Epigenetic changes are a hallmark of short- and long-term transcriptional regulation, and hence instrumental in the control of cellular identity and plasticity. Epigenetic mechanisms leading to changes in chromatin structure, accessibility for recruitment of transcriptional complexes, and interaction of enhancers and promoters all contribute to acute and chronic adaptations of cells, tissues and organs to internal and external perturbations. Similarly, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is activated by stimuli that alter the cellular energetic demand, and subsequently controls complex transcriptional networks responsible for cellular plasticity. It thus is of no surprise that PGC-1α is under the control of epigenetic mechanisms, and constitutes a mediator of epigenetic changes in various tissues and contexts. In this review, we summarize the current knowledge of the link between epigenetics and PGC-1α in health and disease.

Group-B enteroviruses (EV-B) are ubiquitous naked single-stranded positive RNA viral pathogens that are responsible for common acute or persistent human infections. Their genome is composed in the 5'end by a non-coding region, which is crucial for the initiation of the viral replication and translation processes. RNA domain-I secondary structures can interact with viral or cellular proteins to form viral ribonucleoprotein (RNP) complexes regulating viral genomic replication, whereas RNA domains-II to -VII (IRES) are known to interact with cellular ribosomal subunits to initiate the viral translation process. Natural 5’ terminally deleted viral forms lacking some genomic RNA domain-I secondary structures have been described in EV-B induced murine or human infections. Recent in vitro studies have evidenced that the loss of some viral RNP complexes in the RNA domain-I can modulate the viral replication and infectivity levels in EV-B infections. Moreover, the disruption of secondary structures of RNA domain-I could impair viral RNA sensing by RIG-I or MDA5 receptors, a way to overcome antiviral innate immune response. Overall, natural 5′ terminally deleted viral genomes resulting in the loss of various structures in the RNA domain-I could be major key players of host-cell interactions driving the development of acute or persistent EV-B infections.

Cu-ions dispersed on reduced graphene RGo prepared and characterized in a liquid state in ethanol. Either constant ultrasounds or a sequence of ultrasounds (15s working, 15s stop) were applied for 6 min or 2h overall time, at a power of 500 W. Commercial graphite in ethanol was introduced at a concentration of 0.04 g/mL and CuCl2 2.5 H2O concentrations between 0.012 and 0.04 g/mL were used. The structural characterizations performed by XRD, microscopic, and spectroscopic techniques, after a centrifugation at 5000 rpm applied 12 min before Cu-introduction, led to conclude that: 1) Without copper, negative peaks in UV spectra were detected with concentrated pure graphene solutions, indicating light emission as nicely confirmed next by fluorescence measurements, 2) After addition of copper chloride and equilibration for 2 min , very intense and narrow peaks of intensity larger than 10 were observed. These peaks due to collective excitations generating plasmons were suppressed at a higher dilution and also if the cell with one cm optical path was replaced by a narrower cell with a 0.2 cm path. When plasmons were suppressed, in the UV spectral range, a band gap due to the energy transition between the valence filled  orbitals and conducting empty * orbitals, was observed. The presence of Cu (II) and Cu (I) cations were evidenced by Visible NIR spectroscopy. The formed “green” liquors containing Cu (II) Cu (I) /graphene in ethanol were stable in air for months and had good photocatalytic visible properties as demonstrated by the decomposition of two dyes.

The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of several studies, still little is known about the nanoscopic impact of target oxygenation on the radical yields. We present here an extension of the chemical module of the Monte Carlo particle track structure code TRAX, taking into account the presence of dissolved molecular oxygen in the target material. The impact of the target oxygenation level on the chemical track evolution and the yields of all the relevant chemical species is studied in water under different irradiation conditions: different linear energy transfer (LET) values, different oxygenation levels, and different particle types. Especially for low LET radiation, a large production of two highly toxic species (HO₂^• and O₂^•− ), which are not produced in anoxic conditions, is predicted and quantified in oxygenated solutions. The remarkable correlation between the HO₂^• and O₂^•− production yield and the oxygen enhancement ratio observed in biological systems suggests a direct or indirect involvement of HO₂^• and O₂^•− in the oxygen sensitization effect. The results are in agreement with available experimental data and previous computational approaches. An analysis of the oxygen depletion rate in different radiation conditions is also reported.

The process of oxygenic photosynthesis is primarily driven by two multiprotein complexes known as photosystem II (PSII) and photosystem I (PSI). PSII facilitates the light–induced reactions of water–splitting and plastoquinone reduction, while PSI functions as the light–driven plastocyanin-ferredoxin oxidoreductase. In contrast to the highly conserved structure of PSII among all oxygen–evolving photosynthetic organisms, the structures of PSI exhibit remarkable variations, especially for photosynthetic organisms that grow in special environments. In this review, we make a concise overview of the recent investigations of PSI from photosynthetic microorganisms including prokaryotic cyanobacteria and eukaryotic algae from the perspective of structural biology. All known PSI complexes contain a highly conserved heterodimeric core; however, their pigment compositions and peripheral light-harvesting proteins are substantially flexible. This structural plasticity of PSI reveals the dynamic adaptation to environmental changes for photosynthetic organisms.

The research methods were used to investigate the following questions: Does a mobility training intervention change tissue stiffness, joint range of motion, and compensate for possible imbalances? Do the interventions influence the pressure pain threshold and the overall well-being?

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

Design process can be divided into stages of analysis and synthesis. This paper presents the application of the object-oriented technique to the analysis as well as theoretical considerations concerning to design of gear size ranges. This analysis consists in decomposition of the designed artefact (a gear) according to the rule “from general to details view”. The basics of the object-oriented analysis were formulated. Furthermore, design phases and the objects related to theses phases were discussed. The following models have been considered: hierarchical model, entity-relationship model, data-flow model and object model. Analysis is additionally connected with interactions between particular design phases.

Combining the Job Demands-Resourses model and the Work Adjustment theory, this research aims to create a theoretical model that considers Leader-Member Exchange (LMX) and Work Adjustment as protective factors, capable of reducing job exhaustion and turnover intention. A convenience sample of 257 Italian employees filled an online self-report questionnaire. A sequential mediation model was tested, which showed that the relationship between LMX and turnover intention is mediated by Work Adjustment and Job Exhaustion. The results show that the higher the LMX, the higher the work adjustment of the workers and the less they will perceive job exhaustion and, consequently, intent to leave the organisation. With a view to primary prevention, the aim was to investigate possible protective factors at work and the risk factors to look out for in order to move in the direction of preventing a malaise phenomenon before it develops with the aim of promoting wellbeing in organisations.

Lifespan extension was recently achieved in Caenorhabditis elegans nematodes by mitochondrial stress and mitophagy, triggered via iron depletion. Conversely in man, deficient mitophagy due to Pink1/Parkin mutations triggers iron accumulation in patient brain and limits survival. We now aimed to identify murine fibroblast factors, which adapt their mRNA expression to acute iron manipulation, relate to mitochondrial dysfunction and may influence survival. After iron depletion, expression of the plasma membrane receptor Tfrc with its activator Ireb2, the mitochondrial membrane transporter Abcb10, the heme-release factor Pgrmc1, the heme-degradation enzyme Hmox1, the heme-binding cholesterol metabolizer Cyp46a1, as well as the mitophagy regulators Pink1 and Parkin showed a negative correlation to iron levels. After iron overload, these factors did not change expression. Conversely, a positive correlation of mRNA levels with both conditions of iron availability was observed for the endosomal factors Slc11a2 and Steap2, as well as for the iron-sulfur-cluster (ISC)-containing factors Ppat, Bdh2 and Nthl1. Positive correlation only after iron depletion was observed for the iron export factor Slc40a1, mitochondrial iron transporters Slc25a28, Abcb7 and Abcb8, mitochondrial ISC-containing factors Glrx5, Nfu1, Bola1 and Abce1, cytosolic Aco1 and Tyw5, as well as nuclear Dna2, Elp3, Pold1 and Prim2. The latter are regulators of nucleotide synthesis and DNA quality control, which have known importance for growth and lifespan. The only Pink1-/- triggered transcript modulation was the reduced expression of the ISC-containing ribosomal factor Abce1. These mammalian findings support previous fly data that Pink1 influences co-translational quality control via Abce1, as well as mitophagy. Our findings provide the first systematic survey how iron dosage triggers homeostatic transcriptional regulations and elucidate how iron deprivation results in mitophagy.

Groove pancreatitis represents a chronic focal form of pancreatitis affecting the zone between the pancreatic head and the duodenal „C” loop, known as the groove area. This is a rare condition that affects the pancreatic periampullary part, including the duodenum and the common bile duct, associated usually with long-term alcohol and tobacco misuse and being more frequent in men than in women. The most common clinical symptoms of groove pancreatitis include weight loss, acute abdominal pain, nausea, and jaundice. This report is about a 66 year old woman with a history of heavy smoking, presenting with weight loss, nausea, and upper abdominal pain. Contrast enhanced computed tomography revealed the existence of a chronic pancreatitis as well as the dilatation of the main pancreatic duct, a cyst of the pancreatic head and enlargement of the biliary tract. Conservatory treatment was initiated but with no improvement of symptoms. Since there was no indication for endoscopic retrograde cholangiopancreatography, we decided to perform a pancreatoduodenectomy, as surgery appears to be the single effective treatment.

Background: Endovascular treatment of popliteal aneurysms (PA) has increased in the last few years, quickly becoming the main treatment in many vascular centers, based on the acceptable and promising outcomes reported in the literature. However, endograft infections are the most dangerous complication as a serious local compromise and usually require open surgical conversion and device explantation to preserve the affected extremity. Case report: We reported two patients admitted to the emergency room for pain and edema in the lower leg. Both patients have undergone exclusion of ruptured PA a few years before by endovascular graft. CTA showed a significant volume of fluid-corpuscular collection related to perianeurysmal abscess collection in both cases. Blood cultures and drained material cultures were positive for Staphylococcus Capitis in the first case and S. Aureus in the second. The antibiotics prophylaxis was performed for 10 days, then, patients underwent an open surgical conversion with a complete explantation of endovascular material and a femoro-popliteal bypass using an autologous vein in the first case and biological bovine pericardium prosthesis in the other case. Furthermore, we have questioned the literature and found eight more cases described in case report article referred to popliteal graft infections by different microorganisms, mostly presenting acute limb ischemia as the first symptom and suggesting endograft explantation with open conversion and autologous vein bypass as the commonest therapeutic choice. Conclusions: Open surgical conversion of popliteal endograft infection is the best strategy to manage peripheral infection of the popliteal stent.

This research aims to apply Artificial Intelligence (AI) methods, specifically Artificial Immune Systems (AIS), to design an optimal control strategy for a multivariable control plant. Two specific industrial control approaches are investigated: I-PD (Integral-Proportional Derivative) and PI-D (Proportional-Integral Derivative) control. The motivation for using these variations of PID controllers is that they are functionally implemented in modern industrial controllers, where they provide precise process control. The research results in a novel solution to the control synthesis problem for the industrial system. In particular, the research deals with the synthesis of I-P control for a two-loop system in the technological process of a distillation column. This synthesis is carried out using the AIS algorithm, which is the first application of this technique in this specific context. Methodological approaches are proposed to improve the performance of industrial multivariable control systems by effectively using optimization algorithms and establishing modified quality criteria. The numerical performance index ISE justifies the effectiveness of the AIS-based controllers in comparison with conventional PID controllers (ISE₁ = 1.865, ISE₂ = 1.56). The problem of synthesis of the multi-input multi-output (MIMO) control system is solved, considering the interconnections due to the decoupling procedure.

The broad emission bump in the electromagnetic spectra observed following the detection of gravitational waves created during the kilonova event of merger of two neutron stars in August 2017, GW170817, has been linked to the heavy elements of lanthanides (Z=57-71), and a new understanding of creation of heavy elements in the r-process. The initial spectral emission bump has a wavelength range of 3000 - 7000 \AA, thus covering the region of ultraviolet (UV) to optical (O) wavelengths, and is similar to those seen for lanthanides. Most lanthanides have large number of closely lying energy levels which introduce extensive sets of radiative transitions which often form broad region of lines of significant strength. The current study explores these broad features through photoabsorption spectroscopy of 25 lanthanides ions, Ho I-III, Er I-IV, Tm I-V, Yb I-VI and Lu I-VII. With excitations only to a few orbitals up beyond the ground configurations, we find most of these ions cover large number of bound levels with open $4f$ orbital and produce tens to about hundred thousands lines that may form one or multiple broad features in X-ray to UV, O, and infrared (IR) regions. Spectrum of each of 25 ions is presented indicating presence, shape and wavelength region of the features. Accuracy of atomic data to interpret the merger spectra has been a outstanding problem. The present study aims at providing improved atomic data for energies and transition parameters obtained using relativistic Breit-Pauli approximation implemented in the atomic structure code SUPERSTRUCTURE. The present data have been benchmarked with available experimental data for energies and transition parameters. The study finds that number of ions under the present study are possible contributors of the emission bump of GW170817. All atomic data will be made available online at NORAD-Atomic-Data database.

Therapeutic measures aimed at optimising organ function prior to transplantation - whether by conditioning the donor after determination of brain death or by improving organ preservation after kidney removal - have the potential to enhance outcomes after transplantation. The particular advantage is that, unlike any optimised immunosuppressive therapy, a positive effect can be achieved without side effects for the organ recipient. In recent years, several such measures have been tested in controlled clinical trials on large patient cohorts following kidney transplantation. Hypothermic pulsatile machine perfusion in particular has become the focus of interest, but interventions in the donor prior to organ removal, such as the administration of low-dose dopamine until the start of cold perfusion as an example of conditioning antioxidant therapy, and therapeutic donor hypothermia in the intensive care unit after brain death confirmation have also significantly reduced the frequency of dialysis after transplantation with far less effort and cost. With regard to a favourable effect on graft survival in the long-term, the database for all procedures is less clear and controversial. The aim of this review article is to re-evaluate the available clinical evidence on the basis of the large multicentre controlled trials, which have also significantly influenced later meta-analyses, and to assess the significance for use in routine clinical practice.

The article presents several innovative systems developed through student laboratory projects, including two autonomous vehicles, a four-legged walking robot, an active ankle-foot orthosis, a ball on beam balancing mechanism, a ball on plate system, and a manipulator arm—all powered by pneumatic artificial muscles (PAMs). Fluidic muscles offer significant potential in various mechatronic systems, robots, and manipulators due to their flexible, lightweight nature and compliance. Their ability to produce smooth and adaptable motions is particularly beneficial in applications requiring natural and human-like movement, such as rehabilitation and assistive devices. Although PAMs powered control systems face challenges with nonlinear phenomena, their biologically inspired design holds promise for future applications across various industries. These may include innovative applicability in industrial, automotive, and aerospace sectors, as well as use in sports, medical aids, entertainment, and animatronics. Incorporating self-made laboratory systems actuated by PAMs into control systems education offers a comprehensive learning opportunity that combines theoretical concepts with hands-on experience. This approach develops the necessary skills of future engineers, expanding their understanding of technical principles and preparing them for future challenges in engineering practice.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

Intercropping cover crops have become mandatory in areas at risk of nitrogen leaching to groundwater. These covers include several attractive late-flowering entomophilous species. They can therefore represent crucial floral resources (pollen and nectar) for pollinating insects in early autumn. Pesticides used in previous crops, however, represent a potential risk for pollinators when they are transferred to the intercropping cover plants and their floral resources. We studied the potential transfer of clothianidin (a neonicotinoid insecticide), applied two years earlier in a beet cultivation, from soil to plants and to the floral resources of three common cover species: Phacelia tanacetifolia, Sinapis alba, and Vicia faba. Soils, entire plants, flowers, and nectar were collected from plants grew in greenhouses, and soils and pollen were collected on a treated field. Our results showed that clothianidin was still present in soils (4.5 ng g−1). The residues accumulated in plants (5-15 times higher concentrations than in soils) and were present in pollen of both Vicia faba (0.07 ng g−1) and Sinapis alba (1.7 ng g−1) and in nectar of both Sinapis alba and Phacelia tanacetifolia.

The serendipitous discovery of antiparasitic drugs, such as quinine and artemisinin from plant origin reveals that the search for new chemical pharmacophores from medicinal plants is valuable. The present study sought to explore the antiplasmodial, antileishmanial, and antitrypanosomal activities of extracts from Lippia adoensis. Crude extracts of L. adoensis leaves and twigs, which were obtained by extraction using 70% ethanol in water, were assayed for antiplasmodial activity against P. falciparum 3D7 and Dd2 through the SYBR green I-based fluorescence assay; and for antileishmanial, antitrypanosomal, and cytotoxic effects on Leishmania donovani, Trypanosoma brucei brucei, and Vero cells, respectively, using the resazurin colorimetric assays. The phytochemical analysis of the extracts was performed using a liquid chromatography-mass spectrometry (LC-MS) feature-based detection and molecular networking flow on Global Natural Product Social (GNPS). As a result, the crude extracts from L. adoensis inhibited growth of P. falciparum (3D7 and Dd2) (IC50s; (3D7): 10.008 and 97.467 μg/mL; (Dd2): 29.48 and 26.96 μg/mL), L. Donovani (IC50s: 22.879-10.522 μg/mL), and T. brucei brucei (IC50s: 2.3085-55.06 μg/mL). The extracts were found to be non-cytotoxic to Vero cells, thus yielding median cytotoxic concentrations (CC50s) above 100 μg/mL. The LC-MS tandem molecular networking flow predicted that the extracts contain valsafungin A and bacillamidin on the first cluster, and fatty acids, ketone and aldehyde derivatives on the second cluster. Overall, the present study demonstrated the antiparasitic effects of L. adoensis extracts, thus justifying the use of this plant in the traditional treatment of fever and malaria conditions. Nevertheless, detailed metabolomic studies and antiparasitic mechanisms of action of the extracts are expected to unveil the potential antiparasitic hit compounds.

(1) Background: As part of the Scottish Governments five-year recovery plan to address the backlog in NHS care following the COVID-19 pandemic, community pharmacies in Scotland are planned to provide a Hospital Discharge Medicines Supply and Medicines Reconciliation Service. We aimed to qualitatively explore patients’ experience of this new service; (2) Method: Adult patients (≥18yrs age) who consented to participate in the Community Pharmacy Hospital Dis-charge and Medicines Reconciliation Service were invited for interview within 21 days of dis-charge from hospital. Qualitative, one-to-one, semi-structured, patient interviews were conducted by telephone and audio-recorded using Microsoft Teams®. The interview audio recordings were transcribed verbatim and underwent thematic analysis; (3) Results: 12 patients were inter-viewed, evenly split by sex and with a median age of 62 years (range; 36 to 88 years). Analysis generated main five themes; Patient Engagement, Stakeholder Communication, Practical Factors, Human Factors, and Comparative Experiences. Many of these were interdependent; (4) Con-clusions: Patients appreciated that the service ensured a quicker discharge from hospital. Good stakeholder communication, practical factors (including choice, location, and the realities of ob-taining their medication from the community pharmacy), and a pre-existing and trusted rela-tionship in their usual community pharmacy were the key factors that regulated the patient ex-perience. In the main, patients were positive about the introduction of this new service. However, a lack of previous relationship or trust with a community pharmacy, and previous experiences with medication supply problems were factors which had the potential to negatively impact on patient experiences.

Diarrhea remains one of the leading causes of mortality worldwide, especially among children. Recent epidemiological studies conducted in developing countries identified Shigella species as the most predominant pathogenic bacteria responsible for diarrhea. Antimicrobial therapy is necessary for Shigella infections; however, the rapid emergence of resistance against existing antimicrobials in Shigella spp. poses a serious global health problem. To identify alternative antimicrobial compounds with activity against Shigella species, the pathogens responsible for bacterial diarrhea. In this study, we have applied antibacterial phenotypic screening to identify potent anti-Shigella compounds across a broad chemical diversity, including selected acetaminophen derivatives containing benzothiazoles backbone, and their combination with certain antibiotics. In continuation to our effort in searching potent antimicrobial compounds, we have found this time around that two acetaminophen derivatives containing benzothiazoles backbone (4a and 4b) could inhibit the growth of Shigella flexneri with common MIC value of 12.5 µg/ml. These compounds were established through a time-kill kinetics’ study to be bactericidal. Meanwhile, the 2-aminobenzothiazoles (1a and 1b) used for the synthesis of compounds 4 (a & b) were found to be poorly active (MIC: 100 µg/ml) against this pathogen. Combination studies of 4a and 4b with the least susceptible antibiotics (ceftriaxone and cotrimoxazole) demonstrated synergistic anti-Shigella activity. The present study demonstrates that the azobenzothiazole dyes 4 (a & b) can be repurposed as potential anti-Shigella compounds, which can serve as scaffolds for the development of new agents against infectious diarrhea caused by Shigella and other enteric pathogens, especially in developing countries.

The cellular stress response corresponds to the molecular changes that cell undergoes in response to various environmental stimuli. It induces drastic changes in the regulation of gene expression, at transcriptional and post-transcriptional levels. Actually, translation is strongly affected with a blockade of the classical cap-dependent mechanism, whereas alternative mechanisms are activated to support translation of specific mRNAs. One of the major mechanisms involved in stress-activated translation is the internal ribosome entry site (IRES)-driven initiation. IRESs, first discovered in viral mRNAs, are present in cellular mRNAs coding for master regulators of cell responses, whose expression must be tightly controlled. IRESs allow translation of these mRNAs in response to different stresses, including DNA damage, amino-acid starvation, hypoxia or endoplasmic reticulum stress, as well as to physiological stimuli such as cell differentiation or synapse network formation. Importantly, cellular mRNA IRESs are regulated by IRES trans-acting factor (ITAFs), exerting their action by at least nine different mechanisms. This review presents an update of the reported ITAFs regulating cellular mRNA translation and of the different mechanisms allowing them to control translation initiation in specific conditions. The impact of ITAFs on coordinated expression of mRNA families and consequences in cell physiology and diseases are also highlighted.

The study of the impact of polyQ expansion driven proteotoxicity on cell metabolism has evi-denced NAD molecule as a central player in regulating metabolic response and cell repair in neurodegeneration. The decline in NAD intracellular levels represents a hallmark of ageing aris-ing from a dysregulation between NAD-consuming and biosynthetic enzymatic reactions in which NMNAT plays a key role. By an integrated bioanalytical and proteomic experimental design, the derangement of NAD metabolism deriving from the accumulation of polyQ-Htt protein has been analysed in Saccha-romices cerevisiae harbouring a 103Q-Htt and compared with wild-type Htt, in absence and in presence of a phenolic extract from EVOO, as a source of antioxidant bioactive compounds. Quantification of NAD and its precursors and proteomic analysis of the differential protein ex-pression has been performed by LC-DAD-MS. Chronological lifespan and NAD homeostasis was strongly impaired by proteotoxic polyQ-Htt, eliciting a depletion of NAD levels and accumulation of NaMN. In parallel a downregulation of Sirt2 expression levels has been observed. Phenolic extract administration had no meaningful ef-fects on NAD replenishment to prevent proteotoxicity. NaMN can represent a biomarker of accel-erated aging, and/or a signaling molecule for cell repair.

The lack of knowledge on the link between the manufacturing process and performances constitutes a major issue of brake lining development. This study focuses on the effect of mixing duration on properties and tribological behavior of organic friction composite materials. The adopted methodology is based on efficient simplified formulations to limit synergic effects by the reduction of number and size distribution of constituents. Microstructural characteristics are analyzed and correlated to thermo physical and mechanical properties. Wear mechanisms and tribological behavior are studied in relation with the given microstructure and material properties. In the elaboration process, mixing duration has an impact on particle distribution and fibre arrangement. Distribution and size of fibre entanglements are found to cluster carbonaceous particles, which creates bulk thermal bridges improving thermal conductivity. Moreover, rockwool fibre arrangements affect density, porosity and thermo-physical properties. In addition, mixing duration disrupts cohesion of fibre bundles with the matrix, affecting compressive modulus and wear behaviour. This microstructural defect fosters an abundant third-body source flow, which results in a high wear flow. Porosities induced by fibre entanglements, presenting large and irregular size and distribution on the friction surface, lead to a low wear resistance and change the stability of friction.

Wheat dwarf disease (WDD) is an important disease of monocotyledonous species, including economically important cereals. The causative pathogen, the wheat dwarf virus (WDV), is a monopartite Mastrevirus that has a circular single-stranded (ss)DNA genome and is transmitted persistently and propagatively mainly by the leafhopper Psammotettix alienus. The disease can induce high yield losses in many European countries in a range of 20-100%. Due to climate change the periods of vector activity increased and the vectors spread to new habitats, leading to an increased importance of WDV in large parts of Europe. In the light of integrated pest management approaches cultivation practices and the use of resistant/tolerant host plants are currently the only effective methods for controlling WDV. To date, there is limited knowledge of the pathosystem and epidemiology of the disease. The few sources of genetic tolerance, indicate the need for further research. Considering the economic importance of the disease, and its likely increasing relevance in the coming decades, this review was prepared to compile and update knowledge on aspects of WDV.

Photovoltaic modules should pass series of tests and examinations, verifying the electrical and thermal characteristics of the module, before being released to the market, examining the properties of the modules should undergo appropriate durability and efficiency tests under real outdoor conditions with exposure to climatic conditions and under laboratory conditions. The performance of photovoltaic cells depends on many factors, such as solar irradiance, module operating temperature, installation location, weather conditions and module shading. In this paper, three selected photovoltaic modules were examined using a large-scale steady-state solar simulator. The current-voltage (I-V) characteristics of the photovoltaic modules were experimentally tested and analyzed. The next step was to implement a three-layer artificial neural network model (MLP). The experimental data obtained in the previous step coupled with output data from MLP were then used in global sensitivity analysis (GSA). Experiments carried out on a large-scale stationary solar simulator showed differences between the values declared by the manufacturer and the values obtained from measurements of PV modules. The first module tested achieved the maximum power point greater than that specified by the manufacturer, while the other two showed power drops; it was 85-87% for the second module, and 95-98% for the third, respectively. The performed global sensitivity analysis (GSA) for the MLP model showed that the parameters: eff (22.9) and Voc/V (14.19) have the largest effect on the power-voltage relationship, while U (7.29) has the smallest effect. The usefulness of machine learning (ML) methods in the comparative analysis of PV modules has been proved.

Li4Ti5O12 (LTO) exhibits zero-strain behavior, exceptional cycle stability, low cost, and high safety. However, it is still low in electronic and ionic conductivity. Incorporating Sn into LTO materials can increase electronic conductivity and specific capacity. However, Sn still experiences volumetric expansion during the charging/discharging process. Adding activated carbon (AC) into the LTO/Sn composite can help improve the expansion resistance and electronic conductivity. In this work, the AC was first synthesized from charcoals through the carbon activation process and mixed with LTO precursors through the sol-hydrothermal method followed by mixing with Sn through the mechanochemical process to produce LTO@AC/Sn composites. The Sn content was fixed at 15 wt.%, while the AC contents were varied at 1 wt.%, 3 wt.%, and 5 wt.%. The AC specific surface area is increased by more than 100% compared to the non-activated one. The best effects of AC on grain morphology and distribution were found in the LTO/Sn contained 3 wt.% of AC, leading to transfer resistance, ohmic resistance, specific capacity, and coulombic efficiency were found to be 48.1 Ω, 8.5 Ω, 138 mAhg-1, and near 100%, respectively. The result suggests that the LTO@AC/Sn could be a favorable anode active material in lithium-ion batteries.

Background: Despite advances in the treatment of hepatocellular carcinoma (HCC) over the last few decades, treatment opportunities for patients with HCC remain limited. HCC is the most common form of liver cancer, accounting for approximately 90% of all cases worldwide. Moreover, apart from the current pharmacological interventions, hepatic resection and liver transplantation are the mainstay curative approaches for patients with HCC. Methods: This systematic review included phase I, II, III, and IV clinical trials (CTs) and randomized controlled trials (RCTs) on current treatments for patients with HCC in an Asian population (2013–2023). A total of 427 articles were screened, and 184 non-duplicate publications were identified. After screening titles and abstracts, 96 publications were excluded, and another 28 were excluded after full-text screening. The remaining 60 eligible RCTs/CTs were finally included. Results: Sixty clinical trials fulfilled our inclusion criteria and screened 36 drugs as monotherapy or combination therapy for HCC. Most studies used sorafenib alone or in combination with any of the treatment regimens. Lenvatinib or atezolizumab with bevacizumab was used for HCC after initial sorafenib treatment. Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. Conclusion: This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicated that sorafenib alone or in combination with atezolizumab and bevacizumab has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in an Asian population

Crystalline silver thin layers were obtained by high-energy pulsed laser ablation without heating of the deposition substrate. The fluid Plateau-Rayleigh (PRI), Rayleigh – Taylor (RTI) and Richtmyer – Meshkov (RMI) instabilities, as well as crown splash induced during pulsed laser deposition (PLD) in high energy regime, resulting in ring and pearl shaped structures, offer the benefit of increased sorption surface. These morphological structures obtained for the silver thin layers make them of interest for catalytic applications. The study presented with this work addresses both the fundamental and applied issues on the morphological structures obtained for the silver thin layer and their catalytic function in organic processes. In this sense, the catalytic action of the thin silver layer was highlighted by modifications of the Reactive Blue 21 dye (C.I.) in aqueous solution with sodium bicarbonate. Specific investigations and analyzes were carried out by electron microscopy and elemental analysis (SEM-EDX), atomic force microscopy (AFM) and profilometry, mass spectrometry, ablation plasma diagnosis, diffractograms (XRD), as well as IR spectroscopy (FTIR). In addition to the experimental investigation and analyzes, simulation of the ionization energy threshold was conducted in COMSOL for complementary evaluation on the involved processes and phenomena.

The Upper Hunter Valley is a major coal mining area containing approximately 40% of the currently identified total coal reserves in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. This paper summarises the spatial and temporal variability modes of PM10 pollution in the region, based on long-term multi-site monitoring data and the application of the rotated principal component analysis (RPCA) and wavelet analysis techniques. RPCA identified two distinct air quality clusters/subregions in the valley, one in the west/northwest, the other in the southeast. Wavelet analysis revealed the annual cycle to be most persistent temporal mode of PM10 variability in both subregions, with intermittent signals observed at time scales of around 120, 30~90 and under 30 days. How these variation modes are related to the effects of local PM10 emissions and the influence of meteorology at different time scales deserves further attention in future work. The findings will be used in air quality reporting and forecasting in NSW. The methodology and results can also be useful for air quality research in similar regions elsewhere.

(1) Background: A wide literature based on loading and unloading bending tests has been carried out over the half past century for assessing the force released by superelastic wires. The aim of this investigation is not only to characterize a broadly described superelastic NiTi and a novel CuNiTi archwire, but also to provide novel insights into the load vs deflection profiles. A harmonic scenario for superelastic wires will be shown as temperature is kept constant at 37°C. However, a completely different picture will be highlighted as a temporary heating step up to 50°C is introduced within the force vs deflection profiles. (2) Methods: A variety of NiTi and a novel CuNiTi round and rectangular cross-section archwires have been investigated. Static 3-point bending tests up to a deflection level of 3.0 mm have been carried out for detecting the unloading force plateau levels occurring at 37°C. A hold deflection step of 5 min at deflection levels occurring along the unloading plateau extension is introduced. The effect of a temporary heating up to 50°C on the force plateau level released by the investigated wires is analyzed. (3) Results: Mechanical profiles suggest that the plateau force levels detected at 37°C are consistent with those broadly reported in the literature, but they only represent a single block puzzle of the force scenario that a superelastic wire releases during the orthodontic treatment. (4) Conclusions: Once a superelastic wire is bent and clinically applied, the effect of a temporary heating up to 50°C (e.g. hot food or drink ingestion) produces a significant plateau force increase whose magnitude depends on the deflection level. The highest force increase of about 50% and 40% have been detected at deflection levels located at the beginning of the unloading plateau extension for NiTi and CuNiTi wires, respectively.

“Pecorino” is a typical semi-hard cheese obtained with raw or heat-treated sheep milk using procedures to valorize the raw material's chemical and microbiological properties. In the present study, using a high throughput method of 16S rRNA gene sequencing, we assessed the evolution of the microbiome composition from milk to Pecorino cheese in artisanal processes using milk from Comisana and Lacaune sheep breeds. The comparative analysis of the bacterial com-munity composition revealed significant differences in the presence and abundance of specific taxa in the milk microbiome of the Comisana and Lacaune breeds. NGS analysis also revealed differences in the curd microbiome related to dairy farming practices, which have a relevant effect on the final structure of the Pecorino-cheese microbiome.

MicroRNAs are small non-coding RNAs, which contribute to the regulation of many physiolog-ical and pathological processes. Conventionally, miRNAs perform their activity in the cyto-plasm, where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus. This review summarizes current findings regarding the molecular activities of nuclear miRNAs. These molecules can regulate gene expression at the transcriptional level by directly binding DNA on the promoter or the enhancer of regulated genes. MiRNAs recruit to these regions dif-ferent protein complexes, resulting both in activation or repression of transcription, through a number of molecular mechanisms. Haematopoiesis is presented as a paradigmatic biological process whereby nuclear miRNAs possess a relevant regulatory role. Nuclear miRNAs may af-fect gene expression also acting on nuclear mRNA processing and on the biogenesis of miRNA themselves by regulating pri-miRNA maturation. Overall, nuclear miRNAs are biologically ac-tive molecules that can be critical for the fine tuning of gene expression and deserve further studies in a number of physiological and pathological conditions

Most cervical cancer cases are a result of persistent high-risk Human papillomavirus (HPV) infections. Cervical cancer is prevalent in LMICs especially in SSA where it is second most prevalent cancer. In South Africa, it is the second most common cancer affecting women aged between 15 and 44 years. The host immune response has been shown as an important factor in controlling the progression or regression of high-risk HPV infection of the cervix to cervical cancer. The risk of cervical cancer is known to be influenced by the host's genetic diversity, particularly by immune response-regulating genes such as the Human Leukocyte Antigen (HLA) class I and II genes. HLA class I genes present viral peptides to CD8+ T cells which are restricted and pre-programmed for cytotoxic functions. There is very little known about the HLA genes of South African women and how these influence outcome of HPV infections. This review aims to understand the role and influence of HLA class I genes in HPV clearance, persistence, and CD8+ T cell mediated immunity in African women by examining existing literature in this area. Understanding this role can influence and inform therapeutic vaccine design that is population specific.

Organisms are adapted to each other and the environment, not as tradition would have it, because natural selection made them that way, but because there is inbuilt striving towards stability and equilibrium. A General Theory of Behaviour connects imagery, affect and action with the central executive system we call Consciousness. The General Theory is founded on the assumption that the primary motivation of all of Consciousness and intentional behaviour is Psychological Homeostasis. Psychological homeostasis is as important to the organisation of mind and behaviour as Physiological Homeostasis is to the organisation of bodily systems. Consciousness processes quasi-perceptual images independently of the input to the retina and sensorium. Consciousness is the “I-Am” control centre for integration and regulation of (my) thoughts, (my) feelings and (my) actions with (my) conscious mental imagery as foundation stones. Imagery vividness, a combination of clarity and liveliness, is essential to imagining, remembering, thinking, predicting, planning and acting. Assessment of vividness using introspective report is validated by objective means such as fMRI. A significant body of work shows that vividness of visual imagery is determined by the similarity of neural responses in imagery to those occurring in perception of actual objects and performance of activities. I am Conscious, therefore I am.

Drosophila melanogaster serves as a important research model both for genetic investigations and for the study of metal toxicity, facilitating the elucidation of physiological mechanisms comparable to those of human organisms. In our research, we evaluated the toxicity effect resulting from exposure to various concentrations of lead and copper on the prolificity rates throughout the life cycle (egg-adult) of four genotypes of Drosophila melanogaster: wild-type (control), white, brown, and white-vestigial. During our study, the prolificity rates were examined across three repetitions under the impact of exposure to concentrations of 0.50, 1.00, 2.00, and 4.00 mM of copper (CuSO₄) and lead (Pb(C₂H₃O₂₎₂). Prolificity rates throughout the life cycle exhibited variations as a direct consequence of genetic factors, the concentration of exposure, and the specific type of metal, either copper or lead. The mutant white-vestigial genotype revealed an IC₅₀ concentration for prolificity inhibition at lower doses of 2.00 mM for copper and 4.00 mM for lead, in contrast to the control genotype (wild-type), which exhibited an inhibition concentration rate >IC₅₀ of 4.00 mM only in the case of copper. Our results concluded that the (i) dose influences the prolificity rate in a directly proportional manner, (ii) comparative analyses between copper and lead revealed that copper displayed toxicity across all genotypes within the concentration range of 0.50 mM to 2.00 mM. In contrast, lead exhibited toxicity within the concentration range of 1.00 mM to 4.00 mM, highlighting a (iii) more acute toxicity characteristic in the case of copper. Thus, the results of this research reflect the importance of using Drosophila melanogaster as a genetic model in the comparative study of the interaction between genetic factors and the toxicity of metals, offering significant insights into monitoring their impact and defining the maximum permissible doses on organisms.

In the dynamic landscape of 6G and smart cities, Visible Light Communication (VLC) assumes critical significance for IoT (Internet of Things) applications spanning diverse sectors. The escalating demand for bandwidth and data underscores the need for innovative solutions, positioning VLC as a complementary technology within the electromagnetic spectrum. This paper focuses on the relevance of VLC in the 6G paradigm, shedding light on its applicability across smart cities and industries. The paper highlights the growing efficiency of lighting LEDs in infrastructure, facilitating the seamless integration of VLC. The study then emphasizes VLC’s robustness in outdoor settings, demonstrating effective communication up to 10 meters. This resilience positions VLC as a key player in addressing the very last meter of wireless communication, offering a seamless solution for IoT connectivity. By introducing an a freely available open-source simulator combined to an alternative waveform, UFMC, the study empowers researchers to dimension applications effectively, showcasing VLC’s potential to improve wireless communication in the evolving landscape of 6G and smart cities.

We currently face several, interlinked environmental crises, including climate change, habitat destruction and biodiversity loss. However, many governments seem unwilling to take strong and immediate action to address these threats, preferring to promote neoliberal approaches to allow consumers and the general public to make environmentally friendly choices. This is despite neoliberal approaches being much less likely to be successful than government leadership, taxation, subsidies, and legislation in addressing environmental issues. In this study, we examine public perception of environmental threats and solutions to these threats, in a survey, mainly completed in the UK. Climate change is seen as the biggest issue, likely due to recent activist campaigns and subsequent media attention on the issue. Neoliberal attitudes, such as green consumer choices to environmental concerns, do still dominate in a series of possible presented solutions, and score more highly than lifestyle changes such as changing diet. However, when questioned specifically about plastic pollution, government intervention to ban all unnecessary plastic scored very strongly, indicating a shift from a consumer driven response. Furthermore, most participants think they are at best only partly ‘doing their bit’ to protect the environment. The results demonstrate that the public are aware that not enough is happening to protect the environment and provide evidence that there is willingness for stronger government intervention to address environmental issues, although there is potential resistance to major lifestyle changes.

Here we present 1. a model for amplicon sequencing 2. a definition of the best assignment of a read to a set of reference sequences 3. strategies and structures for indexing reference sequences and computing the best assign- ments of a set of reads efficiently, based on (ultra)metric spaces and their geometry The models, techniques, and ideas are particularly relevant to scenarios akin to 16S taxonomic profiling, where both the number of reference sequences and the read diversity is considerable.

Curcumin attracts a huge attention because of its biological properties: antiproliferative, antioxidant, anti-inflammatory, immunomodulatory and so on. However, its usage has been limited by poor water solubility and low bioavailability. Herein, to solve these problems we developed curcumin-loaded nanoparticles based on end-capped amphiphilic poly(N-vinylpyrrolidone). Nanoparticles were obtained using the suspension method and were characterized by dynamic and electrophoretic light scattering, transmission electron microscopy and atomic force microscopy. The average particle size was 200 nm, and ζ-potential was -4 mV. Curcumin release studies showed that nanoparticles are stable in water solution. In vitro release study showed prolonged action in gastric, intestinal and colonic fluids, consistently and in PBS. In vitro studies on epidermoid carcinoma and human embryonic kidney cells showed that the cells absorbed more curcumin in nanoparticles compared to pure curcumin. Nanoparticles are safe for healthy cells and show high cytotoxicity for glioblastoma cells in cytotoxicity studies in vitro. Median lethal dose was determined in acute toxicity assay on Zebrafish and was 23 μM. Overall, the curcumin-loaded nanoparticles seem promising for cancer treatment.

The effect of doublet state metalloradical complex in a solar cell inside the common active layer poly(3-hexylthiophene)/ [6,6]-phenyl-C61-butyric acid methyl ester (P3HT/PC60BM) is explored. In this work is demonstrated that the role of the Bis-[1,3-Bis-(2,6-diisopropylphenyl)-4,5-dichloroimidazol-2-ylidene]palladium(I) hexafluoridophosphate dopant, [Pd(IPrCl)2][PF6], is crucial because, by having a stable unpaired electron in the molecule, it significantly improves the optoelectronic performance of the devices. We found the optimal concentration of this molecule in the active layer, and we demonstrated that the presence of this additive in the active layer helps to significantly improve the morphology of the device. The improvements in optoelectronic and morphological parameters are associated with a remarkable increase of photocurrent generation due to more favourable mechanisms of charge separation at the donor/acceptor (D/A) interfaces of the active layer and reduced recombinations. Moreover, the presence of this additive improves the stability of the unencapsulated solar cell against photochemical degradation produced by sunlight.

DIEP-based breast reconstruction necessitates wide undermining at the abdominal donor-site, creating large wound areas. Flap harvesting is usually conducted using electrosurgical dissection devices. This study sought to compare the clinical outcomes in patients after using the PEAK PlasmaBlade (PPB) versus monopolar electrocautery (MPE). This retrospective cohort study included 128 patients with DIEP-based breast reconstruction. Patient characteristics as well as information on the postoperative course were collected and a comparative evaluation was conducted. The MPE group exhibited significantly (p* = 0.0324) higher abdominal drainage volume (351.11 ± 185.96 ml) compared to the PPB group (279.38 ± 183.38 ml). Subgroup analysis demonstrated that PPB significantly reduced postoperative wound fluid in patients with BMI > 30 kg/m² (p* = 0.0284), without prior neoadjuvant chemotherapy (p** = 0.0041), and among non-smokers (p = 0.0046). Furthermore, postoperative pain was significantly (p**** < 0.0001) lower in the PPB cohort. This study confirms the non-inferiority of the PEAK PlasmaBlade to conventional electrocautery for abdominal flap harvesting. The PPB demonstrated advantages, notably reduced drainage volume and lower postoperative pain levels. Recognizing patient subsets that benefit more from the PPB highlights the importance of personalized device selection based on patient characteristics.

Predicting the prices of cryptocurrency owing to its volatility, instability, and other factors has been challenging; investors and traders especially in Nigeria have been on a constant look for a more reliable way of knowing market trends and prices and while there has been so many research conducted using deep learning, the results for which has fall short of what investors could called a strong predictor. This research reviewed the results of many works that had been done and proposed two types of recurrent neural network (RNNs) namely Long Short-Term Memory and Gated Recurrent Unit (GRU) for predicting the future prices of two of the most common crypto assets namely Bitcoin (BTC) and Ethereum (ETH), these two were selected based on their popularity, the volume traded and their market capitalization. The experiment was conducted in a GPU Jupyter Notebook environment and the performance of our experiment was evaluated on a test set using root mean square error (RMSE) and based on its values, the LSTM presented a better performance with rsme scores of 654.66, and 80.30 respectively for BTC and ETH as compared to GRU. The paper proceeds further to compare the results of this experiment with other related works and we discovered that its performance is a great improvement.

Iron deprivation activates mitophagy and extends lifespan in nematodes. In patients suffering from Parkinson’s disease (PD), PINK1-PRKN mutations via deficient mitophagy trigger iron accumulation and reduce lifespan. To evaluate molecular effects of iron chelator drugs as a potential PD therapy, we assessed fibroblasts by global proteome profiles and targeted transcript analyses. In mouse cells, iron shortage decreased protein abundance for iron-binding nucleotide metabolism enzymes (prominently XDH and ferritin homolog RRM2). It also decreased the expression of factors with a role for nucleotide surveillance, which associate with iron-sulfur-clusters (ISC), and are important for growth and survival. This widespread effect included prominently Nthl1-Ppat-Bdh2, but also mitochondrial Glrx5-Nfu1-Bola1, cytosolic Aco1-Abce1-Tyw5, and nuclear Dna2-Elp3-Pold1-Prim2. Incidentally, upregulated Pink1-Prkn levels explained mitophagy induction, the downregulated expression of Slc25a28 suggested it to function in iron export. The impact of PINK1 mutations in mouse and patient cells was pronounced only after iron overload, causing hyperreactive expression of ribosomal surveillance factor Abce1 and of ferritin, despite ferritin translation being repressed by IRP1. This misregulation might be explained by the deficiency of the ISC-biogenesis factor GLRX5. Our systematic survey suggests mitochondrial ISC-biogenesis and post-transcriptional iron regulation to be important in the decision, whether organisms undergo PD pathogenesis or healthy aging.

There are guidelines on lactation following maternal analgo-sedative exposure, but these do not consider the effect of maternal fasting, nor fluid abstention on human milk macronutrient composition. We therefore performed a structured search (PubMed) on ‘human milk composition’ and screened title, abstract and full paper on ‘fasting’ or ‘abstention’ and ‘macronutrient composition’ (lactose, protein, fat, solids, triglycerides, cholesterol). This resulted in 6 papers and one abstract related to religious fasting (n=129 women) and observational studies in lactating women (n=23, healthy volunteers, fasting). These data reflect two different ‘fasting’ patterns: an acute (18-25h) model in 71 (healthy volunteers, Yom Kippur/Ninth of Av) women and a chronic fasting (Ramadan) model in 81 women. Changes were most related to electrolytes and were moderate, with almost no changes in macronutrients during acute fasting. We therefor conclude that neither short term fasting nor fluid abstention (18-25h) affect human milk macronutrient composition, so that women can be reassured when this topic were raised during consulting. Besides the nutritional relevance, this also matters as clinical research samples – especially to estimate analgo-sedative exposure by lactation - are commonly collected after maternal procedural sedation, associated with maternal fasting and physiology-based pharmacokinetic (PBPK) models assume stable human milk composition.

This study investigated the influence of single nucleotide polymorphisms (SNPs) in genes asso-ciated with the interferon pathway (IFNAR2 rs2236757), antiviral response (OAS1 rs10774671, OAS3 rs10735079), and viral entry (ACE2 rs2074192) on COVID-19 severity and their association with non-alcoholic fatty liver disease (MAFLD). We did not observe a significant association between the investigated SNPs and COVID-19 severity. While the IFNAR2 rs2236757 A allele correlated with higher creatinine levels upon admission and the G allele with lower band neu-trophils upon discharge, these findings require further investigation. The distribution of OAS gene polymorphisms (rs10774671, rs10735079 did not differ between MAFLD and non-MAFLD patients. Our study population's distribution of ACE2 rs2074192 genotypes and alleles differed from the European reference population. Overall, our findings suggest that these specific SNPs may not be major contributors to COVID-19 severity in our patient population, highlighting the potential role of other genetic factors and environmental influences.

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) frequently require primary radiochemotherapy (RCT). Despite intensity-modulation, desired radiation-induced effects observed in HNSCC, may also be observed as side-effects in healthy tissue e.g. the sternocleidomastoideus muscle (SCM). These side-effects (e.g. tissue fibrosis) depend on the interval between completion of RCT and restaging-CT. For salvage surgery, the optimal time window for surgery is currently postulated between 6 and 12 weeks after completion of RCT. Thus, no extensive tissue fibrosis is to be expected. This interval is based on studies exploring surgical complications. Studies directly exploring radiation-induced changes of the SCM in HNSCC-patients are sparse. The present study quantifies tissue alterations in SCM and paravertebral musculature (PVM) after RCT applying radiomics to determine the optimal time window for salvage surgery. Three radiomic key parameters 1) volume, 2) mean positivity of pixels (MPP) and 3) uniformity were extracted with mint lesionTM in the staging-CTs and restaging-CTs of 98 HNSCC-patients. Of these, 25 were female, the mean age was 62 (±9.6) years and 80.9% were UICC Stage IV. The mean restaging-interval was 55 (±28; range29-229) days. Only the mean volume significantly decreased after RCT from 9.0 to 8.4 and 96.5 to 91.9 ml for SCM and PVM, respectively (both p=0.007, both Cohen’s d=0.28). In addition, the mean body mass index (BMI) decreases from 23.9 (±4.2) to 21.0 (±3.6) kg/m² (p<0.001); Cohen's d = 0.9). The mean BMI-decrease significantly correlated with the volume decrease for SCM (r=0.27; p=0.007) and PVM (r=0.41; p<0.001). If t-test p-values were adjusted for the BMI-decrease, no significant change in volumes for SCM and PVM was observed (both p>0.05). The present data supports the postulated optimal interval for salvage surgery of 6 to 12 weeks. Irrespective of the remaining risk-benefit ratio of salvage surgery, the risk of additional surgical complications due to fibrosis is not supported by the present observations.

The present study aimed at investigating the in vitro and in vivo susceptibility of malaria parasites to crude extracts and fractions from Polyalthia suaveolens, Uvaria angolensis, and Monodora tenuifolia. The ethanolic extracts were prepared by maceration, and were further partitioned using water, dichloromethane, hexane, and methanol. The most promising fraction was subjected to column chromatography and the sub-fractions tested for activity in vitro. The antiplasmodial effect of extracts and fractions was tested against the Chloroquine resistant (PfK1) strain in 96 wells microtiter plate format using SYBR green florescence assay. The promising fraction was further assessed for cytotoxicity and acute toxicity in Swiss albino mice and subsequently against the rodent malaria parasite, P. berghei. Qualitative phytochemical screening was also performed on the promising fraction. The methanol fractions exerted the overall better effect with that of the twigs of P. suaveolens (PStw(Ace)) showing the highest potency with a IC50 value of 3.24 µg/mL followed by the fractions of leaf of M. tenuifolia (MoTel(Ace), IC50= 3.84 µg/ml) and stem bark of P. suaveolens (IC50= 4.90 µg/ml). The phytochemical screening showed the presence of alkaloids, lactones, and phenols in the more active fraction of P. suaveolens (PStw(Ace)). The chromatographic fractionation of this fraction led to 12 sub-fractions with PS8 sub-fraction being the most active (IC50= 4.42 µg/mL). In vivo, oral administration of 2000 mg/kg b.w of fraction PStw(Ace) in mice showed no signs of toxicity. Also, fraction PStw(Ace) at 400 mg/kg b.w exerted the highest suppressive effect against P. berghei strain B throughout the 4 days experiment (% parasitaemia below 5.2%). Overall, the results achieved supported the use of the three plants in the traditional treatment of malaria in Cameroon. More interestingly, the methanolic fraction of the twigs extract from P. suaveolens might be of interest in future development of an antimalarial phytodrug.

Sea ice surface roughness affects ice-atmosphere interactions, serves as an indicator of ice age, shows patterns of ice convergence and divergence, affects the spatial extent of summer melt ponds, and ice albedo. We have developed a method for mapping sea ice surface roughness using angular reflectance data from the Multi-angle Imaging SpectroRadiometer (MISR) and lidar-derived roughness measurements from the Airborne Topographic Mapper (ATM). Using an empirical data modeling approach, we derived estimates of Arctic sea ice roughness ranging from centimeters to decimeters meters within the MISR 275-m pixel size. Using independent ATM data for validation, we find that histograms of lidar and multi-angular roughness values are nearly identical for areas with roughness <20 cm but that for rougher regions, the MISR-derived roughness has a narrower range of values than the ATM data. The algorithm is able to accurately identify areas that transition between smooth and rough ice. Because of its coarser spatial scale, MISR-derived roughness data have a variance of about half that ATM roughness data.

Shiga toxins (Stxs), and more specifically the Stx2a subtype, are the major virulence factors involved in enterohemorrhagic Escherichia coli (EHEC)-associated hemolytic uremic syndrome (eHUS); a life-threatening disease causing acute kidney injury, especially in children. Cleavage of Stxs A subunit, when followed by reduction, boosts the enzymatic activity causing damage to targeted cells. This cleavage was assumed to be mostly mediated by furin during Stx intracellular trafficking. Cleavage of A subunit, without reduction, changes the binding properties of Stxs for blood components during HUS pathogenesis. To investigate whether the cleavage could occur in the intestine, even prior entering target cells, Stx2a structure was characterized after its exposure to specific host factors present in human stool. The structure of Stx2a A subunit was determined by immunoblotting after electrophoretic separation under reducing conditions. Trypsin and chymotrypsin-like elastase 3B (CELA3B), two serine proteases, were identified as potential candidates that may trigger the extracellular cleavage of Stx2a A subunit directly after its secretion by EHEC in the gut. Whether this observation indeed translates to natural infections and plays a role in eHUS pathogenesis has yet to be determined as well as whether host's protease profile could affect disease development by changing the toxin’s biological features.

Keywords: Pain; Nociception; Disorders of Consciousness; Consciousness

Spodoptera frugiperda is an invasive pest that has spread in various parts of the world. These pests have the ability to spread and adapt highly to new habitats. Until now, it is not known with certainty the distribution of these invasive pests in Eastern Indonesia, especially Bali and Nusa Tenggara. This study aims to map the spatial distribution and genetic distribution of S. frugiperda which damages maize in the areas of Bali and Nusa Tenggara. This research was conducted using a survey method from May to September 2022 covering the islands of Bali, Lombok, Sumbawa, Sumba, Flores, and Timor. The results showed that S. frugiperda had spread evenly in Bali and Nusa Tenggara. The results of PCR amplification in the COI gene from 9 sample isolates from all research locations showed the similarity of DNA bands leading to the Spodoptera frugiperda species with a banding pattern length of 683 – 697. These results indicated that the distribution of genetic variants of corn caterpillars in Bali, NTB, and NTT was confirmed as S. frugiperda species. However, the isolated gene S. frugiferda, which was shown by the alignment results of the sequences from Lombok, was confirmed as a different strain from strains from Bali, Sumba, Sumbawa, Flores, and Timor. This incident can be seen from the difference in the protein base composition of S. frugiperda from Bali, Sumba, Sumbawa, Timor, and Flores. The results of phylogenetic analysis in this study confirmed 3 clusters of the genetic closeness of S. frugiperda. Cluster-1 comes from the results of the search for specimens of JB FAW and KB FAW from Bali, SB FAW and SB FAW Sorghum from Sumba, SW FAW from Sumbawa, KP FAW from Timor, and FL FAW from Flores. Cluster-2 is an isolate outside of our species. Cluster-3 comes from the search for LT and LS FAW specimens from Lombok. The genetic distance between cluster-1 and cluster-3 is quite far, which is 0.20 mu.

Visible-light photocatalysis, particularly in its application to organic synthesis, has experienced a big renaissance in the past decade. The rational design of new photocatalysts with designed and improved photocatalytic properties, that at the same time circumvents the necessity of using scarce and toxic transition metals, will predictably play a key role in photocatalysis in the next few years. Although free-base porphyrins were identified some years ago as a promising, easily accessible and easily tunable class of organic photoredox catalysts, a systematic study on the effect of the electronic nature and of the position of the substituents on both the ground-state and the excited-state redox potentials of these compounds is still lacking. We have prepared a set of known functionalized derivatives of meso-tetraphenyl porphyrin containing different substituents either in one of the meso-positions or at a beta-pyrrole carbon and we have determined their ground- and (singlet) excited-state redox potentials. This survey has led us to conclude that the introduction of a carbonyl group at the beta-pyrrolic position strongly increases the facility of the monoelectronic reduction of the porphyrin both in the ground state and in the singlet excited state. We have also prepared a second set of four previously unknown benzoyl derivatives of meso-tetraphenylporphyrin, and we have confirmed the validity of our conclusions.

The majority of investigations on microbial communities from various environments are presently built on culture-independent methods. Many studies point to the pivotal, selective role of primers targeting hypervariable regions of 16S rRNA in the metabarcoding of bacteria, including cyanobacterial communities. The selectivity of primers designed to amplify targeted regions of the 16S rRNA gene, which has been highlighted by many authors, limited effective amplification. Moreover, the type and specificity of the studied material can also negatively influence the results of 16S metabarcoding. Most of the studies of cyanobacterial communities have been performed for planktonic microbial communities that are often represented by common, well-studied species. In this study, we present the results of 16S metabarcoding analysis using three primer pairs - two already well-known and a third designed in this study - that amplify divergent regions of the 16S rRNA gene (V3-V4, V4-V6, V6) for benthic, microbial mat-forming cyanobacteria communities. Such communities can be a source of toxigenic cyanobacterial taxa and should be monitored with adequate primers. The comparison of three primer pairs suggested that those designed within the present study describe the structure and composition of highly heterogeneous cyanobacterial mats’ communities better than the others

Ecological footprint calculators are digital tools that help individuals calculate their environmental or climate impact, with the aim of stimulating pro-environmental behaviour change. These footprint calculators typically take an information-provision approach, but this strategy assumes that increased levels of knowledge result in increased levels of pro-environmental behaviour (i.e., a reduced footprint). This is not a given – existing literature on the relationship between environmental knowledge and pro-environmental behaviour is inconclusive, and this relationship may be different from that of environmental knowledge and ecological footprint. As such, we investigated the relationship between environmental knowledge and ecological footprint as estimated by a footprint calculator. 448 Dutch participants completed an online survey, including an ecological footprint calculator. We found no evidence for a relationship between environmental knowledge and ecological footprint calculator outcome. Rather, an exploratory analysis of our data showed that environmental values were more important predictors of ecological footprint. The finding that increased levels of knowledge are not related to a reduced ecological footprint suggests that calculators would do well to move beyond information provision, and employ additional behaviour change strategies. Based on our exploratory analysis, we provide several concrete examples of potential strategies.

HLA class-I (HLA-I) polyreactive monoclonal antibodies (mAbs) reacting to all HLA-I alleles were developed by immunizing HLA-E monomeric heavy chain (HC) (Open Conformers, OCs). Two of the mAbs (TFL-006 and TFL-007) bound to the HC’s coated on a solid matrix. The binding was inhibited by a peptide 117AYDGKDY123, present in all alleles of the six HLA-I isoforms but masked by 2-microglobulin -m) in intact HLA-I trimers (Closed Conformers, CCs). Identical HLA-I polyreactivity is observed in IVIg administered to lower anti-HLA antibodies (Abs) in HLA-sensitized patients, but the mechanism is unknown. We hypothesized that the mAbs that mimic IVIg HLA-I polyreactivity might mimic the immunomodulatory functions of IVIg. We tested the relative binding affinity of the mAbs and IVIg for both OCs- and CCs and compared their effects on (a) the phytohemagglutinin (PHA)-activation T-cells, (b) the production of anti-HLA-II antibody (Ab) by B-memory cells, and anti-HLA-I Ab by immortalized B-cells, and (c) the upregulation of CD4+, CD25+, and Fox P3+ T-regs. The mAbs bound only to OCs, whereas IVIg is bound to both CCs and OCs. The mAbs suppressed blastogenesis and proliferation of PHA-activated T-cells, anti-HLA Ab production by B-cells and expanded the T-regs, better than IVIg. We conclude that a humanized version of the TFL-mAbs could be an ideal therapeutic IVIg-mimetic.

Sparkling wines elaborated by means Ancestral method, also called Pét-Nats, are nowadays gaining an increasing share of the market. However, the scientific information about these wines is very scarce. For that reason, the aim of this research was to compare the physicochemical composition and sensory attributes of a representative sampling of commercial sparkling wines elaborated by Ancestral and Traditional methods. Ancestral sparkling wines were more heterogenous than Traditional sparkling wines because some of them showed lower internal pressure, higher turbidity, higher colour intensity and less foamability. These differences would be probably because the ancestral elaboration protocol is not so well defined as in the case of Traditional sparkling wines. However, Ancestral method has the advantage of being able to work with riper grapes and with lower doses of sulphur dioxide.

Breast cancer is the most common cancer in women globally, often necessitating mastectomy and subsequent breast reconstruction. Silicone mammary implants (SMIs) play a pivotal role in breast reconstruction, yet their interaction with the host immune system and microbiome remains poorly understood. This study investigates the impact of SMI surface topography on host antimicrobial responses, wound proteome dynamics, and microbial colonization. Biological samples were col-lected from ten human patients undergoing breast reconstruction with SMIs. Mass spectrometry profiles were analyzed for acute and chronic wound proteomes, revealing a nuanced interplay between topography and antimicrobial respondseproteins. 16S rRNA sequencing assessed mi-crobiome dynamics, unveiling topography-specific variations in microbial composition. Surface topography alterations influenced wound proteome composition. Microbiome analysis revealed heightened diversity around rougher SMIs, emphasizing topography-dependent microbial inva-sion. In vitro experiments confirmed staphylococcal adhesion, growth, and biofilm formation on SMI surfaces, with increased texture correlating positively with bacterial colonization. This comprehensive investigation highlights the intricate interplay between SMI topography, wound proteome dynamics, and microbial transmission. The findings contribute to understanding host-microbe interactions on SMI surfaces, essential for optimizing clinical applications and minimizing complications in breast reconstruction.

Despite the Australian Government’s attempts to reduce domestic violence (DV) incidences, impediments that exist within the social and health systems and interventions designed to identify DV victims may contribute to female victims’ reluctance to disclose DV experiences to their primary healthcare providers. This scoping review aimed to provide the state of evidence about reasons for such reluctance to reveal DV, symptoms and comorbidities patients present to healthcare providers, detection and interventions in the clinical setting, and recommendations to generate more effective responses to DV. Female victims are reluctant to reveal DV because they do not trust or believe that general practitioners can help them to solve the issue, they do not acknowledge they are in an abusive relationship or are unaware that they are, or had been, victims of DV. The most common symptoms and comorbidities victims present with are sleep difficulties and fear. DV screening programs are the most prominent intervention type within Australian primary health services. This scoping review provides formative evidence that further research and interventions are required to increase professional skills, knowledge, sensitivity and referral processes among primary healthcare professionals treating patients experiencing DV in Australia.

Aluminum, a contentious trace element found in the environment, has been demonstrated to have harmful effects on both humans and animals. In contrast, Sempervivum tectorum, an evergreen plant, has been found to offer numerous beneficial effects for both humans and animals. Therefore, this study aims to assess the protective effect of S. tectorum on certain reproductive biomarkers in male rats exposed to aluminum. Thirty-five Wistar rats were randomly divided into five groups: NTC (no-treatment control) received distilled water; NC (negative control) received drinking water containing 1 mg/L aluminum sulfate (AS); E1 received 1 mg/L AS along with an 8% S. tectorum extract; PC (positive control) received only 8% S. tectorum extract; E2 received 1 mg/L AS for three months followed by 8% extract for one month. The study analyzed testosterone, LH, FSH, body weight, and the histological structure of the testis, epididymis, and prostate, as well as the levels of zinc, manganese, copper, and iron in these organs. Significant decreases in body weight, testis, and epididymis size were observed in the aluminum-exposed groups compared to the control, whereas these decreases were not significant in the S. tectorum-treated groups compared to the control. Aluminum exposure led to significant decreases in testosterone and LH levels, with FSH levels showing a non-significant decrease in males, which were mitigated significantly by the administration of the plant extract. Histological analysis revealed alterations in the testis, epididymis, and prostate of the AS-exposed groups, including necrosis of seminiferous tubule epithelium and Leydig cells in the testis, and basal epithelial necrosis in the epididymis and prostate. Aluminum levels increased in all organs studied, while levels of zinc, copper, iron, and manganese decreased, showing a negative and significant correlation with aluminum levels. The aqueous extract of S. tectorum demonstrated a protective effect on certain studied biomarkers in male rats affected by aluminum exposure.

Background: Microscopic examination of acid-fast stained sputum smears for detecting mycobacterial acid-fast bacilli (AFB) remains the most economical and readily available method for laboratory diagnosis of tuberculosis (TB). However, this conventional approach has limitations, including low sensitivity and labor-intensive procedures. Methods: An automated microscopy system incorporating artificial intelligence (AI) and machine learning for AFB identification was evaluated. The study was conducted at an Infectious Disease Hospital in Jiangsu Province, China, utilizing an intelligent microscope system (TB-Scan, Wellgen Medical, Kaohsiung). A total of 1,000 sputum smears were included in the analysis, with the system capturing digital microscopic images and employing an image recognition model to automatically identify and classify AFB. Referee technicians provided the gold standard for discrepant results. Results: The automated system demonstrated an overall accuracy of 95.00% (950/1,000), sensitivity of 91.24% (177/194), and specificity of 95.91% (773/806). Notably, the system identified 21 smears as positive that were previously reported as negative, with referee technicians confirming 17 of these as true positive and retracting the test results accordingly. Recalculating the performance, the accuracy increased to 96.70% (967/1,000), sensitivity to 91.94% (194/211), and specificity to 97.97% (773/789), with a false negative rate of 8.06% (17/211) and a false positive rate of 2.03% (16/789). Conclusions: The incorporation of AI and machine learning into an automated microscopy system demonstrated the potential to enhance the sensitivity and efficiency of AFB detection in sputum smears compared to conventional manual microscopy. This approach holds promise for widespread application in TB diagnostics and potentially other fields requiring labor-intensive microscopic examination.

Heterochromatin formation plays a pivotal role in regulating chromatin organization and influences nuclear architecture, and genome stability and expression. Among the regions at which heterochromatin is present, pericentric regions are known to recruit the histone variant macroH2A1. However, the factors and mechanisms behind macroH2A1 incorporation into these regions have not been explored. In this study, we probe different conditions that lead to the recruitment of macroH2A1 to pericentromeric regions and elucidate its underlying functions. Through experiments conducted on murine fibroblastic cells, we discover that partial chromatin relaxation resulting from DNA damage, senescence or histone hyper-acetylation, is necessary for the recruitment of macroH2A1 to pericentric regions. Furthermore, macroH2A1 is required for up-regulation of noncoding pericentric RNA expression but not for pericentric chromatin organization. Our findings shed light on the functional rather than structural significance of macroH2A1 incorporation into pericentric chromatin.

The osseointegration process in and around additively manufactured (AM) lattice structures of a new titanium alloy, Ti–19Nb–14Zr, was evaluated. Three different implants, including lattices with increasing high sidewalls gradually closing them, were designed, manufactured and implanted in the tibia and metatarsal bone of two sheep for twelve weeks. After removal, they were characterized with X-ray computed tomography (XCT). The 3D XCT images were segmented using machine learning. The bone-interface implant (BII) and bone-implant contact (BIC) were studied. The results show that, since AM naturally leads to high roughness surface finish, the wettability of the implant is increased. The new alloy possesses an increased affinity to the bone enhancing the quality of osseointegration. The lattice provides crevices, in which the biological tissue can jump in and cling. The combination of these factors is pushing ossification beyond its natural limits. Therefore, the quality and speed of the ossification and osseointegration in and around these Ti–19Nb–14Zr AM laterally closed lattice implants open the possibility of bone spline key of prostheses. This enables the stabilization of the implant into the bone while keeping the possibility of punctual hooks allowing the implant to be removed more easily if required.

Research focused on succinate dehydrogenase (SDH) and its substrate, succinate, culminated in the 50’s accompanying the rapid development of research dedicated to bioenergetics and intermediary metabolism. This allowed to uncover the implication of the SDH in both the mitochondrial respiratory chain and the Krebs cycle. Nowadays this theme is experiencing a real revival following the discovery of the role of SDH and succinate in a subset of tumors and cancers in human. The aim of this review is to enlighten the many questions yet unanswered, ranging from fundamental to clinically oriented aspects, up to the danger of the current use of SDH as a target for a sub class of pesticides.

To monitor adherence to diets and to design and evaluate nutritional interventions it is essential to obtain objective knowledge about eating behavior. In most research, measures of eating behavior are based on self-reporting, such as 24-h recalls, food records (food diaries), and food frequency questionnaires. Self-reporting is prone to inaccuracies due to inaccurate and subjective recall and other biases. Recording behavior using non-obtrusive technology in daily life would overcome this. We here provide an up-to-date systematic overview encompassing all (close-to) publicly or commercially available technologies to automatically record eating behavior in real-life settings. 1328 studies were screened and after applying defined inclusion and exclusion criteria, 122 studies were included for in-depth evaluation. Technologies in these studies were categorized by what type of eating behavior they measure and which type of sensor technology they use. In general, we found that relatively simple sensors are often used. Depending on the purpose, these are mainly motion sensors, microphones, weight sensors, and photo cameras. While several of these technologies are commercially available, there is still a lack of publicly available algorithms that are needed to process and interpret the resulting data. We argue that future work should focus on developing robust algorithms and validating these technologies in real-life settings. Combining technologies (e.g., prompting individuals for self-reports at sensed, opportune moments) is a promising route toward ecologically valid studies of eating behavior.

Introduction: OS2966 is a fist-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin. CD29 expression is highly upregulated in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy. Here, we present a novel Phase I clinical trial design addressing several factors plaguing effective treatment of high-grade gliomas (HGG). Study Design: This 2-part, ascending-dose, Phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinically-indicated resection. In Study Part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which will be used for intratumoral, convection-enhanced delivery (CED) of OS2966. Subsequently, patients will undergo their clinically-indicated tumor resection followed by CED of OS2966 to the surrounding tumor-infiltrated brain. Matched pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. Dose escalation will be achieved using a unique concentration-based accelerated titration design. Discussion: The present study design leverages multiple innovations including: 1) the latest CED technology, 2) 2-part design including neoadjuvant intratumoral administration, 3) a first-in-class investigational therapeutic, and 4) concentration-based dosing. Trial registration: A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active. A Phase I trial is registered at clinicialtrials.gov (NCT04608812).

The most important prognostic factors in curatively treated prostate cancer at the initial diagnosis are T and N stage, histological subtype, Gleason score, initial PSA, PSA density and percentage of core biopsy positivity. Newer, but non-standard prognostic factors are urine PCA3 and genetic markers of prostate cancer. A simple, but seemingly underestimated standard test is serum Calcium (Ca) level, which has been shown by a previous study group to be a good predictor of lethal prostate cancer, but there is scarce evidence regarding the prognostic value of calcium levels at diagnosis. We aimed to determine whether a Ca level in the upper part of normal values has a prognostic value in curatively treated prostate cancer. We have retrospectively included 84 consecutive patients with prostate cancer, who underwent curative radiotherapy (primary or adjuvant; external beam RT with or without brachytherapy). We have performed statistical analysis of available prognostic factors. Ca level at diagnosis was found to be a statistically significant predictor of disease-free survival.

Cytokines secreted by individual immune cells regulate tissue regeneration and allow communication between various cell types. Cytokines bind to cognate receptors and trigger the healing process. Determining the orchestration of cytokine interactions with their receptors on their cellular targets is essential to fully understand the process of inflammation and tissue regeneration. To this end, we have investigated the interactions of Interleukin-4 cytokine (IL-4)/Interleukin-4 cytokine receptor (IL-4R) and Interleukin-10 cytokine (IL-10)/Interleukin-10 cytokine receptor (IL-10R) using in situ Proximity Ligation Assays in a regenerative model of skin, muscle and lung tissues in the mini-pig. The pattern of protein-protein interactions was distinct for the two cytokines. IL-4 bound predominantly to receptors on macrophages and endothelial cells around the blood vessels while the target cells of IL-10 were mainly receptors on muscle cells. Our results show that in situ studies of cytokine-receptor interactions can provide unravel the fine details of the mechanism of action of cytokines.

Metabolic-associated fatty liver disease (MAFLD) is a risk factor for severe COVID-19. This study explores the potential influence of gut hormone receptor and immune response gene expression on COVID-19 outcomes in MAFLD patients. Methods: We investigated gene expression levels of AHR, FFAR2, FXR, and TGR5 in patients with MAFLD and COVID-19 compared to controls. We examined associations between gene expression and clinical outcomes. Results: COVID-19 patients displayed altered AHR expression, potentially impacting immune response and recovery. Downregulated AHR in MAFLD patients correlated with increased coagulation parameters. Elevated FFAR2 expression in MAFLD linked to specific immune cell populations and hospital stay duration. Significantly lower FXR expression was observed in both MAFLD and severe COVID-19. Conclusion: Our findings suggest potential modulatory roles for AHR, FFAR2, and FXR in COVID-19 and MAFLD.

This paper introduces a rigorous and comprehensive approach for the assessment of marine shafting systems through the utilization of an advanced Pi-Theorem based scaling methodology. Integrating journal bearing similarity assessment and shaft-line scaling methodology with advanced dimensional analysis, the study aims to provide a methodology foundation for systematic replication and analysis of marine shafting systems through scaled models. The proposed scaling methodology ensures geometric and mechanical similarity in terms of shaft-line deflection, considering key scaling parameters such as shaft length, diameter, weight, loads, rotational speed, material properties, bearing locations, and offsets. The advanced dimensional analysis computes specific non-dimensional ratios to guarantee a close resemblance between a real-size system and a scaled lab model, enabling meaningful experimentation. The methodology is analytically derived and validated with numerical simulations for a case study, conducting comparative analysis, evaluating discrepancies, and utilizing the integrated framework for experimentation.

Background: Bacteria, among the earliest life forms on Earth, are integral to both human health and environmental ecosystems. They contribute to essential processes such as digestion, nutrient absorption, and immune defense, and play key roles in the biogeochemical cycles that sustain life. Objective: This paper explores the indispensable role of bacteria in human life and environmental health, emphasizing their contributions to digestion, nutrient absorption, immune protection, and ecosystem functioning. It also discusses advances in understanding the human microbiome and their implications for health and therapeutic interventions. Methods: The study reviews existing literature on the human microbiome, probiotics, and the role of bacteria in environmental nutrient cycling. It analyses experimental evidence and case studies, particularly focusing on the impact of fecal microbiota transplantation (FMT) as a therapeutic tool. Metagenomic analysis techniques are examined to highlight the diversity and functionality of gut bacteria. Results: Bacteria are found to be essential for breaking down food, providing vital nutrients, and protecting against pathogens. They play a critical role in maintaining a healthy immune system and are involved in the biogeochemical cycles necessary for ecosystem health. Metagenomic analysis reveals significant variations in bacterial populations associated with health and disease, emphasizing the importance of a balanced microbiota. FMT shows promise as an effective treatment for various diseases, including gastrointestinal, metabolic, and neurological disorders. Conclusions: Bacteria are crucial for human health and environmental stability. Maintaining a balanced microbiota is vital for overall well-being, and interventions such as probiotics and FMT can offer significant health benefits. Future research should focus on further understanding the complex interactions between bacteria and their hosts to develop targeted therapies for various health conditions.

Consumer preference not only dictates what food is consumed but how that food is produced. Ingredients in livestock feed that are not antibiotics, not genetically modified, not of animal origin, and that are nutrient-like, tend to be more acceptable to consumers, retailers, and producers. Mono- and diglycerides (MDG) fit these criteria, are commonly used in food, and are generally recognized as safe. But beyond being emulsifiers and a source of energy, MDG are also known to have antimicrobial, immune and microbiome modulation, and angiogenic activity. MDG in broiler diets have been shown to impact a variety of immune-related functions such as regulation of circulating antibodies, as well as decreased gene expression or protein concentration of pro-inflammatory cytokines like TNF-α, IL-1β, IL-6, and IFN-γ. In addition, MDG can affect metabolic function and intestinal integrity. Results of this review show that MDG can serve as antimicrobial and growth-supporting alternatives for reducing poultry production losses, improving resource utilization, and meeting consumer demand for sustainably produced and safe animal protein.

Orthohepadnavirus causes chronic hepatitis in a broad range of mammals, including primates, cats, woodchucks, and bats. Hepatitis B virus (HBV) X protein inhibits type-I interferon (IFN) signaling, promoting HBV escape from the innate immune system to establish persistent infection. However, whether X proteins of Orthohepadnavirus viruses in the other species have similar inhibitory activity remains unknown. Here, we investigated the anti-IFN activity of 17 Orthohepadnavirus X proteins derived from various hosts. We observed conserved activity of Orthohepadnavirus X proteins in inhibiting TIR-domain-containing adaptor protein inducing IFN-β (TRIF)-mediated IFN-β signaling pathway through TRIF degradation. X proteins from domestic cat hepadnavirus (DCH), a novel member of Orthohepadnavirus, inhibited mitochondrial antiviral signaling protein (MAVS)-mediated IFNβ signaling pathway comparable with HBV X. These results indicate that inhibition of IFN signaling is conserved in Orthohepadnavirus X proteins.

Abstract: With the growing integration of the Internet of Things (IoT) in smart buildings, it is crucial to ensure the precise implementation and operation of wireless sensor networks (WSNs). This paper aims to study the implementation aspect of Wireless Sensor Networks (WSNs) in a commercial multi-story building, specifically addressing the difficulty of dealing with variable environmental conditions on each floor. This research addresses the disparity between simulated situations and actual deployments, offering valuable insights that have the potential to signifi-cantly improve the efficiency and responsiveness of building management systems. We obtain real-time sensor data to analyze and evaluate the system’s performance. Our investigation is grounded in the growing importance of incorporating WSNs into buildings to create intelligent environments. By leveraging the capabilities of Contiki operating system, this study employs a specialized simulator to generate simulated data, allowing for a comparison between real-world and simulated scenarios. We provide an in-depth analysis to scrutinize the disparities and commonalities between the datasets obtained from real-world deployments and simulated en-vironments. We highlight the necessity of precise simulation to validate real-life sensor data, shedding light on the challenges and opportunities associated with implementing WSNs in in-telligent buildings. Results obtained show the significance of accurate simulation models for re-liable data representation, providing a roadmap for further developments in the integration of WSNs into intelligent building scenarios. The findings highlight the potential for optimizing living and working conditions based on the real-time monitoring of critical environmental pa-rameters. This includes insights into temperature, humidity, and light intensity, offering oppor-tunities for enhanced comfort and efficiency in intelligent environments.

With increased participation in telework expected to continue, to support emerging hybrid work models in the aftermath of the Covid-19, it is important to consider the long-term impact this practice could have on sustainability outcomes. This paper describes a systematic review of 113 academic journal articles and identifies associations between telework and sustainability, explored by previous researchers. Those associations were categorized and discussed, based on their contributions to different United Nations Social Development Goals. Most of research was found to focus on countries classified as having a very high human development index status, and regions with a low, medium or high human development index, largely ignored. The SWOT matrix technique was used to illustrate the strengths and weaknesses identified in the current literature as well as threats and opportunities for future work. This can help to ensure policy coherence and that strategies to promote one outcome, such as economic productivity improvements, does not undermine another, such as improved health. Practical implications and potential research opportunities were identified across a range of SDG impact areas, including good health and well-being, gender equality, reduced inequality, climate mitigation, sustainable cities and resilient communities. On the whole, our impression is that increased rates of telework present an important opportunity to improve sustainability outcomes, however, it will be important that integrated and holistic policy is developed that mitigates key risks.

The practice of collecting, treating and management of solid waste prior to disposal has become a necessity in developing and modern societies. Over the years, it is known that most wastes that are disposed have a second hand value. However, the construction cost for conventional Material Recovery Facility(s) (MRFs) has been a major barrier for implementation. These technologies require considerable technical expertise, which is often not available in developing nations to successfully operate the MRFs. Covenant University; a private mission institution through her waste to wealth scheme is focused on managing and processing used materials to reusable products. These include Pet bottles, Paper wastes, Food wastes from cafeteria, plastic food packs, nylon, tin cans and others. Specific areas chosen for the Survey include the residential areas for staff and students and the two cafeterias. The waste generated was characterized based on the waste stream so as to quantify the amount of recyclable waste generated and most occurring. The survey involved the use of structured questionnaires, on-site observations and measurements. The study reveals an average amount of recyclable waste generated per day in the institution as 13.46% pet bottles, 4.03% paper, 55.56% food waste, 12.64% plastic, 9.63% nylon and 4.68% tin cans. The study established that adequate waste characterization is a requirement for effective integrated solid waste management which would boost resource recovery, reuse and recycling.

Background and Objectives: Metastases are the most common tumors of the spine. As an important increase in the annual incidence of spinal metastases (SM) has been observed in the last decade, the aim of this study was to describe the epidemiology and histopathological types of SM surgically treated in the neurosurgery clinics of a regional hospital in North-Eastern Romania over a period of 5 years, in order to define a certain tumor profile that would benefit from an early screening. Materials and Methods: We retrospectively evaluated 115 adult patients, searching for demographic data (gender and age of the patients), primary tumor characteristics (location and histological type), topography and histopathological type of the spinal metastasis, and the time interval between the diagnosis of the primary tumor and the surgery for the spinal metastasis. Results: The patients were elderly (average age = 58.96 years), with a male predominance (67.82%). Main location of SM was in thoracic region (44.34%), with multiple vertebral metastases in 30.43% patients. Only 33.04% of the patients had a known cancer at the time of admission. Primary tumor was located mainly in lung (47.82%), gastrointestinal tract (15.65%), breast (11.30%), prostate (10.43%) and kidney (9.56%). SM from lung cancer mostly expressed squamous cell carcinoma (19.13%), and those from the digestive system mostly exhibited a moderately/poor colorectal adenocarcinoma (8.69%). Conclusions: Our data suggest the need for close surveillance of patients diagnosed with lung cancer and colorectal cancer because these malignancies most frequently develop spinal metastases. Smoking prevention actions and screening programs for the detection and removal of precancerous colorectal lesions must be developed and expanded.

Tumor to stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study we proposed to confirm or dismiss the hypothesis that a simple measurement of stroma quantity is an easy-to-use and strong prognostic tool. We have included 74 consecutive patients with colorectal cancer who underwent primary curative abdominal surgery. The tumors have been grouped into stroma-poor (stroma &lt;10%), medium-stroma (between 10 and 50%) and stroma-rich (over 50%). The proportion of tumor stroma ranged from 5% to 70% with a median of 25%. Very few, only 6.8% of patients had stroma-rich tumors, 4% stroma-poor tumors and 89.2%tumors with a medium quantity of stroma. The proportion of stroma, at any cut-off, had no statistically significant influence on the disease specific survival. This can be explained by the low proportion of stroma-rich tumors in our patient group and the inverse correlation of stroma proportion with tumor grade. The real-life proportion of stroma-rich tumors and the complex nature of the stroma-tumor interaction has to be further elucidated.

Background: Mental health has a special relevance in adolescence. Therefore, this study aimed to analyze the possible association between emotional distress and suicidal ideation among adolescents. Methods: The article presents the results of a survey of secondary school students (N=1419) in the city of Tarragona, Spain. The aim of the analysis was to verify the existence of an association between suicidal ideation and risk factors such as emotional distress and low self-esteem. All the data were also analysed to determine the existence of statistically significant differences between girls and boys. Bivariate analyses were performed with chi-square, point-biserial coefficient and non-parametric tests for independent groups. Logistic regression analysis was also performed to calculate the probability of suicidal ideation. Results: These analyses showed that both emotional distress and low self-esteem increase the likelihood of suicidal ideation among adolescents. This was more evident among boys with high levels of emotional distress. Conclusion: Schools should develop suicide ideation prevention programs for adolescents based on situations that cause emotional distress.

Rats, including those of the Sprague Dawley strain, may kill mice. Because of this muridical behavior, it is standard practice in many research animal housing facilities to separate mice from rats (i.e., the predators) to minimize stress for the mice. We therefore tested the effect of cohousing on the stress levels of mice from either the C57BL/6J (BL6) or the CD1 strain and Sprague Dawley (SD rat) by determining their fecal corticosterone or cortisol metabolites (FCM) concentration and investigated how cohousing impacts a behavioral assay, i.e., conditioned place preference for intragenus (i.e., mouse-mouse or rat-rat) dyadic social interaction (DSI CPP) that had been shown be sensitive to social factors, especially to handling by humans. We found that the two delivery batches of BL6 mice or SD rats, respectively, had different stress levels at delivery that were statistically significant for the BL6 mice. Even so, the BL6 mice cohoused with rats had significantly increased FCM concentrations, indicative of higher stress levels, as compared to (1) BL6 mice housed alone or (2) BL6 mice at delivery. In contrast to their elevated stress levels, the attractiveness for contextual cues associated with mouse-mouse social interaction (DSI CPP) even increased in rat-cohoused BL6 mice, albeit nonsignificantly. Thus, cohousing BL6 mice and rats did not impair a behavioral assay in BL6 mice that had proved to be sensitive to handling stress by humans in our laboratory. SD rats cohoused with BL6- or CD1 mice and CD1 mice cohoused with SD rats showed DSI CPP that was not different from our previously published data on SD rats and BL6 mice of the Jackson- or NIH substrain obtained in the absence of cohousing. Our findings suggest that the effect of cohousing rats and mice under the conditions described above on their stress levels as opposed to their behavior might be less clearcut than generally assumed and might be overriden by conditions that cannot be controlled, i.e., different deliveries. Our findings can help to use research animal housing resources, which usually are limited, more efficiently.

The free energy principle (FEP) is a mathematical and scientific principle that describes the relationship between the physical behavior of a dynamical system and the interpretation of such behavior as carrying out inference. It blurs the boundary between the ontological mode of the system of interest and the epistemological significance it acquires through its dynamic interaction with the environment. New materialism (or neo-materialism), despite lacking a single definition, refers to a range of emerging perspectives that attempt to dismantle the long-held divisions between ontology, epistemology, and even ethics, with the aim of achieving a comprehensive transformation of naturalized thinking. In this context, new materialism provides powerful tools to reframe some of the conceptual foundations of the FEP. This paper is the first in a series that aims to systematically construct a neo-materialistic perspective for the FEP, exploring its wide-ranging implications. It serves as an introduction to the series, arguing for the justification of deploying new materialism to reframe the FEP and introducing some essential concepts to be utilized in developing a neo-materialistic account of the FEP.

Since their identification over twenty-five years ago, the plethora of cell penetrating peptides (CPP) and their applications has skyrocketed. These 5 to 30 amino acid long peptides have the unique property of breaching the cell membrane barrier while carrying cargoes larger then themselves into cells in an intact, functional form. CPPs can be conjugated to fluorophores, activatable probes, radioisotopes or contrast agents for imaging tissues, such as tumors. There is no singular mechanism for translocation of CPPs into a cell, and therefore, many CPPs are taken up by a multitude of cell types, creating the challenge of tumor specific translocation and hindering clinical effectiveness. Varying strategies have been developed to combat this issue and enhance their diagnostic potential by derivatizing CPPs for better targeting by constructing specific cell activated forms. These methods are currently being used to image integrin expressing tumors, breast cancer cells, human histiocytic lymphoma and protease secreting fibrosarcoma cells, to name a few. Additionally, identifying safe, effective therapeutics for malignant tumors has long been an active area of research. CPPs can circumvent many of the complications found in treating cancer with conventional therapeutics by targeted delivery of drugs into tumors, thereby decreasing off-target side effects, a feat not achievable by currently employed conventional chemotherapeutics. Myriad types of chemotherapeutics such as tyrosine kinase inhibitors, anti-tumor antibodies and nanoparticles can be functionally attached to these peptides leading to the possibility of delivering established and novel cancer therapeutics directly to tumor tissue. While much research is needed to overcome potential issues with these peptides, they offer a significant advancement over current mechanisms to treat cancer. In this review, we present a brief overview of the research leading to identification of CPPs with a comprehensive state of the art review on the role of these novel peptides in both cancer diagnostics as well as therapeutics.

Insect outbreaks are major drivers of natural disturbances in forest ecosystems. Outbreaks can have both direct and indirect effects on the composition of soil arthropod communities, through canopy opening, nutrient addition and predator-prey interactions. In this study, we aim to understand the effects of forest tent caterpillar (Malacosoma disstria; FTC) outbreaks on ant communities in both temperate and boreal forests in Canada. Using pitfall traps and Berlese funnels, we compared the ant communities as well as the surrounding arthropod communities between control and outbreak sites in boreal andboreal and temperate forests (in Québec, Canada). Using the Sørensen dissimilarity index, we determined the alpha and beta diversity of the ant community. Other arthropods collected in the traps were counted to evaluate the richness and abundance of potential prey for the ants and other potential predators of the FTC. We used an indicator species analysis to examine the species associated with sites defoliated by the outbreak. In the boreal forest, we found that FTC outbreaks caused decreases in species richness and increases in the evenness of ant communities in defoliated sites. In the boreal forest sites, species composition varied significantly between control and outbreak sites. This pattern was driven by the presence of other predators. We also saw no changes in beta diversity in the boreal forest but did see a significant decrease in the temperate forest between the outbreak sites and the control sites. A similar, but weaker pattern was observed in the temperate forest. Ant species in the boreal forest tended to exhibit a more marked preference for either control or previously defoliated sites than species in the temperate forest. Our study showed that disturbances like insect outbreaks can drive changes in the ant community. While we saw small effects of outbreaks, manipulation experiments using resource addition could help us validate the mechanisms behind these relationships.

As new treatment modalities are being explored in neuro-oncology, viruses are emerging as a promising class of therapeutics. Virotherapy consists of introduction of either wild-type or engineered viruses to the site of disease, where they exert anti-tumor effect. These viruses can either be non-lytic, in which case they are used to deliver gene therapy, or lytic, which induce tumor cell lysis and subsequent host immunologic response. Replication-competent viruses can then go on to further infect and lyse neighboring glioma cells. This treatment paradigm is being explored extensively in both preclinical and clinical studies for a variety of indications. Virus-based therapies are advantageous due to the natural susceptibility of glioma cells to viral infection, which improves therapeutic selectivity. Furthermore, lytic viruses expose glioma antigens to the host immune system and subsequently stimulate an immune response that specifically targets tumor cells. This review surveys the current landscape of oncolytic virotherapy clinical trials in high-grade glioma, summarizes preclinical experiences, identifies challenges associated with this modality across multiple trials, and highlights potential to integrate this therapeutic strategy into promising combinatory approaches.

The etiology of exaggerated fibrous capsule formation around silicone mammary implants (SMI) is multifactorial but primarily induced by immune mechanisms toward the foreign material silicone. The aim of this work was to enlighten the disease progression from implant insertion and immediate tissue damage response reflected in (a) the acute wound proteome, and (b) the adsorption of chronic inflammatory wound proteins at implant surfaces. An intra-individual absolute quantitation TMT-liquid chromatography-tandem mass spectrometry approach was applied to profile wound proteome formed around SMI the first five days post-implantation. Compared to plasma, the acute wound profile resembled a more complex composition comprising plasma-derived and locally differentially expressed proteins (DEPs). DEPs were subjected to functional enrichment analysis, which revealed the dysregulation of signaling pathways mainly involved in immediate inflammation response and ECM turnover. Moreover, we found time-course variations in protein enrichment immediately post-implantation and adsorbed to SMI surfaces after 6-8 months. Characterization of the expander-adhesive proteome by label-free approach uncovered a long-term adsorbed acute wound and the fibrosis-associated proteome. Our findings propose a wound biomarker panel for the early detection and diagnosis of excessive fibrosis that could potentially broaden insights into the characteristics of fibrotic implant encapsulation.

This work (in two parts) will review the recently developed predictive modeling methodology called “4th-BERRU-PM” and its applicability to energy systems as exemplified by an illustrative application to the Polyethylene-Reflected Plutonium (acronym: PERP) OECD/NEA reactor physics benchmark. The acronym 4th-BERRU-PM designates the “Fourth-Order Best-Estimate Results with Reduced Uncertainties Predictive Modeling” methodology, which yields best-estimate results with reduced uncertainties for the first fourth-order moments (mean values, covariance, skewness, and kurtosis) of the optimally predicted posterior distribution of model results and calibrated model parameters. The 4th-BERRU-PM uses the Maximum Entropy (MaxEnt) principle to incorporate fourth-order experimental and computational information, including fourth (and higher) order sensitivities of computed model responses to model parameters, thus incorporating, as particular cases, the results previously predicted by the second-order predictive modeling methodology 2nd-BERRU-PM, and vastly generalizing the results produced by extant data assimilation and data adjustment procedures. The 4th-BERRU-PM methodology encompasses the scopes of high-order sensitivity analysis (SA), uncertainty quantification (UQ), data assimilation (DA) and model calibration (MC). The application of the 4th-BERRU-PM methodology to energy systems is illustrated by means of the above-mentioned OECD/NEA reactor physics benchmark, which is modeled using the neutron transport Boltzmann equation involving 21976 imprecisely known parameters, the solution of which is representative of “large-scale computations.” The model result (“response”) of interest is the leakage of neutrons through the outer surface of this spherical benchmark, which can be computed numerically and measured experimentally. Part 1 of this work illustrates the impact of high-order sensitivities, in conjunction with parameter standard deviations of various magnitudes, on the determination of the expected value and variance of the computed response in terms of the first four moments of the distribution of the uncertain model parameters. Part 2 of this work will illustrate the capabilities of the 4th-BERRU-PM methodology for combining computational and experimental information, up to and including forth-order sensitivities and distributional moments, for producing best-estimate values for the predicted responses and model parameters while reducing their accompanying uncertainties.

The article presents the results of research work devoted to the study of composite materials on polymer binder with the content of modified mineral filler - water-dispersion paint and varnish materials on acrylic polymer with modified filler - diatomite. The aim of the study is to obtain polymer-based composites with modified diatomite (water-dispersion paint on acrylic binder) with improved performance properties. Methods: determination of porosity, adhesion, elasticity, hiding power of the control composition; determination of porosity, adhesion, elasticity, hiding power of the obtained composites with the use of modified filler; investigation of the influence of radiation in the infrared radiation (IR) region of the spectrum of the paint coating surface using FLIRB620 thermal imager. As a result of work it is noticed that modification of water dispersions by silica activated diatomite promotes elimination of the main disadvantages of materials and coatings on the basis of acrylate binder - low water resistance and low physical and mechanical characteristics, introduction of modified diatomite into water emulsion paint on acrylate basis does not lead to deterioration of the main operational characteristics of paint and varnish coatings - porosity, adhesion, elasticity and covering. When analyzing the effect of emissivity in the IR region of the spectrum of the paint coating surface, a significant effect of the quantitative content of modified diatomite on the reduction of emissivity of paint coatings in the IR region of the spectrum was established and it was shown that a significant effect of the reduction of emissivity of paint coatings in the IR region of the spectrum is provided by the introduction of modified diatomite in the amount of 40 wt.h. into the mixture. The influence of the time of full-scale tests in the investigated small range regardless of the quantitative composition of modified diatomite on the performance characteristics of the paintwork was established.

The aim of this work was to classify the business incubators in Spain according to the four phases of startups incubation. Taking into account that the graduation rate implies greater survival and business success of the incubated companies, they have been identified at each stage of the incubation (spread of entrepreneurship, pre-incubation, advanced incubation, and graduation). The activities that present higher impacts on the success of the incubated companies and the activities carried out by the incubator that have a greater relevance on the graduation of the companies have concretely been considered. Principal component (PC) cluster analysis have been applied. All the incubation variables were used simultaneously, reducing their number, and grouping them into factors, finally the cases were grouped according to these latent variables. Principal components analysis reduced dimensionality to 8 factors with a 74 % of explained variance. Factor 1 was positively related to pre-incubation variables, factor 2 was linked to training and collaboration variables within the entrepreneurship diffusion phase. Factor 3 called activity monitoring and control and was related to phase 3 or basic incubation variables. Clusters analysis facilitates the grouping of incubators into three clusters: Group 1 (16 % of the total), incubators with strong deficits in incubation phases 1, 2 and 3. They are small Business Incubators, often located in rural areas or cities and low graduation rate. Group 2 (30 %), business incubators with very high graduation rate, and strongly positive values in factor 1 and 2. Factor 3 although positive is susceptible to improvement. They are the largest incubators and usually located in industrial and technological parks. Group 3 (54 %) is the majority, with values close to cluster 2 and 3.

Spiral galaxies and their rotation curves have key characteristics of differentially spinning objects. Oblate spheroid shapes are a consequence of spin and reasonably describe galaxies, indicating that their matter is distributed in gravitationally interacting homeoidal shells. Previously published equations describing differentially spinning oblate spheroids with radially varying density are here applied to 51 galaxies, mostly spirals. A constant volumetric density (rho, kg m-3) is assumed for each thin homeoid in these formulae, after Newton, which is consistent with RC being reported simply as a function of equatorial radius r. We construct parameter-free inverse models that uniquely specify mass inside any given r, and thus directly constrain rho vs. r solely from velocity v(r) and galactic aspect ratios (assumed as 1:10 when data are unavailable). Except for their innermost zones, rho is proven to be closely proportional to rn, where n for all 36 spirals studied equals -1.80±0.40. Our values for interior densities compare closely with independently measured baryon density in appropriate astronomical environments: for example, calculated rho at galactic edges agrees with estimated rho of intergalactic media (IGM). Our finding that central densities increase with galaxy size is consistent with behavior exhibited by diverse self-gravitating entities. Our calculated mass distributions are consistent with visible luminosity and require no non-baryonic component. Empirical luminosity-velocity relationships for galaxies, such as the Tully-Fisher rule, originate in Newtonian physics.

Hospitalized patients frequently have disordered and poor-quality sleep due to a variety of both intrinsic and extrinsic factors. These include frequent nighttime intrusions, insomnia related to pain and unfamiliar environments, dark conditions during the day with loss of natural light, and disruption of natural sleep cycle due to illness. Sleep wake disturbances can result in deleterious consequence on physical, emotional and cognitive status, which may impact patient satisfaction, clinical recovery, and hospital length of stay. Despite this, clinicians frequently fail to document sleep disturbances and are generally unaware of best practices to improve sleep quality in the hospital. The purpose of this review is to discuss sleep disturbances in hospitalized patients with a focus on causes of sleep disturbance, effect of poor quality sleep, high risk populations, considerations for surveillance and prevention, as well as pharmacologic and non-pharmacologic options for treatment.

This study aimed to expand and inform the growing body of research on Postpartum Depression, from a netnographic standpoint, for the social media platform of Pinterest. More specifically, it aimed to assess the type of content present on Pinterest regarding Postpartum Depression shared by women in 2018 and 2021, as well as examine the subjective experience of women who have experienced this mood disorder. Data were collected following a search using the keywords “Postpartum Depression” on Pinterest on two separate timestamps (2018 and 2021); pins were limited to those in English or French. Master themes were identified among all pins and those identified as “self-disclosure” were subsequently further analyzed. Self-disclosure data were separately analysed using thematic analysis, specifically adopting a deductive thematic approach for the 2021 data set stemming from the coding scheme created from analysis of the 2018 data. Major themes were identified, and an analysis of frequency was performed for each sub-theme, along with qualitative examples associated with each theme. A total of 483 Pinterest pins from two different time points of 2018 (169 pins) and 2021 (314 sample pins) were analyzed. Five primary categories were identified in both 2018 and 2021, with five additional categories being identified in the 2021 dataset. Comparative results from 2018 and 2021 self-disclosure pins show individuals’ varying yet similar subjective manifestations of PPD, the potential need to adopt a multidisciplinary treatment approach, and the societal fears, such as mental health stigma, that are playing a part in help-seeking behavior hesitancies. Our findings provide imperative insight into individuals’ subjective experiences with PPD; experiences that involve a sensitive and vulnerable topic. Netnographic research, along with Pinterest, must be taken into consideration for future work delving into women’s health issues, including those surrounding perinatal mental health.

The most common long-term complication of silicone breast implants (SMI) remains capsular fibrosis. The etiology of this exaggerated implant encapsulation is multifactorial but primarily induced by the host response towards the foreign material silicone. Identified risk factors included specific implant topographies. Of note, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), has only been observed in response to textured surface implants. We hypothesize that reduction of SMI surface roughness causes less host response hence better cosmetic outcome with fewer complications for the patient. A total of 7 patients received the routinely used CPX®4 breast expander (~60 µM Ra) and the novel SmoothSilk® (~ 4 µM Ra), fixed prepectoral with a titanised mesh pocket and randomized to the left or right breast after bilateral prophylactic NSME (nipple-sparing mastectomy). We aimed to compare the postoperative outcome regarding capsule thickness, seroma formation, rippling, implant dislocation as well as comfortability and practicability. Our analysis shows that surface roughness is an influential parameter in controlling fibrotic implant encapsulation. First time intra-individually compared in patients, our data confirm an improved biocompatibility with minor capsule formation around SmoothSilk® implants with an average shell roughness of 4 µM and in addition an amplification of host response by titanised implant pockets.

The hygromycin B phosphotransferase gene from Escherichia coli and the pyrithiamine resistance gene from Aspergillus oryzae are two dominant selectable marker genes widely used to genetically manipulate several fungal species. Despite the recent development of CRISPR/Cas9 and marker-free systems, in vitro molecular tools to study Aspergillus fumigatus, a saprophytic fungus causing life threatening diseases in immunocompromised hosts, still rely extensively on the use of dominant selectable markers. The limited number of drug selectable markers is already a critical aspect, but the possibility that their introduction into a microorganism could induce enhanced virulence or undesired effects on metabolic behavior, constitutes another problem. In this context, here we demonstrate that the use of ptrA in A. fumigatus leads to secretion of a compound that allows recovery of thiamine auxotrophy. In this study we developed a simple modification of the two commonly used dominant markers in which the development of resistance can be controlled by the xylose-inducible promoter PxylP from Penicillium chrysogenum. This strategy provides an easy solution to avoid undesired side effects since the marker expression can be readily silenced when not required.

Montiaceae comprise a clade of at least 270 species plus about 20 accepted subspecific taxa, primarily of western America and Australia. The present paper is the first of a two-part work that seeks to evaluate evolutionary theory via metadata analysis of Montiaceae. In particular, it uses metadata analysis to evaluate the theory in theory-laden methods that have been applied in evolutionary analyses of Montiaceae. This part focuses on phylogeny and phylogeography. The second part focuses on phenotypic and ecological diversification. An emergent theme in this paper is the degree to which historical idiosyncrasy during Montiaceae evolution misleads quantitative methods of evolutionary reconstruction and phylogeographic interpretation. This suggests that idiosyncraticity itself is a fundamental property of evolution. The second part of this work elaborates this notion as the Principle of Evolutionary Idiosyncraticity. The present part describes idiosyncraticity in molecular phylogenetic and phylogeographic data and uses this notion to refine ideas on Montiaceae evolution. Phylogenetic metadata conflicts and conflicting phylogeographic interpretations are discussed. I conclude that, owing to PEI, quantitative methods of evolutionary analysis cannot be globally accurate, though they are useful heuristically. In contrast, classical narrative analysis is robust in the face of PEI.

Background: Older adults with bipolar disorder (OABD) are individuals aged 50 years and older with bipolar disorder (BD). People with BD may have fewer coping strategies or resilience. A long course of the disease, such as in OABD, could impact the development of resilience strategies, but this remains under-researched in OABD. Therefore, this study aims to assess resilience levels within the OABD and explore associated factors, hypothesizing that resilience could improve psychosocial functioning, wellbeing and quality of life of OABD patients. Methods: This study sampled 33 OABD patients from the OABD cohort at the Bipolar and Depressive Disorders Unit of Hospital Clinic of Barcelona. This was an observational, descriptive and cross-sectional study. Demographic and clinical variables as well as psychosocial functioning, resilience and cognitive reserve were analyzed. Resilience was measured using the CD-RISC-10. Non-parametric tests were used for statistical analysis. Results: The average CD-RISC-10 score was 25.67 points (SD 7.87). Resilience negatively correlated with the total number of episodes (p = 0.034), depressive episodes (p = 0.001), and the FAST (p < 0.001). Participants with normal resilience had a lower FAST (p = 0.046), a higher CRASH (p = 0.026), and more EOBD (p = 0.037) compared to those with low resilience. Conclusions: OABD individuals may exhibit lower resilience levels which correlate with more psychiatric episodes, particularly the number of depressions and worse psychosocial functioning and cognitive reserve. Better understanding and characterization of resilience could aid in early identification of patients requiring additional support to foster resilience and enhance OABD management.

In the context of the H1N1 pandemic and the Pandemrix vaccination campaign, an increased number of narcolepsy cases were noted in several countries. In Sweden, this phenomenon was attributed to the effect of the Pandemrix vaccination in the first place. Interestingly, Denmark, a neighboring country, also had an increased incidence during this period, despite a low vaccination rate. Additionally, studies from China indicated that narcolepsy could occur as a consequence of the H1N1 infection itself. Against these background factors, and due to the clinical impression that narcolepsy patients who were vaccinated tend to dominate in the Swedish narcolepsy polyclinic, we performed an analysis of the increase with a specific interest in age and sex distribution. We also aimed to validate the origin of the excess cases, post hoc. Materials & Methods: The data for narcolepsy patients (ICD code G 47.4) distributed by sex and age at 5-year intervals, annually between 2005 and 2017, was retrieved from the National Patient Register. Information on the total population was collected from the Swedish Population Register and was used for calculations of the narcolepsy prevalence. Results: The number of narcolepsy cases increased markedly from 2009 to 2014 compared to the period before 2009. A particular increase in 2011 among children and teenagers was observed, which resulted in increased cases among the age group 20-39 years in the following years. The sex ratio did not change significantly during the study period. The excess cases found in our study exceeded the number of patients who so far (December 2023) received economic compensation for vaccine side effects (n=450). Conclusions: Our results confirm an association between the increased prevalence of narcolepsy cases and the Pandemrix vaccination. Consequently, the effect of the virus itself cannot be ruled out as a contributing factor. The delayed timing in diagnostics is crucial when determining the number of cases with onset during the pandemic.

Panoramic and periapical radiograph tools help dentists diagnose the most common dental diseases. Generally, dentists identify dental caries manually by inspecting X-ray images. However, due to their heavy workload, or poor image quality, dentists may sometimes overlook some unnoticeable dental caries, which may ultimately hinder the patient treatment. The purpose of this study was to develop an algorithm that classifies the teeth X-Ray images into three categories of “Normal”, “Caries”, and “Filled”. Our study used a dataset of 116 patients and 3712 single teeth images for training, validation and testing. Images were pre-processed using a sharpening filter and an intensity color map. We used a pre-trained transfer learning model, the NASNetMobile, which served as the feature extractor and the Convolutional Neural Network (CNN) model served as the classifier. The training dataset had a “Recall” of 0.92, 0.90 and 0.91 for “Normal”, “Caries” and “Filled” respectively and the test dataset had a “Recall” of 0.86, 0.81 and 0.85 for “Normal”, “Caries” and “Filled” respectively. The classification of the teeth X-Rays was successful and can be valuable for dentist as the artificial intelligence algorithm can serve as a decision support tool to aid dentists when they need to diagnose dental treatment.

Sea ice roughness can serve as a proxy for other sea ice characteristics such as ice thickness and ice age. Arctic-wide maps that represent spatial patterns of sea ice roughness can be used to better characterize spatial patterns of ice convergence and divergence processes. Sea ice surface roughness can also control and quantify turbulent exchange between sea ice surface and atmosphere and therefore influence surface energy balance at the basin scale. We have developed a data processing system that produces georeferenced sea ice roughness rasters that can be mosaicked to produce Arctic-wide maps of sea ice roughness. This approach starts with Top-of-Atmosphere radiance data from the Multi-angle Imaging SpectroRadiometer (MISR). We used red-band angular data from three MISR cameras (Ca, Cf, An). We created a training data set in which MISR pixels were matched with co-located and concurrent lidar-derived roughness measurements from the Airborne Topographic Mapper (ATM). We used a K-nearest neighbor algorithm with the training data to calibrate the multi-angle data to values of surface roughness and then applied the algorithm to Arctic-wide MISR data for two 16-day periods in April (spring) and July (summer). After georeferencing the roughness rasters, we then mosaicked each 16-day roughness dataset to produce Arctic-wide maps of sea ice roughness for spring and summer. Assessment of the results shows good agreement with independent ATM roughness data, not used in model development. A preliminary exploration of spatial and seasonal changes in sea ice roughness for two locations shows the ability to characterize the roughness of different ice types and the results align with previous studies. This processing system and its data products can help the sea ice research community to gain insights into the seasonal and interannual changes in sea ice roughness over the Arctic.

The Solvency II regulatory framework specifies procedures and parameters for determining solvency capital requirements (SCRs) for insurance companies. The proposed standard SCR calculations involve two steps. The Value–at–Risk (VaR) of each risk driver is measured and, in a second step, all components are aggregated to the company’s overall SCR, using the Standard Formula. This formula has two inputs: the VaRs of the individual risk drivers and their correlations. The appropriate calibration of these input parameters has been the purpose of various Quantitative Impact Studies that have been conducted during recent years. This paper demonstrates that the parameter calibration for the equity–risk module—overall, with about 25%, the most significant risk component—is seriously flawed, giving rise to spurious and highly erratic parameter values. As a consequence, an implementation of the Standard Formula with the currently proposed calibration settings for equity–risk is likely to produce inaccurate, biased and, over time, highly erratic capital requirements.

A shrimp oil rich in omega-3 lipids and carotenoids is obtained in remarkably high 5 wt% yield extending to pink shrimp processing waste (head and carapace) the circular economy approach to extract fish oil from fish processing by-products using d-limonene. Biobased limonene, a powerful antimicrobial and antioxidant agent, is an excellent solvent for both lipids and astaxanthin-based carotenoids preventing oxidative degradation during the extraction cycle including solvent and oil separation at 85°C. A new low cost route is established to extract valued marine oil from biowaste annually made available in over 2.2 million tonnes.