Relationships between drought and fire danger indices are examined to 1) incorporate fire risk information into the National Integrated Drought Information System California-Nevada Drought Early Warning System and 2) provide a baseline analysis for application of drought indices into a fire risk management framework. We analyzed four drought indices that incorporate precipitation and evaporative demand (E₀) and three fire indices that reflect fuel moisture and potential fire intensity. Seasonally averaged fire danger indices were most strongly correlated to multi-scalar drought indices that use E₀ (the Evaporative Demand Drought Index [EDDI] and Standardized Precipitation Evapotranspiration Index [SPEI]) at approximately annual time scales that reflect buildup of antecedent drought conditions. Results indicate that EDDI and SPEI can inform seasonal fire potential outlooks at the beginning of summer. An E₀ decomposition case study of conditions prior to the Tubbs Fire in Northern California indicate high E₀ (97th percentile) driven predominantly by low humidity signaled increased fire potential several days before the start of the fire. Initial use of EDDI by fire management groups during summer and fall 2018 highlights several value-added applications, including seasonal fire potential outlooks, funding fire severity level requests, and assessing set-up conditions prior to large, explosive fire cases.

Dhaka one of the fastest-growing megacities in the world is increasingly vulnerable to urban flooding due to rapid urbanization, inadequate drainage infrastructure, and climate change-induced extreme weather events. This study presents the development of an urban flood forecasting system for Dhaka City using the MIKE+ hydrodynamic modeling software. The system integrates detailed hydrological and hydraulic models to simulate urban flooding scenarios, accounting for complex drainage networks and catchment characteristics. Real-time data from river gauges, rainfall stations, and drainage systems are incorporated to enhance the accuracy and reliability of the forecasts. The model's predictive capability is validated against historical flood events, demonstrating its effectiveness in forecasting flood extents, depths, and durations in critical areas of the city. This system serves as a valuable tool for city planners, emergency response teams, and decision-makers, enabling proactive flood management and risk mitigation. The study underscores the importance of such advanced modeling tools in safeguarding urban populations and infrastructures from the increasing threat of urban floods in Dhaka and similar rapidly urbanizing cities.

We describe an efficient and cost effective data access mechanism for Sentinel-1 TOPS 1 mode bursts. Our data access mechanism enables burst-based data access and processing, thereby 2 eliminating ESA’s Sentinel-1 SLC data packaging conventions as a bottleneck to large scale processing. 3 Pipeline throughput is now determined by available compute resources and efficiency of the analysis 4 algorithms. For targeted infrastructure monitoring studies, we are able to generate coregistered, 5 geocoded stacks of SLCs for any AOI in the world in a few minutes. In addition, we describe our 6 global scale radar backscatter and interferometric products and associated pipeline design decisions 7 that ensure geolocation consistency across the suite of derived products from Sentinel-1 data. Finally, 8 we discuss the benefits and limitations of working with geocoded SAR SLC data.

We describe an efficient approach to radiometrically flatten geocoded stacks of calibrated synthetic aperture radar (SAR) data for terrain-related effects. We use simulation to demonstrate that, for the Sentinel-1 mission, one static radiometric terrain flattening factor derived from actual SAR imaging metadata per imaging geometry is sufficient for flattening interferometrically compliant stacks of SAR data. We quantify the loss of precision due to application of static flattening factors, and show that these are well below stated requirements of change detection algorithms. Finally, we discuss the implications of applying radiometric terrain flattening to geocoded SAR data instead of the traditional approach of flattening data provided in the original SAR image geometry. The proposed approach allows for efficient and consistent generation of five different Committee of Earth Observation Satellites (CEOS) Analysis Ready Dataset (ARD) families - Geocoded Single Look Complex (GSLC), Interferometric Radar (InSAR), Normalized Radar Backscatter (NRB), Polarimetric Radar (POL) and Ocean Radar Backscatter (ORB) from SAR missions in a common framework.

Inexpensive piezoelectric diaphragms can be used as sensors to facilitate both nozzle height setting and build platform leveling in FFF (Fused Filament Fabrication) 3D printers. Tests simulating nozzle contact are conducted to establish the available output and an output of greater than 8 Volts found at 20 ºC, a value which is readily detectable by simple electronic circuits. Tests are also conducted at a temperature of 80 ºC and, despite a reduction of greater than 80% in output voltage, this is still detectable. The reliability of piezoelectric diaphragms is investigated by mechanically stressing samples over 100,000 cycles at both 20 ºC and 80 ºC and little loss of output over the test duration is found. The development of a nozzle contact sensor using a single piezoelectric diaphragm is described.

We report a broadband radio frequency (RF) channelizer with up to 92 channels using a coherent microcomb source. A soliton crystal microcomb, generated by a 49 GHz micro-ring resonator (MRR), is used as a multi-wavelength source. Due to its ultra-low comb spacing, up to 92 wavelengths are available in the C band, yielding a broad operation bandwidth. Another high-Q MRR is employed as a passive optical periodic filter to slice the RF spectrum with a high resolution of 121.4 MHz. We experimentally achieve an instantaneous RF operation bandwidth of 8.08 GHz and verify RF channelization up to 17.55 GHz via thermal tuning. Our approach is a significant step towards the monolithically integrated photonic RF receivers with reduced complexity, size, and unprecedented performance, which is important for wide RF applications ranging from broadband analog signal processing to digital-compatible signal detection.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

This review stresses the need for geoscience and mining engineering students to be educated during their undergraduate studies in social and sustainability issues so they would have the skills and knowledge in their work after graduation, as professionals, to engage Indigenous People for mutual benefit. Large - scale mining development often takes place on Indigenous land and these educated mining professionals in their contact with these vulnerable communities must act in a responsible way. This includes the important mining policy issues and standards of corporate social responsibility (CSR), social license to operate and free, prior and informed consent from the Indigenous People before mining. For example, these policy standards issues would have been important to consider in Indonesia where the Indigenous Muluy Dayak community in East Kalimantan tried to resist large-scale mining operations by depicting their small-scale mining as part of their Indigenous customs and identity and in Australia where there was the recent destruction of an Aboriginal sacred site during large scale mining operations.

As an International Union for Conservation of Nature (IUCN) voluntary reviewer of the natural World Heritage sites nominations focusing on criteria (vii) superlative natural phenomena and (viii) geological history I had the opportunity of evaluating 13 nominations from 12 countries from 2009 - 2022 from the Central Highlands of Sri Lanka to the Vatnajokull National Park Iceland. An early appreciation of the natural history and landscapes were developed as a geologist studying, working and visiting various areas in the USA and Canada. Further experience, as an academic in Sri Lanka and Australia, where I also had the opportunity of various assignments and meetings that afforded field trips and study tours to many World Heritage sites in Asia, Africa, South America and Europe. In this paper, I highlight the following sites that were subject to IUCN World Heritage evaluations and their potential for geo-education: Central Highlands Sri Lanka, China Danxia, Ningaloo Australia, Trang An Vietnam, Lut Desert Iran, Barberton South Africa, Trondek Klondike Canada, Vatnajokull Iceland, Classic Karst Slovenia, Sof Omar Ethiopia, Ha Long Bay – Cat Ba Archipelago, Vietnam and Evaporitic Karst Caves of Northern Apennines, Italy. From these experiences it is apparent that this relevant topic, the conservation of nature, should be an important part of the geoscience’s study curriculum along with other social and environmental subjects.

Micro-combs [1-4] - optical frequency combs generated by integrated micro-cavity resonators – offer the full potential of their bulk counterparts [5,6], but in an integrated footprint. The discovery of temporal soliton states (DKS – dissipative Kerr solitons) [4,7-11] as a means of mode-locking micro-combs has enabled breakthroughs in many fields including spectroscopy [12,13], microwave photonics [14], frequency synthesis [15], optical ranging [16,17], quantum sources [18,19], metrology [20,21] and more. One of their most promising applications has been optical fibre communications where they have enabled massively parallel ultrahigh capacity multiplexed data transmission [22,23]. Here, by using a new and powerful class of micro-comb called “soliton crystals” [11], we achieve unprecedented data transmission over standard optical fibre using a single integrated chip source. We demonstrate a line rate of 44.2 Terabits per second (Tb/s) using the telecommunications C-band at 1550nm with a spectral efficiency – a critically important performance metric - of 10.4 bits/s/Hz. Soliton crystals exhibit robust and stable generation and operation as well as a high intrinsic efficiency that, together with a low soliton micro-comb spacing of 48.9 GHz enable the use of a very high coherent data modulation format of 64 QAM (quadrature amplitude modulated). We demonstrate error free transmission over 75 km of standard optical fibre in the laboratory as well as in a field trial over an installed metropolitan optical fibre network. These experiments were greatly aided by the ability of the soliton crystals to operate without stabilization or feedback control. This work demonstrates the capability of optical soliton crystal micro-combs to perform in demanding and practical optical communications networks.

We demonstrate a photonic RF integrator based on an integrated soliton crystal micro-comb source. By multicasting and progressively delaying the input RF signal using a transversal structure, the input RF signal is integrated discretely. Up to 81 wavelengths are provided by the microcomb source, which enable a large integration time window of ~6.8 ns, together with a time resolution as fast as ~84 ps. We perform signal integration of a diverse range of input RF signals including Gaussian pulses with varying time widths, dual pulses with varying time intervals and a square waveform. The experimental results show good agreement with theory. These results verify our microcomb-based integrator as a competitive approach for RF signal integration with high performance and potentially lower cost and footprint.

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.

The present article addresses the long-standing problem of the polymer brush bilayers under stationary shear flow at non-linear response regime where the system gets a non-Newtonian fluid. The main idea behind this research would be the fact that the immense lubricity of the polymer brush bilayers originates from a global restructuring that takes place at large shear rates. It is shown here that physical quantities like, stress tensor, viscosity tensor, the friction coefficient and the chain extensions could become dependent on the shear rate at non-Newtonian regime. Apparently, the sub-linear scaling of the physical quantities at large shear rates is solely due to the fact that the chains stretch in the shear direction.

A diagnostic method is presented for analysing the large-scale behaviour of the Met Office Unified Model, which is a comprehensive atmospheric model used for weather and climate prediction. Outside the boundary layer, on scales larger than the radius of deformation, semigeostrophic theory will give an accurate approximation to the model evolution. In particular, the ageostrophic circulation required to maintain geostrophic and hydrostatic balance against prescribed forcing and a rate of change of the geostrophic pressure can be calculated. In the tropics the balance condition degenerates to the weak temperature gradient approximation. Within the boundary layer the semigeostriptic approximation has to be used because friction and rotation are equally important. Assuming the calculated pressure tendency and ageotriptic circulation match the observed model behaviour, the influence of the large-scale state and the nature of the forcing on the model response can be deduced in a straightforward way. This process is illustrated by comparing predictions of the ageotriptic circulation from the theory and the model. It is then used to show that the effects of latent heat release can be included by modifying the static stability, and to show the effect of an idealised tropical heat source on the subtropical jet. Finally the response of the ageotriptic flow to boundary layer heating in the tropics is demonstrated. These illustrations show that the model behaviour on large scales conforms with theoretical expectations, so that the results of the diagnostic can be used to aid the development of further improvements to the model.

Multimedia resources, such as instructional videos, are currently enjoying a certain popularity in training programmes for medical and dental students. The major challenge is to create such resources that have quality content and are acceptable to students. We investigated the opinions of a sample of 551 students from 4 medical universities in Romania in order to identify the characteristics of the instructional videos that students prefer and we comparatively analysed these characteristics according to gender, age group, but also according to their general preferences for using Internet services. We used univariate (hypothesis testing) and multivariate (Two-Step Clustering) data analysis techniques and revealed three clusters of students, primarily determined by perceptions of the visual appearance of instructional videos. The structure of the clusters by gender and age group is relatively similar, but we recorded differences between them associated with students' expressed preferences for certain Internet services compared to others. Students who prefer instructional videos to contain images used only for aesthetic purposes, to fill in breaks, use Internet services mainly for communication, while students who prefer in videos the use of already drawn explanatory diagrams are slightly younger than the others and use Internet services mainly for information and communication.

The County of Avon in England was abolished in 1996 and replaced by four unitary planning authorities. Recently the authorities have been working closely to develop a West of England Joint Spatial Plan to facilitate better integration of policies on transport, housing, the environment etc. The Joint Spatial Plan team commissioned a multidisciplinary study to investigate whether the West of England has special characteristics of 'place' that engender shared interest and regional affinity, i.e. ‘sense of place’, to which emerging planning policies might positively respond. In this regard the present article is particularly focused on identifying whether the West of England has unique and unifying landscape characteristics, relating to topography, rural scenery, and flora and fauna, which combine with human experiences to distinguish the Region from adjoining areas. It is concluded that the West of England does indeed have real geographical integrity, being bound on all sides by attractive and prominent landscape features - the Mendip Hills, Cotswold Hills and Severn Estuary – that contribute to a sense of identity and belonging among its inhabitants. The alternating limestone ridges and broad clay vales that prevail across the Region’s heart, combined with low lying flatlands on the Region’s western fringe, provide further contrast with neighbouring regions, reinforcing the emotional bond to the landscape. Furthermore, it is suggested that the inhabitants of the West England show a particularly special environmental consciousness that sets them apart from neighbouring populations, complementing the influence of the physical environment in making the Region a special place to live.

Optical artificial neural networks (ONNs) — analog computing hardware tailored for machine learning [1,2] — have significant potential for ultra-high computing speed and energy efficiency [3]. We propose a new approach to architectures for ONNs based on integrated Kerr micro-comb sources [4] that is programmable, highly scalable and capable of reaching ultra-high speeds. We experimentally demonstrate the building block of the ONN — a single neuron perceptron — by mapping synapses onto 49 wavelengths of a micro-comb to achieve a high single-unit throughput of 11.9 Giga-FLOPS at 8 bits per FLOP, corresponding to 95.2 Gbps. We test the perceptron on simple standard benchmark datasets — handwritten-digit recognition and cancer-cell detection — achieving over 90% and 85% accuracy, respectively. This performance is a direct result of the record small wavelength spacing (49GHz) for a coherent integrated microcomb source, which results in an unprecedented number of wavelengths for neuromorphic optics. Finally, we propose an approach to scaling the perceptron to a deep learning network using the same single micro-comb device and standard off-the-shelf telecommunications technology, for high-throughput operation involving full matrix multiplication for applications such as real-time massive data processing for unmanned vehicle and aircraft tracking.

1) Background- Coronary artery bypass grafting (CABG) is a common surgical intervention for patients with severe coronary artery disease. The Model for End-Stage Liver Disease (MELD) score has been widely used to predict mortality risk in patients with end-stage liver disease, but its utility in predicting postoperative outcomes in cardiac surgery patients is less well-established. 2) Methods-This retrospective study aims to investigate the association between preoperative MELD score and post-operative complications, length of hospital stay, and mortality in patients under-going coronary artery bypass grafting. This is a single-center, retrospective cohort study conducted at a tertiary care academic medical center. The study includes all adult patients who underwent elective coronary artery bypass grafting between January 2011 and December 2020. Preoperative MELD scores were calculated for each patient, and postoperative outcomes including major ad-verse cardiac events, length of hospital stay, and 30-day mortality was assessed. To ensure a homogeneous study cohort, we excluded patients who underwent emergent cardiac procedures or had incomplete data necessary for the calculation of MELD scores and assessment of postoperative outcomes. Data was extracted from the electronic medical records, including patient de-mographics, comorbidities, preoperative laboratory values, operative details, and postoperative outcomes. The study protocol was approved by the Institutional Review Board, and the require-ment for informed consent was waived due to the retrospective nature of the study.3) Results- This study reveals a statistical association between the MELD score calculated at admission and the length of hospital stay, duration in the ICU, patient age, and the duration of aortic clamping and extracorporeal circulation. Specifically, there is an exponential increase in the MELD score corre-lating with the rise in these factors, both collectively and individually, highlighting a significant relationship between the duration of extracorporeal circulation and aortic clamping time. 4) Conclusion-Patients with a high MELD score had an increased risk of postoperative complications and mortality compared to those with a low MELD score. Careful preoperative patient selection and optimization of the patient's clinical condition may improve outcomes in patients with advanced liver disease undergoing cardiac surgery.

Plant growth-promoting rhizobacteria (PGPR) are members of the plant rhizomicrobiome that enhance plant growth and stress resistance by increasing nutrient availability to the plant, producing phytohormones or other secondary metabolites, stimulating plant defense responses against abiotic stresses and pathogens, or fixing nitrogen. The use of PGPR to increase crop yield with minimal environmental impact is a sustainable and readily applicable replacement for a portion of chemical fertilizer and pesticides required for the growth of high-yielding varieties. Increased plant health and productivity have long been gained by applying PGPR as commercial inoculants to crops, although with uneven results. The establishment of plant-PGPR relationships requires the exchange of chemical signals and nutrients between the partners, and polyamines (PAs) are an important class of compounds that act as physiological effectors and signal molecules in plant-microbe interactions. In this review we focus on the role of PAs in interactions between PGPR and plants. We describe the basic ecology of PGPR and production and function of PAs in them and in the plants with which they interact. We examine the metabolism and the roles of PAs in PGPR and plants individually and during their interaction with one another. Lastly, we describe some directions for future research.

(1) Background: The RDW-CV has predictive value in many pregnancy-related conditions. Re-search question: Can the RDW-CV be utilized predictively in pregnant patients with thrombo-philia? Aim of the study: To carry out a detailed analysis of the RDW-CV in pregnant patients with treated thrombophilia as compared with pregnant patients without thrombophilia who de-livered via cesarean section at term. (2) Methods: We studied 160 pregnant patients, including 80 pregnant patients with treated thrombophilia in the study group, and another 80 patients of a similar age and parity. The patients were referred to our hospital for delivery at term by means of a cesarean section between 1/10/2017 and 1/12/2021. Every patient received a sonogram during the first 1–2 days after the cesarean section, and their uterine evaluation was interpreted using the PUUS (Postpartum Uterine Ultrasonographic Scale). (3) Results: Our PUUS≥1 pregnant and postpartum patients with treated thrombophilia were the only group with an RDW-CV value over 14. No deep vein thrombosis was observed during hospitalization, showing that the antico-agulant treatment was necessary and effective. An RDW-CV of 14.5 was the highest value in the Rh-negative group of pregnant patients with treated thrombophilia. An RDW-CV of 14.48 was the highest level in the Rh-negative postpartum patients with treated thrombophilia. (4) Conclu-sion: An RDW-CV of ≥14 can predict uterine hematometra (PUUS≥1). The RDW-CV values were higher in Rh-negative patients.

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.

Abstract: In Australia adoption of reduced tillage and stubble retention cropping systems to conserve soil moisture by growers has seen an increase in the prevalence of the disease Fusarium crown rot (FCR) caused by the stubble-borne fungal pathogen Fusarium pseudograminearum. Durum wheat is particularly susceptible to FCR expressing significant yield and quality losses in the presence of infection. Increasing rates of nitrogen (N) application at sowing exacerbates FCR. However, to achieve the desired grain protein and quality suited to pasta manufacture, N application is necessary and this creates a dilemma for growers. The purpose of this study was to investigate the effects of FCR infection in the presence of different N fertiliser application rates in durum wheat varieties on yield and technological quality. Two durum varieties were evaluated at the same location over two seasons (2020 and 2021). These seasons were characterised by being wetter than normal and showed different responses to FCR and N application. In general, the 2021 season showed better responses to applied N with no impact of FCR. The FCR inoculation while it resulted in significant infection, it had no impacts on yield or grain quality in 2021 while in 2020 yield was reduced and only gluten index was reduced. Jandaroi was found to hold its kernel vitreosity at all protein levels obtaining the premium grade while DBA Lillaroi did not and would suffer downgrade if N application was insufficient. However, higher N application rates needed to achieve 12% + protein saw a reduction in dough strength with Jandaroi holding its dough strength much better than DBA Lillaroi. This was related to the lower glutenin/gliadin (Gli/Glu) ratio in response to applied N at sowing in Jandaroi which helped retain kernels with high vitreousness. This suggests genetics plays an important role in a genotype response to N fertilisation and should be considered when selecting a variety where higher premium grades are desirable.

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.

We study L_2-approximation problems in the weighted Hilbert spaces in the worst case setting. Three interesting weighted Hilbert spaces appear in this paper, whose weights are equipped with two positive parameters $\ga_j$ and $\az_j$ for $j=1,\,2,\dots,\,d$. We consider the worst case error of algorithms that use finitely many arbitrary continuous linear functionals. We discuss the exponential convergence-(t,s)-weak tractability (EC-(t,s)-WT) of these L_2-approximation problems under the absolute or normalized error criterion. In particular, we obtain the sufficient and necessary conditions for EC-(1,1)-WT and EC-(t,1)-WT with t

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.

(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.

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).

There is a growing notion that biomass are the best resource to replace the declining fossil fuels, yet both share the long lived human threat: toxic combustion emissions. Among the toxic combustion products is carbon monoxide (CO) that not only causes acute but also chronic ailments. This brief review discusses the solid fuel processing technologies from combustion, thermochemical and biochemical processing to kinetics and thermodynamics including the mechanism for release of CO. It further expounds on the burden that CO has caused England and Wales in the last 25 years. The main gist are the systems that have been developed to minimize human exposure to CO including cooking, heating, catalytic and detection systems. Finally, alternative technologies are discussed that work by changing the chemical nature of solid fuels as a way to minimize CO emissions.

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.

The topical therapy with rifampicin (RF)-based formulations is beneficial to treat infections and to healing the wounds. Despite recent research highlighting the antibiotic's significant an-ti-inflammatory properties, limited topical wound healing products are currently available. Present study aimed to prove that the newly synthesized nanoparticles based on grafted alginate and poly(N-vinylcaprolactam (pNVCL) and poly-lactic-co-glycolic acid (PLGA) contributes to the healing process of a wound. The methods used were at first the synthesis of the copolymer of al-ginate and pNVCL via grafting from technique and radical polymerization followed by wa-ter-in-oil-in water (W/O/W) emulsification by using as oil phase PLGA dissolved in dichloromethane (DCM). The formed nanoparticles were than characterized. The loaded RF was determined to be 160 µg/mL for a 20 mg formulation and within a four-hour time frame approximately 10% of the total loaded amount was released. The inhibitory concentrations (IC50) were 192 µg/mL for the nanoparticle, 208 µg/mL for pure rifampicin, and 718 µg/mL for the rifampicin-loaded nanopar-ticles. Considering the double role Rifampicin was used for, the result was considered satisfactory in the way that these formulations could be used more with the wound irrigation post-surgery to avoid infections and to contribute to the healing.

The main objective of this paper is to develop a readiness index model that can serve as an analytical tool for exploring the achievements of electrification of transportation systems. We have applied this readiness index model to evaluate the readiness positioning of China, Norway, and Sweden to-wards transport electrification. We have chosen these three countries as they represent diversity among countries that are in the process of adopting electric transport system solutions. Our developed readiness index model has four key dimensions, technological readiness, political readiness, societal readiness, and economic readiness. The embeddedness of all four dimensions in one model provides a multi-perspective way of analyzing and evaluating the readiness levels of countries moving towards transforming the transportation system. Therefore, we named the model a “multidimensional readiness index.” Our main conclusions are that the political processes and political decisiveness involved are the most important factors followed by the societal needs and economic ability, with the current technology available as the fourth. Without the participation of dedicated and determined political decision-makers being involved, the other three factors are challenging to obtain. Political decision-makers need to facilitate the use of economic means to support the transformation in the society and affected industries to balance the initial economic disadvantages of the electrically powered systems until they pass the cost disadvantage turning point. The development of the relevant technology is no longer a great barrier as it was at the beginning of this transformation, about 20 years ago. The technology for electrically powered transportation systems and devices is widely available now, although it is continuously evolving and being improved. Associated industries cannot be expected to initiate, finance, take the risk, and take the lead in this global societal transformation without clear and strong political support.

Learning models of the cerebellum propose that the cerebellum implements an algorithm which makes iterative adjustments to synaptic transmission strength that collectively determine the response to input in learned patterns following training. We propose instead that pattern recognition and control of firing by output cells are separately handled functions which process independently variable data. This can account for the evidence without a machine learning algorithm. The model is a hybrid of physiological arguments and computational methods used to test and quantify the ideas. We argue inter alia that learning operates at the level of functional groups of Purkinje cells defined by their shared climbing fibre input; Golgi cells have several functions and regulation of parallel fibre activity by Golgi cells is not in the expected way; recoding of input to the cerebellum received in the granular layer converts the number of input variables (variables expressed in mossy fibre input to the system) into a much reduced number of functional variables expressed by internal signals traffic; circuits simultaneously execute separate but integrated functions of pattern memory and output coding; they are able to operate separately because the expression of data used in each varies independently of the other; output rates are not learned but controlled by recent relevant input signals in a window opened by pattern memory; the moment-to-moment probability that a Purkinje cell spikes is synchronised across a microzone; a principal function of functional organisation of Purkinje cells into microzones is to increase resolution of rate coded information received by the output cells of the circuit, and to do so in a very short integration window, so that circuit architecture can be explained partly as a device with this function.

Background and Aims: Sustained virologic response (SVR) lead to the decrease of portal hypertension, the regression of fibrosis, the improvement of the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in HCV cirrhotic patients treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological and coagulation tests were collected at baseline, EOT and SVR12/24. Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVR. The MELD score decrease at EOT (13.48 ± 4.273; p =0.001), and SVR (9.88 ± 2.774; p = 0.000), compared to baseline (14.92 ± 4.707). Fibroscan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT) there was a trend towards improvement during treatment, changes that were statistically significant for the majority of patients. Factor II low at baseline (75.40 ± 7.506), increases at EOT (87.40 ± 9.587), and later at SVR (99.12 ± 11.695; p = 0.000). FVIII values increased at baseline (175.52 ± 16.414) decrease at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). FvW values decreased during treatment (146.84 ± 9.428 – baseline, 141.32 ± 9.690; p =0.000 – EOT, 126.68 ± 17.960 – SVR). In regards to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the “reset” of the coagulopathy might be due to the improving of the liver function due to viral eradication secondary to AAD therapy.

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

This article aims to analyze the relationship between non-obstructive coronary artery disease (NOCAD) and atrial fibrillation (AF), exploring the underlying pathophysiological mechanisms and implications for clinical management. NOCAD and AF are prevalent cardiovascular conditions that often coexist, yet their interrelation is not well understood. NOCAD, characterized by the presence of atherosclerotic plaques without significant luminal stenosis, can lead to ischemic necrosis of cardiomyocytes and their replacement with fibrous tissue, in this way sustaining the focal ectopic activity in atrial myocardium. Atrial fibrillation, on the other hand, is the most common sustained cardiac arrhythmia, associated with an increased risk of stroke and heart failure, which may accelerate atherosclerosis and may increase oxygen consumption in the myocardium, creating a mismatch between supply and demand, thus promoting the development or worsening of coronary ischemia. Therefore, NOCAD and AF seems to be a complex Interplay with one begets another.

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.

Non-woven jute (NWJ) produced from the carpet industry waste was oxidized by H2O2 or alkali treated by NaOH and compared with water-washed samples. Changes in the structure of the NWJ, tracked by XRD, showing that both chemical treatments disrupt hydrogen bond networks between cellulose Iβ chains of the NWЈ fibers. Thereafter, nano carbon nitride (nCN) was impregnated, using layer-by-layer technique, onto water washed jute sample (nCN-Jw), NaOH treated sample (nCN-Ja) and H2O2 treated sample (nCN-Jo). Analysis of the FTIR spectra of the impregnated samples, revealed that nCN anchors to the water washed NWЈ surface through hemicellulose and secondary hydroxyl groups of the cellulose. In the case of chemically treated samples nCN is preferentially bonded to the hydroxymethyl groups of cellulose. The stability and reusability of nCN-J samples were assessed by tracking the photocatalytic degradation of Acid Orange 7 (AO7) dye under simulated solar light irradiation. Results from up to ten consecutive photocatalytic cycles demonstrated varying degrees of effectiveness across different samples. nCN-Jo and nCN-Ja samples exhibited declining effectiveness over cycles, attributed to bond instability between CN and jute. In contrast, the nCN-Jw sample consistently maintained high degradation rates over ten cycles, with a dye removal percentage constantly above 90%.

Background: Virtual Reality (VR) is an emerging tool in the management of anxiety, one of the most disturbing symptoms of Alcohol Use Disorder (AUD), which often leads to relapse. Still, patients with Alcohol Use Disorder frequently have a history of Acute Symptomatic Seizures, and they are subsequently excluded from studies using VR because of the hypothesized fear of inducing photosensitive seizures. The first part of this narrative review explores the pathophysiological mechanisms of seizures associated with AUD, specifically acute symptomatic seizures. In contrast, the second part explores virtual reality’s safe use in seizure-prone individuals, highlighting that the current state-of-the-art is based on a biased per-ception and old epidemiological data from studies conducted on photosensitive seizures in the late 90s. VR exposure has yet to be reported as triggering seizures within known pharmacovigilance databases. Significance: The implications weigh heavily on VR research currently associated with this significant adverse event. Further studies are necessary to address the risk of seizures triggered by VR in patients predisposed to developing seizures, like alcohol use disorder patients with a history of acute symptomatic seizures. Such research is essential to ensure that the potential benefits of Virtual Reality as a tool for managing anxiety in individuals with alcohol use disorder and acute symptomatic seizures are not unduly restricted. Furthermore, AUD can also serve as an intervention model feasible to de-bias attitudes toward the current lack of evidence base concerning the significant adverse events of VR-induced seizures, therefore facilitating the clinical implementation of this unharnessed digital treatment interface.

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.

Despite the Hebrides and Cleveland basins being geographically close, research has not previously been carried out to determine faunal similarities and assess the possibility of links between the dinosaur populations. The palaeogeography of both areas during the Middle Jurassic shows that there were no elevated landmasses being eroded to produce conglomeratic material in the basins at that time. The low-lying landscape and connected shorelines may have provided connectivity between the two dinosaur populations. The dinosaur fauna of the Hebrides and Cleveland basins has been assessed based primarily on the abundant ichnites found in both areas as well as their skeletal remains. In the two basins the dinosaur faunas are very similar, consisting of non-neosauropod eusauropods, a possible basal titanosauriform, large and small theropods and ornithopods and europodan thyreophorans. The main difference in the faunas is in the sizes. In the Cleveland Basin the ichnites suggest that there were medium and large theropods alongside small to medium sized ornithopods whereas in the Hebrides Basin the theropods were from small to large and the ornithopods were medium to large. It is suggested that migrations could have taken place between the two areas during the Middle Jurassic. A tentative food chain from the herbivorous dinosaurs to the top predators can be inferred from the footprints.

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 study employed e-Vol DX cone beam computed tomography (CBCT) software to assess dentin remnants in the furcation area of mesial canals in mandibular molars during root canal retreatment (RCR). Four groups (Reciproc®, ProTaper Next®, Race Evo®, Protaper Gold®) were subjected to RCR, and CBCT images were captured before (T1) and after (T2) treatment. Measurements of remaining dentin thickness at 1 mm and 3 mm below the furcation were scrutinized. Results revealed no significant differences in mean thicknesses of mesiobuccal (MB) and mesiolingual (ML) canals at 1 mm and 3 mm from the furcation pre-treatment (T1). Post-treatment (T2) showed analogous findings, with no significant differences in mean thicknesses. However, disparities surfaced between MB and ML canals at both distances, both before and after retreatment. In essence, the evaluated instruments exhibited safety in RCR, implying their appropriateness for use in critical areas of mandibular molars without inducing excessive wear. This study underscores the instruments' reliability in navigating danger zones during RCR, contributing valuable insights for dental practitioners handling complex root canal scenarios in mandibular molars.

Background. Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5-7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature is inconsistent. Material and methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, not previously reported, a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C>T, not yet reported, and c.838C>T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.

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.

The primary objective of this study is to determine the existence of a significant correlation between inflammation levels, as measured by inflammatory markers IL-6, IL-1β, and TNF-α, and the severity of depressive symptoms assessed using HAM-D assessment scale. This could provide additional evidence supporting the hypothesis that inflammation plays a notable role in the pathogenesis of depression. The data analysis supports the hypothesis that the biological mechanisms of inflammation contributes to the clinical manifestations of depression. Elevated levels of inflammatory markers, especially interleukins (IL6, IL1β), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) have been identified in patients with major depressive disorder compared to the findings in healthy controls. Materials and Methods: Inflammatory markers (IL-6, IL-1β, and TNF-α) were measured in a sample of 31 patients hospitalized at the Socola Institute of Psychiatry in Iasi, Romania, and compared to a control group with no psychiatric or inflammatory conditions. One of the main objectives is to determine if there is a significant correlation between inflammation levels, measured by inflammatory markers (IL-6, IL-1β, and TNF-α), and the severity of depressive symptoms assessed using HAM-D scores. Conclusions: The study results suggest a significant correlation between inflammation levels measured by inflammatory markers IL-1β and IL-6 and the severity of depressive symptoms evaluated by HAM-D scores in the study group. These findings support the hypothesis that inflammation may play an important role in the development or exacerbation of depressive symptoms. The relationship between inflammation and depression is also influenced by risk and protective factors that require further research.

Hyaluronic acid, in the form of a gel or viscoelastic colloidal solution, is currently used for viscosupplementation of joints affected by osteoarthritis, but its effectiveness is under debate in relation to newer alternatives. Based on meta-analytical arguments, the present article reinforces the opinion that there are still no decisive arguments for its complete replacement, but for its use adapted to the peculiarities of the disease manifestation and of the patients. A “broad” comparison is first made with almost all alternatives studied in the last decade, and then a meta-regression study is performed to compare and predict the effect size induced by viscosupplementation and platelet-rich plasma therapies. If they are computerized, the developed models can represent tools for clinicians in determining the appropriateness of the option or not for viscosupplementation, in a manner adapted to the pain felt by the patients, to their age, or to other clinical circumstances. The models were generated using the latest algorithms for meta-analysis and meta-regression implemented in the R language and assembled in different R packages. All primary data and necessary R scripts are provided in accordance with the philosophy of reproducible research. Finally, HA-based products, currently under circumspection, are still clinically useful.

Abstract: Reserve starch, the main component of durum wheat semolina, is constituted by two glucan homopolymers (amylose and amylopectin) that differ in their chemical structure. Amylose is mainly a linear structure formed of α-1,4 linked glucose units, with a lower polymerization degree, whereas amylopectin is a highly branched structure of α-1,4 chains linked by α-1,6 bonds. Variation of the amylose/amylopectin ratio has a profound effect on the starch properties which may impact wheat technological and nutritional characteristics and their possible use in the food and non-food sector. Therefore, some breeding programs were focused on the production of high (HA) and low amylose (LA) genotypes using transgenic and conventional strategies. A great interest was aroused by new genotypes enriched in amylose for their beneficial effects for human health in the prevention of non-communicable diseases. Differently the low-amylose genotypes find applications in different industrial sectors (i.e. frozen and baby foods; starch-based sweeteners and industrial alcohol) for their unique properties. In this work a set of genotypes, with a range of amylose from 14.9 to 57.8%, derived from the durum wheat cv. Svevo was characterized at biochemical and rheological level and used for the production of pasta. A negative correlation was observed between amylose content and semolina swelling power, starch peak viscosity and pasta stickiness. A worsening of the firmness was observed in the low amylose pasta compared to the control (cv. Svevo), whereas no difference was highlighted in the high amylose samples. The resistant starch was higher in the HA pasta compared to the control and LA pasta. Noteworthy, the extent of starch digestion was reduced in the high amylose pasta while the low amylose genotypes offered a higher starch digestion, suggesting other possible applications.

This study investigates the comparative performance of autoencoders and traditional machine learning (ML) algorithms in predicting tumor dynamics following Gamma Knife radiosurgery (GKRS) for brain metastases (BMs). The research retrospectively analyzed clinical data from 77 patients (median age: 64 years; 45 males, 32 females) treated at the “Prof. Dr. NicolaeOblu” Emergency Clinic Hospital-Iasi. The dataset comprised 12 variables, including socio-demographic, clinical, treatment, and radiosurgery-related factors. The primary outcome was tumor progression or regression within three months post-GKRS, with 71 cases of regression and 6 cases of progression observed. Traditional ML models—Logistic Regression, Support Vector Machine (SVM), K-Nearest Neighbors (KNN), Extra Trees, Random Forest, and XGBoost—were evaluated, achieving accuracy rates ranging from 0.91 (KNN) to 1.00 (Extra Trees). When incorporating features extracted by autoencoders, the performance of these models generally improved, especially with compression in the bottleneck layer. For instance, Logistic Regression's accuracy increased from 0.91 to 0.94, while SVM's accuracy improved significantly from 0.85 to 0.96. XGBoost consistently performed well across both traditional and hybrid setups, maintaining an accuracy of 0.94 with an AUC of 0.98. The findings suggest that hybrid approaches combining deep learning with traditional ML techniques can significantly enhance predictive accuracy and robustness, particularly in the context of GKRS for BMs. This improved performance has potential implications for more informed clinical decision-making in personalized medicine.

Layered two-dimensional (2D) graphene oxide (GO) films are integrated with micro-ring resonators (MRRs) to experimentally demonstrate enhanced nonlinear optics in the form of four-wave mixing (FWM). Both uniformly coated and patterned GO films are integrated on CMOS-compatible doped silica MRRs using a large-area, transfer-free, layer-by-layer GO coating method together with photolithography and lift-off processes, yielding precise control of the film thickness, placement, and coating length. The high Kerr nonlinearity and low loss of the GO films combined with the strong light-matter interaction within the MRRs results in a significant improvement in the FWM efficiency in the hybrid MRRs. Detailed FWM measurements are performed at different pump powers and resonant wavelengths for the uniformly coated MRRs with 1−5 layers of GO as well as the patterned devices with 10−50 layers of GO. The experimental results show good agreement with theory, achieving up to ~7.6-dB enhancement in the FWM conversion efficiency (CE) for an MRR uniformly coated with 1 layer of GO and ~10.3-dB for a patterned device with 50 layers of GO. By fitting the measured CE as a function of pump power for devices with different numbers of GO layers, we also extract the dependence of GO’s third-order nonlinearity on layer number and pump power, revealing interesting physical insights about the evolution of the layered GO films from 2D monolayers to quasi bulk-like behavior. These results confirm the high nonlinear optical performance of integrated photonic resonators incorporated with 2D layered GO films.

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.

(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.

The field of program classification, a critical aspect of software engineering, facilitates understanding and categorization of code across various applications, including anomaly detection, and code quality assessment. The advancement of cross-language program classification opens up avenues for efficient code translation among different programming languages, significantly aiding developers in rapid coding and reducing development cycles. Existing research primarily focuses on semantic code analysis, with limited emphasis on cross-linguistic challenges. To address this, we introduce an innovative neural network model, CodeSemanticsNN, which leverages a refined Syntax Structure (SS) approach. This model consists of two integral mechanisms: first, it adopts a novel SS representation that combines sequential and graph-based SS structures, enhancing semantic feature capture. Second, it employs a 'unified vocabulary' strategy to bridge the gap between diverse programming languages, facilitating efficient cross-language classification. Additionally, we have compiled a comprehensive dataset of 20,000 files spanning five programming languages, serving as a benchmark for cross-language classification. Our experiments on this dataset demonstrate that CodeSemanticsNN surpasses existing models in four key metrics: Precision, Recall, F1-score, and Accuracy.

We report world record high data transmission over standard optical fiber from a single optical source. We achieve a line rate of 44.2 Terabits per second (Tb/s) employing only the C-band at 1550nm, resulting in a spectral efficiency of 10.4 bits/s/Hz. We use a new and powerful class of micro-comb called soliton crystals that exhibit robust operation and stable generation as well as a high intrinsic efficiency that, together with an extremely low spacing of 48.9 GHz enables a very high coherent data modulation format of 64 QAM. We achieve error free transmission across 75 km of standard optical fiber in the lab and over a field trial with a metropolitan optical fiber network. This work demonstrates the ability of optical micro-combs to exceed other approaches in performance for the most demanding practical optical communications applications.

Convolutional neural networks (CNNs), inspired by biological visual cortex systems, are a powerful category of artificial neural networks that can extract the hierarchical features of raw data to greatly reduce the network parametric complexity and enhance the predicting accuracy. They are of significant interest for machine learning tasks such as computer vision, speech recognition, playing board games and medical diagnosis [1-7]. Optical neural networks offer the promise of dramatically accelerating computing speed to overcome the inherent bandwidth bottleneck of electronics. Here, we demonstrate a universal optical vector convolutional accelerator operating beyond 10 Tera-OPS (TOPS - operations per second), generating convolutions of images of 250,000 pixels with 8-bit resolution for 10 kernels simultaneously — enough for facial image recognition. We then use the same hardware to sequentially form a deep optical CNN with ten output neurons, achieving successful recognition of full 10 digits with 900 pixel handwritten digit images with 88% accuracy. Our results are based on simultaneously interleaving temporal, wavelength and spatial dimensions enabled by an integrated microcomb source. This approach is scalable and trainable to much more complex networks for demanding applications such as unmanned vehicle and real-time video recognition.

Histone deacetylase inhibitors (HDACis) are being recognized as a potentially effective treatment approach for peripheral T-cell lymphoma (PTCL), which is a diverse group of aggressive lymphomas with a bleak prognosis. Recent evidence has shown that HDACi are effective in treating PTCL, especially in cases where the disease has relapsed or is resistant to other treatments, and there are few available options. Several clinical trials have demonstrated that HDACi, such as romidepsin and belinostat, can elicit long-lasting positive outcomes in individuals with PTCL, either when used alone or in conjunction with conventional chemotherapy. They exert their anti-tumor actions by regulating gene expression through inhibiting histone deacetylases, which results in the halting of cell division, programmed cell death, and the transformation of cancerous T-cell, as indicated by gene expression profile studies. Importantly, besides clinical trials, real-world evidence indicated that the utilization of HDACi presents a significant and beneficial treatment choice for PTCL. However, although HDACi showed potential effectiveness, they couldn’t cure most patients. Therefore, new combination with conventional drugs as well as new targeted agents are under investigation.

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.

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.

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.

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 inhibition of localised corrosion is known to involve multiple processes taking place over a range of time and length scales that are difficult to study by conventional electrochemical methods. This work demonstrates an approach to probing complex localised electrochemical processes by combining an electrochemically integrated multi-electrode array (also known as wire beam electrode (WBE)), scanning vibrating electrode technique, scanning electrochemical microscopy and surface analytical techniques. Each technique reveals certain aspects of the dynamically changing, multi-scale, inhibitor-microstructure interactions and local chemistry over a heterogeneous AA2024-T3 alloy surface in the presence of an environmentally friendly inhibitor; cerium diphenyl phosphate (Ce(dpp)3).

Adjunctive treatment of periodontitis lacks solutions allowing enough time for wound healing in the periodontal pockets by avoiding a fast re-colonization. Such a solution might be an antibiotic containing formulation with a controlled release over weeks. Here, a recently described minocycline containing approach is qualified for further clinical development by focusing on proof-of-concept, systemic burden, resistance development and degradation studies. Animal studies were done in two different (mouse-chamber, rat Porphyromonas gingivalis challenging) models, including effects on inflammation markers, bone loss and bone structure. Also, serum concentrations of minocycline after local application were determined by HPLC-MS/MS. The resistance status of bacterial clinical isolates against minocycline was investigated and the degradation of the formulation was characterized by laser scanning- and scanning electron microscopy. Animal studies clearly demonstrated the applicability of the new formulation in the investigated models. Inflammation markers decreased dosage dependent and reduced bone loss compared to non-treated group was observed. Thereby, the systemic burden of the antibiotic was neglectable. Minocycline is still effective against oral pathogens; resistance development was not seen. The biodegradable thread was first swollen and subsequently degraded over weeks. The results support the continued clinical development of this new formulation. A phase I clinical trial is planned to further evaluate its safety and efficacy.

Electrolyte disturbances are common in patients with traumatic brain injury (TBI), particularly affecting sodium, potassium, chloride and calcium levels. This study aims to provide insights into these disturbances within the first 24 hours post-injury. We conducted a cross-sectional analysis of 50 TBI patients, excluding those with conditions affecting electrolyte balance. Electrolyte levels were measured, and correlations with demographic data, trauma mechanisms, imaging findings, and Glasgow Coma Scale (GCS) scores were analyzed. Results indicated that chloride levels inversely correlated with GCS scores (ρ = -0.515; p = 0.002), suggesting that elevated chloride may indicate severe neurological impairment. Potassium levels were significantly associated with subdural hematoma (p = 0.032) and subarachnoid hemorrhage (p = 0.043), highlighting their potential as markers for severe brain injuries. No significant associations were found between sodium or calcium levels and the studied variables. These findings underscore the importance of early monitoring of chloride and potassium levels in TBI patients to improve management and outcomes. Future research should focus on larger, multi-center studies to validate these findings and develop comprehensive guidelines for managing electrolyte imbalances in TBI patients.

In this paper, we report a comprehensive and consistent annotation of the locus encoding the horse T cell receptor b-chain (TRB), as inferred from the most recent genome assembly. The horse TRB locus spans approximately 1 Mb, making it the largest locus among the mammalian species stud-ied to date, with a significantly higher number of genes related to extensive duplicative events. In the region, 136 TRBV, belonging to 29 subgroups, 2 TRBD, 13 TRBJ and 2 TRBC genes, were iden-tified. The general genomic organization resembles that of other mammals, with a V-cluster of 135 TRBV genes, located upstream of two in-tandem aligned TRBD-J-C clusters, and an inverted TRBV gene at the 3’ end of the last TRBC gene. However, the horse b-chain repertoire would be affected by a high number of non-functional TRBV genes. Thus, we queried a transcriptomic da-taset derived from splenic tissue of a healthy adult horse, using each TRBJ gene as a probe to ana-lyse clonotypes encompassing the V(D)J junction. This analysis provided insights into the usage of the TRBV, TRBD and TRBJ genes and the variability of the juxtaposition region. Our results clearly demonstrated that the horse β-chain constitutes a complex level of variability broadly like that described in other mammalian species.

Follicular helper CD4+ T cells (TFH) are a major cellular pool for the maintenance of HIV reservoir. Therefore, the delineation of the follicular (F)/germinal center (GC) immune landscape will significantly advance our understanding of HIV pathogenesis. We have applied multiplex confocal imaging, in combination with relevant computational tools, to investigate, F/GC in situ immune dynamics in viremic (vir-HIV), antiretroviral treated (cART HIV) People Living With HIV (PLWH) and compare them to reactive, non-infected controls. Lymph nodes (LNs) from viremic and cART PLWH could be further grouped based on their TFH cell densities in high-TFH and low-TFH subgroups. These subgroups were also characterized by different in situ distribution of PD1hi TFH cells. The significantly accumulated follicular, compared to extrafollicular, FOXP3hi CD4+ T cells found in the low-TFH cART-HIV group were characterized by a less scattered in situ distribution and strongly correlated with the cell density of CD8+ T cells in this group. An inverse correlation between plasma viral load and LN GrzBhiCD8+ T and CD16hiCD15lo cells was found. Our data reveal the complex GC immune landscaping in HIV infection and suggest that follicular FOXP3hi CD4+ T cells could be negative regulators of TFH cell prevalence in cART-HIV.

Background: Existing human cell immortalization methods made the cells obtain oncogenesis phenotype and/or caused the cells gain and/or lose chromosomes. Immortalized normal human T cells lines provide critical in vitro models for basic research and therapeutic products development.Methods: We utilized a CRISPR/Cas9 system to replace a single copy of the exon 2 of the cell cycle inhibitor gene CDKN2A (encoding p16 and p14 proteins) with a single copy of human telomerase reverse transcriptase (hTERT) to immortalize human primary CD8⁺ T cells (hCD8⁺T-TERT). By using Cas9 protein and low donor DNA copies/cell, we successfully immortalized hCD8⁺T cells with a single copy of hTERT transgene, which also avoided uncontrolled insertion of Cas9 gene and guide RNA vector.Results: Human primary CD8+ cells were immortalized and expanded more than 2.6 × 10⁷ times. Characterization of the cells revealed that the immortalized CD8⁺ T-TERT cells retained most of the cell surface markers and normal karyotype. The CD8⁺ T-TERT cells also retained the dependence of IL-2 and CD3/CD28 activator for survival and expansion.Conclusion: we established a stable immortalized CD8⁺ T cell line that had a phenotype consistent with T cells and will be a useful research model.

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.

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.

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.

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.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

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.

The epidemiology of invasive fungal infections (IFIs) is currently changing, driven by aggressive immunosuppressive therapy, leading to an expanded spectrum of patients at risk of IFIs. Aspergillosis is a leading cause of IFIs, which usually affects immunocompromised patients. There is a limited number of antifungal medications available for treating IFIs and their effectiveness is often hindered by rising resistance rates and practical limitations. Consequently, new antifungals, especially those with novel mechanisms of action, have become increasingly required. This study assessed the activity of four novel antifungal agents with different mechanisms of activity: manogepix, rezafungin, ibrexafungerp, and olorofim against 100 isolates of Aspergillus section Terrei, containing amphotericin B (AmB) wildtypes/non-wildtypes and azole-susceptible/-resistant strains, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method. In general, all tested agents showed potent and consistent activity against tested isolates, exhibiting a geometric mean (GM) and minimum effective concentration (MEC)/minimum inhibitory concentrations (MIC) range respectively as follows: manogepix (0.048 mg/L, 0.032-0.5 mg/L), rezafungin (0.020 mg/L, 0.016-0.5 mg/L), ibrexafungerp (0.071 mg/L, 0.032-2 mg/L), and olorofim (0.008 mg/L, 0.008-0.032 mg/L). In terms of MIC90/MEC90, olorofim had the lowest values (0.008 mg/L), followed by rezafungin (0.032 mg/L), manogepix (0.125 mg/L), and ibrexafungerp (0.25 mg/L). All antifungals tested demonstrated promising in vitro activity against Aspergillus section Terrei, including A. terreus and cryptic species that were azole-resistant and AmB non-wildtype.

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.

This manuscript explores significant advancements and emerging challenges in CAR T cell therapies, focusing on the production methodologies and regulatory complexities. The discussion highlights ongoing challenges like the lack of in vivo persistence, lengthy production times, and elevated costs associated with current CAR T cell therapies. It analyzes innovative solutions such as genetic engineering techniques aimed at enhancing cellular efficacy and endurance, alongside cutting-edge manufacturing processes, including closed systems and development of allogeneic products. These advancements hold promise for reducing costs and improving production efficiency, potentially increasing patient access to these transformative therapies globally. Furthermore, the manuscript underscores the necessity for expanding ongoing research and enhancing regulatory frameworks to fully realize and implement these innovations in CAR T cell manufacturing and bring these innovations to fruition.

Biofilm formation is important in the free-living and symbiotic lifestyles of Sinorhizobium meliloti. Here we show that the S. meliloti NspS-MbaA system is homologous to the c-di-GMP modulating NspS-MbaA system described in Vibrio cholerae and modulates biofilm formation, exopolysaccharide (EPS) production and motility in S. meliloti in response to exogenous polyamines. Biofilm and EPS production in quorum sensing-deficient wild type strain 1021 decreased in cultures containing putrescine, 1,3-diaminopropane or spermine, but were unaffected in a 1021 nspS mutant (1021 nspS). Decreases in biofilm formation caused by these polyamines paralleled decreases in EPS production and increases in nspS transcription. Cell aggregation did not differ markedly between strain 1021 and 1021 nspS. The S. meliloti quorum sensing-proficient Rm8530 wild type strain and nspS mutant (Rm8530 nspS) produced similar levels of biofilm under control conditions and 3.2- and 2.2-fold more biofilm in cultures with norspermidine, but these changes did not correlate with EPS production. Rm8530 nspS aggregated up to several fold more than the wild type under most conditions. Changes caused by polyamines in swimming and swarming motility were not generally dependent on NspS-MbaA in either 1021 or Rm8530. We speculate that the S. meliloti NspS-MbaA system could modulate biofilm formation in response to environmental polyamines.

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.

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.

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.

The use of cardiac implantable electronic devices (CIEDs) has increased considerably, becoming a cornerstone of management for patients with brady- or tachyarrhythmia or for the prevention of sudden cardiac death. On the other hand, tricuspid regurgitation (TR) associated with CIEDs is progressively accepted as a serious clinical issue; prognostic impact of TR is profound, as it is independently associated with increased mortality and a higher risk of heart failure hospitalization. Additionally, management of established CIED-related TR continues to be challenging, with limited options for intervention once significant TR has developed. The balance between the lifesaving benefits of CIEDs and the risk of TR underlines the necessity for cautious patient selection and innovative approaches to device implantation and management. This review highlighting the clinical importance, underlying mechanisms, and challenges associated with lead-related tricuspid regurgitation in patients with CIEDs.

Since its conception with the smallpox vaccination, worldwide-used vaccines have thwarted multiple pandemics including the recent COVID-19 outbreak. Insightful studies uncovered complexities of different functional networks of CD4 T cells [T helper 1 (Th1); Th2, Th17] and CD8 T cells (T cytotoxic; Tc) as well as B cells (BIgM, BIgG, BIgA and BIgE) subsets during response to vaccination. Both T and B cell subsets forge central, peripheral and tissue-resident subsets during vaccination. It also became apparent that each vaccination formed the network of T regulatory subsets, namely CD4+CD25+Foxp3+ T regulatory (Treg) cells and interleukin-10 (IL-10)-producing CD4+Foxp3− T regulatory 1 (Tr1) as well as many others, are shaping the quality/quantity of vaccine-specific IgM, IgG, and IgA antibody production. These components are especially critical for immunocompromised patients, such as older individuals and allograft recipients, as their vaccination may be ineffective or less effective. This review focuses on presenting how pre- and post-vaccination Treg/Tr1 levels influence the vaccination efficacy. Experimental and clinical work revealed that the Treg/Tr1 involvement evoked different immune mechanisms in diminishing vaccine-induced cellular/humoral responses. Alternative steps may be considered to improve the vaccination response by increasing a dose, changing the delivery route and/or repeated booster doses of vaccines. Vaccination may be combined with anti-CD25 (IL-2Ra chain) or anti-PD-1 (programmed cell death protein) monoclonal antibody (mAb) to decrease Tregs and boost the T/B cell immune response. All these data and strategies for immunizations are presented and discussed, aiming to improve the efficacy of vaccination in humans and especially in immunocompromised and older individuals as well as organ transplant patients.

Despite concerns about the negative effects of social distancing and prolonged school closures on children’s lifestyle and physical activity (PA) during the COVID-19 pandemic, robust evidence is lacking on the impact of the COVID-19 pandemic on children’s wellbeing and daily life. This study aimed to examine changes in the PA levels, sleep patterns and screen time of school-aged children during the different phases of COVID-19 outbreak in Hong Kong using a repeated cross-sectional design. School students (Grades 1 to 12) were asked to report their daily electronic device usage and to fill in a sleep dairy recording their daily sleep and wake-up time. They were equipped with a PA monitor, Actigraph wGT3X-BT, to obtain objective data on their PA levels and sleep patterns. Students were recruited before the pandemic (Sep 2019 – Jan 2020; n=577), during school closures (Mar 2020 – Apr 2020; n=146), and after schools partially reopened (Oct 2020 – Jul 2021; n=227). Our results indicated lower PA levels, longer sleep duration, and longer screen time among participants recruited during school closures than those recruited before the COVID-19 outbreak. Primary school students were found to sleep on average for an extra hour during school closures. Our findings illustrate the impact of social distancing policies during the COVID-19 pandemic on the sleep pattern, screen time, and PA level in school-aged children in Hong Kong. Professionals should reinforce the importance of maintaining a physically active lifestyle, good sleep hygiene, and healthy use of electronic devices to parents and school-aged children during the COVID-19 Pandemic.

This article discusses a focused study on visualizing the flow patterns in a two-phase pulsating heat pipe (PHP) using Fe₃O₄/water as the working fluid at 3 V/V% concentration. The research also aims to meticulously examine phase change phenomena in the heating section, particularly focusing on bubble formation and expansion processes. A high-speed video camera was utilized to capture dynamic insights into the behavior of the Fe₃O₄/water mixture. Based on the findings, a straightforward model was developed to explain bubble generation and growth in the mixture, serving as a useful reference for future PHP designs and optimizations. Visual observations also noted the stable nature of the Fe₃O₄/water nanofluid over a four-day period, confirming its consistency throughout the experiments. Moreover, the impact of heat load variation on the evaporator section was assessed using controlled heat inputs ranging from 10 to 80 Watts. Observations on the arrangement of slugs and plugs at a 50% filling ratio revealed interesting self-adjusting flow patterns in response to increasing heat inputs, providing valuable insights into PHP operational dynamics. Notably, the oscillatory flow behavior of Fe₃O₄/water, the chosen working fluid, exhibited greater activity in comparison to water. This distinctive flow behavior contributed to achieving heightened thermal performance efficiency for the Fe₃O₄/water system, attributed to its faster attainment of the annular flow condition.

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 a growing interest in the endocannabinoid system and the gut microbiota. Both areas have been suggested to play a role in endometriosis, however this is yet to be studied comprehensively. The purpose of this narrative review is to identify the gaps in endometriosis research in the context of these two areas. It underscores the limited knowledge regarding the involvement of the endocannabinoid system and gut microbiota in endometriosis. Further research in these areas is essential to unlock the therapeutic potential of cannabis and enhance the understanding of endometriosis pathogenesis.

For quantitative determination of honokiol (HNK) and metformin hydrochloride (M-HCl) by HPLC from formulations and from dissolution studies, a QbD approach using three factors - three levels design was implemented to optimize the chromatographic conditions. To study the impact of each variable on the peak area of both compounds and retention time of last compound eluted, the 3D response surface plots were developed. HNK and M-HCl were separated on a Thermoscientific ODS Hypersyl TM (250 x 4.6 mm, 5 μm) column mantained at 30 C, using 0.02 M acetate buffer (pH = 3) / methanol (15 / 85, v / v) as mobile phase with a flow rate of 1 mL/min. The injected volume was 20 L, and the detection wavelengths were 256 nm for HNK and 236 nm for M-HCl. The validation of proposed method showed a linearity range of 4 – 1200 μg/mL for M-HCl (r2 = 0.9992) and 1 – 300 μg/mL for HNK (r2 = 0.9998), good precision (RSD &lt; 2% for both HNK and M-HCl, in intra- and inter-day studies) and accuracy (mean recovery = 100.09% in the range 99.80 – 100.43% for M-HCl and mean recovery = 100.12% in the range 99.70 – 100.38% for HNK). The environmentally friendly nature of the method was confirmed by the evaluation of the method’s greenness. The proposed method was applied for the determination of HNK and M-HCl from oral dosage forms and in dissolution studies.

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the key focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection in pre-clinical models and human trials. While deploying these spike-based vaccines saved millions of lives worldwide, it has become clear that the immunological mechanisms of protection against severe disease are multifaceted and involve non-neutralizing antibody components. Here, we describe a novel pan-sarbecovirus T-cell vaccine, ChAdOx1.COVconsv12, designed to complement and broaden the protection of spike vaccines. The vaccine immunogen COVconsv12 employs the two regions in the viral proteome most conserved among sarbecoviruses delivered by replication-deficient vector ChAdOx1. It focuses T cells towards epitopes shared among sarbecoviruses including evolving SARS-CoV-2 variants. Here, we show that ChAdOx1.COVconsv12 induced broad T-cell responses in the BALB/c and C57BL/6 mice. In the Syrian hamster challenge model, ChAdOx1.COVconsv12 alone did not protect against the SARS-CoV-2 infection, but when co-administered with 1/50th of the ChAdOx1 nCoV-19 spike vaccine protective dose, faster recovery and lower oral swab viral load were observed. Induction of CD8+ T cells may decrease COVID-19 severity and extend the T-cell response coverage of variants to match the known (and as yet unknown) members of the beta-coronavirus family.

Magnetic resonance (MR) image acquisitions are usually time-consuming, limiting utilization in neuroimaging. For multiple sclerosis (MS) patients, MR imaging plays a major role in drug therapy decision-making. The purpose of this study was to evaluate whether an ultrafast, T2-weighted (T2w), deep-learning-enhanced (DL), echo-planar-imaging-based (EPI) fluid-attenuated inversion recovery (FLAIR) sequence (FLAIRUF) that has been targeting neurological emergencies so far might even be an option to detect MS lesions of the brain compared to conventional FLAIR sequences. Therefore, 17 MS patients were enrolled prospectively in this exploratory study. Standard MR protocols and ultrafast acquisitions were conducted at 3 tesla (T), including three-dimensional (3D)-FLAIR, turbo/fast spin echo (TSE)-FLAIR, and FLAIRUF. Inflammatory lesions were grouped by size and location. Lesion conspicuity and image quality were rated on an ordinal five-point Likert scale, and lesion detection rates were calculated. Statistical analyses were performed to compare results. Altogether, 568 different lesions were found. Data indicated no significant differences in lesion detection (sensitivity and positive predictive value [PPV]) between FLAIRUF and axially reconstructed 3D-FLAIR (lesion size ≥ 3 mm × ≥ 2 mm) and no differences in sensitivity between FLAIRUF and TSE-FLAIR (lesion size ≥ 3 mm total). Lesion conspicuity in FLAIRUF was similar in all brain regions except for superior conspicuity in the occipital lobe and inferior conspicuity in central brain regions. Further findings include location-dependent limitations of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as well as artifacts such as spatial distortions in FLAIRUF. In conclusion, FLAIRUF could potentially be an expedient alternative to conventional methods for brain imaging in MS patients since the acquisition can be performed in a fraction of time while maintaining good image quality.

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

Qatar and other Gulf States have a diverse range of marine vegetation that is adapted to the stressful environmental conditions of seawater. The industrial wastewater produced by oil and gas activities adds further detrimental conditions for marine aquatic photosynthetic organ-isms on the Qatari coastlines. Thus, these organisms experience severe stress from both seawater and industrial wastewater. This review discusses the biodiversity in seawater around Qatar, as well as remediation methods and metabolic pathways to reduce the negative impacts of heavy metals and petroleum hydrocarbons produced during these activities. These methods include phyto-stabilization phyto-accumulation, phyto-volatilization, and phyto-degradation. Phy-to-degradation in particular is discussed in detail, including metabolic pathways such as alkane and aromatic-compound degradation pathways. The role of microorganisms that are adjacent to or associated with these aquatic marine organisms is discussed, including rhizosphere biodeg-radation. In this type of biodegradation, exudates are released by plant roots and supply nutrients to microorganisms in the rhizosphere, which enhances their ability to degrade organic pollutants. Special attention is paid to mangrove forests and their roles in remediating shores polluted by industrial wastewater. Seagrasses (Halodule uninervis, Halophila ovalis, and Thalassia hemprichii) and seaweeds (Chlorophyta, Phaeophyta, and Rhodophyta) around the peninsula of Qatar are also discussed.

Electricity distribution network operators face several operational constraints in the provision of safe and reliable power given that investments for network area reinforcement must be commensurate with improvements in network reliability. This paper provides an integrated approach for assessing the impact of different operational constraints on distribution network reliability by incorporating component lifetime models, time-varying component failure rates as well as the monetary cost of customer interruptions in an all-inclusive probabilistic methodology that applies a time-sequential Monte Carlo simulation. A test distribution network based on the Roy Billinton test system is modelled to investigate the system performance when overloading limits are exceeded as well as when preventive maintenance is performed. Standard reliability indices measuring the frequency and duration of interruptions, and the energy not supplied are complemented with a novel monetary reliability index. The comprehensive assessment includes not only average indices but also their probability distributions to adequately describe the risk of customer interruptions. Results demonstrate the effectiveness of this holistic approach as the impacts of operational decisions are assessed from both reliability and monetary perspectives. This informs network planning decisions through optimum investments and consideration of customer outage costs.

The need for Transit Oriented Development (TOD) around railway stations has been well accepted and continues to be needed in cities looking to regenerate both transit and urban development. Large parts of suburban areas remain without quality transit down Main Roads which are usually filled with traffic resulting in reduced urban value. The need to regenerate both the mobility and land development along such roads will likely be the next big agenda in transport policy. This paper learns from century-old experiences in public-private approaches to railway systems from around the world, along with new insights from entrepreneurship theory and urban planning to create the notion of a ‘Transit Activated Corridor’ (TAC). TAC’s prioritise fast transit and a string of station precincts along urban Main Roads. TOD’s were primarily a government role, whereas TAC’s will be primarily a private sector, entrepreneurship role. The core policy processes for a TAC are outlined with some early case studies. Five design principles for delivering a TAC are presented in this paper, three principles from entrepreneurship theory and two from urban planning. The potential for Trackless Trams to enable TAC’s is used to illustrate how these design processes can be an effective approach for designing, financing and delivering a ‘Transit Activated Corridor’.

The UK economy is overly reliant on unsustainable production and consumption practices, depleting finite resources at rates that will increase production costs, business risk and economic instability. This over-consumption produces emissions and waste that cause climate change and environmental degradation, impacting on the wellbeing of people in the UK and beyond. The Resource Recovery from Waste programme (RRfW) promotes a transition towards waste and resource management in a circular economy that restores the environment, creates societal benefits and promotes clean growth by engaging relevant actors in the transition process. RRfW collaborates with academia, government, and industry to co-produce a shared vision and approach to realise such a transition. Reflecting insights from RRfW’s government engagement, this article presents a positive outlook for changing the UK economy and society. It envisions a long-term future for waste and resource management that maximises the value of materials by circulating them in the economy for as long as possible. Four themes and an approach are proposed, including recommendations for regulatory instruments and a stable policy framework. It recommends further collaborative research to capitalise on opportunities for economic growth, innovation and resilient infrastructure whilst contributing to quality jobs and welfare in all four UK nations.

In 1990 the Malaysian Government launched Vision 2020 with the goal of Malaysia becoming a ‘fully developed country’ by the year 2020. In this drive for development the country has been examining many of its key natural assets, exploring how to both preserve them whilst ensuring that they make the maximum possible contribution to national development goals. Endau Rompin is one of these assets, being the second largest National Park in Peninsula Malaysia. The rich tropical rainforest flora and fauna of the Park and its hinterland, however, are threatened by various anthropogenic forces, most notably deforestation and poaching; both of which have taken the Park’s flagship species - the Tiger Panthera tigris jacksoni – towards the brink of local extinction. Malaysia’s statutory East Coast Economic Region Development Council commissioned a study to consider ways of increasing tourism revenues from the Park while at the same time reversing these threats. The key conclusion drawn is that a more holistic, landscape-scale approach should be adopted, with Endau Rompin forming part of a wider strategic economic zone based around sustainable tourism and land management. The proposed expanded zone extends eastwards beyond the confines of the Park, across the coastal plain to the South China Sea, and onwards to the neighbouring Mersing Islands. This expanded zone is referred to as Malaysia’s new ‘Rainforest to Reef Region’.

Our hypothesis that controlled ozone applications interfere into the redox balance of the biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication), has been verified over the last 2 decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes, diabetes-2 and in prevention of intoxications. Low-dose ozone acts as a redox bioregulator: The restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase of the antioxidant repair markers, here mainly shown as glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, relevant data are displayed, evaluated and comprehensively discussed: The repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone treated groups and depending on the indication; the stress markers are simultaneously reduced, the redox system regains its balance.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

The relationship between the host and the microbiome, or the assemblage of microorganisms (including bacteria, archaea, fungi, and viruses), has been proven crucial for its health and disease development. The high dimensionality of microbiome datasets has often been addressed as a major difficulty for data analysis, such as the use of Machine Learning (ML) and Deep Learning (DL) models. Here we present BiGAMi, a bi-objective genetic algorithm fitness function for feature selection in microbial datasets to train high-performing phenotype classifiers. The proposed fitness function allowed us to build classifiers that outperformed the baseline performance estimated by the original studies by using as few as 0.04% to 2.32% features of the original dataset. In 19 out of 21 classification exercises, BiGAMi achieved its results by selecting 6-68% fewer features than the highest performance of a Sequential Forward Feature Selection algorithm. This study showed that the application of a bi-objective GA fitness function against microbiome datasets succeeded in selecting small subsets of bacteria whose contribution to understood diseases and the host state was already experimentally proven. Applying this feature selection approach to novel diseases is expected to quickly reveal the microbes most relevant to a specific condition.

A synoptic review of plant disease epidemics and outbreaks was made using two complementary approaches. The first approach involved reviewing scientific literature published in 2021, in which quantitative data related to new plant disease epidemics or outbreaks were obtained via surveys or similar methodologies. The second approach involved retrieving new records added in 2021 to the CABI Distribution Database, which contains over a million global geographic records of organisms from over 50,000 species. The literature review retrieved 186 articles, describing studies in 62 categories (pathogen species/species complexes) across >40 host species on 6 continents. Pathogen species with >5 articles were: Bursaphelenchus xylophilus, Candidatus Liberibacter asiaticus, cassava mosaic viruses, citrus tristeza virus, Erwinia amylovora, Fusarium spp. complexes, Fusarium oxysporum f. sp. cubense, Magnaporthe oryzae, maize lethal necrosis co-infecting viruses, Meloidogyne spp. complexes, Pseudomonas syringae pvs, Puccinia striiformis f. sp. tritici, Xylella fastidiosa, and Zymoseptoria tritici. Automated searches of the CABI Distribution Database identified 617 distribution records new in 2021 of 283 plant pathogens. A further manual review of these records confirmed 15 pathogens reported in new locations: apple hammerhead viroid, apple rubbery wood viruses, Aphelenchoides besseyi, Biscogniauxia mediterranea, Ca. Liberibacter asiaticus, citrus tristeza virus, Colletotrichum siamense, cucurbit chlorotic yellows virus, Erwinia rhapontici, Erysiphe corylacearum, Fusarium oxysporum f. sp. cubense Tropical Race 4, Globodera rostochiensis, Nothophoma quercina, potato spindle tuber viroid, and tomato brown rugose fruit virus. Of these, 4 pathogens had at least 25% of all records reported in 2021. We assessed two of these pathogens – tomato brown rugose fruit virus and cucurbit chlorotic yellows virus – to be actively emerging in/spreading to new locations. Although three important pathogens – Ca. Liberibacter asiaticus, citrus tristeza virus and Fusarium oxysporum f. sp. cubense – were represented in the results of both our literature review and our interrogation of the CABI Distribution Database, in general our dual approaches revealed distinct sets of plant disease outbreaks and new records, with little overlap.

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.

The article explores the concept of 'synthetic man' (SM) in the context of 'synthetic biology' (SB), analysing the potential, challenges, and ethical implications of these achievements. Through dialogue with ChatGPT 4, an in-depth understanding of the evolution, contributions of SM, ChatGPT's contribution, and concerns associated with SM is sought, providing insight into how this technology could affect our society. Our study uses a structured dialogue framework with ChatGPT that addresses essential SM questions regarding SM history, contributions, challenges, and concerns. ChatGPT responses are analysed to extract relevant information and identify trends and insights. The ChatGPT dialogue reveals that MS is still a theoretical and speculative concept with significant advances in gene therapy and genetic engineering. The potential contributions of SM in addressing global challenges such as health, environment and education are identified. Ethical and social concerns such as health risks and psychological impact are also highlighted. Differences in ChatGPT responses were observed between different sessions or even within the same session, which highlighted the limitations in the replicability of the research and sometimes the need for clarification of the questions. The article is distinguished by its unique approach of using an advanced language model to explore a complex and speculative topic. The LLM Dialogue Framework on Technology (LLM-DFonTech) framework proposal for structured dialogue with ChatGPT on various technological topics related to the original contribution provides an adaptable tool for interdisciplinary research in emerging technologies. This methodology opens up new possibilities for analyzing and developing trends in technology and society.

Atomic structure of N-electron atoms is often determined using the Hartree-Fock method, which is an integro-differential equation. The exchange term of the Hartree-Fock equations is usually treated as an inhomogeneous term of a differential equation, or with a local density approximation. This work uses matrix methods to solve for the Hartree-Fock equations, rather than the more commonly-used shooting method to integrate an inhomogeneous differential equation. It is well known that a derivative operator can be expressed as a matrix made of finite-difference coefficients; energy eigenvalues and eigenvectors can be obtained by using computer linear-algebra packages. We extend the same technique to integro-differential equations, where a discretized integral can be written as a sum in matrix form. This method is compared against experiment and standard atomic structure calculations. We also can use this method for free-electron wavefunctions. This technique is important for spectral line broadening in two ways: improving the atomic structure calculations, and improving the motion of the plasma electrons that collide with the atom.