst exponent is proposed and the feasibility of their control from the parameters of the proposed model is shown.

Background: The t (2; 5) chromosomal rearrangement and resulting nucleophosmin (NPM1) -ALK fusion was first observed in 1994 in anaplastic large cell lymphoma (ALCL), a T-cell lymphoma responsive to cyclophosphamide, abriblastine, vincristine and prednisone in approximately 80% of cases; refractory cases usually respond favorably to brentuximab-vedotin. These treatments are regarded as a bridge to allogeneic hematopoietic stem cell transplantation (allo-SCT). Nowadays, transplant procedures and monitoring of chemotherapy patients proceed very slowly because the SARS-CoV-2 pandemic has heavily clogged the hospitals in all countries. Results: A 40-year-old Caucasian woman was first seen at our clinical center in June 2020. She had ALCL ALK +, a history of failure to two previous therapeutic lines and was in complete remission after 12 courses of Brentuximab, still pending allo-SCT after two failed donor selection. Facing of a new therapeutic failure, we requested the Italian drug regulatory agency, and obtained the authorization, to administer 250 mg twice a day of Crizotinib, a drug incomprehensibly not registered for ALCL ALK +. Conclusions: The response to Crizotinib was optimal, since no adverse event occurred, and CT-PET persisted negative; this drug has proved to be a valid bridge to allo-SCT

RAS oncogenes are amongst the most commonly mutated proteins in human cancers. They regulate a wide range of effector pathways that control cell proliferation, survival, differentiation, migration and metabolic status. Including aberrations in these pathways, RAS dependent signaling is altered in more than half of human cancers. Targeting mutant RAS proteins and their downstream oncogenic signaling pathways has been elusive. However, recent results comprising detailed molecular studies, large scale omics studies and computational modeling have painted a new and more comprehensive portrait of RAS signaling that helps us to understand the intricacies of RAS, how its physiological and pathophysiological functions are regulated, and how we can target them. Here, we review these efforts particularly trying to relate the detailed mechanistic studies with global functional studies. We highlight the importance of computational modeling and data integration to derive an actionable understanding of RAS signaling that will allow us to design new mechanism based therapies for RAS mutated cancers.

In the energy-momentum density expressions for a relativistic perfect fluid with a bulk motion, one comes across a couple of pressure-dependent terms, which though well known, are to an extent, lacking in their conceptual basis and the ensuing physical interpretation. In the expression for the energy density, the rest mass density along with the kinetic energy density of the fluid constituents due to their random motion, which contributes to the pressure as well, are already included. However, in a fluid with a bulk motion, there are, in addition, a couple of explicit, pressure-dependent terms in the energy-momentum densities, whose presence to an extent, is shrouded in mystery, especially from a physical perspective. We show here that one such pressure-dependent term appearing in the energy density, represents the work done by the fluid pressure against the Lorentz contraction during transition from the rest frame of the fluid to another frame in which the fluid has a bulk motion. This applies equally to the electromagnetic energy density of electrically charged systems in motion and explains in a natural manner an apparently paradoxical result that the field energy of a charged capacitor system decreases with an increase in the system velocity. The momentum density includes another pressure-dependent term, that represents an energy flow across the system, due to the opposite signs of work being done by pressure on two opposite sides of the moving fluid. From Maxwell's stress tensor we demonstrate that in the expression for electromagnetic momentum of an electric charged particle, it is the presence of a similar pressure term, arising from electrical self-repulsion forces in the charged sphere, that yields a natural explanation for the famous, more than a century old, 4/3 factor in the electromagnetic mass.

Breast cancer is the leading cause of cancer deaths worldwide in women. This aggressive tumour can be categorized into two main groups: in situ and infiltrative, with the latter being the most common malignant lesions. The current use of Magnetic Resonance Imaging (MRI) was shown to provide highest sensitivity in the detection and discrimination between benign vs. malignant lesions, when interpreted by expert radiologists. In this article, we present the prototype of a Computer-Aided Detection/Diagnosis (CAD) system that could provide valuable assistance to the radiologist for the discrimination between in situ and infiltrating tumours. The system consists of two main processing levels: 1) Localization of possibly tumoral regions of interest (ROIs) through an iterative procedure based on intensity values (ROI Hunter) followed by a deep-feature extraction and classification method for false-positive rejection; 2) Characterization of the selected ROIs and discrimination between in situ and invasive tumour, consisting of Radiomics feature extraction and classification through a machine-learning algorithm. The CAD system was developed and evaluated using a DCE-MRI image database, containing at least one confirmed mass per image, as diagnosed by an expert radiologist. When evaluating the accuracy of the ROI Hunter procedure with respect to the radiologist-drawn boundaries, sensitivity to mass detection was found to be 75%. The AUC of the ROC curve for discrimination between in situ and infiltrative tumors was 0.70.

We argue that the problem of time is not a crucial issue inherent in the quantum picture of the universe evolution. On the minisuperspace model example with the massless scalar field, we demonstrate four approaches to the description of quantum evolution, which give similar results explicitly. The relevance of these approaches to building a quantum theory of gravity is discussed.

Single nucleotide polymorphisms (SNP) are associated with diseases and drug response variabilities in humans. Elucidating the damaging and disease-associated SNPs using wet-laboratory approaches can be challenging and resource-demanding due to the large number of SNPs in the human genome. Due to the growth in the field of computational biology and bioinformatics, algorithms have been developed to help screen and filter out the most deleterious SNPs that are worth considering for wet-laboratory studies. Here we review the existing in-silico based methods used to predict and characterize the effects of SNPs on protein structure and function. This cutting-edge approach will facilitate the search for novel therapeutics, help understand the etiology of diseases and fast-track the personalized medicine agenda.

A significant part of the literature on innovative practice in medicine relates to seizing opportunities and curbing harms for patients in desperate situations. Unfortunately, the term innovation has multiple meanings and a rich rhetorical flourish that adds confusion and misunderstanding to an already difficult debate. This paper aims to enhance the current definition of innovative practice for medicine. First, we replace the term innovation with the more literal of new non-validated practice. To identify this meaning, we analyse the traditional research ethics’ distinction between research, validated practice, and innovation in the Belmont Report. Second, we propose the following explicit definition of new non-validated practice: the first or recent use of diagnostic, therapeutic or preventive interventions that introduce a significant change, with an insufficient level of evidence of safety or efficacy for regular healthcare, and with the main aim to benefit individual patients. This definition is a promising conceptual tool to inform empirical research, ethicists, and the harmonization of its regulation and legislation (e.g. right-to-try laws).

This paper presents findings of a study on continuous feed-in management and continuous synthetic inertia contribution with wind turbines. A realistic case study, based on real measurements, is outlined. A wind turbine feeds into a weak feeder, such that its power has to be adapted to the permissible loading of this feeder. At the same time the wind turbine is to provide inertia to the grid by applying the previously published variable inertia constant controller. It is discussed that optimal grid utilisation and simultaneous inertia contribution are mandatory for the frequency control in power systems that are heavily penetrated with renewable energies. The study shows that continuous feed-in management can be combined well with continuous inertia provision. There are hardly any negative consequences for the wind turbine. The benefits for the grid are convincing, both in terms of increased system utilisation and in terms of provided inertia. It is concluded that wind turbines can enhance angular stability in a power system to a larger extent than conventional power plants.

Three kinds of hydrophobic groups grafted starches of maleic anhydride grafted starch (MAH-g-starch), lactic acid grafted starch (LA-g-starch), and methyl acrylate grafted starch (MA-g-starch) were prepared by in-situ solid phase polymerization. The results of Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) were confirmed successful grafting. The grafting ratios of MAH-g-starch, LA-g-starch and MA-g-starch were 6.50%, 12.45%, and 0.57%, respectively. Influenced by the grafting ratio, LA-g-starch had the best hydrophobic properties and the largest molecular weight, and those for MA-g-starch was the worst. The surfaces of grafted starches were covered with graft polymer, with obvious surface roughness and bond degree of MAH-g-starch and LA-g-starch. The crystalline structure of grafted starches showed some damage, with LA-g-starch exhibiting the greatest decrease in crystallinity, and less of a change for MA-g-starch. Overall, the grafting reaction improved thermoplasticity, with LA-g-starch the most improved, followed by MAH-g-starch, and then MA-g-starch.

This is a theoretical and empirical article. In the first part, an original definition of the cross-border market for cultural services has been developed, based on classic market definitions. The structure and conditions of functioning for this market have also been presented. The next part of the article discusses the supply side of the cross-border market of cultural services for the two twin towns: Cieszyn (Poland) and Český Těšín (Czech Republic). Next, based on the surveys conducted, the participation of residents of both towns in the most important cultural events organised by cultural institutions on both sides of the border was examined.

This paper reports on the production and mechanical properties of Ti6Al4V micro-lattice structures, with strut thickness nearing the single-track width of the laser-based powder bed fusion (LPBF) system used. Besides providing new information on the mechanical properties and manufacturability of such thin-strut lattices, this paper also reports on the in-situ deformation imaging of micro-lattice structures with 6 unit cells in every direction. LPBF lattices are of interest for medical implants, due to the possibility of creating structures with an elastic modulus close to that of the bones and small pore sizes which allow effective osseointegration. In this work four different cubes were produced by laser powder bed fusion and subsequently analyzed using microCT, compression testing and one selected lattice was subjected to in-situ microCT imaging during compression. The in-situ imaging was performed at 4 steps during yielding. The results indicate that mechanical performance (elastic modulus and strength) correlate well with actual density and that this performance is remarkably good, despite the high roughness and irregularity of the struts at this scale. In-situ yielding is visually illustrated.

The past decade has witnessed enormous progress, which has seen the noncoding RNAs (ncRNAs) turn from the so called dark matter RNA to critical functional molecules, influencing most physiological processes in development and disease contexts. Many ncRNAs interact with each other and are part of networks that influence the cell transcriptome and proteome and consequently the outcome of biological processes. The regulatory circuits controlled by ncRNAs have become increasingly more relevant in cancer. Further understanding of these complex network interactions and how ncRNAs are regulated, is paving the way for the identification of better therapeutic strategies in cancer.

Collision avoidance is an important feature in advanced driver-assistance systems, aiming at providing correct, timely and reliable warnings before an imminent collision (objects, vehicles, pedestrians, etc.). A co-simulation framework is proposed in this paper to address the design and evaluation of collision avoidances in a cyber-physical system. The co-simulation framework is supported on the interaction between SCANeR and Matlab/Simulink. From the best of authors’ knowledge, two main contributions are reported in this paper. Firstly, the modelling and simulation of virtual on-chip LIDAR sensors in a cyber-physical system (CPS) considering traffic scenarios is presented. The CPS is designed and implemented in SCANeR. Secondly, an obstacle recognition library with three specific Artificial Intelligence-based methods is also designed based on sensory information database provided by SCANeR. Three methods for collision avoidance detection are considered, i.e.; a multi-layer perceptron neural network, a self-organization map and a support vector machine. Finally, a comparison among these methods for detecting obstacles before different weather conditions is done with very promising results in terms of accuracy. The best results are achieved using the multi-layer perceptron in sunny and fog conditions, the support vector machine in rainy and self-organized map in snowy conditions.

In the study of relativistic jets one of the key open questions is their interaction with the environment on the microscopic level. Here, we study the initial evolution of both electron–proton (e^- - p⁺) and electron–positron (e^±) relativistic jets containing helical magnetic fields, focusing on their interaction with an ambient plasma. We have performed simulations of "global" jets containing helical magnetic fields in order to examine how helical magnetic fields affect kinetic instabilities such as the Weibel instability, the kinetic Kelvin-Helmholtz instability (kKHI) and the Mushroom instability (MI). In our initial simulation study these kinetic instabilities are suppressed and new types of instabilities can grow. In the e^- - p⁺ jet simulation recollimation-like instability occurs and jet electrons are strongly perturbed. In the e^± jet simulation a recollimation-like instability occurs at early times followed by a kinetic instability and the general structure is similar to a simulation without helical magnetic field. Simulations using much larger systems are required in order to thoroughly follow the evolution of global jets containing helical magnetic fields.

Myo-inositol (MYO) and D-chiro-inositol (DCI) are the two most significant isomeric forms of inositol, playing a critical role in intracellular signaling. MYO is the most abundant form of inositol in nature; DCI is produced from MYO through epimerization by an insulin-dependent enzyme. Recently, it has been demonstrated that inositols may influence oocyte maturation, improve intracellular Ca2⁺ oscillation in the oocytes and have been proposed as potential interventions for restoring spontaneous ovulation. MYO concentration in human follicular fluid is considered a bioindicator of oocyte quality. In the ovary, DCI modulates the activity of aromatase thus regulating androgen synthesis. Under physiological conditions, MYO/DCI ratio is maintained at 40:1 in the plasma. In women with PCOS, MYO/DCI ratio lowers to 0:2:1, contributing to elevated androgen production. By regulating FSH signaling, MYO administration increases the number of high-quality embryos available for transfer in poor responder patients. Finally, by acting downstream to insulin signaling inositol administration during pregnancy may represent a novel strategy for counteracting gestational diabetes. These findings show that diet supplementation with inositols may be a promising strategy to address female infertility and sustain healthy pregnancy.

Building Information Modeling (BIM) is a revolutionary method in the construction industry that enhances project coordination, minimizes mistakes, and enables efficient project completion. An essential aspect of achieving successful BIM implementation is the creation of a BIM Execution Plan (BEP). The BEP facilitates effective communication, defines roles and responsibilities, and establishes standardized processes for all stakeholders involved. Although BIM is being used more widely, the absence of standardized BEPs frequently leads to inefficiencies in projects, especially those of significant scale [3]. This paper introduces the development of a new dynamic platform designed specifically for automating and standardizing the creation of BEPs. The platform aligns with ISO 19650 standards and offers customizable workflows to suit various project needs, improving collaboration, data management, and project outcomes. In addition, the paper emphasizes the advantages of utilizing this platform, including the efficient creation of BEPs, improved collaboration through centralized data management, and the ability to tailor BEPs to specific project requirements. The platform's user-friendly interface and extensive data management capabilities not only increase efficiency but also minimize risks and enhance project results. The survey results indicate that the BEP platform is effective in resolving common issues encountered in the creation of BEPs, such as miscommunication and inconsistencies. Additionally, it helps to improve project outcomes and reduce risks.

Hearing-loss (HL) is a major public health issue albeit data is limited. Objectives: were to determine the frequency and factors. Design: was descriptive cross-sectional using web-based self-administered google-form questionnaire. Data analyzed by-IBM SPSS-V-24-Windows. Results: In 789 responses, 6.6 % reported HL, 62.4% from Eastern-region of which 41.2% were employed and 31.7% students. Despite 36.5% reported HL &gt; 5-years, 21.2% sought treatments. 19.2% reported diabetes and 51.9% had family-history. Ages 11– 50 years showed female predominance (females 59.1%, males 41%). Age was significant in HL (P &lt;0.001) irrespective of gender (males 6.8%, females 6.4%, P value =0.838) reaching peaks at 17.2% 51-60 years and 25% in 71-80 implying a potential risk (OR = 1.43, 95% CI: 0.78-2.81, p = 0.032). 34.6% indicated genetics then noise (26.9%), while infections, stroke, and fevers made 19.2%. Air or sea travels (7.7%) were insignificant (P = 0.628) while head injuries (11.5%), or low- and high-altitudes showed 21.2%. Noise-hazard (P = 0.048) and medications (P = 0.017) were significant in HL. Conclusion: thus, we show geriatric age, noise, and inheritance-history as major predispositions. However, the study was limited by small sampling. Future large cohort multicenter studies on factual clinical data would gain more insights into the HL.

Pandemic human influenza detections are dependent on complex, time-consuming DNA molecular amplifications that require sophisticated PCR electrophoresis, cell culture amplification and complex spectrophotometric absorption techniques. In this study, simplified rapid electrochemical sensing methods were sought via a remote cyclic voltammetry and stripping amplifier circuit using our workstation systems. A sensing probe was prepared using human DNA and a Covid 19 antigen immobilized antibody sensing amplifier with rapid accumulation time of 30 sec. Optimal experimentation was performed using a telematics WiFi wearable circuit equipped with a bioelectrochemical analyzer-2 amplifier three electrode system. Diagnostic accumulation voltammetry and cyclic redox scanning were attempted at -2.0V~2.0V potential windows and 0.2V/Sec scan rate. Anodic and cathodic real time assay was performed using saliva swab from female patients that tested negative and positive. Diagnostic results are expected to be useful for non-contact analysis and for rapid personal testing anytime, anywhere.

The rapid integration of Generative AI technologies in academic and research environments marks the beginning of a new digital era, characterized by enhanced efficiency and innovative capabilities. This technological advancement, however, brings forth significant challenges and ethical dilemmas. One of the primary concerns is the potential diminishment of authentic human intellect in scholarly works, fueled by the capabilities of AI to generate ambiguous, fabricated, or even biased and inappropriate content. These issues highlight the critical need for developing comprehensive frameworks and establishing a dedicated field of study to govern the use of AI-generated content in academic and professional contexts. This autoethnography explores the impact of generative AI on educational practices, detailing the development of the SPARRO framework in healthcare and nursing classes. Through personal reflections, interviews, and observations, it addresses specific challenges, offering insights into integrating GenAI ethically and effectively to enhance teaching and learning.

This study examined how Information Use Environments (IUEs) influence the information behavior of people living with neglected tropical diseases (PLWNTDs) and how this affects their participation in diagnosis and treatment programs. The author demonstrated that local information use environments (IUEs) significantly impacted the information behavior of people living with neglected tropical diseases (PLWNTDs'), which can be harnessed to improve their involvement in diagnosis and treatment programs. The author compared user-centered and program-centered approaches within common IUEs in remote and impoverished areas, finding that NTDs persist due to a disconnect between program organizers and the affected individuals’ information use environments (IUEs). Data was sourced from published papers, and OpenAI (ChatGPT) was used to generate list of local sources (IUEs) in affected remote communities. The findings indicated that understanding local IUEs can help program organizers enhance participation rates of individuals with NTDs in diagnosis and treatment initiatives.

It was aimed evaluate the nutritive value of three foods (Cecropia sp., Pterodon sp., and Inga sp.), for sloths (Bradypus variegatus), based on in vitro gas production. After a 14-day adaptation period to these foods, approximately 500g of gastric contents were collected from three female sloths, processed, and incubated with food samples to evaluate digestibility and in vitro degradation kinetics. The neutral detergent fiber (NDFcp) was greater (P&lt;0,05) in the leaves of Cecropia sp. The non-fibrous carbohydrate contents were greater in Pterodon sp. The greatest cellulose content was found in the leaves of C. pachystachya, as well as lowest value for hemicellulose. There were differences in the in vitro digestibility of crude protein (P&lt;0.05), higher for Inga sp. In terms of kinetic parameters, Pterodon sp. demonstrated higher production of total gases (Vt) and digestion rates of fibrous carbohydrates (kdNFC) (P&lt;0.05), possibly related to the lower NDF content and higher values of soluble carbohydrates, which favored fermentative processes. The leaves of Pterodon sp. and Inga sp. demonstrated potential for feeding B. variegatus. Feeding B. variegatus with Cecropia sp., due to the NDF content, can cause negative effects on dry matter consumption.

Urban environments play a crucial role in shaping the lived experiences of women, yet traditional urban design practices often neglect the diverse needs and identities of women, perpetuating social barriers and gender inequalities. This review paper seeks to explore the existing research on how urban design influences women's social challenges in cities. By synthesizing literature from urban planning, architecture, gender studies, and sociology, this review provides a comprehensive overview of the impact of urban design on women's experiences and opportunities in urban spaces. The review highlights gender disparities in urban design, inclusivity in urban planning, and the need for gender-sensitive approaches to address these disparities. Key scholars, including Susan S. Fainstein, Leslie Kern, Sharon Zukin, Daphne Spain, and Vandana Shiva, have contributed significantly to understanding gender disparities in urban spaces and advocating for more inclusive and equitable urban environments. The discussion emphasizes the importance of community engagement, participatory planning processes, and an intersectional lens in urban design to ensure that women's voices and needs are effectively incorporated into decision-making processes. Future research directions include exploring the role of technology, smart city initiatives, and addressing the impacts of gentrification and urban redevelopment on women's access to housing and resources. By advancing research on gender equity in city planning, we can work towards creating more inclusive, equitable, and sustainable urban environments that benefit all residents.

The Ethnographic Museum in Dubrovnik holds an extensive textile collection that includes a range of dress and costume from Croatia and neighbouring countries. Until recently, the costumes were displayed on mannequins created by the academic artist Zvonimir Lončarić (1927–2004). His sculptures are expressive forms constructed from terracotta, fibreglass, wood, metal, acrylic paint and other materials selected for their visual appeal. Due to their importance, the museum considered the mannequins as protected artworks in the permanent exhibition, however, they had a harmful effect on the costumes displayed. In 2018, after completing a series of conservation-restoration projects within the collection, it was decided to replace the existing mounts with new, museum–quality mannequins. Two project–based learning workshops were organised, led by a team of textile conservators from the University of Dubrovnik and the Croatian Conservation Institute, in cooperation with the curator of the Ethnographic Museum. This case study highlights the challenges of exhibiting ethnographic costumes by discussing past presentation methods and how new solutions have been implemented conforming with the modern conservation-restoration profession. The new solutions consider ethics, decision–making processes, and the understanding of contemporary materials and methodology.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Simple Summary: Breast cancer is the most common invasive cancer among women. Triple-negative breast cancer (TNBC) accounts for 15–20% of newly diagnosed breast cancers and has the worst prognosis. However, TNBC patients are not a homogeneous group, and there are differences in the course of the disease as well as in response to treatment. For this reason, differentiation of subtypes of this tumor is important for optimal therapeutic decision and risk prediction. The presented study focuses on the expression of the androgen receptor (AR) and the infiltration of T-lymphocytes in the tumor stroma (TILs) of TNBC patients. Correlation of these tested biomarkers with standard prognostic factors. Defining new prognostic factors for 3-year overall survival (OS). Abstract: Background: Analysis of the practical benefit of testing the expression of AR and the TILs in patients with TNBC and their correlation with standard prognostic factors. Methods: The study group consisted of 86 female patients treated for TNBC. T-lymphocyte infiltration was examined in H+E staining. AR expression, CD8 and CD4 T-lymphocytes were evaluated in immunohistochemistry. Results: Significantly negative correlation was found between AR expression and the CD8 T-lymphocyte infiltration levels. A significant negative correlation was found between the AR expression and G and Ki 67, and a positive correlation between the TILs levels and G and Ki 67. Patients with AR expression and low TILs levels had the highest percentage of diagnosed distant metastases and 3-years OS. Patients with high TILs no distant metastases or deaths were diagnosed. The level of TILs turned out to be a significant independent prognostic factor. Conclusions: Based on the assessment of AR expression and TILs infiltration, the group of highest and lowest risk was determined. The prognostic factor of known parameters such as TNM and a new factor - TILs was confirmed. On the other hand, parameters such as G and Ki 67 and the tested factor - AR had no effect on the prognosis.

The aim of this article is to present the course of the COVID-19 pandemic in Poland in 2020-2022, the formation of ad hoc health and anti-crisis policies, an assessment of crisis management and the perceived impact of the pandemic and anti-crisis measures.The paper draws on literature, official reports on the pandemic, data from Eurostat and other information from state institutions and public organisations.Particular attention was paid to the analysis and evaluation of the objectives, instruments and effects of the policies pursued by the state in a coordinated manner, i.e. the anti-pandemic policy and the anti-crisis policy. The anti-pandemic policy in Poland has failed to protect the country from significant personal losses and negative impacts on the health of the population and demographic processes.The anti-crisis policy of the state carried out with the mobilisation of businesses and disciplined society, in the form of anti-crisis shields supplemented and adjusted on an ongoing basis, allowed Poland to avoid a deep crisis and economic recession. Attention was drawn to the need to coordinate the management of health and economic crises nationally and internationally, and to the need to have a medium-term anti-crisis state strategy and a system for the early detection of crisis symptoms.

Cured-in-place pipe (CIPP) lining is a widely adopted method for pipeline renewal, offering advantages such as rapid installation and cost-effectiveness. However, concerns regarding the environmental impacts of volatile organic compound (VOC) emissions during the installation process have raised issues regarding the CIPP method. The literature review conducted in this paper indicated the need for stringent monitoring and management practices to mitigate adverse effects, emphasizing the importance of safe installation protocols. This paper presents the initial results of a case study focusing on VOC emissions, specifically investigating non-styrene polyester resins and water curing. To capture emissions from CIPP activities, the methodology involved air sampling using various equipment, including photoionization detectors (PID), summa canisters, passive worker sampler sorbent tubes, and method 13 cartridges. The preliminary findings indicate that non-styrene polyester resins do not exceed the exposure limits set out by the OSHA and USEPA. The future phases of this project will explore different resins and curing methods.

The study looks at how joining live video chats with native English speakers on TikTok helps people who are learning English feel more ready to talk in English and less nervous about it. This study looks at EFL students who join TikTok live sessions. The researcher wants to understand how confident and nervous the students feel when they communicate. He uses qualitative research methods to do this. The study shows that using TikTok in a fun and calming way could help people learn a new language and reduce feelings of worry. This is helpful for teachers and language experts who want to use social media to help people learn languages.

This study investigates the transformative impact of ChatGPT, a cutting-edge AI language model developed by OpenAI, on the financial sector. We explore ChatGPT's applications in financial analysis, focusing on its ability to perform tasks traditionally handled by human analysts. By creating a set of multi-step and advanced reasoning financial tasks, and establishing several task-specific evaluation metrics, our experimental results demonstrate that ChatGPT-4o can effectively perform both basic and some complex financial analysis tasks comparable to those executed by humans. However, our empirical evaluation reveals limitations in its performance on complex tasks that require comprehensive understanding and critical thinking. The study highlights the necessity for meticulous task formulation and robust evaluation to achieve consistent functionality. While ChatGPT enhances efficiency in financial analysis, its integration with human expertise remains crucial for effective decision-making. This study contributes to the understanding of AI's role in finance and provides insights into its potential and constraints, guiding future integration of AI technologies in financial practices.

During the development of new medicines mutually exclusive specificity appears to be required but hitherto is most often included at the late clinical trial stage. Here, I describe the use of Hedgehog signalling in Drosophila as a model to represent a mutually exclusive relationship within the context and report the identification of CG43658, a putative Rho guanine nucleotide exchange factor and orthologue of the Charcot-Marie-Tooth disease associated gene ARHGEF10. Furthermore, a Computer that is able to consider the whole and describe the sum of everything in it absolutely in unambiguous terms is a useful tool. Here I describe such a computer with a suggestion for an application to examine any component in the context where a medicine is sought. Taken, together I would like to propose this method as a fundamental necessity and improvement upon current existing methods related not only to Hedgehog signalling but plausibly to life science research and the search for medicines in general.

Background: The study aimed to explore the association between the prognostic nutrition index (PNI) and in-hospital complication and mortality in patients with spontaneous intracerebral hemorrhage (ICH). Methods: We conducted a retrospective analysis using data from the Changhua Christian Hospital Clinical Research Database (CCHRD) between January 2015 and December 2022. 2402 patients were included, with the median PNI value set at 42.77. The restricted cubic spline model, Kaplan-Meier and ROC analysis for overall survival were used to evaluate the association of PNI with medical complications and mortality. Propensity score matching (PSM) analysis was performed to balance these clinical variables between groups, which could reduce potential bias to some extent. Results: PNI was significantly associated with in-hospital complications and 28-day and 90-day mortality in multivariate analysis. The main finding of our study is that a low PNI score at admission was independently associated with a poor ICH outcome. The Kaplan-Meier curves revealed higher survival rates in the high PNI group. PNI demonstrated sensitivity to predict medical complications and mortality based on ROC analysis. Conclusions Our study suggests that PNI could serve as a valuable marker for predicting medical complications and mortality in patients with spontaneous ICH.

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

Disulfiram (DSF), an anti-alcoholism medicine, exerts treatment effects in patients suffering from persistent Borreliosis and also exhibits anti-cancer effects by its copper chelating derivatives. Since chronic/persistent borreliosis is characterized by increased amounts of proinflammatory macrophages, this study investigated opsonin-independent phagocytosis, migration and surface marker expression of in vivo activated human monocyte-derived macrophages and dendritic cells with and without DSF treatment. Phagocytosis of non-opsonized Dynabeads® M-450 and migration of macrophages and dendritic cells were monitored using live cell analyzer Juli™ Br for 24h by imaging every 3.5 min. Results were analyzed by a newly developed software based on the differential phase contrast images of cells before and after ingestion of Dynabeads bearing an electron dense iron core. As a control, phagocytosis was also monitored by visual counting of ingested beads. DSF decreased the phagocytic capacities exhibited by global macrophages and dendritic cells. DSF also impaired the migration of human monocyte-derived macrophages and dendritic cells (hMDMD) and significantly reduced the expression densities of surface antigens CD45 and CD14. In cells consisting of anti-inflammatory M2 macrophages, DSF led to a remarkable cell death and also increased oxidative stress as determined by MitoSox staining. Mitochondrial oxidative stress was a prominent feature in M2 macrophages which were more sensitive to DSF-induced cytotoxicity.

Sanctuaries devoted to Asclepius were established and operated for almost a thousand years in various Greek and Roman cities throughout the Mediterranean region. The Asclepieion sanctuary in Lenta (formerly known as Ancient Lebena) in Crete was famous for receiving water from a sacred spring. In the Ancient Lebena, Levinaion was a famous centre for hydrotherapy, physiotherapy and a psychiatric hospital. In the present paper, we aim to assess the hydrochemical status of this sacred spring that holds a prominent position in archaeological and historical studies. The main objectives of this study are: Initially, to present supervisory evidence (archaeological, geological, hydrochemical) of an area that was a water resource management model for many centuries, carrying out therapeutic work. The second objective is to present and compare hydrochemical data in the last century, i.e. from 1915 to 2021. The third objective is to highlight and warn of an incipient saltwater intrusion in the area along the Lentas coast. The fourth objective is to propose an alternative and sustainable form of water resources management in the region that requires the study and rational utilization of the sporadic small water springs in the region. Our study focuses on a basic hydrochemical analysis of spring and borehole water in the remains of Levinaion in the Lentas region and their comparison with spare historical data of the sacred spring water, aiming to interpret the impact of the changes in the spring water resources that occurred in the last decades due to urban modernization. Our results highlight (i) visible fluctuations in chemical composition of borehole water samples, (ii) a neutral to alkaline pH in borehole waters, and an alkaline pH in spring waters, (iii) un-detectable arsenic of Lentas borehole water, unlike historical data of Lentas spring water, (iv) low values of dissolved radon of Lentas borehole water and spring water of Kefalovrysa, and (v) a timeless constant and hypothermic nature of the water of both sacred spring and borehole of Lenta, but also of Kefalovrysa spring. The recorded historical data, i.e. from 1915 to 1957, due to the absence of substantial anthropogenic activity in the area, can be used as reference values (natural background levels, NBLs) for the Lentas area. Our findings emerge with the need to bring again the flowing spring water of the sacred spring of Lentas in its original form through sustainable management and re-discover its beneficial therapeutical effects.

The object of study is a transversely bent triangular plate made of orthotropic material fixed along the edges of the plate under the action of a uniformly distributed load. Fourth-order differential equilibrium equations with variable orthotropy parameters were used. The equations were approximated by finite differences for a grid of scalene triangles. This type of mesh accurately describes the boundary contour of the triangular-shaped plates. The boundary conditions for the mesh consider the orthotropy of the plate material. Seven standard finite-difference equations have been developed considering the boundary conditions along the three edges of the plate and the presence of three angles of an irregularly shaped triangle. A finite difference matrix is obtained. The matrix structure makes calculating a triangular plate at different base angles possible. The boundary conditions were varied in the form of rigid or hinged support of triangular plates. The calculation method considers the orthotropic parameters of the material in two mutually perpendicular planes. The adaptation of the numerical method to the calculation of orthotropic plates of arbitrary shape is described. Relationships are given for determining the rigidity characteristics of orthotropic materials. An algorithm for simple engineering calculation of triangular orthotropic plates is proposed, which makes it possible to perform accurate calculations in variant design.

We prove a quasi-pseudometric version of the strong Ekeland principle proved by P. Georgiev and T. Suzuki.

The chemical reaction of ion-adsorption type rare earth during in-situ leaching process is accompanied by ion migration and charge movement, making the leaching process electrochemical in nature. The chemical reaction rate plays an important role in the leaching rate of rare earth elements. In this work, electrochemical impedance spectroscopy (EIS) was used to reveal characteristics of electrical resistance alteration and leaching rate of rare earth elements during in-situ leaching. The equivalent circuit model of the leaching process was established, and two critical parameters of solution resistance Rs and charge transfer resistance Rt were analyzed to reflect the electrochemical characteristics. According to the characteristics of electrical resistance alteration, the leaching process was divided into four stages: wetting, reaction, equilibrium, and top water stage. The resistance parameters Rs and Rt decreased first and then increased during the leaching process. The maximum value of Rs was 1330Ω∙cm2 at the end of the top water stage, and the minimum value was 135Ω∙cm2 at the beginning of the equilibrium stage. The maximum value of Rt was 8310Ω∙cm2 at the beginning of the leaching stage, and the minimum value was 21Ω∙cm2 at the end of the reaction stage. Rs and Rt were negatively correlated with the pore size and chemical reaction rate during leaching. With increasing of pore size and reaction rate , the resistance parameter decrease. This study provide a new idea for intelligent monitoring of rare earth ore.

Pharmaceutical aerosols play a key role in the treatment of lung disorders, but also systemic diseases, due to their ability to target specific areas of the respiratory system (RS). This article focuses on identifying and clarifying the influence of various factors involved in the generation of aerosol micro- and nanoparticles on their regional distribution and deposition in the RS. Attention is given to the importance of process parameters during aerosolization of liquids or powders and the role of aerosol flow dynamics in RS. The interaction of deposited particles with the fluid environment of the lung is also pointed out as an important step in the mass transfer of the drug to the RS surface. The analysis presented highlights the technical aspects of preparing the precursors to ensure that the properties of the aerosol are suitable for a given therapeutic target. Analyzing existing technical limitations, several potential strategies for enhancing the efficiency of targeted therapeutic delivery to or through the respiratory system are identified and presented, including the use of smart inhaling devices incorporating AI algorithms.

In order to reveal the frost heaving mechanism of void water behind the lining of high-speed railway tunnels in cold regions，the voids were first classified according to the positional relationship between voids and waterproof panels，and then the water supply and discharge conditions of different types of voids were investigated，then the influence of the excretion conditions on the frost heave force was experimentally studied. Based on these conditions，circular wedge-shaped and flying saucer-shaped void freezing models were established to analyze the evolution process of accumulated water frost heave. Then，according to the relative position of the excretion channel and the void，the excretion coefficient was introduced，and the calculation method of the frost heaving force of the voided water was proposed，and the influencing factors and laws of the frost-heave force were revealed. The results are shown as follows: 1) The blockage of the excretion channel will lead to the generation of frost heaving force; 2) The freezing and thawing process of the water within the cavity develops from the thinnest part of the void edge to the thicker part，and the process of frost heave-thaw，water replenishment-re-freeze heave of the water within the cavity leads to greater and greater frost heave force; 3) The frost-heaving force of the water within cavity is controlled by the void height and the position of the excretion channel. The larger the cavity height is or the closer the excretion channel is to the bottom surface of the void，the greater the frost-heave force is.

Artificial intelligence (AI)-based conversational models, such as ChatGPT, Microsoft Bing, and Google Bard, emerged as valuable sources of health information for the lay individuals. However, the accuracy of information provided by these AI models remains a significant concern. This pilot study aimed to test a new tool referred to as “CLEAR”, designed to assess the quality of health information delivered by AI-based models. Tool development involved a literature review on health information quality, followed by initial establishment of the CLEAR tool comprising five items that aimed to assess the following: completeness of content in response to the prompt, lack of false information, evidence support, appropriateness, and relevance of the generated content. Each item was scored on a 5-point Likert scale from excellent to poor. Content validity was checked by expert review of the initial items. Pilot testing involved 32 healthcare professionals using the CLEAR tool to assess content on eight different health topics deliberately designed with varying qualities. The internal consistency was checked using the Cronbach α. Feedback through the pilot test resulted in language modifications to improve the clarity of the items. The final CLEAR tool was used to assess health information quality generated through four different AI-based models in five different, yet common health topics. The AI models were ChatGPT 3.5, ChatGPT 4, Bing, and Bard, and the content generated was scored by two independent raters with Cohen κ to assess the inter-rater agreement. The final five CLEAR items were: (1) Is the content sufficient? (2) Is the content accurate? (3) Is the content evidence-based? (4) Is the content clear, concise, and easy to understand? and (5) Is the content free from irrelevant information? Pilot testing using the eight different health topics revealed an acceptable internal consistency with a Cronbach α range of 0.669–0.981. The use of the final CLEAR tool yielded the following average scores: Bing (mean=24.4±0.42), ChatGPT-4 (mean=23.6±0.96), Bard (mean=21.2±1.79), and ChatGPT-3.5 (mean=20.6±5.20). The inter-rater agreement revealed the following Cohen κ values: for ChatGPT-3.5 (κ=0.875, P<.001), ChatGPT-4 (κ=0.780, P<.001), Bing (κ=0.348, P=.037), and Bard (κ=.749, P<.001). The CLEAR tool is a brief yet helpful tool that can aid to standardize testing of the quality of health information generated by the AI-based conversational models. Future studies are recommended to validate the utility of the CLEAR tool to assess the quality of the AI-generated health-related content using a larger sample across various complex health topics.

The radiation stability of polymer test objects fabricated by direct laser writing is studied. The two groups of 6 cubes (50×50×50 μm3) were printed on a common silicon substrate. 6 cubes were irradiated with X-rays in the synchrotron radiation beam (12 keV, 1010 photons/mm2/s), the other 6 kept non-irradiated for the reference. In each group, the fabrication parameters (laser power and slicing step) were uniformly varied from cube to cube. Each irradiated cube was exposed with the dose of 1013 X-ray photons. The calibration of this dose in the radiological units (Gy) was carried out using the tissue-equivalent thermoluminescent detectors (TLD-800). The corresponding exposition dose was estimated as 30 kGy for each cube. The radiation effects were evaluated by Raman spectroscopy and by morphological changes observed with the raster electron microscope. The primary radiation effect appears in the essential increase of the polymerization degree with consuming carbon-carbon double bonds in favor of the polymer cross-linking. Only one cube of 6 has changed the size and shape due to this effect, while the others retained the initial shape. Morphological changes are connected with the improper fabrication parameters (laser power and slicing step). Properly fabricated objects withstand the X-rays of the synchrotron radiation beam.

The rising prevalence of autism internationally has been accompanied with an increased appreciation of the poorer mental health experienced by people with this condition and also of their family care-givers. In particular higher incidences of anxiety and depression are reported in high income nations and these conditions are likely to be under-recognised and under-reported in lower resourced regions or countries. Mainstream mental health services seem to be ill-equipped to respond adequately to the needs of autistic persons and their care-givers. This scoping review of 30 recently published literature reviews covering over 1,000 journal articles, summarises the insights and strategies that have been shown to promote the mental health and emotional wellbeing of autistic persons. In particular, a focus on family-centred, community-based supports is needed that aim to enhance social communication, extend social connections and promote an individual’s self-esteem, self-determination and social motivation. These low-cost interventions are especially pertinent in low resourced settings but they can be used internationally to prevent mental illness and assist in the treatment of anxiety and depression in autistic persons and their family carers. The priority is to focus on primary care responses with cross-sectoral working rather than investing in high-cost psychiatric provision.

Zinc, being a part of many proteins and enzymes, plays an important role in the vital processes of the body. Racemic α-lipoic acid (LA) has a wide range of biological activities: antioxidant, antidiabetic, anticancer, and it is also used in diseases such as Parkinson's and Alzheimer's. Nowadays, the synthesis and structural studies of new zinc complexes with biologically active compounds are of great importance for drug discovery. This work shows the studies carried out on the synthesis, structure, identification, also biological activity using in silico methods of a complex compound based on LA and zinc. A complex compound of zinc with LA (ZnLA) was synthesized in the presence of LA and zinc acetate in ethanol. The identification of ZnLA by (FT-IR, XRD and TGA-DTA), also DFT calculations at the B3LYP/def2-TZVPP level of theory was performed. The molecular docking investigation involved docking ZnLA with two different protein receptors such us Glycogen phosphorylase (2GPA) and Kv potassium channel beta subunit (1ZSX) using CB-Dock 2 server and Auto-Dock Vina program to determine the mechanism of action and biological activity. This study reveals potential ligand-protein interactions at the atomic level and suggests that the treatment of diabetes (non-insulin dependent) with ZnLA.

Wild-type p53 cancer therapy-induced senescent cells frequently engulf and degrade neighboring ones inside a massive vacuole in their cytoplasm. After clearance of the internalized cell, the vacuole persists, seemingly empty, for several hours. Despite large vacuoles being associated with cell death, this process is known to confer a survival advantage to cancer engulfing cells, leading to therapy resistance and tumor relapse. Previous attempts to resolve the vacuolar structure and visualize their content using dyes were unsatisfying for lack of known targets and ineffective dye penetration and/or retain. Here, we overcame this problem by applying optical diffraction tomography and Raman spectroscopy to MCF7 doxorubicin-induced engulfing cells. We demonstrated a real ability of cell tomography and Raman to phenotype complex microstructures, such as cell-in-cells and vacuoles, and detect chemical species in extremely low concentrations within live cells in a completely label-free fashion. We show that vacuoles had a density indistinguishable to the medium, but were not empty, instead contained diluted cell-derived macromolecules, and we could discern vacuoles from medium and cells using their Raman fingerprint. Our approach is useful for the non-invasive investigation of senescent engulfing (and other peculiar) cells in unperturbed conditions, crucial for a better understanding of complex biological processes.

Abstract: rainfall is the main driver of soil erosion. With the daily rainfall, riverine flow discharge and sediment load in the upper Lianjiang River watershed from 1990 to 2020, extreme rainfall events were defined by the 95th percentile method and minimum event interval time (MIT), change trends and mutations of yearly rainfall, riverine flow discharge and sediment load were identified using the Mann-Kendall test, then the optimum lag response time and antecedent rainfall were investigated with the multiple linear regression. The results showed that (1) the sediment changed significantly and abruptly in 1995 due to the expansion of the garden land. (2) Compared with ordinary rainfall, extreme rainfall events explained more variations of riverine flow and sediment with a higher degree, and had a more significant effect on the lag time of runoff and sediment. (3) Garden land expansion in extreme rainfall scenarios resulted in longer lag times for runoff and sediment and decreased demand for antecedent rainfall with more pre-event time. Therefore, taking the rainfall event as a breakthrough, analyzing the antecedent rainfall and the lag response of riverine flow discharge and sediment load is conducive to revealing the response mechanism of riverine flow discharge and sediment load and improving the simulation accuracy of riverine flow and sediment under extreme rainfall condition, thus help for the soil erosion control under extreme rainfall.

Efficient thermal management of modern electronics requires the use of thin films with highly anisotropic thermal conductivity. Such films enable the effective dissipation of excess heat along one direction while simultaneously providing thermal insulation along the perpendicular direction. In this study, we investigate the thermal conductivity of bilayer graphene (BLG) sheets using non-equilibrium molecular dynamics, examining both in-plane and cross-plane thermal conductivities. The in-plane thermal conductivity of 10 nm × 10 nm BLG with zigzag and armchair edges at room temperature is found to be around 204 W/m.K and 124 W/m.K, respectively. The in-plane thermal conductivity of BLG increases with sheet length. For all sizes, BLG with a zigzag edge exhibits higher thermal conductivity than that of the armchair edge, with this difference becoming more pronounced as the lengths of the sheets increase. In addition, increasing temperature from 300 K to 600 K decreases the in-plane thermal conductivity of a 10 nm× 10 nm zigzag BLG by about 34%. Similarly, the application of a 12.5% tensile strain induces a 51% reduction in its thermal conductivity compared to the strain-free values. Armchair configurations exhibit similar responses to variations in temperature and strain, but with less sensitivity. Furthermore, the cross-plane thermal conductivity of BLG at 300 K is estimated to be 0.05 W/m·K, significantly lower than the in-plane results by approximately four orders of magnitude. The cross-plane thermal conductance of BLG decreases with increasing temperatures, specifically, at 600 K, its value is almost 16% of that observed at 300 K.

In recent, Chae found that, at weak gravitational acceleration g_N≲10⁻⁹ms⁻², the observed orbit of the wide binary stars is not accordant with current theory of binary star. Here, we present, this finding should be an observational evidence for that Newtonian theory of orbit perturbation is still valid in galactic scale.

With the rapid increase in diabetes worldwide, the number of patients with diabetic kidney disease (DKD), a complication of diabetes mellitus, is also on the rise. DKD is a major cause of chronic kidney disease progressing to end-stage renal failure; however, current medical treatments for DKD do not achieve satisfactory outcomes. Molecular hydrogen (H2) is an antioxidant that selectively reduces hydroxyl radicals, a reactive oxygen species with a very potent oxidative capacity. H2 was recently shown to exert not only antioxidant, but also anti-inflammatory, cell lethality-regulating, and signal transduction-regulating effects, and is now being applied clinically. Many factors contribute to the onset and progression of DKD, with mitochondrial dysfunction, oxidative stress, and inflammation being strongly implicated. Recent preclinical and clinical trials reported that substances with antioxidant properties may slow the progression of DKD. Therefore, we conducted a literature review on animal models and human clinical trials in which H2 showed efficacy against various renal diseases. This literature review and our previous findings collectively suggest that H2 exerts therapeutic effects in patients with DKD by improving mitochondrial function. Future large-scale clinical studies are needed to confirm these findings.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often causes severe viral pneumonia, especially among older individuals and those with underlying health conditions. The C57BL/6 mouse is widely used to develop mouse models of obesity, diabetes, hypertension, and immune disorders, conditions that are associated with increased risk of severe COVID-19. Although many studies using these mouse models have examined the pathogenicity of SARS-CoV-2, COVID-19 pathogenesis remains poorly understood. In vivo imaging analysis using two-photon excitation microscopy is useful for elucidating the pathology of COVID-19, providing pathological insights that are not available from conventional histological analysis. However, there is no reporter SARS-CoV-2 that demonstrates pathogenicity in C57BL/6 mice and emits sufficient light intensity for two-photon in vivo imaging. Here, we generated SARS-CoV-2 expressing the fluorescent protein Venus to facilitate in vivo pathological studies using C57BL/6 mouse models. We generated a mouse-adapted strain of SARS-CoV-2, by performing sequential lung-to-lung passages in BALB/c mice, followed by in C57BL/6 mice. We observed that the C57BL/6-adapted SARS-CoV-2 (named MASCV2-p25) replicated efficiently in the lungs of C57BL/6 mice, causing fatal pneumonia. Histopathologic analysis revealed severe inflammation and infiltration of immune cells in the lungs of MASCV2-p25-infected C57BL/6J mice, not unlike that observed in COVID-19 patients with severe pneumonia. Subsequently, we generated a mouse-adapted reporter SARS-CoV-2 (named MASCV-Venus-p9) by inserting the fluorescent gene Venus into MASCV2-p25, and sequential lung-to-lung passages in C57BL/6 mice. C57BL/6 mice infected with MASCV2-Venus-p9 exhibited severe pneumonia similar to that induced by MASCV2-p25. In addition, two-photon excitation microscopy of the lungs of the infected C57BL/6J mice showed that the infected cells emitted sufficient levels of fluorescence for easy observation. These findings suggest that MASCV2-Venus-p9 will be useful for two photon in vivo imaging studies of the pathogenesis of severe COVID-19 and for the development of therapeutic agents for severe pneumonia.

Transmembrane carriers of the Slc11 family catalyze proton (H+)-dependent uptake of divalent metal-ions (Me2+) such as manganese and iron - vital elements coveted during infection. Slc11 mechanism of high affinity Me2+ cell import is selective and conserved between prokaryotic (MntH) and eukaryotic (Nramp) homologs, though processes coupling the use of the proton motive force to Me2+ uptake evolved repeatedly. Adding bacterial piracy of Nramp genes spread in distinct environmental niches suggests selective gain of function that may benefit opportunistic pathogens. To better understand Slc11 evolution Alphafold (AF2)/Colabfold (CF) 3D predictions for bacterial sequences from sister clades of eukaryotic descent (MCb and MCg) were compared using both native and mutant templates. AF2/CF model an array of native MCb intermediates spanning the transition from outward open (OO) to inward open (IO) carrier. In silico mutagenesis targeting i) a set of (evolutionary coupled) sites that may define Slc11 function (putative synapomorphy), and ii) residues from networked communities evolving during MCb transition, indicate Slc11 synapomorphy primarily instructs Me2+-selective conformation switch which unlocks carrier inner gate, and contributes to Me2+ binding site occlusion and outer gate locking. Inner gate opening apparently proceeds from interaction between transmembrane helix (h) h5, h8 and h1a. MCg1 xenologs revealed marked differences in carrier shape and plasticity, owing partly to altered intramolecular H+-network. Yet, targeting Slc11 synapomorphy also converted MCg1 IO models to OO state, apparently mobilizing the same residues to control gates. But MCg1 response to mutagenesis differed, extensive divergence within this clade correlating with MCb-like modeling properties. Notably, MCg1 divergent epistasis marks emergence of the genus Bordetella-Achromobacter. Slc11 synapomorphy localizes to the 3D areas that deviate least among MCb and MCg1 models (either IO or OO) implying it constitutes a 3D network of residues articulating Me2+-selective carrier conformation switch which is maintained in fast evolving clades at the cost of divergent epistatic interactions impacting carrier shape and dynamics.

In recent times, the process control network (PCN) of oil and gas installation has been subjected to amorphous cyber-attacks which include Denial-of-Service (DoS), Distributed-Denial-of-Service (DDoS), Man-in-the-Middle (MitM) attacks, and this may have been caused majorly by the integration of open network to Operation Technology (OT) as a result of low-cost network expansion. The connection of the OT to the internet for firmware updates, third-party support, or vendor interventions, has exposed the industry to attacks. The inability to detect these unpredictable cyber-attacks exposes the PCN and a successful attack can lead to devastating effects. This paper reviews the different forms of cyber-attacks in PCN of oil and gas installations and proposes the use of machine learning algorithms to monitor data exchanges between the sensors, controllers, processes, and the final control elements on the network so as to detect anomalies in such data exchanges. Python 3.0 Libraries, Deep-Learning Toolkit, MATLAB, and Allen Bradley RSLogic 5000 PLC Emulator software were used in the simulation of process control. The outcome of the experiments shows the reliability and functionality of the different machine-learning algorithms in detecting these anomalies with significant precise attack detections identified using a coarse tree algorithm.