Reptile behaviour and welfare are understudied in comparison with mammals. In this study, behavioural data on three species of tortoises were recorded before and after an environmental change which was anticipated to be positive in nature. The environmental changes differed for each population, but included a substantial increase in enclosure size, the addition of substrate material, and a change in handling procedure. A tortoise-specific ethogram was created to standardise data collection. Focal behaviour sampling was used to collect behavioural data. Changes in the duration of performance of co-occupant interaction and object interaction in the leopard (Stigmochelys pardalis) and Aldabra (Aldabrachelys gigantea) tortoises were observed following the environmental changes. The Shannon-Weiner’s diversity index did not yield a significant increase after the changes but had a numerical increase which was relatively greater for the leopard tortoise group, which had experienced the greatest environmental change. The leopard tortoises also demonstrated changes in a greater number of behaviours compared to the other species, and this was sustained over the study period. However, this included a behaviour indicative of negative affect; aggression. Whilst we are unable to conclude that welfare was improved by the management changes, there are suggestions that behavioural diversity increased, and some promotion of positive social behaviours occurred.

Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2,500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72h of cultivation. The analysis of mean PI showed significant differences between 45,X and 46,XN lineages; however there were no intraindividual differences. On the other hand, mean SCE frequencies showed no differences between the two lineages, but there were intraindividual differences in 5 patients. The absence of mean SCE frequency differences between 45,X and 46,XN lineages may indicate that both were equally unstable, as more than 70% of the 46,XN lineages had an anomalous karyotype. However, 46,XN had a higher mean PI, suggesting that the amount of cells with a karyotype distinct from 45,X may increase with time in mosaic TS women.

The Safe Drinking Water Act Amendments of 1996 require community water systems in the United States to send consumers Consumer Confidence Reports (CCRs). CCRs contain information on detected contaminants and required educational information about drinking water. The authors of this study developed a survey to evaluate how utilities track consumer feedback, understanding, and the role of the CCR in shaping consumer perceptions about water quality. Responses from this survey indicate it is common for utilities to indirectly track the effectiveness of their CCRs, but few utilities indicated directly evaluating consumer understanding or the effect of CCRs on consumer perceptions.

For 80 years high-intensity focused ultrasound (HIFU) has been a significant area for medical research. It is a non-invasive procedure which causes cell death in a highly localised area at a defined distance from the transducer. Since 2000, the clinical indications have broadened considerable as the technology has improved. This review looks back at the history of HIFU and the current clinical indications.

Barry Turner’s 1978 Man-made Disasters and Charles Perrow’s 1984 Normal Accidents were seminal books but a detailed comparison has yet to be undertaken. Doing so is important to establish content and priority of key ideas underpinning contemporary safety science. Turner’s research found socio-technical and systemic patterns that meant that major organisational disasters could be foreseen and were preventable. Perrow’s macro-structuralist industry focus was on technologically deterministic but unpredictable and unpreventable ‘system’ accidents, particularly rare catastrophes. Andrew Hopkins and Nick Pidgeon respectively suggested that some prominent writers who wrote after Turner may not have been aware of, or didn’t properly acknowledge, Turner’s work. Normal Accidents didn’t cite Turner in 1984 or 1999. Using a methodology involving systematic reading and historical, biographical and thematic theory analysis, a detailed review of Turner’s and Perrow’s backgrounds and publications sheds new light on Turner’s priority and accomplishment, highlighting substantial similarities as well as clear differences. In a previously unpublished letter, Perrow confirmed reading Man-made Disasters while writing Normal Accidents. Turner became better known after a 1997 second edition but under-acknowledgment issues continued. Ethical citation and potential reasons for under-acknowledgment are discussed. It is concluded that Turner’s foundational importance for safety science should be better recognised.

T cell Non-Hodgkin lymphoma is a heterogeneous disease ranging from malignancies arising from thymic T cells halted in development, through to mature, circulating peripheral T cells. The latter cases are diagnostically problematic with many entering the category of peripheral T cell lymphoma, not otherwise specified (PTCL, NOS). Anaplastic Large Cell Lymphoma is one of the exceptions to this whereby aberrant expression of Anaplastic Lymphoma Kinase and distinctive presence of cell surface CD30 places this entity in its own class. Besides expression of a well-studied oncogenic translocation, ALCL, ALK+ may also have a unique pathogenesis with a thymic origin like T lymphoblastic lymphoma but a peripheral presentation akin to PTCL. This review discusses evidence towards the potential origin of ALCL, ALK+ and mechanisms that may give rise to its unique phenotype.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

We consider new insights into the origin and nature of pointer states and their role in wave function collapse in macroscopic quantum coherence. The work includes new theory of quantum coherence underpinned by turbulence, generated by a field of pointer states in the form of recirculating vortices (toroids), interconnected via a vortex cascade. Decoherence occurs when the interconnected field of vortices between pointer states is disrupted by external forces, leading to their localisation. The applicability of this work is considered in addressing unresolved questions in high temperature superconductivity and macroscopic quantum processes in biological systems. We also consider its implications for our understanding of intrinsic spin and pointer states within the standard "point source" representation of a quantum particle, which intuitively requires a more complexed description.

Turner syndrome (TS) is a chromosomal disorder that is caused by a missing or structurally ab-normal second sex chromosome. Subjects with TS are at an increased risk of developing intrauterine growth retardation, low birth weight, short stature, congenital heart diseases, infertility, obesity, dyslipidemia, hypertension, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular diseases (stroke and myocardial infarction). The underlying pathogenetic mechanism of TS is unknown. The assumption that X chromosome-linked gene haploinsufficiency is associated with the TS phenotype is questioned since such genes have not been identified. Thus, other pathogenic mechanisms have been suggested to explain this phenotype. Morphogenesis encompasses a series of events that includes cell division, the production of migratory precursors and their progeny, differentiation, programmed cell death, and integration into organs and systems. The precise control of the growth and differentiation of cells is essential for normal development. The cell cycle frequency and the number of proliferating cells are essential in cell growth. 45,X cells have a failure to proliferate at a normal rate, leading to a decreased cell number in a given tissue during organogenesis. A convergence of data indicates an association between a prolonged cell cycle and the phenotypical features in Turner syndrome. This review aims to examine old and new findings concerning the relationship between a prolonged cell cycle and TS phenotype. These studies reveal a diversity of phenotypic features in TS that could be explained by reduced cell proliferation. The implications of this hypothesis for our understanding of the TS phenotype and its pathogenesis are discussed. It is not surprising that 45,X monosomy leads to cellular growth pathway dysregulation with profound deleterious effects on both embryonic and later stages of development. The prolonged cell cycle could represent the beginning of the pathogenesis of TS, leading to a series of phenotypic consequences in embryonic/fetal, neonatal, pediatric, adolescence, and adulthood life.

The physiological response to a psychological stressor broadly impacts energy metabolism. In-versely, changes in energy availability affect the physiological response to the stressor in terms of hypothalamus, pituitary adrenal axis (HPA) and sympathetic nervous system activation. Glu-cocorticoids, the endpoint of the HPA axis, are critical checkpoints in endocrine control of ener-gy homeostasis and have been linked to metabolic diseases including obesity, insulin resistance and type 2 diabetes. Glucocorticoids, through the glucocorticoid receptor, activate transcription of genes associated with glucose and lipid regulatory pathways and thereby control both physi-ological and pathophysiological systemic energy homeostasis. Here, we summarize the current knowledge of glucocorticoid functions in energy metabolism and systemic metabolic dysfunc-tion, particularly focusing on glucose and lipid metabolism. There are elements in the external environment that induce lifelong changes in the HPA axis stress response and glucocorticoid levels, the most prominent are early-life adversity, or exposure to traumatic stress. We hypothe-sise that when the HPA axis is so disturbed after early-life adversity, it will fundamentally alter hepatic gluconeogenesis, inducing hyperglycaemia, and hence crystalise the significant lifelong risk of developing either the metabolic syndrome, or type 2 diabetes. This gives a “Jekyll and Hyde” role to gluconeogenesis, providing the necessary energy in situations of acute stress, but driving towards pathophysiological consequences when the HPA axis has been altered.

This article is about a framework for determining the degree of realism of any given 1 passenger ride motion discomfort measurement formula. After providing some context and reviewing 2 evidence of deficiency in currently popular ride motion discomfort measurement formulas, the article 3 outlines the research program that needs to be carried out in order to establish such a framework. 4 The research begins with gathering recordings of uncomfortable ride motion episodes encountered in 5 a chosen type of passenger transport service. It then has test subjects compare the episodes via a ride 6 motion simulator and adjust their amplitudes pair wise until they cause equal discomfort. It explains 7 how to take the pair wise amplitude adjustments and determine amplitude adjustments that bring all 8 of the motion episode recordings to a common level of discomfort so that they form a normalized set. 9 Then, the lower the scatter of the scores assigned by any given discomfort measurement formula to 10 the members of that set, the more realistic that formula will be for the chosen service.

Development of accelerometer-based lameness (mobility) detection has focused on cow behaviors such as lying and walking. Several studies, usually small, have reported levels of accuracy up to 91%. However, there has been limited independent replication of these results. In this study, behavior measures previously identified as being associated with lameness such as lying bouts and walking time are examined in relation to mobility score. On a research farm and a commercial farm, four trials were completed with 65 grazing cows. The cows had differing mobility scores ranging from perfect mobility to impaired mobility. Behavior was monitored using leg worn accelerometers. In general, behavior and mobility associations identified in previous studies were not found. Behavior monitoring with accelerometers as a basis to classify impaired mobility in pasture-based contexts thus remains challenging.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

(1) Background: Thrombophilia is a tendency towards hypercoagulability, and it is increased by pregnancy, peaking around delivery. Research question: does thrombophilia stimulate the in-flammatory state of the patient, already suppressed by pregnancy? (2) Methods: Eighty thrombo-philia patients admitted for delivery between 1/10/2017 and 1/12/2021 were prospectively stud-ied, together with eighty age- and para-matched control patients. Patients were admitted for de-livery at term by means of cesarean section. The inflammation indexes from the complete blood count values analysis during both the 24 hours before and after labor—extracted from the hospi-tal’s medical records—were calculated and then correlated with uterine involution. (3) Results: Except for the PLR, most of the numerous inflammation indexes studied were not significantly different in treated thrombophilia patients, before and after delivery, compared to non-thrombophilia patients. Only when we split the patients, based on the uterine haematometra in the first 24-48 hours postpartum, we found out that the few treated thrombophilia patients with haematometra (14 with haematometra out of 79 with treated thrombophilia) had elevated SII and AISI antepartum. In pregnant patients treated for thrombophilia, MLR is higher in pa-tients without the Rh factor than in those with the Rh factor. In non-thrombophilia patients, MCVL and NLPR increased with age and before labor, while SII and AISI increased with age postpartum. (4) Conclusions: Thrombophilia did not stimulate the inflammatory state of the pa-tient, already suppressed by pregnancy.

This study explores the complexities involved in the extraction and purification of catechins, prominent bioactive compounds found in plant extracts and tea. It addresses challenges arising from the intricate molecular structure of catechins and their inherent variability across botanical sources. Despite these obstacles, catechins present significant potential, particularly in healthcare. Their potent antioxidant properties have been extensively investigated and associated with numerous health benefits, positioning them as promising therapeutic agents for combating chronic diseases. Furthermore, catechins have diverse applications across various industries, including food and beverage, cosmetics, agriculture, and materials science. This abstract emphasizes the importance of continued research and innovation in catechin extraction and utilization, which hold promise for advancing human health and technological progress across multiple domains.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

Dirofilariosis is an infectious disease caused by species of the Dirofilaria genus. It is manifested by the appearance of a subcutaneous swelling, especially in the eye region. We present the case of a 29-year-old patient that accused facial asymmetry in the right genian region. Following clinical and paraclinical evaluations, the diagnosis of parasitic cyst was established in the context of dirofilariosis with Dirofilaria repens (D. repens). Treatment consisted of surgical excision of the formation associated with prophylactic antibiotic medication. Macroscopic analysis of the excision piece revealed a structure that contains a cystic cavity and a filamentous form with a length of approximately 10 mM and a diameter of 1 mM. This is the first case of dirofilariosis located in the genian region reported in Romania. The overview of this pathology is important to raise awareness among physicians about its presence and its clinical variations.

There are many ‘faces’ of early life adversity (ELA), such as childhood trauma, institutionalization, abuse or exposure to environmental toxins. These have been implicated in the onset and severity of a wide range of chronic non-communicable diseases later in life. The later-life disease risk has a well-established immunological component. This raises the question as to whether accelerated immune-ageing mechanistically links early-life adversity to the lifelong health trajectory resulting in either ‘poor’ or ‘healthy’ ageing. Here we examine observational and mechanistic studies of ELA and inflammageing, highlighting common and distinct features in these two life stages. Many biological processes appear in common including reduction in telomere length, increased immuno-senescence, metabolic distortions and chronic (viral) infections. We propose that ELA shapes the developing immune, endocrine and nervous system in a non-reversible way, creating a distinct phenotype with accelerated immuno-senescence and systemic inflammation. We believe that ELA acts as an accelerator for inflammageing and age-related diseases. Furthermore, we now have the tools and cohorts to be able to dissect the interaction between early life adversity and later life phenotype. This should, in the near future, allow us to identify the ecological and mechanistic processes that are involved in ‘healthy’ or accelerated immune-ageing.

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

This research addresses a gap in the literature by conducting a comprehensive analysis of patients’ level of satisfaction with dental care. Methods: By combining quantitative and qualitative survey methods with the PSQ questionnaire this study aims to augment ongoing initiatives to enhance dental patients’ experiences by painting a more comprehensive depiction of patients' level of satisfaction; Results: When asked about their overall level of satisfaction 77,1% of the patients said they received excellent services from the office personnel and 72,2% said they trust their doctors; Conclusions: Assessing patient satisfaction in the realm of dental services quality is crucial for enhancing service quality and accuracy, benefiting both patients and dentists, and ultimately improving public health.

A set of polymer composite bolted T-joints with novel configuration consisting of internal skeleton and external skin was fabricated using a prepreg-RTM co-curing molding process. Experiments were conducted to study their mechanical properties under bending load. A finite element model with a polymer resin area between the skin and skeleton was established and verified by the experimental results. Then, the damage propagation process and failure mechanism of the joint and the influence of three factors related to the layer characteristics of the skin and skeleton were investigated by the validated models. The results show that the bending stiffness and the yield limit load of the novel composite T-joint are 0.81 times and 1.65 times that of the 2A12 aluminum T-joint respectively, while at only 55.4% of its weight. The damage of the joint initiates within the resin area and leads to a degradation of the joint bending performances. The preferred stacking sequence of the skeleton is [0/+45/90/-45]ns when primarily subjected to bending loads. The decrease in bending performances is within 5% with the inclining angle of the skeleton less than 12 degrees. The more layers of 90° in the skin, the better bending performances of the joints, while the more layer of 0°, the poorer bending performances.

Neuroinflammation is considered to be a significant component in a range of neuropathologies. Unfortunately, whilst its role is well recognized, the options for therapeutic intervention are limited. As such, there is a need to identify novel targets in order to increase treatment options. Given its role as both a neurotransmitter and an immune modulator, substance P and its NK1 receptor have been widely studied as a potential therapeutic target. There is evidence that NK1 receptor antagonists may exert beneficial effects in a range of conditions, including traumatic brain injury and stroke. Blocking the NK1 receptor has been shown to reduce blood-brain barrier dysfunction, reduce cerebral oedema, and reduce the levels of pro-inflammatory cytokines. These actions are associated with improved survival and functional outcomes. The NK1 receptor has also been shown to be involved in the inflammatory reaction to CNS infection, and hence antagonist may have some benefit in reducing infection-driven inflammation. However, the NK1 receptor may also play a role in the host immune response to infection, and so here, the potential beneficial and detrimental effects need to be carefully balanced. As such, the purpose of this review is to provide a summary of the involvement of substance P in acute inflammation, particularly in the context of traumatic brain injury and stroke.

The rock joint fissure slope in cold regions is prone to deformation and failure problems such as relaxation, tension and collapse under freeze-thaw (F-T) cycles. Based on the ideology of clean production and promoting the structural integrity of geotechnical projects in cold areas, this study designed and prepared aeolian-sand (AS) to replace part of river sand as a filling mortar material by taking advantage of the low cost and easy availability of AS. Investigations were carried out to determine the impact of varying proportions of AS in mortar on the microstructure and shear properties of the mortar-rock interface under F-T cycles. Therefore, F-T cycle testing, nuclear magnetic resonance (NMR) testing and shear testing were carried out on grout with different proportions of AS. The results show that the right proportion of AS replacement could enhance the shear deformation resistance and F-T resistance of the mortar-rock interface, and 30% proportion is the optimal proportion. By increasing of F-T cycles, the three types of specimens showed different degrees of particle spalling, shedding and cracking. The slurry-rock interface layer in the A (0%) group exhibited the most severe F-T deterioration, while the B (15%) group showed a lesser degree, and the C (30%) group performed the best. T2 spectrum curve and total spectrum area change law from the microscopic point of view to verify the 30% AS proportion mortar-rock interface F-T resistance is the strongest, followed by 15% AS proportion mortar, the weakest is ordinary mortar. The degradation of the mortar-rock bond is primarily due to the conversion of solid to liquid phases and the movement of internal water caused by fluctuating temperatures. The extent of F-T deterioration in the slurry-rock interface layer is greatly affected by the varying proportions of AS. The shear strength and shear stiffness of specific proportion of AS decreased with the increase of F-T cycles. For same F-T cycles, the shear strength and shear stiffness of group C (30%) were the highest, followed by group B (15%) and group A (0%). The grout material not only reinforces the F-T joint fissure slope, but also reduces the cost of grout reinforcement and promotes the clean production of geotechnical structures.

Landiolol is an ultra-short-acting, selective ß1- adrenergic receptor blocker that was originally approved by Japan for the treatment of intraoperative tachyarrhythmias. It has gained attention for its use in the management of tachyarrhythmias and perioperative tachycardia, especially atrial fibrillation for both cardiac and non-cardiac surgeries. It can be the ideal agent for heart rate control due to its high β1‐selectivity, the potent negative chronotropic effect, a limited negative inotropic potential, and an ultrashort elimination half‐life (around 4 min); moreover, it may have a potential therapeutic effect for sepsis and pediatric patients. Landiolol seems to be superior to other short‐acting and selective beta‐blockers such as esmolol. This review aims to provide a comprehensive overview of landiolol, a new ultra-short-acting ß1 selective antagonist, including its pharmacology, clinical applications, efficacy, safety profile, and future directions in research and clinical data.

(1) Background: The prediction of cervical lesions evolution is a challenge for clinicians. The prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors for the prediction of progression, regression or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions that underwent follow-up. Descriptive statistics and sensitivity analysis for individual or combined index tests were used for data analysis; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model that comprised a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least 3 clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesions regression or persistence was modest; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

Background: By 2025, road traffic injuries are projected to rank third in the global burden of disease, posing a significant challenge that affects health, social well-being, and economic aspects. According to data from the Romanian Police National Statistics Center, there has been an average of 342 traffic accidents per year involving pediatric patients over the past 10 years. Materials and Methods: A retrospective research study was conducted, encompassing 358 cases of road traffic accidents identified for the study. Data collection was conducted at "St. Mary’s" Emergency Hospital for Children in Iasi, Romania, from January 2015 to December 2022. To facilitate statistical analyses, participants were categorized into three specific age groups, correlating between the anatomical region affected and different types of accidents was examined, and the classification of injury types was determined based on the characteristics of the harm inflicted. Results: An oscillating trend is observed from 2015 to 2020, with its lowest value recorded in 2017 at around 6.8% and its peak in 2019 at 20.1%. Notably, post-pandemic (Covid-19), the cases underwent a substantial decline of approximately 50%. At least 78.7% of those who did not undergo orthopedic reduction required surgery, whereas among those who underwent orthopedic reduction, only 23.4% needed surgery. Regarding the frequency of complications 7,9% of the total cases experienced complications. Conclusion: The increased frequency of pediatric traffic accidents is attributed to the extensive services provided by "St. Mary’s" Emergency Hospital for Children, Iasi, to a significant number of patients from both rural and urban areas across the seven counties of the Moldova, Romania.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

Distant Retrograde Orbits in the Earth-Moon system are gaining in popularity as stable `parking' orbits for various conceptual missions. To investigate the stability of potential Distant Retrograde Orbits, simulations were executed, with propagation running over a thirty-year period. Initial conditions for the vehicle state were limited such that the position and velocity vectors were in the Earth-Moon orbital plane, with the velocity oriented such that it would produce retrograde motion about Moon. The resulting trajectories were investigated for stability against the eccentric relative orbits of Earth and Moon in an environment that also included gravitational perturbations from Sun, Jupiter, and Venus, and the effects of radiation pressure. The results appear to indicate that stability is enhanced for certain resonant states within the Earth-Moon system.

Precise monitoring of individual crop growth and health status is crucial for precision agriculture practices. However, traditional manual inspection methods are time-consuming, labor-intensive, and often lack the spatial resolution required for detailed analysis. This research addresses the need for efficient and high-resolution crop monitoring by leveraging Unmanned Aerial Vehicle (UAV) imagery and advanced computational techniques. The primary objective was to develop a methodology for precise identification, extraction, and monitoring of individual corn crops throughout their growth cycle. This was achieved by integrating UAV-derived data with image processing, computational geometry, and machine learning techniques. UAV imagery was ac-quired bi-weekly at altitudes of 40m and 70m, capturing the entire growth cycle of a corn crop from planting to harvest. A time-series Canopy Height Model (CHM) was generated by analyzing the differences between the Digital Terrain Model (DTM) and the Digital Surface Model (DSM) derived from the UAV data. Local spatial analysis and image processing techniques were em-ployed to determine the local maximum height of each crop. Subsequently, a Voronoi data model was developed to delineate individual crop canopies, successfully identifying 13,000 out of 13,050 corn crops in the study area. For enhanced accuracy in canopy size delineation, vegetation indices were incorporated into the Voronoi model segmentation, refining the initial canopy area esti-mates by eliminating interference from soil and shadows. The proposed methodology enables precise estimation and monitoring of crop canopy size, height, biomass reduction, lodging, and stunted growth over time, providing valuable insights for precision agriculture practices. This work contributes to the scientific community by demonstrating the potential of integrating UAV technology, computational geometry, and machine learning for accurate and efficient crop mon-itoring at the individual plant level.

A co-curing resin system consisting of 9368 epoxy resin for prepreg and 6808 epoxy resin for resin transfer molding (RTM) was developed. A corresponding preparation method of novel polymer composite bolted T-joint with internal skeleton and external skin was proposed based on prepreg-RTM co-curing process, and novel T-joints were fabricated. A series of conventional configuration T-joints based on RTM process and T-joints made of 2A12 aluminum alloy were prepared simultaneously. Bending performances were studied on these T-joints experimentally. The results indicate that 9368 epoxy resin and 6808 epoxy resin exhibit good compatibility in rheological and thermophysical properties. The novel T-joints prepared with prepreg-RTM co-curing process show no obvious fiber local winding or resin-rich regions inside, and the interface quality between internal skeleton and external skin is excellent. The main failure modes of the novel T-joint under bending load include separation of skin and skeleton and fracture along the thickness on the base panel; the skeleton carries the main bending load, but there is still load transfer between external skin and internal skeleton through their interface. The internal damages of the novel T-joint are highly consistent with surface damages observed visually, facilitating the detection and timely discovery of damages. The initial stiffness, damage initiation load, and ultimate load of the novel T-joint are 1.65 times, 5.89 times, and 3.45 times that of conventional T-joint, respectively. When considering the influence of density, the relative initial stiffness and relative ultimate load of the novel T-joint are 1.44 times and 2.07 times that of aluminum alloy T-joint, respectively.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

We investigate and discuss in detail the structure of the restricted singular value decomposition for a tensor triplet under t-product (T-RSVD). The algorithm is provided with a numerical example illustrating the main result. For applications, we consider color image watermarking processing with T-RSVD.

This paper offers insights into the nexus of youth, masculinity and right-wing populism in Australia. Here we make reference to a wide body of international literature on the topic. There is some affinity between disenfranchised (white) working-class young men and the radical right. Survey data were collected for a project on masculinity and the far right in Australia. 203 young men worked primarily in “blue collar” sectors of the Australian labour force. Some survey responses locate them partly or potentially within the field of the populist right-wing, with many expressing anti-government sentiments and the discourse of white male victimhood. The majority were nostalgic for stereotypical masculinity. While right-wing populist movements across the world certainly differ, they often share a discourse promoting traditional gender roles.

The quinolone decoquinate (DCQ) is widely used in veterinary practice for the treatment of bacte-rial and parasitic infections, most notably coccidiosis in poultry and in ruminants. We have in-vestigated the effects of treatment of Toxoplasma gondii in infected human foreskin fibroblasts (HFF) with DCQ. It induced distinct alterations in the parasite mitochondrion within 24h, which persisted even after long-term (500 nM, 52 days) treatment, although there was no parasiticidal effect. Based on the low half-maximal effective concentration (IC50) of 1.1 nM and the high selec-tivity index of >5000, the efficacy of oral treatment of pregnant mice experimentally infected with T. gondii oocysts with DCQ at 10 mg/kg/day for 5 days was assessed. However, the treatment had detrimental effects, induced higher neonatal mortality than T. gondii infection alone, and did not prevent vertical transmission. Thus, three quinoline-O-carbamate derivatives of DCQ antici-pated to have better physicochemical properties than DCQ were assessed in vitro. One such com-pound RMB060 displayed an exceedingly low IC50 of 0.07 nM when applied concomitantly with infection of host cells and had no impact on HFF viability at 10 µM. As was the case for DCQ, RMB060 treatment resulted in alteration of the mitochondrial matrix and loss of cristae, but the changes became apparent at just 6h after commencement of treatment. After 48h, RMB060 induced the expression of the bradyzoite antigen BAG1, but TEM did not reveal any other features remi-niscent of bradyzoites. Exposure of infected cultures to 300 nM RMB060 for 52 days did not re-sult in complete killing of all tachyzoites, although mitochondria remained ultrastructurally damaged and there was a slower proliferation rate. Treatment of mice infected with T. gondii oocysts with RMB060 did reduce parasite burden in non-pregnant mice and dams, but vertical transmission to pups could not be prevented.

Grain quality, cooking quality and nutritional quality traits are some of the major attributes that enhance uptake and utilisation of improved cowpea varieties. Therefore, there is need for a better understanding of the genetic variation and inter-relationships among these quality traits in cowpea to integrate them in cowpea breeding programs. The study was conducted to determine genetic variability among 306 cowpea genotypes for grain quality, cooking quality and nutritional quality traits and to understand the interrelationships among these traits for exploitation in breeding programs. The results showed highly significant differences (P

The latest IPCC report forcefully states that immediate, decisive, and large-scale actions are needed to avert climate catastrophe. This essay presumes that democratic governments are best and most desirably positioned to take these actions. Yet in the countries most pivotal to global climate, significant voting blocs are uninterested in environmental issues. The essay urges adding bottom-up dialog between environmental and anti-environmental voters, to current and future top-down technocratic “solutions.” To make this combination result in a unified pro-environment electorate, we must understand: religious objections to environmentalism; the capital-vs.-knowledge strife that slows polluting corporations’ green transitions; and the psychological mechanisms that can make inter-group dialog fruitful.

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic blasts/LSCs from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to get a deeper insight and segregation between leukemic and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34⁺/CD38^- hematopoietic stem cells (HSCs) or CD34⁺ cells with a strong coexpression of CD45RA/CD123, respectively. CD34⁺ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The virus infection can evolve asymptomatically or generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia in patients affected with COVID-19 according to the severity of symptoms is frequent. However, the profile of CD4+ and CD8+ T-cells regarding cytotoxicity and antiviral factor expression has not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study is to evaluate the phenotypic and functional profile of T-lymphocytes in patients with moderate and severe/critical COVID-19. During this pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Albeit lymphopenia, we observed an increase in the expression of CD28, co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T-lymphocytes as well as an increase in the frequency of CD4+ T-cells, CD8+ T-cells, and NK cells that express the immunological checkpoint protein, PD-1, in patients with severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T-cells already at baseline level was observed, scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T-lymphocytes decreased cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed in the t-SNE technique CD4+ T-cytotoxic and CD8+ T with low granzyme production evidencing their dysfunctionality in severe/critical conditions. In addition, purified CD8+ T-lymphocytes from patients with severe COVID-19 showed an increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and curiously, reduced expression of TNF-α. The cytotoxic profile, by CD4+ T-cells, may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T-cells and CD8+ T-cells in the severity of acute COVID-19 infection.

In this work, we study the existence of strange star in the background of f(T,T) gravity in the Einstein spacetime geometry, where T is the torsion tensor and T is the trace of the energy-momentum tensor. The equations of motion are derived for anisotropic pressure within the spherically symmetric strange star. We explore the physical features like energy conditions, mass-radius relations, modified TOV equations, principal of causality, adiabatic index, redshift and stability analysis of our model. These features are realistic and appealing to further investigation of properties of compact objects in f(T,T) gravity as well as their observational signatures.

The Combined Elevation Test (CET) is a musculoskeletal screening technique (MST) replicates the streamline position in swimming and is commonly used in various sports. Although the CET is widely used, no normative data exist within an adolescent population. Therefore, the purpose of this study was to develop a normative data set for the CET within an adolescent population and to evaluate the influence various demographic and anthropometric variables. Data was collected for 416 participants aged between 8 and 18 years old. Age and arm span showed a significant correlation with CET scores (arm span r_s (105) = .478, p = .000, age r_s (416) = .238 p = .000). Regression analysis further quantified the influence of arm span and age on CET scores accounting for 23.1% and 5.3% of variability respectively. These results can be used as a reference point for clinicians and coaches who are using the CET within their assessment.

Boutique hotels emerged in the late 1970s since then the product has become more mainstream. The draw of boutique hotels is more personalized services. When marketing and providing services to a niche market it is smart to be able to differentiate potential guests to best meet their needs. The generational cohort theory states that a population may be divided into segments based on their generation. This research focuses on Generation X to find out what they are seeking in a boutique hotel product. Based upon how they chose their travel destination there were significant differences between culinary experience, attractions/activities, and cost/budget.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4+ T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD+ T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4+ T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit.

Remanufacturing is a viable option to extend the useful life of an end-of-use product or its parts, ensuring sustainable competitive advantages under the current global economic climate. Challenges typical to remanufacturing still persist, despite its many benefits. According to the European Remanufacturing Network a key challenge is lack of accurate, timely and consistent product knowledge as highlighted in a 2015 survey of 188 European remanufacturers. With more data being produced by electric and hybrid vehicles, this adds to the information complexity challenge already experienced in remanufacturing. Therefore, it is difficult to implement real-time and accurate remanufacturing for the shop floor; there are no papers that focus on this within an electric and hybrid vehicle environment. To address this problem this paper attempts to (1) identify the required parameters/ variables needed for fuel cell remanufacturing by means of interviews (2) rank the variables by Pareto analysis (3) develop a casual loop diagram for the identified parameters/ variables to visualise its impact on remanufacturing (4) model a simple stock and flow diagram to simulate and understand data and information-driven schemes in remanufacturing.

This paper presents a new methodology to derive and analyze strategies for a fully decarbonized urban transport system which combines conceptual vehicle design, a large-scale agent-based transport simulation, operational cost analysis, and life cycle assessment for a complete urban region. The holistic approach evaluates technical feasibility, system cost, energy demand, transportation time and sustainability-related impacts of various decarbonization strategies. In contrast to previous work, the consequences of a transformation to fully decarbonized transport system scenarios are quantified across all traffic segments, considering procurement, operation and disposal. The methodology can be applied to arbitrary regions and transport systems. Here, the metropolitan region of Berlin is chosen as a demonstration case. First results are shown for a complete conversion of all traffic segments from conventional propulsion technology to battery electric vehicles. The transition of private individual traffic is analyzed regarding technical feasibility, energy demand and environmental impact. Commercial goods, municipal traffic and public transport are analyzed with respect to system cost and environmental impacts. We can show a feasible transition path for all cases with substantially lower greenhouse gas emissions. Based on current technologies and today’s cost structures our simulation shows a moderate increase in total systems cost of 13-18%.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (&gt;12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

In this paper we study the class of mixed-index time fractional differential equations in which different components of the problem have different time fractional derivatives on the left hand side. We prove a theorem on the solution of the linear system of equations, which collapses to the well-known Mittag-Leffler solution in the case the indices are the same, and also generalises the solution of the so-called linear sequential class of time fractional problems. We also investigate the asymptotic stability properties of this class of problems using Laplace transforms and show how Laplace transforms can be used to write solutions as linear combinations of generalisedMittag-Leffler functions in some cases. Finally we illustrate our results with some numerical simulations.

In 2023, the Bureau of Land Management (BLM) estimated that there were 68,928 mustangs living on United States public lands in 10 western states. The agency uses Appropriate Management Levels to determine the number of mustangs who need to be removed from the land. Once removed and processed, mustangs are sent to adoptions or sales events or retained in short-or long-term holding facilities. Adoptions and sales are the leading avenues for rehoming mustangs; however, the number of horses the BLM can place fluctuates annually and never approaches the greater number removed from the range. To explore opportunities for increasing the number of mustang adoptions, we conducted in-depth interviews with 23 horse trainers located on the U.S. East Coast, asking about participants’ training programs, relationships with horses, perceptions of mustangs, and challenges that mustangs face in the dressage and eventing industries. Participants had varying experiences with mustangs; however, all were willing to work with a mustang in some capacity. Participants voiced the need for more satellite adoption locations on the East Coast to decrease barriers to acquiring a mustang, notably cost and time, and for expanding existing training programs to include eventing and dressage.

Naive CD4+ T cells engage cognate peptide MHC-II complexes (pMHC-IIs) to differentiate and acquire one of several T helper (Th) fates whose specific trajectories are guided by a dynamic cytokine milieu that develops in response to antigenic entity. This physiological process is often erroneously conflated with a pathological one termed Th polarization. Using the SPIRAL model, we argue here that unlike Th fate choice, innate signaling alone is insufficient to initiate Th polarization in naive CD4+ T cells, that it instead develops from pre-existing memory CD4+ T cells that express cross-reactive TCRs, and that it inevitably leads to immunopathology.

This review documents an emerging body of evidence concerning the neurological effect of polycyclic aromatic hydrocarbon (PAH) exposure, with regard to cognitive function and increased risk of neurodegeneration. Two electronic databases PubMed and Web of Science were systematically searched. The 37/428 studies selected included outcomes measuring cognitive function, neurobehavioral symptoms of impaired cognition, and pathologies associated with neurodegeneration from prenatal (21/37 studies), childhood (14/37 studies), and adult (8/37 studies) PAH exposure. Sufficient evidence surrounding prenatal exposure negatively impacting child intelligence, mental development, average overall development, verbal IQ, memory impairment, externalizing, internalizing, anxious, depressed behaviours, behavioural development and child attentiveness was found. Evidence concerning exposure during childhood and as an adult was scarce and highly heterogeneous, however presence of neurodegenerative biomarkers and increased concentrations of cryptic “self” antigens in serum and cerebrospinal fluid samples suggest a higher risk of neurodegenerative disease. Associations with lowered cognitive ability, and impaired attentiveness were found in children and memory disturbances, specifically auditory memory, verbal learning and general memory in adults. Although evidence is not yet conclusive and further research is needed the studies included supported the hypothesis that PAH exposure negatively impacts cognitive function and increases the risk of neurodegeneration in humans, and recommends considering the introduction of a variable “rural vs. urban” as covariate for adjusting analyses where the neurological functions affected (as result of our review) are outcome variables.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and fetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, known for maintaining immune tolerance, are crucial in pregnancy to prevent immune-mediated rejection of the fetus. In HDP, Treg numbers and function imbalance are observed, correlating with disease severity. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring fetal acceptance and placental development. In contrast, HDP is associated with Treg dysfunction, marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, where Tregs fail to adequately modulate the maternal immune response against fetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, the review acknowledges the complexity of translating these findings into effective clinical therapies, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

Inflorescence architecture underpins sexual reproduction in wild Musa species and productivity in edible banana cultivars. In a functional analysis we identified the apical inflorescence and lateral ‘cushion’ meristems and the change in flower type as the three primary components of inflorescence architecture. Five genotypes of two clone-sets of edible plantains (Musa AAB), were grown for four generations along an elevation gradient (1100 m to 2200 m, 16°C to 24°C) straddling the equator in the humid highlands of East Africa. The data consisted of peduncle length at harvest, fruit per hand (Fh) and hands per bunch (Hb). The activity of the apical inflorescence meristem drives peduncle length and lateral ‘cushion’ meristems determine fruit per hand. However, Hb is determined by a change in flower type – from fruit-forming to non-fruit forming. Site temperature affected Hb more than Fh, while development of the genet (rhizome) changed the allocation of resources between Hb and Fh, independently of the effect of site temperature. Clone-sets differed in their response to genet development. Cooler temperatures reduced the number of fruit-forming flowers in an inflorescence and changed the balance away from female towards male flowers. In banana breeding schemes, manipulating inflorescence components independently raises options for producing genotypes better suited to markets, environments, and cultural practices.

The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of tumor microenvironment, Nor-Adrenaline (NA) is poured-in by innervating nerves and tumor tissues itself. The receptors for nor-adrenaline are present on the surface of cancer and immune cells and are often involved in activation of pro-tumoral signaling pathways. β2-adrenergic receptor (β2-AR) is an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate the regulatory immune cells and inhibit the effector immune cells. Blocking β2-AR increases activation, proliferation and cytokine release of T lymphocytes. Moreover β2-AR deficiency during metabolic reprograming of T cells increases mitochondrial membrane potential and biogenesis. In the view of available research data, immunosuppressive role of β2-AR in T cells presents it a targetable checkpoint in CAR-T cell therapies. In this review, we have abridged contemporary knowledge about adrenergic stress mediated β2-AR activation on T lymphocytes inside tumor milieu.

There is growing awareness that “Nature-based Solutions” (NbS) can help to protect us from climate change impacts whilst slowing further warming, supporting biodiversity and securing ecosystem services. However, the potential of NbS to provide the intended benefits has not been rigorously assessed. There are concerns over their reliability and cost-effectiveness compared to engineered alternatives, and their resilience to climate change. Trade-offs can arise if climate mitigation policy encourages NbS with low biodiversity value, such as afforestation with non-native monocultures. This can result in maladaptation, especially in a rapidly changing world where biodiversity-based resilience and multifunctional landscapes are key. Here we highlight the rise of NbS in climate policy—focussing on their potential for climate change adaptation as well as mitigation—and discuss barriers to their evidence-based implementation. We outline the major financial and governance challenges to implementing NbS at scale, highlighting avenues for further research. As climate policy turns increasingly towards greenhouse gas removal approaches such as afforestation, we stress the urgent need for natural and social scientists to engage with policymakers. They must ensure that NbS can achieve their potential to tackle both the climate and biodiversity crisis while also contributing to sustainable development. This will require systemic change in the way we conduct research and run our institutions.

Translation of basic animal research to find effective methods of diagnosing and treating human neurological disorders requires parallel analysis infrastructures. Small animals such as mice provide exploratory animal disease models. However, many interventions developed using small animal models fail to translate to human use due to physical or biological differences. Recently, large-animal minipigs have emerged in neuroscience due to both brain similarity and economic advantages. Medical image processing is a crucial part of research as it allows researchers to monitor their experiments and understand disease development. However, although many algorithms are created and optimized for MR analysis of human data, those tools are not directly applicable or sufficiently sensitive to measure minipig data. In this work, we propose PigSNIPE - a pipeline for the automated handling, processing, and analyzing of large-scale data sets of minipig MR images. The pipeline allows for image registration, AC-PC alignment, landmark detection, skull stripping, brainmasks and intracranial volume segmentation (DICE 0.98), tissue segmentation (DICE 0.82), and caudate-putamen brain segmentation (DICE 0.8) in under two minutes. To the best of our knowledge, this is the first automated pipeline tool aimed at large animal images.

An oxidation resistant coating on cemented tungsten carbides is characterised in this work. Cemented tungsten carbides (cWCs) are routinely used in mining and manufacturing but are also candidate materials for compact radiation shielding in fusion power generation. In both environments, cWCs will suffer significant degradation due to oxidation at relatively low temperatures. In a recent study, a Si-deposition coating method was demonstrated to improve the oxidation resistance of cWCs by up to a factor of 1,000. This work focusses on the growth kinetics, phase composition, and mechanical properties of these coatings. By combining quantitative X-ray diffraction, electron microscopy and nanoindentation, we show that the coating layer has a 20 % higher hardness than the substrate, which was explained on the basis of a previously-unknown presence of a fine distribution of very hard SiC laths. To interpret the coating stability, a coating growth map is developed. The map shows the structure is stable under a broad range of processing temperatures and composite compositions, demonstrating the potential application of these coatings in a variety of nuclear shielding cWCs.

Cholangiocellular carcinoma (CCA) is the second most common primary liver cancer, with increasing incidence worldwide and inadequate therapeutic options. Intra- and extrahepatic bile ducts have distinctly different embryonic origins and developmental behavior, and accordingly intra- and extrahepatic CCAs (ICC vs. ECC) are molecularly different. A promising strategy in oncotherapy is targeted therapy, targeting proteins that regulate cell survival and proliferation; such as the MAPK/ERK and PI3K/AKT/mTOR signaling pathways. Inhibitors of these pathways have been tested previously in CCA cell lines. However, these cell lines could not be clearly assigned to ICC or ECC, and results indicated apoptosis induction by targeted therapeutics. We tested targeted therapeutics (selumetinib, MK2206) in three defined ICC cell lines (HuH28, RBE, SSP25). We observed cooperative effects of dual inhibition of the two pathways, in accordance with inhibition of phospho-AKT and phospho-ERK1/2 expression. Proliferation was blocked more effectively with dual inhibition than with each single inhibition, but cell numbers did not drop below baseline. Accordingly, we observed G1-phase arrest, but not apoptosis (cleaved caspase-3, AIFM1 regulation, subG1-phase) or necroptosis (phospho-MLKL). We conclude that dual inhibition of MAPK/ERK and PI3K/AKT/mTOR pathways is highly effective to block proliferation of ICC cell lines, but therapy must certainly be supplemented with standard therapies.

Pediatric chronic pain is an important public health issue given its notable impact on numerous domains of living. Pediatric chronic pain is also often comorbid with emotional, developmental, or behavioral conditions which can lead to more severe negative outcomes and an even greater reduction in positive outcomes compared to those without comorbidities. Flourishing is a positive outcome that chronic pain status has been shown to impact. We explored flourishing in children aged 6-17 years living with chronic pain as well as those with chronic pain and comorbidities using data from the 2018/2019 National Survey of Child Health. There were significant associa-tions between chronic pain condition status and all demographic variables (sex, age, race/ethnicity, poverty level, parental education, health insurance status). Results of hierarchical logistic regression found that chronic pain condition status significantly predicted flourishing. Children with chronic pain were 2.33 times less likely to flourish, and children with chronic pain plus an emotional, developmental, or behavioral comorbidity were 13 times less likely to flourish than typical peers. Given their significantly lower likelihood of flourishing, there is an urgent need for interventions targeted at children experiencing chronic pain and mental health comor-bidities.

Coccomyxa subellipsoidea KJ (C-KJ) is a green alga with unique immunoregulatory characteristics. Here, we investigated the mechanism underlying the modification of T cell function by C-KJ components. The water-soluble extract of C-KJ was fractionated into protein (P) and sugar (S) fractions [acidic (AS), basic (BS), and neutral (NS)]. These fractions were used for the treatment of peripheral blood mononuclear cells stimulated with toxic shock syndrome toxin-1. Transcriptome analysis revealed that both P and AS enhanced the expression of the genes encoding metallothionein (MT) family proteins, inflammatory factors, and T helper (Th) 17 cytokine and suppressed that of those encoding Th2 cytokines in stimulated T cells. The kinetics of MT1 and MT2A gene expression showed a transient increase in MT1 and maintenance of MT2A mRNA after T cell stimulation in the presence of AS. The kinetics of Th17-related cytokine secretion in the early period were comparable to those of MT2A mRNA. Furthermore, our findings revealed that static, a STAT-3 inhibitor, significantly suppressed MT2A gene expression. These findings suggest that the expression of MTs is involved in the immune regulatory function of C-KJ components, which is partially regulated by Th17 responses, and may help develop innovative immunoregulatory drugs or functional foods.

The adoption of ADS-B in Latin America has been gradual but steady. Some countries, such as Brazil, Chile and Mexico, have made significant progress in the implementation of this system, while others are still in the early stages. It should be noted that the implementation of ADS-B is used in both military and civilian environments. For this reason, this research aims to provide information on the different characteristics that make up the surveillance systems. However, there are fundamental factors to promote the adaptation of ADS-B in Latin America, since they reduce the risk of collisions and air accidents by providing accurate and real-time information on the position and altitude of aircraft. On the other hand, it allows optimizing flight routes and reducing waiting time on the ground, which translates into fuel and cost savings for airlines. ADS-B increases the number of aircraft that can safely operate in the same airspace, which is especially important in regions with growing air traffic. ADS-B adoption in Latin America is expected to continue to grow in the coming years. The drivers for ADS-B adoption remain in place, and governments in the region are taking steps to accelerate its implementation.

The Circular Economy has been of growing significance within academic, policymaking and industry groups. Latest developments in the field of Circular Economy has led to an expansion of CE studies focused on interrogating CE as a paradigm, its relationship with sustainability and concepts and definitions of the Circular Economy. Research has also identified the significant potential of applying circular approaches to areas of the economy, including manufacturing and Industry 4.0, which, with data, is enabling latest the advances in digital technologies. This is the first review paper to integrate the fields of CE and digital technologies resulting in a framework which provides directions for policymakers and guidance for future research. To achieve this, we conduct a systematic literature review of the empirical literature related to digital technologies, industry 4.0 and circular approaches, from the point of the 9 Rs. The systematic literature review (SLR) is based on peer-reviewed articles published between 2000-2018. The findings reveal that while research on the circular economy has been on an annual rise, research on digital technologies enabled circular economy is still relatively an untouched area of research across all nine (9) circular approaches. As such this is an area rife for further research. This paper also presents illustrative charts and graphs to summarize the current trends in circular economy research in manufacturing. From this, a framework for future circular economy research for manufacturing for digital technologies is proposed.

Euler sums are alternating (or level two) extension of multiple zeta values (MZVs). Kaneko and Tsumura initiated the study of multiple T-values (MTVs), another level two generalization, by restricting the summation indices in the definition of MZVs to a fixed parity pattern. In this paper, we shall study finite MTVs and their alternating versions which are level two and level four variations of finite MZVs, respectively. We conjecture that all finite MZVs are in the Q-span of finite MTVs which in turn apparently lie in the span of finite Euler sums, and the inclusions are both proper. We shall first provide some structural results for Euler sums of small weights, guided by the author's previous conjecture that the finite Euler sum space of weight w is isomorphic to a quotient Euler sum space of weight w. Then, by utilizing some well-known properties of the classical alternating MTVs, we shall derive a few important Q-linear relations among the finite alternating MTVs, including the reversal, linear shuffle and sum relations. We then compute the upper bound for the dimension of the Q-span of weight w finite (alternating) MTVs for w<9, both rigorously using the newly discovered relations and numerically aided by computers.

Pharmacovigilance databases are showing evidence of injury in the context of the COVID-19 modified mRNA shots. According to recent publications, adverse event reports linked to the mRNA COVID-19 products largely point to the spike protein as an aetiological agent of adverse events, but we propose that the platform itself may be culpable. To assess the safety of current and future mRNA vaccines, further analysis on the risks due to the platform itself, and not specifically the expressed antigen. If harm can be exclusively and conclusively attributed to the spike protein, then it is possible that future mRNA vaccines expressing other antigens will be safe. If harms are attributable to the platform itself, then regardless of the toxicity, or lack thereof, of the chosen payload therein, the platform may be inherently unsafe, pending modification. In this work, we examine previous studies of RNA-based delivery by a lipid nanoparticle and break down the possible etiological elements of harm.

In chronic myeloid leukemia (CML), a clonal proliferative disorder of granulocytic lineage, the 90%‐95% of cases are characterized by t(9;22) (q34.1;q11.2) translocation, leading to the Philadelphia chromosome (1). Rarely, CML patients directly present a blast crisis, mostly of myeloid origin (2, 3). Herein, we describe one rare CML case, showing an unusual early T lymphoid blastic crisis.

Climate change is challenging the agricultural sector worldwide. The pressure exerted by the altered thermal conditions drives the zonal shift for various cultivations. This study presents the multiyear analysis of the Growing Degree Days (GDD) index over the Northern Mediterranean Basin (NMB), focused on the high-value vine cultivation derived from the E-OBS dataset. To handle this extensive environmental dataset, R-language scripts and packages were applied, along with the capabilities of the GIS software. The investigated time period spans from 1969 to 2018, and the performed analysis indicates a broad shift/expansion in areas of GDD exceeding 2000 heat units. The extracted results specify the viticultural areas where the GDD index surpasses the suitable values for vine cultivation, owing to the increase of the thermal stress risk. In addition to mapping areas with GDD ≥ 2000, spatial calculations of the surface of areas meeting this criterion per country in the study area were made. In the northern parts of the NMB, the rise of the GDD index values indicates the establishment of vine plantations in the future.

Background Hop creep continues to present an unresolved issue for the brewing industry, specifically stemming from those hops added to beer during fermentation. Hops have been found to contain four dextrin-degrading enzymes: alpha amylase, beta amylase, limit dextrinase, and an amyloglucosidase. One recent hypothesis predicts that these dextrin-degrading enzymes could originate from microbes rather than the hop plant itself. Scope and Approach This review begins by describing how hops are processed and used in the brewing industry. It will then discuss hop creep’s origins with a new beer style, antimicrobial factors from hops and resistance mechanisms that bacteria use to counter them, and finally microbial communities that inhabit hops, focusing on whether they can produce the starch degrading enzymes which drive hop creep. After initial identification, microbes with possible links to hop creep were then run through several databases to search the genomes (if available) and for those specific enzymes. Key Findings and Conclusions Several bacteria and fungi contain alpha amylase as well as unspecified glycosyl hydrolases, but only one contains beta amylase. Finally, this paper closes with a short summary of how abundant these organisms typically are in other flowers.

We present an open-source Star Tracker (ST) for Attitude Determination. Our implementation makes use of open source software of common usage in astronomy running on a Raspberry Pi 2 platform. The developed platform is open and available for parties interested in further development. Evaluation of the system showed that the ST is suitable for Cubesats of 2U or larger. The ST platform is capable of solving the Lost-In-Space (LIS) problem. Currently, the average accuracy reached of the algorithm is close to 5 seconds of arc with an average processing time of 75 seconds. However, a average accuracy of about 3 minutes of arc can be reached with 35 seconds in average processing time. We also describe the evaluation procedure, the found conclusions of this procedure, in particular the section of the algorithm where most of the processing time is spent and other possible source of errors not included in this study.

Extracellular vesicles (EVs) are emerging mediators of intracellular and inter-organ communications in cardiovascular diseases (CVDs), especially in the pathogenesis of heart failure through the transference of EV-containing bioactive substances. microRNAs (miRNAs) are contained in EV cargo and are involved in the progression of heart failure. Over the past several years, a growing body of evidence has suggested that the biogenesis of miRNAs and EVs are tightly regulated, and the sorting of miRNAs into EVs is highly selective and tightly controlled. Extracellular miRNAs, in particular circulating EV-miRNAs, have shown promising potential as prognostic and diagnostic biomarkers for heart failure and as therapeutic targets. In this review, we summarize the latest progress concerning the role of EV-miRNAs in HF and their application in a therapeutic strategy development for heart failure.

It is important to be familiar with the presentation of Turner syndrome and to understand the common causes of death associated with the disease. Using the autopsy case as an example, this case report will outline the classic presentation of Turner syndrome, go over its physiology, epidemiology, pathogenesis and explain the cause of death in this particular case while also highlighting other common causes of death/risk factors within Turner syndrome. Differential diagnosis and mimicking disease processes will also be discussed. This report will also highlight the molecular tests used for the diagnosis of Turner syndrome, discuss developments using in situ hybridization, and discuss why this method is best for the determination of Turner syndrome over conventional karyotyping.

A proportion of osteoarthritis (OA) patients are unsatisfied with post-operative outcomes following total joint replacement surgery (TJR), with insufficient pain relief or poor functional improvement. Predicting those will have poor outcomes would be beneficial for patients and clinicians. The aim of this study was to determine the relationship between baseline anthropometric data and the concentration of pre-operative serum and peri-operative synovial fluid (SF) cytokines with 7-month post-operative outcomes in a cohort of knee and hip OA patients. 160 OA patients were recruited who were scheduled for TJR. The concentration of 24 cytokines were measured in blood and SF by multiplex assay. EQ5Dindex health status was assessed pre-operatively and at 7-months post-operatively. 13% of patients were identified as non-responders based on EQ5Dindex. Compared to responders, non-responders were of higher BMI, had greater waist and hip circumference and had higher levels of SF leptin but lower levels of SF Resistin (p&lt;0.05). Linear regression analysis found a significant relationship between pre-operative body weight and post-operative response (ΔEQ5Dindex; r=0.222, p=0.049). The combination of body weight with SF amphiregulin and SF IL-6 provided an improved predictive model of post-operative response (r=0.470, p=0.035).

Respiratory syncytial virus (RSV) is associated with adverse outcomes among immunocompromised patients. Inhaled ribavirin has been shown to improve mortality rates. The Small-Particle Aerosol Generator delivery system (SPAG-2) is the only FDA-cleared device to deliver inhaled ribavirin. However, it is difficult to set up and maintain. We developed a method for delivery of this medication using the vibrating mesh nebulizer (Aerogen®). We did not observe any adverse events with this method.

In recent years, a range of problems under the broad umbrella of computer vision based analysis of ancient coins have been attracting an increasing amount of attention. Notwithstanding this research effort, the results achieved by the state of the art in published literature remain poor and far from sufficiently well performing for any practical purpose. In the present paper we present a series of contributions which we believe will benefit the interested community. We explain that the approach of visual matching of coins, universally adopted in existing published papers on the topic, is not of practical interest because the number of ancient coin types exceeds by far the number of those types which have been imaged, be it in digital form (e.g., online) or otherwise (traditional film, in print, etc.). Rather, we argue that the focus should be on understanding the semantic content of coins. Hence, we describe a novel approach—to first extract semantic concepts from real-world multimodal input and associate them with their corresponding coin images, and then to train a convolutional neural network to learn the appearance of these concepts. On a real-world data set, we demonstrate highly promising results, correctly identifying a range of visual elements on unseen coins with up to 84% accuracy.

The river Teign in Devon has come under scrutiny for failing to meet Environmental Quality Standards for ecotoxic metals due to past mining operations. A disused mine known as Bridford Barytes mine, has been found to contribute a significant source of Zn, Cd and Pb to the river. Recently, studies have been focused on the remediation of such mine sites using low-cost treatment methods to help reduce metal loads to the river downstream. Red mud is a waste product from the aluminium industry, the utilization of this resource has proven an attractive low-cost treatment method for adsorbing toxic metals. Adsorption kinetics and capacity experiments reveal metal removal efficiencies of up to 70% within the first 2 hours when red mud is applied in pelletized form. Biochar is another effective adsorbent with the potential to remove >90% Zn using agricultural feedstock. Compliance of the Teign has been investigated by analysing dissolved metal concentrations and bioavailable fractions of Zn to assess if levels are of environmental concern. By applying a Real-World Application Model, this study reveals that compressed pellets and agricultural biochar offer an effective, low-cost option to reducing metal concentrations and thus improving the quality of the river Teign.

The current focus on afforestation in climate policy runs the risk of compromising both longterm carbon storage and human adaptation. It also works against efforts to stem the tide of biodiversity loss. We outline why an emphasis on diverse, intact natural ecosystems—as opposed to tree plantations with fast-growing exotic species—will help nations deliver the goals of the Paris Agreement and much more.

Psychological wellbeing can be impacted substantially by changes in body image during youth, which can be a predictive factor for positive or negative attitudes, such as for self-esteem and satisfaction. In this study, adherence to the thinness model and to healthy behaviours were analysed in terms of the emotional patterns and body management of the young female Italian population (N = 2287). Skinny girls fitting better with the thinness model tended to develop higher positive emotional patterns, but their body management was low. Findings suggest the urgent need for preventive programmes to enhance awareness of healthy behaviours against appearance models.

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying non-invasive biomarkers in body fluids such as blood and urine. A source of biomarkers in these biofluids are extracellular vesicles (EVs), nanosized vesicles that contain a wide array of molecular cargo, including small non-coding RNA such as microRNA and transfer RNA-derived fragments (tRF). Here we performed small-RNA next-generation sequencing for urine EVs, serum EVs and serum supernatant from 41 patients with non-muscle invasive BC (27 stage Ta, 14 stage T1) and 15 non-cancer patients (NCP) with benign cystoscopy findings. Serum and urine samples were collected before transurethral resection of bladder tumors (TUR-b) and at routine postsurgery check-ups. Expression levels of tRFs in presurgery samples were compared to those at postsurgery check-ups and to NCPs. To strengthen the reliability of our results, samples from 10 patients with stage T1 disease were resequenced. When comparing tRF expression in urine EVs between BC patients with stage T1 disease and NCPs, 14 differentially expressed tRFs (DEtRFs) were identified. In serum supernatant, six DEtRFs were identified among stage T1 patients when comparing presurgery to postsurgery samples, and four DEtRFs were found when comparing presurgery samples to NCPs. By performing a blast search, we found that sequences of DEtRFs aligned with genomic sequences pertaining to processes relevant to cancer development, such as enhancers, regulatory elements and CpG islands. Our findings display a number of tRFs that may hold potential as biomarkers for the diagnosis and recurrence-free survival of BC.

Recently, microfluidics deformability cytometry has emerged as a powerful tool for high throughput mechanical phenotyping of large populations of cells. These methods characterize cells by their mechanical fingerprints through exerting hydrodynamic forces and monitoring the resulting deformation. These devices have shown great promise for label free cytometry, yet there is a critical need to improve their accuracy and reconcile any discrepancies with other methods, such as atomic force microscopy. In this study, we employ computational fluid dynamics simulations and uncover how the elasticity of frequently used carrier fluids such as methyl-cellulose dissolved in phosphate-buffered saline is significantly influential to the resulting cellular deformation. We conducted CFD simulations that are conventionally used within the deformability cytometry field, which neglect fluid elasticity. Subsequently, we incorporated a more comprehensive model that simulates the viscoelastic nature of the carrier fluid. A comparison of the predicted stresses between these two approaches underscores the significance of the emerging elastic stresses in addition to the well-recognized viscous stresses along the channel. Furthermore, we utilize a two-phase flow model to predict the deformation of a promyelocyte (i.e. HL-60 cell type) within a hydrodynamic constriction channel. The obtained results highlight a substantial impact of the elasticity of carrier fluid on cellular deformation and raise questions about the accuracy of mechanical property estimates derived by neglecting elastic stresses.

In this paper we have defined the effect of bulk viscosity on Quintessence model and scaler field potential as well as on classical field. We have shown the same effect for modified gravity with f(R,T)= R+f(T). In the derivation we have predicted the possibility of time dependent evolution of gravitational constant G and anisotropy.

Obtaining a good socket fit is an iterative process dependent on the skill and experience of the prosthetist creating it, and requiring individualisation based on the size and shape. There is no standard measurement system used to aid prosthetic socket creation, despite the severe impacts on physical health and quality of life if one is ill-fitting. Pressure sensors embedded in a prosthetic socket were used to collect data at the socket-residuum interface. To choose an interpolation method, a 2D grid was used, with previously collected walking test pressure data, to simplify the sensor array with a border for extrapolation. Four multivariable interpolation methods were evaluated to create a colour map of the pressure data. Radial Basis Function interpolation was chosen as it produced a clear image with a graduated interpolation between data points and was used to create a colour map across the surface of a 3D prosthetic socket model. For the model to be accessible to clinical audiences, a desktop application was created using PyQt to view the model. The created application allowed for connection to the sensors via Bluetooth, with the pressure data updating the colour map on the 3D model in real-time. The created application shows the potential for a clinical product, however further development informed by feedback from rehabilitation clinicians and prosthesis users is required

Consumption of prebiotic fibers to modulate the human gut microbiome is a promising strategy to positively impact health. Nevertheless, given the compositional complexity of the microbiome and its inter-individual variances, generalized recommendations on the source or amount of fiber supplements remain vague. This problem is further compounded by availability of tractable in vitro and in vivo models to validate certain fibers. We employed a gnotobiotic mouse model containing an a priori characterized 14-member synthetic human gut microbiome (SM) for their ability to metabolize a suit of fibers in vitro; the SM contains 14 different strains belonging to five distinct phyla. Since soluble purified fibers have been a common subject of studies, we specifically investigated the effects of concentrated raw fibers (CRFs)—containing fibers from pea, oat, psyllium, wheat and apple—on the compositional and functional alterations in the SM. We demonstrate that, compared to a fiber-free diet, CRF supplementation increased the abundance of fiber-degraders namely Eubacterium rectale, Roseburia intestinalis and Bacteroides ovatus and decreased the abundance of the mucin-degrader Akkermansia muciniphila. These results were corroborated by a general increase of bacterial fiber-degrading α-glucosidase enzyme activity. Overall, our results highlight the ability of CRFs to enhance the microbial fiber-degrading capacity.

Background/methods: For mechanistic studies, in vitro human B cell differentiation and generation of plasma cells are invaluable techniques. However, the heterogeneity of both T cell-dependent (TD) and T cell-independent (TI) stimuli and the disparity of culture conditions used in existing protocols makes interpretation of results challenging. The aim of the present study was to achieve the most optimal B cell differentiation conditions using isolated CD19⁺ B cells and PBMC cultures. We addressed multiple seeding densities, different durations of culturing and various combinations of TD stimuli and TI stimuli including B cell receptor (BCR) triggering. B cell expansion, proliferation and differentiation was analyzed after 6 and 9 days by measuring B cell proliferation and expansion, plasmablast and plasma cell formation and immunoglobulin (Ig) secretion. In addition, these conditions were extrapolated using cryopreserved cells and differentiation potential was compared. Results: This study demonstrates improved differentiation efficiency after 9 days of culturing for both B cell and PBMC cultures using CD40L and IL-21 as TD stimuli and 6 days for CpG and IL-2 as TI stimuli. We arrived at optimized protocols requiring 2500 and 25.000 B cells per culture well for TD and TI assays, respectively. The results of the PBMC cultures were highly comparable to the B cell cultures, which allows dismissal of additional B cell isolation steps prior to culturing. In these optimized TD conditions, the addition of anti-BCR showed little effect on phenotypic B cell differentiation, however it interferes with Ig secretion measurements. Addition of IL-4 to the TD stimuli showed significantly lower Ig secretion. The addition of BAFF to optimized TI conditions showed enhanced B cell differentiation and Ig secretion in B cell but not in PBMC cultures. With this approach, efficient B cell differentiation and Ig secretion was accomplished when starting from fresh or cryopreserved samples. Conclusion: Our methodology demonstrates optimized TD and TI stimulation protocols for more indepth analysis of B cell differentiation in primary human B cell and PBMC cultures while requiring low amounts of B cells, making them ideally suited for future clinical and research studies on B cell differentiation of patient samples from different cohorts of B cell-mediated diseases.

Nature-based solutions (NbS) are increasingly recognised for their potential to address both the climate and biodiversity crises. These outcomes are interdependent, and both rely on the capacity of NbS to support and enhance the health of an ecosystem: its biodiversity, the condition of its abiotic and biotic elements, and its capacity to function normally despite environmental change. However, while understanding of ecosystem health outcomes of nature-based interventions for climate change mitigation is growing, the outcomes of those implemented for adaptation remain poorly understood with evidence scattered across multiple disciplines. To address this, we conducted a systematic review of the outcomes of 109 nature-based interventions for climate change adaptation using 33 indicators of ecosystem health across eight broad categories (e.g. diversity, biomass, ecosystem functioning and population dynamics). We showed that 88% of interventions with positive outcomes for climate change adaptation also reported measurable benefits for ecosystem health. We also showed that interventions were associated with a 67% average increase in local species richness. All eight studies that reported benefits in terms of both climate change mitigation and adaptation also supported ecosystem health, leading to a triple win. However, there were also trade-offs, mainly for forest management and creation of novel ecosystems such as monoculture plantations of non-native species. Our review highlights two major limitations of research to date. First, only a limited selection of metrics are used to assess ecosystem health and these rarely include key aspects such as functional diversity and habitat connectivity. Second, taxonomic coverage is poor: 67% of outcomes assessed only plants and 57% did not distinguish between native and non-native species. Future research addressing these issues will allow the design and adaptive management of NbS to support healthy and resilient ecosystems, and thereby enhance their effectiveness for meeting both climate and biodiversity targets.

The COVID-19 pandemic of 2020 changed the way we interact and engage in commerce at a fundamental level. Social distancing and stay-at-home orders leave businesses and cities wondering what economic activity will look like in the future. Given a likely reduction in face-to-face interactions, it is important to better understand how social interactivity influences economic outcomes. Here we measure the effect of social interactions in the workforce on patent production and economic efficiency. We decompose U.S. occupations into individual work activities, determine which of those activities are associated with face-to-face interactions, and reaggregate the labor force of each U.S. metropolitan statistical area (MSA) into a metric of social interactiveness. We then calculate each MSA’s density of social work activities and find that this measure is more highly correlated with an MSA’s per capita patent production than simple population density. This suggests that density of face-to-face interactions is the important driver of a city’s rate of invention. We close by exploring analogies between the development of cities and the development of stars, suggesting ways these analogies may help frame future research on cities.

Sexually transmitted infections in South Africa are increasing at alarming rates. The study setting is no.5, with the highest STIs, pregnancy, and HIV statistics in Limpopo province among 13 to 19-year-old teenagers. This study explored preventative measures against STIs practiced by teenagers in rural areas of Limpopo Province, South Africa. The study was conducted at a selected rural-based clinic using an exploratory, descriptive qualitative research approach. Unstructured, in-depth face-to-face interviews were used to collect data from sixteen conveniently sampled teenagers aged 13 -19 who came to Manavhela Clinic for Youth Friendly Services in Au-gust/September 2022. Open-coding analysis was used to identify themes and sub-themes. Measures to ensure trustworthiness were ensured. Ethical clearance (FSH/21/PH/22/2211) was obtained, and ethics principles were observed throughout the study. Two themes emerged from data analysis: STI preventive measures practiced by teenagers and factors influencing the choice of STI preventive measures practices by teenagers. Only a few participants aged 13 and 14 years practiced abstinence and condom use. Most participants were sexually active and used mythical mixtures made from boiling aloe or morula tree, which they drank before and after sex, applying plain yogurt on the vagina once a week, OR vaginal steaming. Participants cited patriarchy, lack of sex education in rural schools, long distances to clinics, and desire to taste sex as reasons for adopting the practiced preventive measures. Risky sexual behaviour among 13 to 19-year-old teenagers is still rife in rural areas. Rural clinics in Limpopo Province should intensify STI school health education and Youth Friendly Services programs to raise awareness and improve accessibility to condoms

Lameness on dairy goat farms is a welfare concern and could negatively affect milk production. This study's objective was to evaluate the effects of clinical lameness on the daily milk production of dairy goats. Between July 2019 and June 2020, 11,847 test-day records were collected from 3,145 goats on three farms in New Zealand. Locomotion scoring of goats used a 5-point scoring system (0 to 4). The dataset was split into two groups by lactation type, where goats were classified as being in seasonal lactation (≤305 days in milk) or extended lactation (&gt;305 days in milk). A linear mixed model was used to analyze datasets using milk characteristics as the dependent variables. Clinically lame goats (score 3 or 4) in seasonal and extended lactation produced 2.63% and 4.66% less milk than goats not lame, respectively. Severely lame goats (score 4) in seasonal and extended lactation produced 7.10% and 8.56% less milk than goats not lame, respectively. The estimated average daily milk income lost was between NZD 26 and 104 per goat. This study established the negative impact of lameness on milk production and annual income in dairy goats on three farms.

Wheat is widely grown in the Mediterranean region, where plants frequently face water shortages. Recently, more attention to rationalizing irrigation water has been increased due to the adoption of sustainable agricultural systems. Therefore, two field trials were conducted at the Agriculture Research Station of Nubaria, Egypt, in two consecutive seasons (2017/2018 and 2018/2019) to examine three irrigation regimes' effects, i.e., 60, 80, and 100% of crop evapotranspiration (ETc) combined with foliar ascorbic acid (AsA) or vitamin B2 (VB2) on yield and water productivity of wheat in two separate experiments. A split-plot design was used with three replicates. Irrigation treatments occupied the main plots, while the subplot in the first experiment was placed by ascorbic acid (AsA) and vitamin B2 in the second experiment. Results indicated that 100% ETc produced higher wheat yield and its attributes and insignificantly surpassed 80% ETc. Compared to the unsprayed plots, the foliar application of 6 mM ascorbic acid or 2.0 mM vitamin B2 significantly increased grain yield, components, and water use efficiency. The interaction between irrigation regimes (100% ETc or 80% ETc) and foliar application of 6.0 mM ascorbic acid or 2.0 mM vitamin B2 resulted in the highest values with no significant difference. Foliar application of ascorbic acid or vitamin B2 saved 20% of irrigation water while yielding a reduction that did not exceed 10%. The biplot graph of treatments x traits (TT) was a useful statistical tool for examining the impact of treatments on yield and its characteristics and identifying the links between these factors. Results suggest that riboflavin or ascorbic acid may have a potential role as an effective antioxidant for enhancing the tolerance for drought stress in wheat.

Innovative tissue engineering biomimetic hydrogels based on hydrophilic polymers have been investigated for their physical and mechanical properties. 5% to 25% by volume loading PHEMA-nanosilica glassy hybrid samples were equilibrated at 37°C in aqueous physiological isotonic and hypotonic saline solutions (0.15 and 0.05 M NaCl) simulating two limiting possible compositions of physiological extracellular fluids. The glassy and hydrated hybrid materials were characterized both for dynamo-mechanical properties and equilibrium absorptions in the two physiological-like aqueous solutions. Mechanical and the morphological modifications occurring in the samples have been described. The 5% volume nanosilica loading hybrid nanocomposite composition showed mechanical characteristics in the dry and hydrated states that were comparable to those of cortical bone and articular cartilage, respectively, and then chosen for further sorption kinetics characterization. Sorption and swelling kinetics were monitored up to equilibrium. Changes in water activities and osmotic pressures in the water-hybrid systems equilibrated at the two limiting solute molarities of the physiological solutions have been related to the observed anomalous sorption modes using the Flory-Huggins interaction parameter approach. The bulk modulus of the dry and glassy PHEMA-5% nanosilica hybrid at 37°C has been observed to be comparable with the values of the osmotic pressures generated from the sorption of isotonic and hypotonic solutions. The anomalous sorption modes and swelling rates are coherent with the difference between osmotic swelling pressures and hybrid glassy nano-composite bulk modulus: the lower the differences the higher the swelling rate and equilibrium solution uptakes. Bone tissue engineering benefits of use of tuneable biomimetic scaffold biomaterials that can be “designed” to act as biocompatible and biomechanically active hybrid interfaces are discussed.

Coronavirus (COVID-19) pandemic caused sicknesses ranging from mild to deadly, which disrupted lives and healthcare systems across the globe. Despite the availability of vaccines that are effective in significantly reducing the risks of death and severe dis-ease, misperceptions of COVID-19 vaccine safety, efficacy, risks, and mistrust in insti-tutions responsible for vaccination campaigns have been reported as factors contrib-uting to vaccine hesitancy, making vaccination rate not satisfactory, which resulted in some countries implementing mandatory covid-19 vaccination to increase vaccine up-take. This scoping review aimed at mapping global countries that have adopted the mandatory covid-19 vaccination and the reaction of citizens. PRISMA Extension for Scoping Reviews was used. Google Scholar was used to identify papers published in English from December 2019 to February 2022, irrespective of their methodology. One hundred forty studies were identified. After screening for duplication, access, and rel-evance, 24 were eligible for review. About eleven countries implemented mandatory vaccination, mostly among health workers. Citizens’ reactions towards the policy var-ied, with some in support of the policy but with a preference for the healthcare workers, and some in support but with the condition that it will only apply to travel, schools, and shopping areas, while others rejected the policy. Studies that may be relevant but were excluded due to eligibility criteria may be a limiting factor to this study. Several ethical considerations should be explicitly addressed when evaluating whether man-datory COVID-19 vaccination is an ethically justifiable policy option as recommended by the WHO policy brief.

The option of decarbonizing urban freight transport using Battery Electric Vehicle (BEV) seems promising.However, there is currently a strong debate whether Fuel Cell Electric Vehicle (FCEV) might be the bettersolution. The question arises as to how a fleet of FCEV influences the operating cost, the Greenhouse Gas(GHG) emissions and primary energy demand in comparison to BEVs and to Internal Combustion EngineVehicle (ICEV). To investigate this, we simulate the urban food retailing as a representative share of urbanfreight transport using a multi-agent transport simulation software. Synthetic routes as well as fleet size andcomposition are determined by solving a Vehicle Routing Problem (VRP). We compute the operating costsusing a total cost of ownership (Total Cost of Ownership (TCO)) analysis and the use phase emissions as wellas primary energy demand using the Well To Wheel (WTW) approach. While a change to BEV results in 17 -23% higher costs compared to ICEV, using FCEVs leads to 22 - 57% higher costs. Assuming today’s electricitymix, we show a GHG emission reduction of 25% compared to the ICEV base case when using BEV. Currenthydrogen production leads to a GHG reduction of 33% when using FCEV which however cannot be scaled tolarger fleets. Using current electricity in electrolysis will increase GHG emission by 60% compared to the basecase. Assuming 100% renewable electricity for charging and hydrogen production, the reduction from FCEVsrises to 73% and from BEV to 92%. The primary energy requirement for BEV is in all cases lower and forhigher compared to the base case. We conclude that while FCEV have a slightly higher GHG savings potentialwith current hydrogen, BEV are the favored technology for urban freight transport from an economic andecological point of view, considering the increasing shares of renewable energies in the grid mix.

There is now evidence that, based on cytokine profiles, bipolar disorder (BD) is accompanied by simultaneous activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), and that both components may be associated with the staging of illness. Nevertheless, no BD studies have evaluated the IRS/CIRS ratio using CD (cluster of differentiation) molecules expressed by peripheral blood activated T effector (Teff) and T regulatory (Treg) subpopulations. This study examined T cell subsets both before and after ex vivo anti CD3/CD28 stimulation using flow cytometric immunophenotyping in 25 euthymic BD patients and 21 healthy controls as well as human cytomegalovirus (HCMV)-specific IgG antibodies. BD is associated with a significantly lowered frequency of baseline (unstimulated) CD3+CD8+CD71+ and CD4+CD25+FOXP3 and increased CD4+CD25+FOXP3+CD152+ frequencies and with lowered stimulated frequencies of CD3+CD8+CD71+, CD4+CD25+FOXP3+CD152+ and CD4+CD25+FOXP3+GARP cells and, consequently, by an increased stimulated Teff/Treg ratio. Moreover, the number of manic, but not hypomanic or depressive episodes, is significantly and negatively associated with the stimulated proportions of CD3+CD4+CD154+, and CD69+ and CD71+ expression on CD4+ and CD8+ cells, while duration of illness (≥ 10 years) is accompanied by a depleted frequency of stimulated CD152+ Treg, and CD154+ and CD71+ CD4+ T cells. BD and anti-human cytomegalovirus (HCMV) IgG levels significantly interact to decrease the expression of CD4+CD25+FOXP+GARP T phenotypes. In conclusion, BD is characterized by deficits in immune-regulatory functions while the staging of illness is characterized by additional impairments is Teff and Treg activation. HCMV seropositivity may contribute to an immune-risk phenotype associated with BD.

Two extreme wind-driven wildfire events impacted northern and southern California in late 2017 leading to 46 fatalities and thousands of structures lost. This study describes the meteorological and climatological factors that drove and enabled these wildfire events and quantifies the rarity of such conditions over the observational record. Both extreme wildfire events featured fire-weather metrics that were unprecedented in the observational record in addition to a sequence of climatic conditions that preconditioned fuels. The North Bay fires that affected portions of northern California in early October occurred coincident with strong downslope winds. The vast majority of the fires’ devastating effects and acres burned occurred overnight and within the first twelve hours of ignition. By contrast, the southern California fires of December were characterized by the longest Santa Ana wind event on record and included the largest wildfire in California’s history. Both fire events occurred following an exceptionally wet winter that was preceded by the drought of record in California. Fuels were further preconditioned as the warmest summer and autumn on record occurred in northern and southern California, respectively. Accelerated curing of fuels coupled with the delayed onset of autumn precipitation allowed for critically low dead fuel moisture leading up to the foehn wind events. Fire weather conditions were well forecasted several days prior to the fire. However, the rarity of fire-weather conditions that occurred in the wildland urban interface, along with other societal factors were key contributors to wildfire impacts to communities.

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of &lt;1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

Since Darwin’s “Power of movement in plants” the precise mechanism of oscillatory plant growth remains elusive. Hence the search continues for the hypothetical growth oscillator that regulates a huge range of growth phenomena ranging from circumnutation to pollen tube tip growth and stomatal movements. Oscillators are essentially simple devices with few components. A universal growth oscillator with only four major components became apparent recently with the discovery of a missing component, notably arabinogalactan glycoproteins (AGPs) that store dynamic Ca2+ at the cell surface. Demonstrably, auxin-activated proton pumps, AGPs, Ca2+ channels and auxin efflux “PIN” proteins, embedded in the plasma membrane, combine to generate cytosolic Ca2+ oscillations that ultimately regulate oscillatory growth: Hechtian adhesion of the plasma membrane to the cell wall and auxin-activated proton pumps trigger the release of dynamic Ca2+ stored in periplasmic AGP monolayers. These four major components represent a molecular PINball machine a strong visual metaphor that also recognizes auxin efflux “PIN” proteins as an essential component. Proton “pinballs” dissociate Ca2+ ions bound by paired glucuronic acid residues of AGP glycomodules, hence reassesses the role of proton pumps. It shifts the prevalent paradigm away from the recalcitrant “acid growth” theory that proposes direct action on cell wall properties, with an alternative explanation that connects proton pumps to Ca2+ signaling with dynamic Ca2+ storage by AGPs, auxin transport by auxin-efflux PIN proteins and Ca2+ channels. The extensive Ca2+ signalling literature of plants ignores arabinogalactan proteins (AGPs). Such scepticism leads us to reconsider the validity of the universal growth oscillator proposed here with some exceptions that involve marine plants and perhaps the most complex stress-test, stomatal regulation.

The order Mucorales, the largest in number of species within the Mucoromycotina, comprises typically fast-growing saprotrophic fungi. During a study of the fungal diversity of undiscovered taxa in Korea, two novel mucoralean strains, CNUFC-GWD3-9 and CNUFC-EGF1-4, were isolated from specific habitats including freshwater and fecal samples, respectively, in Korea. On the basis of their morphological characteristics and sequence analyses of internal transcribed spacer (ITS) and large subunit (LSU) of 28S ribosomal DNA regions, the CNUFC-GWD3-9 and CNUFC-EGF1-4 isolates were confirmed to be Gilbertella persicaria and Pilobolus crystallinus, respectively. It is ecologically, pathologically and mycologically significant to find such rare zygomycetous fungi in such specific habitats.

Extracellular vesicles (EV) are a very heterogeneous group of cell-derived vesicles released by almost all kind of living cells. EV are involved in intercellular communication, both locally and systemically, since they induce signals and transfer their contents (proteins, lipids, RNAs) to other cells, which subsequently trigger a wide variety of biological responses in the target cells. How-ever, cell surface receptor-induced EV release is limited to cells from the immune system, includ-ing T lymphocytes. T cell receptor activation of T lymphocytes induces secretion of EV containing T cell receptor for antigen and several bioactive molecules, including proapoptotic proteins. These EV are thus specific for antigen-bearing cells, which make them ideal candidates for a cell-free, EV-dependent cancer therapy. In this review we discuss the generation of EV by T lymphocytes and some potential therapeutic approaches of these EV.

Over the last decades, cellular immunotherapy has revealed its curative potential. However, the inherent physiological characteristics of immune cells can limit the potency of this approach. Best defined in T cells, dysfunction associated with terminal differentiation, exhaustion, senescence, and activation-induced cell death undermine adoptive cell therapies. In this review, we concentrate on how the multiple mechanisms that articulate the various forms of immune dysfunction impact cellular therapies primarily involving conventional T cells, but also other lymphoid subtypes, in addition to the various strategies put in place to circumvent these effects. The repercussions of immune cell dysfunction across the full life cycle of cell therapy, from the source material, during manufacturing, and after adoptive transfer are discussed. Applicable to cellular products prepared from native and unmodified immune cells, as well as genetically engineered therapeutics, the understanding and potential modulation of dysfunctional features is key to the development of improved cellular immunotherapies.

We investigate alternative candidates to dark energy that can explain the current state of the universe in the framework of the generalized teleparallel theory of gravity f(T ) where T denotes the torsion scalar. To achieve this, we carried out a series of reconstruction taking into account to the ordinary and entropy-corrected versions of the holographic and new agegraphic dark energy models. These models used as alternative to dark energy in the literature in order describe the current state of our universe. It is remarked that the models reconstructed indicates behaviors like phantom or quintessence models. Furthermore, we also generated the EoS parameters associated to entropy-corrected models and we observed a transition phase between quintessence state and phantom state as showed by recent observational data. We also investigated on the stability theses models and we created the {r − s}. The behavior of certains physical parameters as speed of sound and the Statefinder parameters are compatible with current observational data.

The study combines two critical aspects of climate research in Nigeria. The first segment focuses on improving predictive performance of global circulation models (GCMs) employing ensemble techniques. ANN ensemble displayed significant improvement in the accuracy of climate projections, particularly in high-altitude geographic areas where traditional models exhibit limitations. Performance evaluation metrics such as Mean Absolute Error (MAE), Root Mean Squared Error (RMSE), and Nash–Sutcliffe Efficiency (NSE) demonstrate the effectiveness of the ANN multimodal ensemble. Building on the improved climate modelling, the second segment delves into a spatial and temporal analysis of rainfall and mean temperature patterns under climate change in Nigeria. By considering two Representative Concentration Pathways (RCPs), namely RCP4.5 and RCP8.5, the study utilizes dynamically downscaled GCMs obtained from the Coupled Model Intercomparison Project phase 5 (CMIP5). The Mann-Kendall test reveals significant spatiotemporal variations in climate trends across the country. The warming trend is particularly pronounced in the northern regions, with RCP8.5 showing more severe impacts compared to RCP4.5. This integrated approach not only highlights the importance of multimodal ensembles in climate modelling but also provides valuable insights into the spatial and temporal patterns of climate change to inform effective adaptation and mitigation strategies for Nigeria.