The time-dependent behavior and long-term stability of deep-buried tunnels in soft rocks have received lots of considerations in tunnel engineering and allied sciences. To better explore and deepen the engineering application of rock creep, extensive research studies are still needed, although fruitful outcomes have already obtained in many related investigations. In this article, the Weilai Tunnel in China’s Guangxi province is studied taking its host rocks as the main research object. In fact, aiming at forecasting the time-varying deformation of this tunnel, a novel elasto-visco-plastic creep constitutive model with two variants is proposed, by exploiting the typical complex load-unload process of rock excavation. The model is well validated and good agreements are found with the relevant experimental data. Moreover, the time-dependent de-formation rules are properly established for the surrounding rocks, by designing two new closed-form solutions based on the proposed creep model and the Hoek-Brown criterion. The convergence deformations calculated from the closed-form solutions conform well to the on-site monitoring data. In only 27 days after excavation, the creep deformation of the Weilai tunnel overtakes 400 mm, which is enormous. To guarantee the long-term stability of this tunnel, a ro-bust support scheme and its long-term monitoring with appropriate remote sensors are strongly suggested.

Distributed deformation based on Fiber Bragg Grating sensors or other kinds of strain sensors can be used to evaluate safety in operating periods of bridges. However, most of the published researches about distributed deformation monitoring are focused on solid rectangular beam rather than box girder—a kind of typical hollow beam widely employed in actual bridges. Considering that the entire deformation of a single-cell box girder contains not only bending deflection but also two additional deformations respectively caused by shear lag and shearing action, this paper again revises the improved conjugated beam method (ICBM) based on the LFBG sensors to satisfy the requirements for monitoring two mentioned additional deformations. The best choice for the LFBG sensor placement in box gilder is also proposed in this paper due to strain fluctuation on flange caused by shear lag effect. Results from numerical simulations show that most of the theoretical monitoring errors of the revised ICBM are 0.3%~1.5%, and the maximum error is 2.4%. A loading experiment for a single-cell box gilder monitored by LFBG sensors show that most of the practical monitoring errors are 6%~8%, and the maximum error is 11%.

The current study investigated the neuroprotective effects of rutin hydrate (RH) in an Alzheimer’s disease (AD)-like learning and memory impairments rat model. Since AD is an age-related degenerative brain disorder characterized by a progressive worsening in cognitive function and memory, RH may be a potential drug for the treatment of AD-like memory loss, and this work is aimed to evaluate whether RH has neuroprotective effects in memory deficits induced by scopolamine (SCO). In our study, RH demonstrated beneficial effects as a neuroprotector in the brain and improved learning, memory, and synaptic plasticity in a rat. Rats were administered RH (100 mg/kg) and SCO (1.5mg/kg), and performed behavioral tests such as Morris water navigation test, Y-maze test, and passive avoidance test to evaluate the ability of learning and memory. In accordance with these findings, RH behaviorally attenuated SCO-induced shortening of step-through latency in the PA test, increased the percent of alternation in the Y-maze, and increased the time spent in the target zone in the MWN. Moreover, the neuroprotective effect of RH on learning and memory was investigated through the long-term potential on organotypic hippocampal slice cultures. RH increased the total activity of field excitatory postsynaptic potential (fEPSP) following theta burst stimulation and attenuated SCO-induced blockade of fEPSP. This approach could potentially be used as a therapeutic strategy for the restoration of learning and memory function and the prevention of the progression of AD. SCO treatment decreased the levels of BDNF/TrkB/ERK/CREB/Bcl2 and increased the Bax protein level in rat hippocampus. RH ameliorated the expression of these proteins by attenuating SCO-induced up or downregulation in the hippocampus. Based on these findings, the results highlight the molecular and cellular mechanisms through which RH is proposed to exert its neuroprotective effects in the prevention and treatment of learning and memory deficit disorders.

Abstract Introduction: Long COVID (LC) affects multiple systems and has a significant health impact on patients and society. Therefore, long COVID services should address patients’ needs through a holistic assessment and monitoring of patients’ symptoms. Aim: The aim was to understand which of the symptoms were most and least likely to improve, after our rehabilitation intervention so that the rehabilitation measures in the clinic could be modified to meet patients’ needs. At the same time, we wanted to assess the feasibility of using C19-YRS ELAROS application in monitoring of LC symptoms during and after the rehabilitation clinic attendance. Methodology: In this study, a total of 50 patients who have attended long COVID rehabilitation clinic in Salford, UK; were assessed by using digitalised C19-YRS ELAROS application. A total of 100 eligible initial and final post rehabilitation assessments were analysed. Conclusion: Pain and anxiety symptoms were the two most likely symptoms to improve after intervention at LC rehabilitation clinic, whereas swallowing difficulty is least likely to improve. Issues with caring for family/ social life (symptoms affecting social role) are likely to worsen even after treatment. It is feasible to monitor and track Long COVID symptoms utilising the digitalised version of C19-YRS via the ELAROS App. This also allows the tracking of symptoms overtime.

Long COVID, also referred to as post-COVID-19 condition, describes the lingering after-effects of COVID-19 infection. This complex syndrome encompasses a range of symptoms affecting physical well-being, cognitive function, and mental health. The widespread impact of long COVID extends beyond individual sufferers, placing significant strain on healthcare systems and causing far-reaching socioeconomic consequences. The scale of this multifaceted health crisis is unparalleled in recent history, affecting millions globally and challenging our understanding of post-viral conditions. This study aimed to explore the possibility of targeting G protein-coupled receptors (GPCRs) signaling pathway-related genes as therapeutics for long COVID using computational analysis. Targeting GPCRs and their signaling pathways holds significant promise for long COVID therapeutics, as these receptors are involved in crucial physiological processes including immune regulation, inflammation control, and neurotransmission. All of these are implicated in the diverse and persistent symptoms of long COVID, potentially offering a versatile approach to addressing multiple aspects of the condition simultaneously. This study identified 21 genes associated with GPCRs for further exploration as potential targets. Notably, GPCR genes such as HRAS, KRAS, GNAQ, and GNA11 were determined to be possible therapeutic targets for the pathophysiological mechanisms of long COVID. FDA-approved drugs targeting these genes were identified, including Binimetinib, Cabozantinib, Selumetinib, Panitumumab, Cetuximab, Adagrasib, Tipifarnib, and Sotorasib. Additionally, Naltrexone and Tipifarnib have emerged as potential new treatment options for long COVID. SARS-CoV-2 may hijack GPCR signaling pathways to dysregulate lung ion and fluid transport, contributing to the pathophysiology of pulmonary edema in patients with COVID-19. Further research is required to translate the findings into the development of therapeutics and to investigate the relationship between viral infection and GPCR signalling.

This paper investigates the long-run relationship between the U.S. dollar and Canadian dollar by defragmenting the bilateral exchange rate induced by nominal and real shocks. The methodology centers on a structural vector autoregressive (SVAR) model, including the analysis of impulse response and variance decomposition to account for the impact of nominal and real shocks on exchange rate movements. The study also decomposes the real shocks into demand and supply factors from both Canada and U.S. and compare their impact on the nominal and real exchange rate. Results are compared to shocks driven by country specific nominal factors. The study is conducted using quarterly based data over December 1972 – December 2023. Findings suggest that the real shocks have a permanent impact on both the nominal and real exchange, compared with nominal shocks which have a temporary impact. Country-specific real supply-side factors have a more discerning impact than country-specific real demand-side factors. Country-specific nominal barely impacted the nominal and real exchange between U.S. and Canada.

Newborn screening (NBS) is hailed as a public health success, but little is known about long-term outcomes following a positive newborn screen. There has been difficulty gathering long-term follow-up (LTFU) data consistently, reliably, and with minimal effort. Six programs developed and tested a core set of minimal LTFU data elements. After an iterative data collection process and the development of a data collection tool, the group agreed on minimal LTFU data elements. The denominator captured all infants with an NBS diagnosis, accounting for children who moved or died prior to the follow-up year. They also agreed on three LTFU outcomes: if the child was still alive, had contact with a specialist, and received appropriate care specific to their diagnosis within the year. The six programs representing NBS public health programs, clinical providers, and research programs provided data across multiple NBS disorders. In 2022, 83.8% (563/672) of the children identified by the LTFU programs were alive and living in the jurisdiction; of those, 92.0% (518/563) saw a specialist, and 87.7% (494/563) received appropriate care. The core LTFU data elements can be applied as a foundation to address the impact of early diagnosis by NBS within and across jurisdictions.

Objective: The long-term care insurance (LTCI) system was introduced in 2000 to provide financial support for long-term care services to older adults. What is known on this topic report focuses on a comparative analysis of how the LTCI system has affected older people in Japan. Methods: We obtained data from the literature about the LTCI system, compared and analysed the collected articles, and concluded. Results: The LTCI system has improved access to long-term care services, with more older adults receiving care than before the system’s implementation. This service has improved the quality of life for many elderly individuals who require assistance with daily activities. Furthermore, the LTCI system has alleviated the financial burden of long-term care services since the insurance covers a large portion of the costs. It has made older adults maintain their independence and dignity, as they can afford the necessary care without relying solely on their savings or burdening their families. Conclusions: Japan’s LTCI system has positively impacted older adults by improving access to long-term care services and alleviating financial burdens. However, challenges such as increasing demand and variations in service quality need to be addressed to ensure the system effectively supports older people in Japan.

Landsat and Sentinel-2 acquisitions are among the most widely used medium-resolution optical data adopted for terrestrial vegetation applications, such as land cover and land use mapping, vegetation condition and phenology monitoring, and disturbance and change mapping. When combined, both data archives provide over 40 years, and counting, of continuous and consistent observations. Although the spatio-temporal availability of both data archives is well-known at the scene level, information on the actual availability of cloud-, snow-, and shade-free observations at the pixel level is lacking and should be explored individually for each study to correctly parametrize subsequent analyses. However, data exploration is time and resource consuming, thus is rarely performed a-priori. Consequently, the spatio-temporal heterogeneity of usable data is often inadequately accounted for in the analysis design, risking ill-advised selection of algorithms and hypotheses, and thus inferior quality of final results. Here we present precomputed data on the daily 1982‑2023 availability of usable Landsat and Sentinel-2 acquisitions across the globe, sampled at a pixel-level in a regular 0.18°-point grid. The dataset comprises separate Landsat- and Sentinel‑2‑specific data records, and is accompanied by a pixel-specific growing season information to facilitate data exploration. The dataset was derived based on freely available 1982-2023 Landsat surface reflectance (Collection 2) and Sentinel-2 top-of-the-atmosphere reflectance (pre‑Collection-1 and Collection-1) scenes from 2015 through 2023, following the methodology developed in the recent study on data availability over Europe [1]. Growing season information was derived based on 2001‑2019 time series of the yearly 500 m MODIS land cover dynamics product (MCD12Q2; Collection 6) [1]. As such, the dataset presents a unique overview of the spatio-temporal availability of usable daily Landsat and Sentinel-2 data at the global scale, hence offering much needed a-priori information aiding identification of appropriate methods and challenges for terrestrial vegetation analyses at local to global scale.

Long COVID–19 syndrome is another vicious feature of COVID-19 infection, the mechanism remains unidentified. Several observational studies suggest that vaccinations might have protective and therapeutic effect on long COVID-19 and our study aimed to assess the influence of vaccination on COVID-19 patients. We performed an observational cohort study from October 2020 to July 2022, which included 503 patients (291 males and 212 females) with a median age of 65. They were hospitalized due to COVID-19 pneumonia and had persistent symptoms (after 1 month of COVID-19 infection. The clinical and demographic data including vaccination status collected during hospitalization and regular visits at the Community Healthcare Center dr. Adolf Drolc Maribor were analyzed. More non-vaccinated patients acquired long COVID-19 than vaccinated. Patients with type 2 diabetes suffered from long COVID-19 in a smaller percentage than patients without diabetes. Gender, inhalational therapy due to chronic pulmonary disease and the number of complications have significantly influenced long COVID-19 development and the mostly vaccinated patients were older and with asthma/COPD. Our study confirmed that vaccination is a safe and effective measure to prevent the severe progression of acute disease and to lower the incidence of developing long COVID.

Long read sequencers, known for their effectiveness in detecting genomic structural variations (SV), are becoming a standard in comprehensive genetic analysis. In preimplantation genetic testing (PGT) for SV carriers, information on breakpoint junctions is required for the determination of carrier status in embryo selection. These sequencers are employed for challenging cases involving SVs that are difficult to analyze with conventional cytogenetical methods or detailed junctions of chromosomal translocations, providing valuable insights. They also play a crucial role in acquiring simultaneous information on surrounding single-nucleotide polymorphisms (SNPs) around causative variants in PGT. Despite their advantages, challenges related to sequencing accuracy and testing costs exist. Thus, understanding long read sequencers’ characteristics is essential for their effective utilization. This review summarizes the advanced applications of long read sequencers in preclinical workups and their integration into PGT. It also highlights in-house clinical cases, showing the implementation of long-read sequencing and discussing prospects in the field.

The COVID-19 pandemic, declared in early 2020, is an unprecedented global health crisis, causing over 7.0 million deaths and ongoing challenges. While the pharmaceutical industry expedited vaccine development, mutant SARS-CoV-2 strains remain a major fear. Moreover, concerns regarding the long-term health repercussions of COVID-19-affected individuals persist since individuals affected by mild and moderate to severe SARS-CoV-2 infection experience long-term cardiovascular complications, liver dysfunction, pulmonary afflictions, kidney impairments, and most importantly neurocognitive deficits. In recent studies, we documented pathophysiological changes in various organs following the post-acute infection of mice with murine hepatitis virus-1 (MHV-1), a coronavirus, at both 7 days and 12 months after infection. One part of the body that can be drastically affected by SARS-CoV-2 is the skin. Studies have shown major changes in the skin post-acute SARS CoV-2 infection in humans. However, long-term dermatologic changes post-COVID have never been explored. For the first time, we show several cutaneous findings both at the acute stages and long-term post-infection of mice with MHV-1 coronavirus (a promising experimental model to study acute and long-COVID). Precisely, we found destruction of the epidermal layer, an increase in the number of hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of the sebaceous glands at the acute stages, along with thinning of the panniculus carnosus, as well as the adventitial layer, which corresponds well with studies in humans. In contrast, the cutaneous investigation in the long-COVID phase shows the absence of hair follicles from both the epidermal and dermal layers, the destruction of adipose tissues, and the devastation of the epidermal layer. Further, treatment of these mice with a 15 amino acid synthetic peptide, SPIKENET (SPK), which was effective in preventing Spike glycoprotein-1 binding with host receptors, as well as has a potent anti-inflammatory response to severe inflammatory stimulus) restored the loss of hair follicles and re-architected the epidermal and dermal layers. Additionally, destruction in fatty tissue in the infected mice was successfully restored post-treatment with SPK. These findings suggest that SARS-CoV-2 initiates the changes early post-infection, leading to devastating skin alterations in the long term which can be prevented by our newly identified peptide drug SPK.

In view of the expected climate changes, a paradigm shift in soil management, through reduced tillage and/or a different use of crop residues, can be a key point in the mitigation of the climate impacts. The transition from a traditional cropping system (i.e., durum wheat in continuous cropping system under conventional tillage and/or straw removal) to those undergoing the conservative practices require to be evaluated in a medium to long time frame to reach an equilibrium and thus to be properly investigated. In this regard, cropping system simulation models are fundamental tools for the in-silico evaluation of the response of crop growth and soil organic matter dynamics to varying cropping scenarios. This paper reports the evaluations on the parameterization and reliability of the ARMOSA crop simulation model calibrated and validated on experimental datasets collected on durum wheat grown in continuous cropping system under several straw and soil management strategies in a Mediterranean environment.

Soft materials bearing rigid, lightweight, and vibration-dampening properties offer distinct advantages over traditional wooden and metal-based fillings for spent fuel transport casks, due to their low density, tunable structure, excellent mechanical properties, and ease of processing. In this study, a novel type of rigid polyurethane foams is prepared using a conventional polycondensation reaction between isocyanate and hydroxy groups. Moreover, the density and size of the pore in these foams are precisely controlled through simultaneous gas generation. The as-prepared polyurethane exhibits high thermal stability exceeding 185 °C. Lifetime predictions based on thermal testing indicate that these polyurethane foams could last up to over 60 years, which is double lifetime of conventional materials of about 30 years. Due to their occlusive structure, the mechanical properties of these polymeric materials meet the design standards for spent fuel transport casks, with maximum compression and tensile stresses of 6.89 and 1.37 MPa, respectively, at a testing temperature of -40 °C. In addition, these polymers exhibit effective flame retardancy; combustion ceased within 2 s after removal of the ignition source. All in all, this study provides a simple strategy for preparing rigid polymeric foams, presenting them as promising prospects for application in spent fuel transport casks.

Training has a significative effect on physiology of blood coagulation both in humans and in horses. Several hemostatic changes have been reported after exercise in the horse but data available are inconclusive. The aim of this study was to investigate the platelet activation and primary platelet-related hemostasis modifications in young untrained Thoroughbred racehorses in the first 4-month timeframe incremental training period in order to improve knowledge on this topic. Twenty-nine clinically healthy, untrained, 2-year-old Thoroughbred racehorses. Never trained Thoroughbreds were followed during their incremental 4-month sprint exercise schedule. Blood collection was performed once a month (T-30, T0, T30, T60, and T90). Platelet aggregation was measured by light transmission aggregometer in response to various agonists: adenosine diphosphate (ADP), collagen and calcium ionophore A23187. Platelet function was evaluated using the Platelet Function Analyzer (PFA-100®) using collagen/ADP and collagen/adrenaline cartridges. Nitrite-nitrate (NOx) plasma concentrations were measured by a colorimetric assay to assess in vivo nitric oxide bioavailability. Platelet activation was investigated also through gene expression analyses (selectin P-SELP, ectonucleotidase CD39-ENTPD1, prostaglandin I2 synthase-PTGIS, endothelial nitric oxide synthase 3-NOS3). Differences among the time points were analyzed and mean±SEM were calculated. Significant modifications were identified compared with T-30 with increase of platelet aggregation (collagen:32.6±4.8 vs 21.6±4.9%; ADP: 35.5±2.0 vs 24.5±3.1%; A23187: 30±4.7 vs 23.8±4%) and a shorter closure time of C-ADP cartridges (75.6±4.4 vs 87.7±3.4 sec) that tended to return to baseline value at T90. NOx concentrations in plasma significantly increased after 30 days of training program compared with baseline. The first long-term training period induce platelet hyperactivity already after 30 days in untrained Thoroughbreds. Regular physical training blunts the negative effects of acute efforts on platelets activation.

The study proposes a theoretical method for evaluating the 'safety against derailment' indicator of a specialized train composition for the transportation of very long rails. A composition of nine wagons, suitable for the transportation of rails with a length of 120 m, is considered. For the remaining recommended rail lengths, the number of wagons is reduced or increased, the method being modified depending on the required configuration. In accordance with the requirements of EN 14363:2019, the composition is in a curve with a radius of R=150 m. The rails bend, some of them contact the vertical stanchions of the wagon and cause additional transverse forces, which are balanced in the rail track. This is a prerequisite for derailment of the vehicle. The goal of the study is to determine the additional transverse forces that arise because of the bent rails. The task is statically indeterminate, and considering the dimensions of the rails, its solution becomes seriously difficult. For the purposes of the study, the finite element method was used. Based on the displacements of the support points of the rails (caused by the geometry of the curve) the bending line of the elastic load is determined and the forces in the supports are calculated. A group of five rails is considered, with results multiplied proportionally for cases other than five. The resulting forces are considered when determining the derailment safety criterion defined by EN 14363:2019.

The chemically synthesized polymer polyacrylamide (HPAM) in conventional reservoirs has achieved excellent oil displacement, but its oil displacement is poor in extreme reservoir environments. To develop biopolymer oil flooding agent under extreme reservoir conditions, the viscosity increasing and rheological properties of three biopolymers, diutan gum, xanthan gum, and scleroglucan, were studied under extreme reservoir conditions (high salt, high temperature, strong acid, and alkali), and the effects of temperature, mineralization, pH, and other factors on their viscosities and long-term stability properties were analyzed and compared. The results showed that under the temperature of 90℃ and below, the three kinds of biopolymers had the best viscosity-increasing ability. The viscosity of the three kinds of biopolymers was 80.94, 11.57, and 59.83mPa·s, respectively, when the concentration was 1500mg/L and the salinity was 220g/L. At the shear rate of 250s-1,100℃~140℃, scleroglucan has the best viscosification. At 140℃, the solution viscosity is 19.74mPa·s, and the retention rate can reach 118.27%. The results of the long-term stability study showed that the solution viscosity of scleroglucan with mineralization level of 220 mg/L was 89.54% viscosity retention in 40 days, and the diutan gum could be stabilized for 10 days, and the viscosity was maintained at 90 mPa·s. All three biopolymers are highly acid and alkali-resistant, with viscosity variations of less than 15% in the pH3~10 range. Rheological tests have shown that both of them have better viscoelastic properties than xanthan gum due to the peculiar double-helix structure of xanthan gum and the rigid triple-helix structure of scleroglucan. Therefore, the two biopolymers, diutan gum, and scleroglucan have the potential for extreme reservoir oil displacement applications, and it is recommended to use diutan gum for oil displacement in reservoirs up to 90℃ and scleroglucan for oil displacement in reservoirs between 100℃ and 140℃.

Humeral resurfacing arthroplasty (HRA) entails the substitution of the articular surface alone with a prosthetic cap without stem. It is a more conservative procedure which can be easily converted in a total arthroplasty if necessary. The present study aimed to evaluate the clinical and radiographical outcomes in a series of patients treated with HRA. 33 patients with a mean fol-low-up of 11 years were clinically (Constant score; Disability of the Arm, Shoulder and Hand score, DASH) and radiographically assessed before and after surgery. Constant and DASH score improved significantly after surgery, and only 2 cases needed revision surgery. HRA represents a valid therapeutic option in selected cases to improve the quality of life and delaying the need for more invasive procedures.

To explore the expression characteristics and biological functions of related genes of medicago terrestris under long day conditions, and to lay a foundation for revealing the molecular mechanism of medicago terrestris under long day conditions. The leaves of 'R108' tribulus Medicago sativa at branch stage (A), bud stage (B), initial flowering stage (C) and full flowering stage (D) were sequenced by RNA-Seq technology. The genome of Medicago sativa, a related species of Tribulus tribulus, was used as a reference genome for sequence comparison. The transcriptomes of three adjacent periods (A vs B, B vs C, C vs D) were analyzed for differentially expressed genes and photoperiod related differentially expressed genes were screened. A total of 6875 differentially expressed genes were detected. GO functional analysis showed that differentially expressed genes were mainly involved in biological processes, cell components and molecular functions, among which the most differentially expressed genes were involved in cell components. KEGG enrichment analysis showed that differentially expressed genes were mainly involved in circadian rhythm, photosynthesis - antenna protein, ribosome metabolism and other pathways. The number of single nucleotide variants detected by cSNP analysis was 312875, and the frequency of A/G and C/T were the highest. The function of eggNOG was divided into 23 categories, with a total of 26745 genes having similarities, 9008 genes were classified as function unknown, 2669 genes were classified as signal transduction mechanism, 2194 genes were classified as transcription, etc. In different developmental stages (A vs B, B vs C, C vs D), 3463 up-regulated and 3412 down-regulated differentially expressed genes were found. The difference between up-regulated and down-regulated genes was the most obvious between bud stage and initial flowering stage. In addition, a total of 79 flowering genes were found, of which 51 differential genes were screened out to participate in photoperiodic regulation pathway, 23 differential genes were up-regulated, and 28 differential genes were down-regulated. The ratio of gene-LOC11410562(GI), gene-LOC11435974(CO), gene-LOC11422615(TOC1) and gene-LOC11432385(LHY) was higher than that of gene-LOC25500742(PHYA) and gene-LOC11 431402(ELF3), gene-LOC11434778(Col13), gene-LOC25498015(Col6), and gene-LOC11415514(Col9) were preexpressed. The above differentially expressed genes were significantly expressed in different development stages of Terrestris alfalfa, which laid a foundation for further study of the molecular mechanism of Terrestris alfalfa.

Long COVID-19 syndrom appears after Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection with acute damages to microcapillaries, microthombi and endotheliitis. However, the mech-anisms involved in these processes remain to be identified. All blood vessels are lined with a monolayer of endothelial cells called vascular endothelium of which one of the major properties is to prevent coagulation. VE cadherin is a component of endothelial cell junctions responsible for maintenance of the integrity of the vessels through homophilic interaction of its Ca++- dependent adhesive extracellular domain. We first provide evidence that VE-cadherin is a target in vitro for ACE2 cleavage because its extracellular domain (hrVE-ED) contains two amino acid sequences for ACE2 substrate recognition at the po-sitions 256P-F257 and 321PMKP-325L. Indeed, incubation of hrVE-ED with the active ecto-peptidase hrACE2 for 16 hrs in the presence of 10M ZnCl2 showed a dose-dependent (from 0.2 ng/ul to 2 ng/ul) decrease of the VE-cadherin immunoreactive band. In vivo, in the blood from patients having severe COVID-19, a circulating form of ACE2 was detected with an apparent molecular mass of 70 kDa while it was barely detectable in patients with mild infection. Of importance, in the patients with severe COVID-19 disease, the presence of three soluble fragments of VE-cadherin (70, 62, 54 kDa) were detected using the antiEC1 antibody while only the 54 kDa fragment was present in patients with mild disease. Altogether, these data clearly support a role for ACE2 on VE-cadherin cleavage leading to potential biomarkers in SARS-CoV2 infection related with the vascular disease in “Long COVID-19”.

The dynamics of suspended sediment involves inherent non-linearity and complexity as a result of the presence of both spatial variability of the basin characteristics and temporal climatic patterns. As a result of this complexity, the conventional sediment rating curve (SRC) and other empirical methods produce inaccurate predictions. Deep neural networks (DNNs) have emerged as one of the advanced modeling techniques capable of addressing inherent non-linearity in hydrological processes over the last few decades. DNN algorithms are used to perform predictive analysis and investigate the interdependencies among the most pivotal water quantity and quality parameters i.e., discharge, suspended sediment concentration (SSC), and turbidity. In this study, the Long short-term memory (LSTM) algorithm of DNNs is used to model the discharge-suspended sediment relationship for the Stony Clove Creek. The simulations were run using primary data on discharge, SSC and turbidity. For the development of the DNN models and examining the effects of input vectors, combinations of different input vectors (namely discharge, and SSC) for the current and previous days are considered. Furthermore, a suitable modelling approach with an appropriate model input structure is suggested based on model performance indices for the training and testing phases. The performance of developed models is assessed using statistical indices such as root mean square error (RMSE), mean absolute error (MAE), and coefficient of determination (R2). Statistically, the performance of DNN-based models in simulating the daily SSC performed well with observed sediment concentration series data. The study demonstrates the suitability of the DNN approach for simulation and estimation of daily SSC, opening up new research avenues for applying hybrid soft computing models in hydrology.

This article presents the implementation of a model to estimate the future price of commodities in the Brazilian market from time series of short-term technical evaluation. For this, data from two databases were used, one referring to the foreign market (opening values, maximum, minimum, closing, closing adjustment and volume) and the other, from the Brazilian market (the price of the day), considering commodities, sugar, cotton, corn, soybean and wheat. Subsequently, the technical indicators were calculated from the TA-Lib technical analysis library. Pearson’s correlation coefficient was applied, records with low correlation were removed, and then the database was consolidated. From the pre-processed data, Long Short-Term Memory (LSTM) recurrent neural networks were used to perform data prediction at the one and three day interval. These models were evaluated using the mean square error (MSE), obtaining results between 0.00010 and 0.00037 on test data one day ahead, and from 0.00017 to 0.00042 three days ahead. However, based on the results obtained, it was observed that the developed model obtained a promising forecasting performance for all the commodities evaluated. As a main contribution, there is the consolidation of databases that can be used in future scientific research. Furthermore, based on its interpretation, it can assist in decision making regarding the buying and selling of commodities to increase financial gains.

Background: COVID-19 made its debut as a pandemic in 2020; since then, more than 607 million cases and at least 6.5 million deaths have been reported worldwide. While the burden of disease has been described, the long-term effects or chronic sequelae are still being described. Objective: To describe the findings of a current systematic review of the long-term effects related to post-COVID-19 sequelae. Design: A systematic review was carried out in which cohort studies, case series, clinical case reports were included, and the PubMed, Scielo, SCOPUS and Web of Science databases were ex-tracted. Information published 2020 to June 1, 2022, was sought. Results: We reviewed 300 manuscripts during the first step of the literature review process. Then 260 abstracts were analyzed. In the end, we included 32 manuscripts: 9 for pulmonary, 6 for cardiac, 2 for renal, 9 for neurological and psychiatric, and 8 for cutaneous sequelae. Conclusion: Studies show that the most common sequelae are those linked to the lungs, followed by skin, cutaneous and psychiatric alterations. Women report a higher incidence of the sequelae, as well as those with comorbidities and severer COVID-19 history. The COVID-19 pandemic has not only caused death and disease since its apparition but has also sickened millions of people around the globe who potentially suffer from serious illnesses that will continue to add to the list of health problems and further burden healthcare systems around the world.

Previous studies have quantified repolarization variability using time-domain, frequency-domain and non-linear analysis in mouse hearts. Here, we investigated the relationship between these parameters and ventricular arrhythmogenicity in a hypokalaemia model of acquired long QT syndrome. Methods: Left ventricular monophasic action potentials (MAPs) were recorded during right ventricular regular 8 Hz pacing during normokalaemia (5.2 mM [K+]), hypokalaemia modelling LQTS (3 mM [K+]) or hypokalaemia with 0.1 mM heptanol in Langendorff-perfused mouse hearts. Results: During normokalaemia, mean APD was 33.5±3.7 ms. Standard deviation (SD) of APDs was 0.63±0.33 ms, coefficient of variation was 1.9±1.0% and the root mean square (RMS) of successive differences in APDs was 0.3±0.1 ms. Low- and high-frequency peaks were 0.6±0.5 and 2.3±0.7 Hz, respectively, with percentage powers of 38±22 and 61±23%. Poincaré plots of APDn+1 against APDn revealed ellipsoid morphologies with SD along the line-of-identity (SD2) to SD perpendicular to the line-of-identity (SD1) ratio of 4.6±1.1. Approximate and sample entropy were 0.49±0.12 and 0.64±0.29, respectively. Detrended fluctuation analysis revealed short- and long-term fluctuation slopes of 1.62±0.27 and 0.60±0.18, respectively. Hypokalaemia provoked ventricular tachycardia in six of seven hearts, prolonged APDs (51.2±7.9 ms), decreased SD2/SD1 ratio (3.1±1.0), increased approximate and sample entropy (0.68±0.08 and 1.02±0.33) and decreased short-term fluctuation slope (1.23 ± 0.20) (ANOVA, P<0.05). Heptanol prevented VT in all hearts studied without further altering the above repolarization parameters observed during hypokalaemia. Conclusion: Reduced SD2/SD1, increased entropy and decreased short-term fluctuation slope are associated with ventricular arrhythmogenesis in hypokalaemia. Heptanol exerts anti-arrhythmic effects without affecting repolarization variability.

Glioblastoma (GBM) is a very aggressive malignant brain tumor with the vast majority of patients surviving less than 12 months (Short-term survivors [STS]). Only around 2% of patients survive more than 36 months (Long-term survivors [LTS]). Studying these extreme survival groups might help in better understanding GBM biology. This work aims at exploring application of machine learning methods in predicting survival groups(STS, LTS). We used age and gene expression profiles belonging to 249 samples from publicly available datasets. 10 Machine learning methods have been implemented and compared for their performances. Hyperparameter tuned random forest model performed best with accuracy of 80% (AUC of 74% and F1_score of 85%). The performance of this model is validated on external test data of 16 samples. The model predicted the true survival group for 15 samples achieving an accuracy of 93.75%. This classification model is deployed as a web tool GlioSurvML. The top 1500 features which retained classification efficiency (Accuracy of 80%, AUC of 74%) were studied for enriched pathways and disease-causal biomarker associations using the HumanPSD^TM database. We identified 199 genes as possible biomarkers of GBM and/or similar diseases (like Glioma, astrocytoma, and others). 57 of these genes are shown to be differentially expressed across survival groups and/or have impact on survival. This work demonstrates the application of machine learning methods in predicting survival groups of GBM.

This work focuses on analyzing acoustic emission (AE) signals as a means to predict failure in structures. Two main approaches are considered: (i) long-range correlation analysis using both the Hurst (H) and the Detrended Fluctuation Analysis (DFA) exponents, and (ii) natural time domain (NT) analysis. These methodologies are applied to the data collected from two application examples: a glass fiber reinforced polymeric plate and a spaghetti bridge model, where both structures were subjected to increasing loads until collapse. A traditional (AE) signal analysis is also performed to reference the study of the other methods. Results indicate that the proposed methods yield a reliable indication of failure in the studied structures.

Indiana Vesiculovirus (IVV; formerly as Vesicular stomatitis virus and Vesicular stomatitis Indiana virus) causes a disease in livestock that is very similar to the foot and mouth disease thereby an outbreak may lead to significant economic loss. Long-read sequencing (LRS) -based approaches revealed a hidden complexity of the transcriptomes in several viruses already. This technique was utilized already for the sequencing of the IVV genome, but our study is the first for the application of this technique for the profiling of IVV transcriptome. Since LRS is able to sequence full-length RNA molecules, and thereby providing more accurate annotation of the transcriptomes than the traditional short-read sequencing methods. The objectives of this study were to assemble the complete transcriptome of using nanopore sequencing, to ascertain cell-type specificity and dynamics of viral gene expression and to evaluate host gene expression changes induced by the viral infection. We carried out a time-course analysis of IVV gene expression in human glioblastoma and primate fibroblast cell lines using a nanopore-based LRS approach and applied both amplified and direct cDNA sequencing, as well as cap-selection for a fraction of samples. Our investigations revealed that, although the IVV genome is simple, it generates a relative complex transcriptomic architecture. In this study, we also demonstrated that IVV transcripts vary in structure and exhibit differential gene expression patterns in the two examined cell types.

Deep neural networks (DNNs) have made a huge impact in the field of machine learning by providing unbeatable humanlike performance to solve real-world problems such as image processing and natural language processing (NLP). Convolutional neural network (CNN) and recurrent neural network (RNN) are two typical architectures that are widely used to solve such problems. Time sequence-dependent problems are generally very challenging, and RNN architectures have made an enormous improvement in a wide range of machine learning problems with sequential input involved. In this paper, different types of RNN architectures are compared. Special focus is put on two well-known gated-RNN’s Long Term Short Memory (LSTM) and Gated Recurrent Unit (GRU). We evaluated these models on the task of force estimation system in pouring. In this study, four different models including multi-layers LSTM, multi-layers GRU, single-layer LSTM and single-layer GRU) were created and trained. The result suggests that multi-layer GRU outperformed other three models.

In fisheries monitoring, catch is assumed to be a product of fishing intensity, catchability, and availability, where availability is defined as the number or biomass of fish present and catchability refers to the relationship between catch rate and the true population. Ecological monitoring programs use catch per unit of effort (CPUE) to standardize catch and monitor changes in fish populations; however, CPUE is proportional to the portion of the population that is vulnerable to the type of gear that is used in sampling, which is not necessarily the entire population. Programs often deal with this problem by assuming that catchability is constant, but if catchability is not constant, it is not possible to separate the effects of catchability and population size using monitoring data alone. This study uses individual-based simulation to separate the effects of changing environmental conditions on catchability and availability in environmental monitoring data. The simulation combines a module for sampling conditions with a module for individual fish behavior to estimate the proportion of available fish that would escape from the sample. The method is applied to the case study of the well-monitored fish species Delta Smelt (Hypomesus transpacificus) in the San Francisco Estuary, where it has been hypothesized that changing water clarity may affect catchability for long-term monitoring studies. Results of this study indicate that given constraints on Delta Smelt swimming ability, it is unlikely that the apparent declines in Delta Smelt abundance are due to an effect of changing water clarity on catchability.

Multicomponent training is recommended for people with dementia living in long-term care homes. Nevertheless, evidence is limited and people with severe dementia are often excluded from trials. Hence, the aim of this study was to investigate (1) the feasibility and (2) the requirements regarding a multicomponent training for people with moderate to severe dementia. The study was conducted as an uncontrolled single arm pilot study with a mixed methods approach. 15 nursing home residents with a mean age of 82 years (range: 75-90 years; female: 64%) with moderate to severe dementia received 16 weeks of multicomponent training. Feasibility and requirements of the training were assessed by a standardized observation protocol. Eleven participants regularly attended the intervention. The highest active participation was observed during gait exercises (64%), the lowest during strength exercises (33%). It was supportive if exercises were task-specific or related to everyday life. This study confirms that a multicomponent training for the target group is (1) feasible and well accepted. To enhance active participation (2) individual instructions and the implementation of exercises related to everyday life is required. The effectiveness of the adapted training should be tested in future randomized controlled trials.

Processing of the RNA polymerase I pre-rRNA transcript into the mature 18S, 5.8S, and 25S rRNAs requires removing the “spacer” sequences. The canonical pathway for the removal of the ITS1 spacer, located between 18S and 5.8S rRNAs in the primary transcript, involves cleavages at the 3’ end of 18S rRNA and at two sites inside ITS1. The process generates a long and a short 5.8S rRNA that differ in the number of ITS1 nucleotides retained at the 5.8S 5’ end. Here we document a novel pathway that generates the long 5.8S for ITS1 while bypassing cleavage within ITS1. It entails a single endonuclease cut at the 3’-end of 18S rRNA followed by exonuclease Xrn1 degradation of ITS1. Mutations in RNase MRP increase the accumulation of long relative to short 5.8S rRNA; traditionally this is attributed to a decreased rate of RNase MRP cleavage at its target in ITS1, called A3. In contrast, we report here that the MRP induced switch between long and short 5.8S rRNA formation occurs even when the A3 site is deleted. Based on this and our published data, we propose that the switch may depend on RNase MRP processing RNA molecules other than pre-rRNA.

The population dynamics of Hazel Grouse was studied by presence/ absence recording at stationary sites along fixed routes (110 km) during 1972-2019 in the central part of the Bohemian Forest (Šumava, Czech Republic). The 100-km² study area covered altitudes between 600 m (Rejstejn) and 1,253 m a.s.l., (mount Sokol). Our data base contained indices of Hazel Grouse occupancy: positive sites/ controlled sites for a yearly increasing number of Hazel Grouse occurrence sites (N = 134) for 48 years. We used a loglinear Poisson-regression method to analyze the long-term population trend for Hazel Grouse in the study area. In the period 1972 to 2006 we found a stable Hazel Grouse population (p = 0.83). From 2006-2007 to 2019, the population index dropped (-3.8% per year, p &lt; 0.05) for the last 13 years. This decline is assumed to be influenced by habitat loss due to succession resulting in older, more open forest stands, by strongly increasing forestry and windstorm “Kyrill” followed by clear cutting, bark-beetle damage, and removal of pioneer trees in spruce plantations, which diminished buds and catkins, the dominant winter food. The influence of disturbance by increasing touristic activities and/or predation is discussed. Our results could help to optimize conservation efforts for Hazel Grouse in the Bohemian Forest.

Long-chain branched metallocene-catalyzed high-density polyethylenes (LCB-mHDPE) were solution blended to obtain blends with varying degrees of branching. A high molecular LCB-mHDPE was mixed with low molecular LCB-mHDPE are varying concentrations, whose rheological behavior is similar but whose molar mass and molar mass distribution is significantly different. Those blends were characterized rheologically to study the effects of concentration, molar mass distribution, and long-chain branching level of the low molecular LCB-mHDPE. Owing to the ultra-long relaxation times of the high molecular LCB-mHDPE, the blends started behaving clearly more long-chain branched than the base materials. The thermorheological complexity showed an apparent increase in the activation energies Ea determined from G’, G”, and especially δ. Ea(δ), which for LCB-mHDPE is a peak function, turned out to produce even more pronounced peaks than observed for regular LCB-mPE and also LCB-mPE with broader molar mass distribution. Thus, it is possible to estimate the molar mass distribution from the details of the thermorheological complexity.

In order to reconstruct the origin and pathways of variola virus (VARV) dispersion, we analyzed 47 VARV isolates available in public databases and their SNPs. The mean substitution rate of the whole genomes was 9.41x10-6 (95%HPD:8.5-11.3x10-6) substitutions/site/year. The time of the tree root was estimated to be a mean 68 years (95%HPD:60.5–75.9). The phylogeographical analysis showed that the Far East and India were the most probable locations of the tree root and of the inner nodes, respectively, whereas for the outer nodes it corresponded to the sampling locations. The Bayesian Skyline plot showed that the effective number of infections started to grow exponentially in 1915-1920, peaked in the 1940s, and then decreased to zero. Our results suggests that the VARV major strains circulating between 1940s-1970s probably shared a common ancestor originated in the Far East; subsequently moved to India, which became the center of its dispersion to eastern and southern Africa, and then to central Africa and the Middle East, probably following the movements of people between south-eastern Asia and the other places with a common colonial history. These findings may help to explain the controversial reconstructions of the history of VARV obtained using long- and short- term calibrations.

Metastatic pancreatic ductal adenocarcinoma pancreatic (PDAC) is characterized by poor prognosis and short survival. Today, the use of new polytherapeutic regimens increases clinical outcome of these patients opening new clinical scenario. A crucial issue related to the actual improvement achieved with these new regimens is represented by the occasional possibility to observe a radiological complete response of metastatic lesions in patients with synchronous primary tumor. What could be the best therapeutic management of these patients? Could surgery represent an indication? Herein we reported a case of a patient with a PDAC of the head with multiple liver metastasis, who underwent first line chemotherapy with mFOLFIRINOX. After 10 cycles, he achieved a complete radiological response of liver metastases and a partial response of pancreatic lesion. A, duodenocephalopancreasectomy was performed. Due to liver a lung metastases after 8 months from surgery, a second line therapy was started with a disease free survival and overall survival of 8 months and 45 months, respectively. Improvement in the molecular characterization of PDAC could help in the selection of patients suitable for multimodal treatments.

A long-term investigation of D. suzukii dynamics in wild blueberry fields from 2012 - 2018 demonstrates relative abundance is still increasing seven years after initial invasion. Relative abundance is determined by physiological date of first detection and air temperatures the previous winter. Date of first detection of flies does not determine date of fruit infestation. The level of fruit infestation is determined by year, fly pressure, and insecticide application frequency. Frequency of insecticide application is determined by production system. Non-crop wild fruit and predation influences fly pressure; increased wild fruit abundance results in increased fly pressure. Increased predation rate reduces fly pressure, but only at high abundance of flies, or when high levels of wild fruit are present along field edges. Male sex ratio might be declining over the seven years. Action thresholds were developed from samples of 92 fields from 2012 - 2017 that related cumulative adult male trap capture to the following week likelihood of fruit infestation. A two-parameter gamma density function describing this probability was used to develop a risk-based gradient action threshold system. The action thresholds were validated from 2016-2018 in 35 fields and were shown to work well in two of three years (2016 and 2017).

Due to its devastating consequences, late life depression is an important public health problem. The aim of the study was the analysis of variables which may potentially influence risk of depression (GDS-SF). Furthermore, the aim was to study possible mediating effect of given variables on the relationship between the total protein concentration and risk of depression in older-adults with chronic diseases, and physical function impairment. The research sample included a total of 132 older adults with chronic conditions and physical function impairments, remaining under a long-term care in residential environment. Negative linear correlation was observed between patients’ physical functionality, total protein concentration, concentration of HDL cholesterol, arm circumference, and the risk of depression. Considerably stronger relationship was observed between total protein concentration, and GDS-SF, in elderly suffering from sensory dysfunction (b = −6.42, 95% CI = −11.27; −1.58). The effect of the mediation between depression risk is correlated to total protein concentration in blood serum, and the mediators are probably low function impairment and low levels of 25 (OH)D vitamin. Cohort control research is suggested to confirm the hypothesis.

The rapid growth rate of the elderly population is a serious current issue in most countries, affecting them economically through needed medical treatment and healthcare planning. The priority concern is how to reduce the number of elderly people requiring long-term healthcare and raise the number who are able to live independently. This study executed a behavior assessment of elderly person’s self-reported use of electric scooters and analyzed their degree of acceptance of these assisted living tools, partly through a related factor analysis of our survey instrument. We used this questionnaire survey as our research method, applying SPSS22 software for factor analysis that revealed five survey facets.

Using recent developments in econometrics and computational statistics we consider the estimation of the instantaneous rate of asset return process when the underlying Data Generating Mechanism (DGM) is an Ornstein-Uhlenbeck process, driven by fractional noise, and sampled at fixed intervals of length h. To address the problem we adopt throughout the paper an exact discretization approach. This enable us to exploit the fact that a flow sampling scheme arises naturally when observing the DGM. For, while the instantaneous rate of return process is unobservable at points in time, its time integral over successive observations is observable since it equals the increment of log-prices. Exact discretization delivers an ARIMA(1,1,1) model for log-prices with a fractional driving noise. Building on the resulting exact discretization formulae and covariance function, a new Markov Chain Monte Carlo (MCMC) scheme is proposed and we examine the properties of both the time and frequency domain likelihoods / posteriors through Monte Carlo. For the exact discrete model we adopt a general sampling interval of length h. This allow us to determine the optimal choice of h independent of the sample size. An empirical application using high frequency stock price data is presented showing the relevance of aggregation over time issues in modelling asset prices.

Background and objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS is a common complex multi-system disease with a significant impact on the quality of life of patients and their families, yet the majority of ME/CFS patients go unrecognised or undiagnosed. For two decades the medical education establishment in the UK has been challenged to remedy these failings, but little has changed. This study was designed to ascertain the current UK medical school education on ME/CFS and to identify challenges and opportunities to inform the future of medical education. Materials and methods: A questionnaire, developed under the guidance of the Medical Schools Council, was sent to all 34 UK Medical Schools to collect data for the academic year 2018-2019. Results: Responses were provided by 22 out of a total of 34 medical schools (65%). 59% of respondents taught ME/CFS, led by specialists drawn from 6 medical disciplines. Teaching delivery was usually by lecture; however, discussion case studies and e-learning were used. 7 schools included questions on ME/CFS in their examinations and 3 schools reported likely clinical exposure to ME/CFS patients. 64% of respondents were interested in receiving further teaching aids in ME/CFS. None of the schools shared details of their teaching syllabus so it was not possible to ascertain what students were being taught. Conclusions: UK medical school teaching in ME/CFS is shown to be inadequate. Several medical disciplines, with known differences about the disease, need to set these aside to give greater clarity in teaching undergraduates so they can more easily recognise and diagnose ME/CFS. Improvements are proposed in ME/CFS medical education consistent with the international paradigm shift in biomedical understanding of this disease. Many medical schools (64% of respondents) acknowledge this need by expressing a strong appetite for the development of further teaching aids and materials. The GMC and MSC are called upon to use their considerable influence to bring about the appropriate changes to medical school curricula so future doctors can recognise, diagnose and treat ME/CFS. The GMC should also consider creating a registered speciality encompassing ME/CFS, post viral fatigue and Long Covid.

In this study, we provided an empirical testability of the FF3FM against the co-moment-augmented FF3FM using the Newey–West GMM methods to account for potential endogeneity. The results showed that value risk is not significantly priced, and systematic skewness and systematic kurtosis play more important roles in explaining asset return than market and size factors. We discovered that there is much to gain in moving from the incumbent FF3FM to the co-moment-augmented FF3FM. By extending this study to Nigeria and using out-of-sample data that span across the recent COVID-19 period, the study has contributed to existing knowledge significantly. The study concludes that the co-moment-augmented FF3FM is superior to the incumbent FF3FM in pricing assets, and the anomalies associated with the return-size risk factor relationship are reduced by accounting for systematic skewness and systematic kurtosis in the FF3FM. Therefore, we recommend that investors should take a long position in size-hedged portfolios and hold systematic skewness and kurtosis as constant, and vice visa.

Asthma is a chronic respiratory disease characterized by hyperreactivity in the airways, which can lead to significant lung damage if not properly managed. While placebos—medications with no active therapeutic ingredients—are sometimes used in clinical trials to gauge the effectiveness of asthma treatments, their long-term use raises concerns. Placebos work primarily through psychological mechanisms by enhancing patients’ expectations of treatment. However, prolonged reliance on placebo treatment in asthma could potentially mask symptoms, delay proper management, and lead to undetected lung damage or other adverse effects. This study explores the potential risks and consequences associated with long-term placebo use in asthma management.

Long COVID, characterized by persistent symptoms lasting from weeks to several months following initial infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), significantly impacts individuals' quality of life and poses a potential long-term burden on global healthcare systems. Clinical manifestations of Long COVID are diverse, affecting multiple systems including respiratory, cardiovascular, neurological, and gastrointestinal. While the precise mechanisms underlying Long COVID remain unclear, emerging evidence suggests involvement of various bodily pathways. This study employs bioinformatics tools to investigate the mechanisms of Long COVID and identify potential drug targets associated with key pathways, including inflammation, cytokines, immune response, coagulation, mitochondrial function, oxidative stress, and autonomic dysfunction. Tools such as the National Center for Biotechnology Information (NCBI) database, PubChem, UniProt, and iGEMDOCK were utilized for pathway analysis and molecular docking. The analysis aimed to identify drug molecules that may interact with target proteins to regulate or inhibit pathway activity, yielding several potential drug candidates for further investigation.

Background and objective: The impairments and duration of PASC (Post-acute sequelae of COVID-19) symptoms in mental health have up to date not been comprehensively examined. Our objective is to provide longitudinal data on the mental health of Post-COVID patients and to identify risk and protective factors associated with a severe or prolonged course. Methods: Mental health of 265 Post-COVID patients of the outpatient Post-COVID centre of the University-Hospital Erlangen was assessed 17.1 (T0) and 22.5 months after infection (T1). An online survey with validated questionnaires for Post-COVID symptoms (Post-COVID-Syndrome-Score), depression (Patient-Health-Questionnaire 9), somatic symptoms (Patient-Health-Questionnaire 15), anxiety (Generalized-Anxiety-Disorder 7), fatigue (Fatigue-Severity-Scale) and Post-Exertional Malaise (PEM) (DePaul Post-Exertional-Malaise Screening) was conducted in the home environment. Results: 80% of patients experienced severe PASC at follow up. Clinically relevant symptoms of depression, persistent somatic symptoms, anxiety, and fatigue were reported by 55.8%, 72.5%, 18.9% and 89.4% respectively. Depressive, anxiety and somatic symptom severity decreased significantly over time; fatigue and PEM remained on an unchanged high level. Risk factor for higher depression scores was older age; prior psychiatric illness treated with psychotherapy was associated with more severe depressive, somatic, anxiety and PASC symptoms. PEM symptoms were significantly associated with longer duration between acute infection and initial presentation in the Post-COVID centre. Conclusion: Our findings align with previous research, claiming severe mental health symptoms in PASC syndrome, lasting for months after infection. In-depth assessment of risk and protective factors for mental health implications of PASC is needed for planning health services and disease prevention.

Acute myeloid leukemias are characterized by genetic alterations that lead to a complete or partial block at various stages of myeloid differentiation, leading to continual proliferation of myeloid progenitor cells. These alterations can include a well-documented chromosomal translocation that leads to the synthesis of the PML-retinoic acid receptor fusion protein that leads to a block in differentiation and the ability to induce differentiation with all-trans retinoic acid and other small molecules. In essence, in large part, the disease is due to stem cell-like cells that are blocked in their ability to undergo terminal differentiation to more mature, non-proliferative cell types. We discovered a long non-coding RNA (lncRNA), lncRNAp53int1, encoded from the first intron of the p53 tumor suppressor gene. Interestingly, lncRNAp53int1 appears to play an important regulatory role in maintaining the undifferentiated and proliferative state in a manner independent from p53 gene expression. lncRNAp53int1 is expressed at high levels in proliferating, undifferentiated promyelocytes and its levels fall significantly during their terminal differentiation to non-proliferating granulocytes or macrophages. Furthermore, forced overexpression of lncRNAp53int1 blocks terminal differentiation. The observation that the expression of this lncRNA is repressed during terminal differentiation of human leukemic cells and its expression blocks differentiation of leukemic myeloid progenitor cells, is likely to have clinical implications with regards to differentiation therapy for myeloid leukemia. Ongoing research aims to identify the molecular partners that it associates with and the signaling pathways that this lncRNA participates in with the long-term goal of identifying molecules that inhibit lncRNAp53int1 activity and serve as potential therapeutic drugs. The goal of this mini-review is to disseminate these novel and interesting findings to readers and to describe where we think this research is headed and the impact it can have on myeloid leukemias.

This study examines the feasibility of using event-related potentials (ERPs) obtained from electroencephalographic (EEG) recordings as biomarkers for long-term memory item classification. Previous studies have identified old/new effects in memory paradigms associated with explicit long-term memory and familiarity. Recent advancements in convolutional neural networks (CNNs) have enabled the classification of ERP trials under different conditions and identification of features related to neural processes at the single-trial level. We employed this approach to compare three CNN models with distinct architectures using experimental data. Participants (N = 25) performed an association memory task while recording ERPs that were used for training and validation of the CNN models. The EEGNET-based model achieved the most reliable performance in terms of precision, recall, and specificity compared with the shallow and deep convolutional approaches. The classification accuracy of this model reached 70% for known items and 62% for unknown items. Good overall accuracy requires a trade-off between recall and specificity and depends on the architecture of the model and the dataset size. These results suggest the possibility of integrating ERP and CNN into online learning tools and identifying the underlying processes related to long-term memorization.

The persistence of symptoms following COVID-19 infection represents a significant challenge in healthcare management. During the outbreak, tele-rehabilitation emerged as a new tool to support healthcare structures in providing rehabilitation services. This study assessed the effectiveness and the feasibility of a 3-week home-based motor and respiratory rehabilitation program for long COVID-19 individuals after traditional rehabilitation. Twenty-three patients completed the program and underwent functional tests at different time points (i.e. baseline, after hospital discharge, and after tele-rehabilitation). Motor function was evaluated using the instrumented Six-Minutes Walking Test (i6MWT), with monitored heart rate and oxygen saturation. Conversely, respiratory function was measured via forced vital capacity (FVC) and maximal voluntary ventilation (MVV) tests. Significant improvements (p &lt; 0.05) in motor and respiratory function were observed throughout the intervention, including an 18.3% increase in walked distance from the baseline. The findings suggest that a home-based tele-rehabilitation can enhance motor and respiratory function in post-COVID patients. Despite limitations such as sample size and lack of control group, the positive outcomes seem to support the feasibility of the proposed tele-rehabilitation program in managing long COVID symptoms and promoting functional recovery. Further research is needed to validate these findings and explore tele-rehabilitation’s potential in broader patient populations.

Recent studies, typically using patient cerebrospinal fluid (CSF), have suggested that different autoantibodies (Aabs) acting on their respective receptors, may underlie neuropsychiatric disorders. The NR1 subunit of the N-methyl-D-aspartate receptor (NMDAR) has been identified as a target of anti-NMDAR Aabs in a number of central nervous system (CNS) diseases including encephalitis and autoimmune epilepsy. However, the role or the nature of Aabs responsible for effects on neuronal excitability and synaptic plasticity is yet to be established fully. Patient-derived anti-NMDAR Aabs have been shown to bind to specific regions within the NR1 subunit; here, peptide immunisation was used to generate Aabs against selected specific NR1 extracellular sequences. ‘Protein A’ purification was used to obtain total IgG and further peptide purification used to obtain a greater percentage of NMDAR-target specific IgG Aabs. Binding and specificity of these anti-NMDAR Aabs was determined using a range of methodologies including enzyme-linked immunosorbent assay, immunocytochemistry and immunoblotting. Functional effects were determined using different in vitro electrophysiology techniques: two-electrode voltage-clamp in Xenopus oocytes and measures of long-term potentiation (LTP) in ex vivo hippocampal brain slices using multi-electrode arrays. We show that anti-NMDAR Aabs generated from peptide immunisation had specificity for NR1 immunisation peptides as well as target-specific binding to the native protein. Anti-NMDAR Aabs had no clear effect on isolated NMDARs in an oocyte expression system. However, we show that peptide-purified anti-NMDAR Aabs prevented the induction of LTP at Schaffer collateral-CA1 synapses in ex vivo brain slices. Our data demonstrate that anti-NMDAR Aabs cause synaptic NMDAR hypofunction at a network level. This work provides a solid basis to address outstanding questions regarding anti-NMDAR Aabs mechanisms of action and, potentially, development of therapies against CNS diseases.

With the escalation of size and complexity of modern Denial of Service attacks, there is a need for research in the context of Machine Learning (ML) used in attack execution and defense against such attacks. This paper investigates the potential use of ML in generating behavioral telemetry data using Long-Short Term Memory network and spoofing requests for the analyzed traffic to look legitimate. For this research, a custom testing environment was built, that listens for mouse and keyboard events and analyzes them accordingly. While the economic feasibility of this attack currently limits its immediate threat, advancements in technology could make it more cost-effective for attackers in the future. Therefore, proactive development of countermeasures remains essential to mitigate potential risks and stay ahead of evolving attack methods.

Stroke represents one of the neurological diseases most responsible for death and permanent disability in the world. Different factors, such as thrombus, emboli and atherosclerosis, take part in the intricate pathophysiology of stroke. Comprehending the molecular processes involved in this mechanism is crucial to developing new, specific and efficient treatments. Some common mechanisms are excitotoxicity and calcium overload, oxidative stress, and neuroinflammation. Furthermore, non-coding RNAs (ncRNAs) are critical in pathophysiology and recovery after cerebral ischaemia. ncRNAs, particularly microRNAs, and the long non-coding RNAs (lncRNAs) are essential for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. This review summarizes the intricate molecular mechanisms underlying ischemic and hemorrhagic stroke and delves into the function of miRNAs in the development of brain damage. Furthermore, we will analyze new perspectives on treatment based on molecular mechanisms in addition to traditional stroke therapies.

Background: Nutritional status and oxidative stress have been implicated in the pathogenesis and persistence of long COVID, but data in patients undergoing hemodialysis (HD) are limited. The present study aimed to investigate the association between pre-infection nutritional status, oxidative stress, and one-year long COVID persistence in HD patients. Methods: This prospective observational cohort study enrolled 115 HD patients with confirmed COVID-19. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score twice: before infection and three months post-infection. Oxidative markers included malondialdehyde (MDAs), ceruloplasmin, transferrin, and sulfhydryl groups. The endpoint was one-year long COVID persistence. Results: Moderate pre-infection CONUT scores were associated with heightened severe undernutrition risk (p &lt; 0.0001), elevated MDAs (p &lt; 0.0001), and reduced ceruloplasmin levels (p = 0.0009) at three months post-COVID-19 compared to light CONUT scores. Pre-infection CONUT score independently predicted post-COVID oxidative damage [OR 2.3 (95%CI 1.2; 4.6), p &lt; 0.0001] and one-year long COVID persistence [HR 4.6 (95%CI 1.4; 9.9), p &lt; 0.0001], even after adjusting for potential confounders. Conclusion: Moderate pre-infection undernutrition in patients undergoing HD associated with increased post-COVID oxidative stress intensity and heightened risk of one-year long COVID persistence.

The severe and complex COVID-19 symptoms, often needing hospital care, occur suddenly, late in the virus replication stage of SARS-CoV-2 infection. Hospitalised patients have tissue damage due to micro-clots at multiple sites. Could long-covid, also clinically variable, be a milder form caused by “nano-clots”, too small to cause detectable tissue damage? The timing and suddenness of the onset of serious disease needs an explanation. A paper reported on the first 20 children needing urgent hospital care. No child had any symptoms prior to suddenly becoming seriously ill, only one had a positive PCR test but all had positive SARS-CoV-2 antibody test. That finding indicated to me that this onset occurred at the moment of sero-conversion. An emerging viral moiety, the virion-IgG-antibody complex, has concentrations rapidly increasing, then decreasing. It is known that influenza-IgG-antibody-complex consists of many virions bound together by the antibody. It seems a reasonable step to propose that SARS-2, being a large virus and having many spike proteins, can form larger clumps of virus-IgG-antibody complexes than with influenza, the former being sufficiently large to initiate micro-clots. Therefore, my hypotheses is that the SARS-CoV-2 virion-antibody complex initiates micro-clot formation. Either before or after sero-conversion, the complex will be at too low a concentration to initiate micro-clots. To be useful, a hypothesis should be testable, provide explanations and give predictions. My presentation will give examples. I like the way that several apparently separate pieces of a jig-saw puzzle have come together to form a single picture. [I suggest that the reader scrolls down to the addenda [10,11 & 12] before reading the ICAR Poster]

The article delves into the intricate phase transitions of 1-Octadecanol and n-Nonadecane within a binary system, unveiling dynamic structural changes under varying conditions. Through Fouri-er-transform infrared (FTIR) analysis, specific molecular vibrations were identified, shedding light on the molecular composition and interactions. The study highlights the challenges in detecting subtle phase transitions and emphasizes the individuality of molecular behaviours in closely related compounds. The findings underscore the complexity of phase transitions in binary systems and advocate for a nuanced approach to studying molecular structures and behaviours. Addi-tionally, the research contributes valuable insights into the molecular dynamics of Organic Polymer Functional Adsorption Materials, offering implications for synthetic waxy layers in plant epidermis.

For the treatment of cancer and other diseases, therapeutic targeting of non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) is an attractive approach. RNA-based therapeutics have been extensively researched over the past decade, with antisense oligonucleotides and small interfering RNAs being the most commonly used. Some of these have even gained FDA approval. However, the results of trials have been mixed, with some studies reporting strong effects while others have shown limited effectiveness or toxicity. Alternative treatments, such as antimiRNAs, are currently in clinical trials. There is growing interest in the use of lncRNA-based therapies. This Perspective discusses the main challenges of ncRNA therapeutics, including specificity, delivery and tolerability. It also highlights emerging approaches that aim to improve their success.

In patients with prior Takotsubo syndrome (TTS), long lasting functional cardiac limitations were described as compared with normal subjects. Emotions-triggered Takotsubo syndrome (E-TTS) has more favorable outcomes than TTS preceded by a physical trigger or by no identifiable fac-tors. The aim of the present study was to assess long-term cardiac functional limitations in a co-hort of asymptomatic E-TTS patients. We enrolled n=39 asymptomatic patients with a diagnosis of E-TTS. Cardiopulmonary exercise tests (CPET) were performed at 30 [12-40] months median fol-low-up from the acute event. A cohort of n=39 individuals matched for age, sex, body mass index and comorbidities served as control. Despite recovery of left ventricular ejection fraction, patients with prior E-TTS had lower peak VO2 and percentage of predicted peak VO2 (17.8 ± 3.6 vs 22.5 ± 6.5; P < 0.001 and 75.2 ± 14.1 % vs 100.6 ± 17.1%, P <0.001), VO2 at anaerobic threshold (AT) (11.1 [10.1-12.9] vs 14.4 [12.5-18.7]; P <0.001), peak O2 pulse (9.7 ± 2.5 vs 13.1 ± 3.5; P <0.001) and higher VE/VCO2 slope (30.4 ± 3.7 vs 27.2 ± 3.5; P <0.001) compared with matched controls. We found no statistically significant differences in heart rate reserve (HRR), respiratory equivalent ratio (RER), mean blood pressure and peak PetCO2 between patients and controls. Despite its favorable out-come, patients with E-TTS in our population were found to have subclinical long-term functional cardiac limitations as compared with a control cohort.

Transcription is carried out in most eukaryotes by three multimeric complexes (RNA polymerases I, II and III). However, plants contain two additional RNA polymerases (IV and V), which have evolved from RNA polymerase II. RNA polymerases II, IV and V contain both common and specific subunits that may specialize some of their functions. In this study, we conducted a search for the genes that putatively code for the specific subunits of RNA polymerases IV and V, as well as the corresponding of RNA polymerase II in olive. Based on the homology with the genes of Arabidopsis thaliana, we identified 13 genes that putatively code for the specific subunits of polymerases IV and V, and 16 genes that code for the corresponding specific subunits of polymerase II in olive. The transcriptomic analysis by RNA-Seq revealed that the expression of the RNA polymerases IV and V genes was induced during the initial stages of fruit development. Given that RNA polymerases IV and V are involved in the transcription of long non-coding RNAs, we investigated their expression and observed relevant changes in the expression of this type of RNAs. Particularly, the expression of the intergenic and intronic long non-coding RNAs tended to increase in the early steps of fruit development, suggesting their potential role in this process. The positive correlation between the expression of RNA polymerases IV and V subunits and the expression of non-coding RNAs supports the hypothesis that RNA polymerases IV and V may play a role in fruit development throughout the synthesis of this type of RNAs.

Cotton cultivation and sustaining its productivity is challenging in temperate arid regions around the globe. Exploring suitable cotton cultivation areas to improve productivity in such climatic regions is essential. Thus, this study explores the ecologically suitable areas of cotton cultivation using the Maxent model, having 375 distribution points of long-staple cotton and various factors, including 19 climatic factors, 2 terrain factors, and 6 soil factors in Xinjiang. The area under the curve (AUC) of the predicted results was greater than 0.9, indicating that the model's predictions had fairly high accuracy. However, the main environmental factors that affect cotton's growth are the lowest temperature in the coldest month, the hottest month, the precipitation in the driest season, and the monthly average temperature difference. Further, the temperature factors contribute 71%, while the contribution ratio of terrain and soil factors is only 22%. The research shows that the current planting area is consistent with the predicted area in many areas of the study. Still, some areas, such as the Turpan region, northwest of Bayingolin Mongol Autonomous Prefecture, are supposed to be suitable for planting cotton, but it is not planted. The current potential distribution area of long-staple cotton is mainly located in Aksu Prefecture and the northern part of the Kashgar Prefecture region. The climatic prediction shows that the growing area of long-staple cotton may expand to southern Altay, central Aksu, and Bortala Mongol Autonomous Prefecture. This study will be helpful for cotton cultivation suitability areas in Xinjiang and other regions with similar environments.

Long Covid is a term used for patients who have recovered from COVID-19 but exhibit persistent cognitive dysfunction, including mental confusion, difficulties in attention, impairment in executive functions and slow movements, among other common symptoms. A study was conducted with 65 patients who had a positive RT-PCR diagnosis and reported symptoms of cognitive impairment, such as memory loss and attention difficulties after recovery. The patients underwent neuropsychological evaluation and completed questionnaires on cognition, mood, and quality of life. During the cognitive screening, 71% of the patients showed alterations, with deficits in visual memory (69%), language (54%), visuospatial construction (49%), verbal episodic memory (37%), executive functions (36%), attentional abilities (34%), and premorbid intelligence (12%). It is important to highlight the need for treatments and further studies to understand the long-term side effects of this disease.

Background: PFO (Patent foramen ovale) is a common defect that affects about 25% of the population. Although its presence is asymptomatic in the majority of the cases, the remaining part becomes overt with different symptoms, including cryptogenic stroke. The PFO closure procedure is widely available to date with the most used Amplatzer PFO Occluder, also in complex anatomy, but the performance of another device, the GORE Septal Occluder (GSO), has not been completely explored with regard to different septal anatomies. Methods: From March 2012 to June 2020, 118 consecutive patients with an indication for PFO closure were treated using the GSO system and included in a prospective analysis and followed. After 12 months, every patient underwent transcranial Doppler to evaluate the effectiveness of treatment. Results: of 111 patients evaluated, 107 showed effective PFO closure (96,4%) and 4 showed a residual shunt (3,6%). To better evaluate the device performance, the overall population was sorted into 2 clusters based on the echocardiographic characteristics. The main difference between groups was for PFO width (4,85 ± 1,8 vs 2,9 ± 1 mm, p <0,001) and PFO tunnel length (12,6 ± 3,8 vs 7,2 ± 2 respectively, p <0,001), allowing identification of complex anatomy and simple anatomy, respectively. Regardless of the aforementioned cluster, the GSO performance to reach an effective closure was independent of anatomy type and the chosen device size. Conclusion: GSO device showed efficacy and safety at 1-year follow-up in patients with at least 1 anatomical factor of complexity of PFO, irrespectively from the level of complexity itself.

Background: Long QT syndrome (LQTS) can lead to ventricular arrhythmia and sudden cardiac death. The most common congenital cause of LQTS is mutations in the channel subunits generating the cardiac potassium current IKs. Zebrafish (Danio rerio) have been proposed as a powerful system to model human cardiac diseases due to the similar electrical properties of the zebrafish heart and the human heart. Methods: We used high resolution all-optical electrophysiology on ex-vivo zebrafish hearts to assess the effects of IKs analogues on the cardiac action potential. Findings: We found that chromanol 293B (an IKs inhibitor) prolonged the action potential duration (APD) in the presence of E4031 (an IKr inhibitor applied to drug-induced LQT2) and to a lesser extent in the absence of E4031. Moreover, we show that PUFA analogues slightly shorten the APD of the zebrafish heart. However, PUFA analogues failed to reverse the APD prolongation in drug-induced LQT2. However, a more potent IKs activator, ML-277, partially reversed the APD prolongation in drug-induced LQT2 zebrafish hearts. Interpretation: Our results suggest that IKs plays a limited role in ventricular repolarizations in the zebrafish heart under resting conditions but plays a more important role when IKr is compromised, as if IKs in zebrafish serves as a repolarization reserve as in human hearts. This study shows that potent IKs activators can restore the action potential duration in drug-induced LQT2 in zebrafish heart.

Fasting, a practice with historical roots in various cultures, has recently garnered significant interest in the field of medicine. In this article, we delve into the mechanisms underlying fasting-induced autophagy and its therapeutic applications for spike protein associated pathology. We explore the therapeutic potential of fasting on spike protein-related pathology and the role of interventions to upregulate autophagy, including compounds like spermidine, resveratrol, rapamycin, and metformin. In conclusion, fasting, coupled with an understanding of its nuances, holds promise as a therapeutic intervention for spike protein related diseases; with broad implications for human health. This review presents the therapeutic possibility of using autophagy to treat spike protein related diseases, and details the interventions to deploy this therapeutic modality.

Fasting, a practice with historical roots in various cultures, has recently garnered significant interest in the field of medicine. In this article, we delve into the mechanisms underlying fasting-induced autophagy and its therapeutic applications for spike protein associated pathology. We explore the therapeutic potential of fasting on spike protein-related pathology. Additionally, we discuss factors that affect fasting, such as duration, type (dry vs. water), and the role of specific compounds like spermidine, resveratrol, rapamycin, and metformin. Furthermore, we analyse the interactions between fasting and other practices such as exercise, and highlight important considerations regarding participant characteristics, including pregnancy, breastfeeding, medication interactions, and metabolic disorders. In conclusion, fasting, coupled with an understanding of its nuances, holds promise as a therapeutic intervention with broad implications for human health.

Fluctuating stock prices make it difficult for investors to see investment opportunities. One tool that can help investors overcome this is forecasting techniques. Long Short-Term Memory (LSTM) is one of deep learning methods used in forecasting time series. The training and success of deep learning is strongly influenced by the selection of hyperparameters. This research uses a hybrid method between the Genetic Algorithm (GA) and LSTM to find a suitable model for predicting stock prices. GA is used in optimizing the architecture such as the number of epochs, window size, and the number of LSTM units in the hidden layer. Tuning optimizer is also carried out using several optimizers to achieve the best value. From method that has been applied, it shows that the method has a good level of accuracy with MAPE values below 10% in every optimizer used. The error rate generated is quite low, in case-1 with a minimum RMSE value of 93.03 and 94.40, & in case-2 with an RMSE value of 104.99 and 150.06 during training and testing. A fairly stable and small value is generated by setting it using the Adam Optimizer.

This article presents the research results on developing professional capital in Lithuanian schools during the national project "Time for leaders". The longitudinal national initiative aimed to develop professional capital as the synergy of human, social and decisional components (Hargreaves and Fullan, 2019) of schools through the various cooperation-based learning experiences of educational professionals. The article provides an overview of project interventions (activities that stimulated cooperative learning of educational professionals) in the light of cooperative learning principles. The assessment of change over two project years in education professionals' perceptions of professional capital is presented using Cohen's d effect size measure. The measurement sample consisted of teachers (n1=5105; n2=4683) and school leaders (n1=439; n2=405) from 189 schools in 30 Lithuanian municipalities. The findings show a statistically significant medium positive change in professional capital. The most considerable change was estimated in the social and decisional capital dimensions and the relatively smallest - in the field of human capital.

Coincident changes in abundance and behavior pose a challenge for interpreting abundance data from monitoring programs. In the San Francisco Estuary, long-term monitoring documented the declines of many species including the anadromous Longfin Smelt (Spirinchus thaleichthys). We identified seasonal patterns in reginal presence of Longfin Smelt through its life cycle using monitoring data and generalized additive modelling. We then investigated the year-to-year variability in the seasonal patterns of presence using functional data analysis (FDA). FDA separated the variability due to population size from variability due to differences in timing of presence. We found that Longfin Smelt have consistent seasonal distribution patterns and that two trawl types were needed to accurately describe those patterns. After accounting for variability due to year-class strength, shifts in the timing of presence were evident in three regions. The most variable period for the upstream regions Suisun Bay and West Delta was for age-0 fish in summer and for the downstream region Central Bay was for age-0 fish in late fall. This manifested as a delay in the typical fall re-occupation of upstream regions that comprise the study area for another monitoring study (Fall Midwater Trawl). Thus, a portion of the recent reductions in Fall Midwater Trawl abundance of Longfin Smelt resulted from changes in behavior rather than a decline in abundance. The presence of multiple monitoring surveys allowed analysis of distribution from one data set to aid interpretation of patterns in abundance from another monitoring survey. This study highlights how identifying portions of the life cycle with the most and least variability in distribution can help inform the types of management strategies that will be most effective. It also illustrates an analytical method that can be used to address the problem of confounded effects of abundance and behavior on patterns in monitoring data.

While the ongoing climate change is well documented, the impacts exhibit a substantial variability, both in direction and magnitude, visible even at regional and local scales. However, the knowledge of regional impacts is crucial for the design of mitigation and adaptation measures, particularly when changes in the hydrological cycle are concerned. In this paper we present hydro-meteorological trends based on observations from a hydrological research basin in Eastern Austria between 1979-2019. The analysed state variables include the air temperature, the precipitation, and the catchment runoff. Additionally, trends for the catchment evapotranspiration were derived. The analysis shows that while the mean annual temperature was decreasing and annual temperature minima remained constant, the annual maxima were rising. The long-term trends indicate a shift of precipitation to the summer with minor variations observed for the remaining seasons and at an annual scale. Observed precipitation intensities mainly increased in spring and summer between 1979-2019. The catchment evapotranspiration, computed based on catchment precipitation and outflow, showed an increasing trend for the observed time period.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) continues to wreak havoc threatening the public health services and imposing economic collapse worldwide. Tailoring public health responses to the SARS-CoV-2 pandemic depends on understanding the mechanism of viral replication, disease pathogenesis, and accurately identifying acute infections and mapping the spreading risk of hotspots across the globe. However, effective identification and isolation of persons with asymptomatic and mild SARS-CoV-2 infections remain the major obstacles to efforts in controlling the SARS-CoV-2 spread and hence the pandemic. Understanding the mechanism of persistent viral shedding, reinfection, and the post-acute sequalae of SARS-CoV-2 infection (PASC) is crucial in our efforts to combat the pandemic and provide better care and rehabilitation to survivors. Here we present a living literature review on SARS-CoV-2 viral persistence, reinfection and PASC. We also highlight potential areas of research to uncover putative links between viral persistence, intra-host evolution, host immune status, and protective immunity to guide and direct future basic science and clinical research priorities.

Beer fermentation is typically monitored by periodic sampling and off-line analysis. In-line sensors would remove the need for time-consuming manual operation and provide real-time evaluation of the fermenting media. This work uses a low-cost ultrasonic sensor combined with machine learning to predict the alcohol concentration during beer fermentation. The highest accuracy model (R2=0.952, MAE=0.265, MSE=0.136) used a transmission-based ultrasonic sensing technique along with the measured temperature. However, the second most accurate model (R2=0.948, MAE=0.283, MSE=0.146) used a reflection-based technique without the temperature. Both the reflection-based technique and the omission of the temperature data are novel to this research and demonstrate the potential for a non-invasive sensor to monitor beer fermentation.

In the last couple of years, the implementation of long-read sequencing (LRS) technologies for transcriptome profiling has uncovered an extreme complexity of viral gene expression. In this study, we carried out a systematic analysis on the pseudorabies virus transcriptome by combining our current data obtained by using Pacific Biosciences Sequel and Oxford Nanopore Technologies MinION sequencings with our earlier data generated by other LRS and short-read sequencing techniques. As a result, we identified a number of novel genes, transcripts, and transcript isoforms, including splice and length variants, and also confirmed earlier annotated RNA molecules. One of the major findings of this study is the discovery of a large number of 5’-truncated putative mRNAs embedded into larger host mRNAs. A large fraction of these RNA molecules contain in-frame ORFs, which may encode N-terminally truncated polypeptides. These study demonstrates that the PRV transcriptome is much more complex than previously appreciated.

This paper aims to investigate the airflow that can transport emission sources of PM2.5 from neighboring countries to contribute to air pollution in northern Thailand. We applied the coupled atmospheric and air pollution model which is based on the Weather Research and Forecasting Model (WRF) and a Hybrid Single-Particle Lagrangian Integrated Trajectory Model (HYSPLIT). The model output was compared to the ground-based measurement from the Pollution Control Department (PCD) to examine model performance. As a result of model evaluation, the meteorological variables fairly agreed well compared to observation with Index of Agreement (IOA) in ranges of 0.57 to 0.79 for temperature and 0.32 to 0.54 for wind speed, while the fractional bias of temperature and wind speed were 1.3 to 2.5 °C and 1.2 to 2.1 m/s. Burma was a country that contributed much of hotpot locations by 37% of the entire hotspot locations of Southeast Asia in March. The influence of the Asian Monsoon can bring pollutants from neighboring countries such as Burma and Laos toward northern Thailand in March that likely contribute to high concentrations of PM2.5 in northern Thailand.

Background: The associations between long-term exposure to particulate matters (PM) in residential ambiance and obesity are comparatively less elucidated among young adults. Methods: Using 2017 Community Health Survey data with aged 19−29 participants in 25 communities, Seoul, the relationship between obesity and long−term PM10 levels of living district was examined. We defined obesity as overweight (25≤BMI&lt;30) or obese (30≤BMI) using Body Mass Index (BMI) from self-reported anthropometric information. Analysis was conducted sampling weighted logistic regression models by fitting municipal PM10 levels according to individual residence periods with 10 years and more residing in a current municipality. Socio-demographic factors were adjusted over all models and age−specific effect was explored among aged 19–24 and 25–29. Results: Total study population are 3,655 [men 1,680 (46.0%) and aged 19–24 1,933 (52.9%)] individuals. Among the communities with greater level of PM10; 2001–2005, associations with obesity were increased for overall with residence period; 10 years ≤ [Odds ratio, OR 1.071, 95% Confidence interval (CI) 0.969–1.185], 15 years ≤ [OR 1.118, 95% CI 1.004–1.245], and 20 years ≤ [OR 1.156, 95% CI 1.032–1.294]. However, decreased associations were detected for PM10; 2006–2010, and age–specific effects were modified according to the residence period. Conclusions: Although currently PM10 levels are decreasing, higher levels of PM10 exposure at the residential area during the earlier life-time may contribute in increasing obesity among young adults.

COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. SARS-CoV-2 nucleic acid, peripheral lymphocyte count, and functionality were assessed. SARS-CoV-2-specific and neutralization antibodies were detected, followed by virus isolation and genome sequencing. The median age of the studied cohort was 59.83±12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. Interferon gamma (IFN-ƴ)-generated CD4+ and CD8+ cells were normal as 24.68±9.60% and 66.41±14.87%. However, the number of IFN-ƴ-generated NK cells diminished (58.03±11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (ID50=157.2, P=0.05). SARS-CoV-2 was not isolated, and a cytopathic effect was lacking. Only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity was observed in COVID-19 patients with long-term SARS-CoV-2 infection.

This paper examines whether the Great Recession has altered the disparities of the US regional health care expenditures. We test the null hypothesis of convergence for the US real per capita health expenditure for the period 1980-2014. Our results indicate that the null hypothesis of convergence is clearly rejected for the total sample as well as for the pre-Great Recession period. Thus, no changes are found in this regard. However, we find that the Great Recession has modified the composition of the estimated convergence clubs, offering a much more concentrated picture in 2014 than in 2008, with most of the states included in a big club, and only 5 (Nevada, Utah, Arizona, Colorado and Georgia) exhibiting a different pattern of behavior. These two estimated clubs diverge and, consequently, the disparities in the regional health sector have increased.

Modeling brain dynamics to better understand and control complex behaviors underlying various cognitive brain functions are of interests to engineers, mathematicians, and physicists from the last several decades. With a motivation of developing computationally efficient models of brain dynamics to use in designing control-theoretic neurostimulation strategies, we have developed a novel data-driven approach in a long short-term memory (LSTM) neural network architecture to predict the temporal dynamics of complex systems over an extended long time-horizon in future. In contrast to recent LSTM-based dynamical modeling approaches that make use of multi-layer perceptrons or linear combination layers as output layers, our architecture uses a single fully connected output layer and reversed-order sequence-to-sequence mapping to improve short time-horizon prediction accuracy and to make multi-timestep predictions of dynamical behaviors. We demonstrate the efficacy of our approach in reconstructing the regular spiking to bursting dynamics exhibited by an experimentally-validated 9-dimensional Hodgkin-Huxley model of hippocampal CA1 pyramidal neurons. Through simulations, we show that our LSTM neural network can predict the multi-time scale temporal dynamics underlying various spiking patterns with reasonable accuracy. Moreover, our results show that the predictions improve with increasing predictive time-horizon in the multi-timestep deep LSTM neural network.

The Ni-Co-Cr-W-Mo system is critical for the design of nickel-based super-alloys. This system stabilizes different topologically close packed (TCP) phases in many of the commercially super-alloys with high W and Mo contents. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermodynamic calculations are applied to investigate the thermodynamics of the precipitates in two different W content Ni-Co-Cr-W-Mo super-alloys. Computational thermodynamics verified experimental observation of the f u phase formation as a function of temperature and alloy chemistry, but the kinetics for the precipitation of M6C phase do not agree with the experimental findings. The major precipitates of alloy 1 at temperatures 700 and 750 °C during long time exposure are M23C6, γ′ phase, and MC, and alloy 2 are M23C6, γ′ phase, MC, M6C and u phase. The W addition is found to promote the precipitation of M6C and u phase during exposure. The M6C has higher W and lower Ni content than that of u phase, meanwhile, M6C is an unstable phase would transform into M12C after 5000 h exposure at 750 °C. A great quantity of needle-like u phases precipitated after exposure at 750 °C for 5000h, which have no effect on the impact property of alloy 2.

Earth's global surface temperature shows variability on an extended range of temporal scales and satisfies an emergent scaling symmetry. Recent studies indicate that scale invariance is not only a feature of the observed temperature fluctuations, but an inherent property of the temperature response to radiative forcing, and a principle that links the fast and slow climate responses. It provides a bridge between the decadal- and centennial-scale fluctuations in the instrumental temperature record, and the millennial-scale equilibration following perturbations in the radiative balance. In particular, the emergent scale invariance makes it possible to infer equilibrium climate sensitivity (ECS) from the observed relation between radiative forcing and global temperature in the instrumental era. This is verified in ensembles of Earth system models (ESMs), where the inferred values of ECS correlate strongly to estimates from idealized model runs. For the range of forcing data explored in this paper, the method gives best estimates of ECS between 2.3 and 3.4 K.

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

Mercury is a toxic pollutant emitted from both natural sources and through human activities. A global interest in atmospheric mercury has risen ever since the discovery of the Minamata disease in 1956. Properties of gaseous elemental mercury enable long range transport which can cause pollution even in pristine environments. Total gaseous mercury (TGM) was measured from winter 2016 to spring 2017 over the Baltic Sea. A Tekran 2357A mercury analyser was installed aboard the research and icebreaking vessel Oden for the purpose of continuous measurements of gaseous mercury in ambient air. Measurements were performed during a campaign along the Swedish east coast and in the Bothnian Bay near Lulea during the icebreaking season. Data was evaluated from Gothenburg using a plotting software and back trajectories for air masses were calculated. The TGM average of 1.365 ± 0.054 ng/m³ during winter and 1.288 ± 0.140 ng/m³ during spring was calculated as well as a total average of 1.362 ± 0.158 ng/m³. Back trajectories showed a possible correlation of anthropogenic sources elevating the mercury background level in some areas. There were also indications of depleted air, i.e., air with lower concentrations than average, being transported from the Arctic to northern Sweden resulting in a drop in TGM levels.

We investigate the stationary and dynamic properties of the celebrated Nosé-Hoover dynamics of many-body interacting Hamiltonian systems, with an emphasis on the effect of inter-particle interactions. To this end, we consider a model system with both short- and long-range interactions. The Nosé-Hoover dynamics aims to generate the canonical equilibrium distribution of a system at a desired temperature by employing a set of time-reversible, deterministic equations of motion. A signature of canonical equilibrium is a single-particle momentum distribution that is Gaussian. We find that the equilibrium properties of the system within the Nosé-Hoover dynamics coincides with that within the canonical ensemble. Moreover, starting from out-of-equilibrium initial conditions, the average kinetic energy of the system relaxes to its target value over a size-independent timescale. However, quite surprisingly, our results indicate that under the same conditions and with only long-range interactions present in the system, the momentum distribution relaxes to its Gaussian form in equilibrium over a scale that diverges with the system size. On adding short-range interactions, the relaxation is found to occur over a timescale that has a much weaker dependence on system size. This system-size dependence of the timescale vanishes when only short-range interactions are present in the system. An implication of such an ultra-slow relaxation when only long-range interactions are present in the system is that macroscopic observables other than the average kinetic energy when estimated in the Nosé-Hoover dynamics may take an unusually long time to relax to its canonical equilibrium value. Our work underlines the crucial role that interactions play in deciding the equivalence between Nosé-Hoover and canonical equilibrium.

The way people innovate and create new ideas and bring them to the market is undergoing a fundamental change from closed innovation to open innovation. Why and how do firms perform open innovation? Firms’ open innovation is measured through the levels of firms’ joint patent applications. Next, we analyze network structures and characters of firms’ joint patent applications such as betweenness and degree centrality, structure hole, and closure. From this research, we drew conclusions as follows. First, the structure of collaboration networks has both direct and indirect effects on firms’ innovative performance. Second, in the process of joint patent applications, there is a long tail phenomenon in networks of joint patent applications. Third, the number of patents and International Patent Classification (IPC) subclasses together constitute a meaningful measure of the innovation performance of firms.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID Syndrome (PCS). A fraction of the PCS patients develops the full clinical picture of ME/CFS. New observations in microvessels and blood from patients suffering from PCS have appeared and include microclots and malformed pathological blood cells. Capillary blood flow is impaired not only by pathological blood components but also by prothrombotic changes in the vascular wall, endothelial dysfunction, and expression of adhesion molecules in the capillaries. These disturbances can finally cause a low capillary flow and even capillary stasis. A low cardiac stroke volume due to hypovolemia and the inability of the capacitance vessels to adequately constrict to deliver the necessary cardiac preload generate an unfavorable low precapillary perfusion pressure. Furthermore, a predominance of vasoconstrictor over vasodilator influences exists, in which sympathetic hyperactivity and endothelial dysfunction play a strong role, causing constriction of resistance vessels and of precapillary sphincters which leads to a fall in capillary pressure behind the sphincters. The interaction of these two precapillary cardiovascular mechanisms causing a low capillary perfusion pressure is hemodynamically highly unfavorable in the presence of a primary capillary stasis already caused by the pathological blood components and their interaction with the capillary wall, to severely impair organ perfusion. The detrimental coincidence of the microcirculatory with the precapillary cardiovascular disturbances may constitute the key disturbance of the Post-COVID-19 syndrome and finally lead to ME/CFS in pre-disposed patients because the interaction causes a particular kind of perfusion disturbance - capillary ischemia-reperfusion - which has a high potential of causing mitochondrial dysfunction by inducing sodium- and calcium-overload in skeletal muscles. The latter in turns worsens the vascular situation by the generation of reactive oxygen species to close a vicious cycle from which the patient can hardly escape.

The Dutch PET@home Toolkit was developed to mitigate challenges and foster conversations and planning concerning pets in long-term care at home. This process evaluation study aimed to evaluate the practical application of the toolkit on four topics: 1) satisfaction; 2) relevance; 3) feasibility; and 4) integration of the PET@home Toolkit materials in home care. Outcomes may be used to improve the toolkit materials to better align with the long-term care at home setting. Accounting for data saturation, professional caregivers (N=6), clients (N=2), and family caregivers (N=2) who used toolkit materials participated in semi-structured interviews. Interviews were analysed by two researchers in ATLAS.ti using an inductive-iterative approach. The researchers reached consensus on themes and clustering within interview topics. This led to the identification of the following topics and (themes): satisfaction (general impression, suggestions for improvement), relevance (awareness, planning, pet-related aspects in practice, impact on healthcare quality), feasibility (healthcare practice, competence, quantity), and implementation (digitalisation, task owner, piloting, timing). Several improvements were made to toolkit materials, such as providing clearer instructions for clients in the information booklet. Participants acknowledged the toolkit could lead to better planning while mitigating potential challenges concerning pets which may lead to longer-lasting relationships between clients and their pets.

Objectives: Persistent symptoms following acute COVID-19 infection, collectively termed Long COVID syndrome, have been increasingly reported. However, data on the prevalence and characteristics of Long COVID remain limited. This study aimed to evaluate the occurrence and presentation of Long COVID syndrome in individuals in-fected with COVID-19 and monitored in outpatient, ward, or intensive care settings. Methods: Patients diagnosed with COVID-19 and followed up at the Department of In-fectious Diseases and Clinical Microbiology, Çukurova University Faculty of Medicine, for a minimum of four weeks post-infection were included in this study. Demographic data, including age, gender, and comorbidities, were recorded. Patients were followed up for 12 months, with symptom assessment at baseline and 1, 3, 6, and 12 months post-infection. Functional status was evaluated using the Post-COVID-19 Functional Status (PCFS) scale, and quality of life was assessed using the SF-36 Health Survey question-naire. Results: 134 patients (71 males, 54.2%) participated in the study, with a mean age of 43.7±15.3 years (median: 45, range: 18-83). The distribution of patients across care settings was as follows: 51.1% outpatient, 35.9% ward, and 13% intensive care unit (ICU). Fatigue during exertion was the most frequently reported Long COVID symptom across all follow-up timepoints. Patients treated in the ICU experienced a higher burden of Long COVID symptoms compared to those in outpatient or ward settings. Furthermore, the PCFS scale revealed significantly poorer quality of life and functional status in patients treated in the ICU and wards than those receiving outpatient care. Conclusions: Long COVID syndrome poses a significant ongoing health concern, particularly for patients requiring intensive care during acute COVID-19 infection. Our findings underscore the importance of vigilant monitoring for long-term sequelae, particularly concerning quality of life and functional status, in all individuals recovering from SARS-CoV-2 infection.

Tsallis entropy has been widely used in image thresholding because of its non-extensive properties. The non-extensive parameter q contained in this entropy plays an important role in various adaptive algorithms and has been successfully applied in bi-level image thresholding. In this paper, the relationships between parameter q and pixels’ long-range correlations have been further studied within multi-threshold image segmentation. It is found that the pixels’ correlations are remarkable and stable for images generated by a known physical principle, such as infrared images and medical CT images. And the corresponding non-extensive parameter q can be evaluated by using self-adaptive Tsallis entropy algorithm. The results of this algorithm are compared with those of Shannon entropy algorithm and the original Tsallis entropy algorithm, in terms of quantitative image quality evaluation metrics PSNR (Peak Signal-to-Noise Ratio) and SSIM (Structural Similarity). Furthermore, we observed that for image series with the same background, the q values determined by the adaptive algorithm are consistently kept in a narrow range. Therefore, similar or identical scenes during imaging would produce similar strength of long-range correlations, which provides potential applications for unsupervised image processing.

The marathon sport events and those who participate in these have grown over the last years reflecting notably an augmentation of women and master runners participation. The aim of the present narrative review was to briefly present the results of studies on anthropometric, physiological and training characteristics, as well as predictors of performance, in marathon runners. It was observed that performance was better in runners with small body weight, body mass index, body fat percentage, and rate of endomorphy. With regards to physiology, an increased maximal oxygen uptake, anaerobic threshold, and improved running economy could result in faster race time. The training variables that could predict performance involved weekly training volume (distance) and intensity (running speed), as well as history of training (years). A combination of these three broad categories of characteristics may offer an approximate estimation of the race speed considering that other aspects (e.g., nutrition, biomechanic and motivation) influence race performance, too. In summary, the findings of the present study provided an overview of anthropometric, physiological and training characteristics associated with marathon race time; thus, an optimization of any of these characteristics would be expected to improve race time.

This study introduces a novel method for early prediction of Kimchi cabbage (Brassica rapa subsp. pekinensis (Lour.) Hanelt) height, utilizing drone imagery and a long short-term memory (LSTM) model. The research was conducted on a testbed at the National Institute of Agricultural Sciences (NAS) in South Korea, encompassing two distinct soil types (loam and sandy loam) to investigate their impact on growth. High-resolution drone images were captured throughout the growing season to generate a canopy height model (CHM) for estimating plant height at various stages. Missing height data were interpolated using a logistic growth curve, and an LSTM model was trained on this data to predict the final height of Kimchi cabbage at harvest. Three LSTM models were developed using time-series data collected at 29, 36, and 44 days after planting (DAP). The model trained on data from DAP 44 demonstrated the highest accuracy with a coefficient of determination (R²) of 0.83, a mean absolute error (MAE) of 2.48 cm, and a root mean square error (RMSE) of 3.26 cm, outperforming models trained on earlier data. Color-coded maps were generated to visualize the spatial distribution of predicted Kimchi cabbage heights, revealing variations in growth patterns across the testbed and confirming the model's potential for site-specific management. Considering the trade-off between accuracy and prediction timing, the model trained on DAP 36 data (MAE = 2.77 cm) was deemed optimal for informing cultivation management decisions. This research demonstrates the feasibility and effectiveness of integrating drone imagery, logistic growth curves, and LSTM models for early and accurate prediction of Kimchi cabbage height. The proposed technology enables data-driven decision-making for farmers, facilitating timely interventions based on predicted growth patterns. This could lead to improved crop yields, resource optimization, and a more sustainable agricultural future. Future research will focus on refining the model's accuracy and exploring its applicability to other crops, further expanding the potential of precision agriculture technologies.

Long-distance Real-Time Kinematic (RTK) positioning is crucial for applications in remote areas, such as maritime environments. Achieving 2-3 cm accuracy with RTK requires successful ambiguity resolution, which involves two main two steps: identifying the best integer ambiguity candidate and confirming its validity. While previous research has largely concentrated on the first step, including the development of Cascading Ambiguity Resolution methods, and reducing tropospheric delay, studies on the validation of ambiguity for long-distance RTK are limited. This study conducts a thorough examination of ambiguity validation for long-distance RTK, focusing on two prevalent methods: the theoretical success rate and the R-ratio test. The results reveal several key insights. Firstly, the six commonly used bounds for the theoretical success rate are not accurate reflection of the actual success rate, making them unsuitable for long-distance RTK applications. Secondly, the R-ratio test proves to be dependable when the threshold is set above 1.7, assuming there is a minimum observation period of one minute and at least ten satellites are visible. However, the probability of successfully resolving ambiguities with the R-ratio test does not surpass 50%. Additionally, if ambiguity resolution is not achieved within 20 minutes, simply prolonging the observation time is generally unproductive. To improve the performance of ambiguity resolution in practical situations that require extended observation times, this research proposes a novel ambiguity validation method. This new approach is based the duration for which an integer ambiguity resolution candidate maintaining the best status. This method aims to provide a reliable means of validating ambiguities in case that the R-ratio test fails.

Various symptoms have been reported to persist beyond acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 have been largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction may be a strong candidate to induce long COVID-19. The angioten-sin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for athero-sclerotic cardiovascular disease (ASCVD) and the history of ASCVD can be the risk for severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in development of ASCVD. We consider the influence of long COVID-19 on development of chronic kidney disease (CKD) and ASCVD. Furthermore, we suggest the therapeutic interventions for long COVID-19 by considering endothelial dysfunction as the treatment tar-gets for long COVID-19. Such interventions may prevent pandemic of CKD and ASCVD in post COVID-19 era.

Long COVID, a name often given to the persistent symptoms following acute SARS-CoV-2 infection, poses a multifaceted challenge for health. This review explores the intrinsic relationship between comorbidities and autoimmune responses in shaping the trajectory of long COVID. Autoantibodies have emerged as significant players in COVID-19 pathophysiology, with implications for disease severity and progression. Studies show immune dysregulation persisting months after infection, marked by activated innate immune cells and high cytokine levels. The presence of autoantibodies against various autoantigens suggests their potential as comorbid factors in long COVID. Additionally, the formation of immune complexes may lead to severe disease progression, highlighting the urgency for early detection and intervention. Furthermore, long COVID is highly linked to cardiovascular complications and neurological symptoms, posing challenges in diagnosis and management. Multidisciplinary approaches, including vaccination, tailored rehabilitation, and pharmacological interventions, are used for mitigating long COVID's burden. However, numerous challenges persist, from evolving diagnostic criteria to addressing the psychosocial impact and predicting disease outcomes. Leveraging AI-based applications holds promise in enhancing patient management and improving our understanding of long COVID. As research continues to unfold, unravelling the complexities of long COVID remains paramount for effective intervention and patient care.

Objective: To examine variations in end-of-life care for breast cancer, heart failure, and dementia patients. Data and methods: Data from four Norwegian health registries were linked using a personal identification number. Longitudinal trends over 365 days and the type of care on the final day of life were analyzed using descriptive techniques and logistic regression analysis. Results: Patients with dementia were most commonly placed in nursing homes, while patients with heart failure and breast cancer were more frequently hospitalized. Breast cancer and heart failure patients had a higher likelihood of dying at home. The presence of general practitioners increased the probability of home-based end-of-life care for cancer patients, while non-physician healthcare workers increased the likelihood of home-based care for the other patient groups. Conclusion: Diagnoses, individual characteristics, and service availability are all associated with the place of death in end-of-life care.

The intricate mechanisms of the immune response elicited by vaccines and the interplay between the immune system and the central nervous system (CNS) are poorly understood. This review explores these mechanisms, emphasizing the interplay between the immune system and the central nervous system (CNS). A critical aspect is the examination of how vaccine-induced immune responses can interact with the CNS, influencing neuroinflammation and neuroimmune interactions. Furthermore, the link between vaccination and persistent symptoms observed in long-COVID patients is discussed. Vaccination initiates a complex cascade of events, starting with the production of specific proteins, such as S1/S2 spike proteins, leading to robust immune activation in the axillary lymph nodes. The role of macrophages and antigen-presenting cells (APCs) in cytokine production, antigen presentation, and the stimulation of B and T cells highlights the sophistication of the adaptive immune response. The migration of immune cell-derived exosomes to the brain plays a dynamic role in CNS inflammation, neurodegenerative processes and long COVID. On the other hand, the prolonged presence of viral and vaccine-derived spike proteins may contribute to the complex pathophysiology of Long-COVID, shedding light on the delicate balance between beneficial immune responses and possible adverse neurological outcomes of vaccination. It is worth rigorous monitoring and further research to understand the mechanisms of neuroinflammation and the persistence of spike proteins and their long-term effects on the brain, emphasising the importance of a nuanced approach to vaccine safety and efficacy in the context of COVID-19 and beyond.Principio del formulario

The demand for precise indoor localization services is steadily increasing. Among various methods, fingerprint-based indoor localization has become a popular choice due to its exceptional accuracy, cost-effectiveness, and ease of implementation. However, its performance degrades significantly as a result of multipath signal attenuation and environmental changes. In this paper, we propose an indoor localization method based on fingerprints using self-attention and long short-term memory (LSTM). By integrating a self-attention mechanism and LSTM network, the proposed method exhibits outstanding positioning accuracy and robustness in diverse experimental environments. The performance of the proposed method is evaluated under two different experimental scenarios, which involve 2D and 3D moving trajectories, respectively. The experimental results demonstrate that our approach achieves an average localization error of 1.76 m and 2.83 m in the respective scenarios, outperforming the existing state-of-the-art methods by 42.67% and 31.64%.

Fungi belong to the species with the highest biodiversity and high potential for use in biotechnology and industry. Therefore, their long-term quality conservation is very important and it is necessary to continuously develop new methods and improve existing methods. Currently, cryopreservation appears to be the best available technique for the preservation of fungi. This study summarises the latest trends and advances in fungal cryopreservation over the last 7 years, i.e. findings from scientific publications from 2017 to 2023 dealing with cryopreservation of both basidiomycetes and non-basidiomycete fungi. The work analyzed the studied organisms and the cryopreservation method used, focused on the use of new procedures and modifications of existing methods; summarized the conditions for successful cryopreservation, such as cryopreservation time and temperature, as well as the substrate and cryoprotectant used.

Long-lasting insecticidal nets (LLINs) have been the main contributor to the reduction of malaria in the past two decades in sub-Saharan Africa. Development of pyrethroid insecticide resistance threatens the effectiveness of these LLINs, especially when nets become holed and the insecticide decays. Three classes of dual active ingredient (AI) LLINs, have been assessed for their physical durability as follows: 1) Royal Guard®, combining pyriproxyfen, which is known to disrupt female reproduction and fertility of eggs, and a pyrethroid alpha-cypermethrin; 2) Interceptor® G2, two adulticides with differing modes of action; chlorfenapyr and alpha-cypermethrin; 3) OlysetTM Plus incorporates permethrin (pyrethroid) and a synergist, piperonyl butoxide, to enhance the potency of pyrethroid insecticides; all nets were compared to standard pyrethroid only net (Interceptor®). About 40,000 nets of each type were distributed in February 2019 to different villages in Misungwi. A total of 3072 LLINs were followed at 6, 12, 24, 30 and 36 months to assess survivorship and fabric integrity in a community setting. The median functional survival were less than three years with Interceptor®, Interceptor® G2 and Royal Guard® having 1.9 year each and 0.9 years for OlysetTM Plus . After 36 months, 90% of OlysetTM Plus and Royal Guard® and 87% of Interceptor® G2 were no longer present (thrown away) in the households due to wear and tear, compared to 79% for standard Interceptor®. Short life spans of all assessed LLINs were driven by material of the net, rather than social economic status and housing material. All dual AI LLINs have a poor textile durability with OlysetTM Plus being the worst of the three.

Despite the fact that SMA restrainers exhibit a superelastic strain capacity of 7%, this capacity appears inadequate for isolated bridges due to the typically greater than 20cm relative dis-placements between girders during intense seismic events. In order to perform such a stroke, a SMA restrainer of greater than 3 metres in length might be required. In order to reduce the length of restrainers, a novel honeycomb damper constructed from superelastic shape memory alloy (SMA) is proposed. The proposed device, denoted as the superelastic SMA honeycomb damper (SHD), is comprised of steel plates to prevent the SMA plane from collapsing and superelastic SMA honeycomb to provide self-centering capability. By incorporating the large strain capacity of SMA and the geometrically nonlinear deformation of honeycomb structures, SHD has been developed to satisfy the requirements of bridge restrainers with large strokes. It is capable of functioning as a restrainer and energy dissipation device when subjected to dynamic tension and compression loads. The SHD was initially investigated from a theoretical perspective. Following this, a mul-ti-cell SHD specimen was manufactured. The specimen underwent axial tensile and compressive experiments in order to examine the mechanical properties of SHDs. Finally, experimental results were investigated through numerical simulation analyses of the SHDs using a three-dimensional high-fidelity finite element model. Additionally, a method for enhancing SHD was proposed. The findings indicate that SHD is capable of exhibiting superior self-centering capability and sta-ble hysteretic responses when subjected to earthquakes.

Considering future tasks in soil health, resources management and environmental protection, farmers are challenged to develop sustainable strategies for managing soil and land resources. In this study, the long-term sustainability of two fertilization strategies, - current, with synthetic fertilizers (SYN) vs conservative, with organic sources of nitrogen (organic amendments plus green manure with a legume - CONS) - was assessed in a processing tomato/durum wheat rotation. The EPIC model was used, validated with field data then run to simulate the management for 30 years under 3 current and future climates. Yield, soil organic carbon (SOC) stock change, nitrogen use efficiency (NUE), water use efficiency (WUE) and nitrate leaching were considered as sustainability indicators. Under all the future climate scenarios, tomato yield increased in CONS, remaining almost stable in SYN. Wheat yield increased both in CONS and SYN, but the average yield in CONS was considerably lower than in SYN. NUE and nitrate leaching followed the same trend, both decreasing in CONS, while WUE was higher in CONS compared to SYN. The effect of CONS on SOC was always positive. Thus, the alternative N fertilization strategy proposed can be a favorable option for maintaining soil health and a sustainable crop production.

Dynamic neural networks (DNN) are types of artificial neural networks (ANN) that are designed to work with sequential data where context in time is important. In contrast to traditional static neural networks that process data in a fixed order, dynamic neural networks use information about past inputs, which is important if dynamic of a certain process is emphasized. They are widely used in natural language processing, speech recognition and time series prediction. In industrial processes, their use is interesting for the prediction of difficult-to-measure process variables. In an industrial process of isomerization, it is crucial to measure the quality attributes affecting the octane number of gasoline. Process analyzers that are commonly used for this purpose are expensive and subject to failures, therefore, in order to achieve continuous production in case of malfunction, mathematical models for estimating the product quality attributes are imposed as a solution. In this paper, mathematical models were developed using dynamic recurrent neural networks (RNN), i.e., their subtype of a long short-term memory (LSTM) architecture. The results of the developed models were compared with the results of several types of other data-driven models developed for an isomerization process, such as multilayer perceptron (MLP) artificial neural networks, support vector machines (SVM) and dynamic polynomial models. The obtained results are satisfactory, which suggests a good possibility of application.

Coronavirus infection disease -2019 (COVID-19) was a global pandemic with high mortality and morbidity, that lead to an increased health burned all over the world. Although the virus affects mostly pulmonary tract, cardiovascular implications were often among COVID-19 positive patients, and are predictive for poor outcomes. Increased values of myocardial biomarkers such as Troponin I or NT-proBNP were proven to be risk factors for respiratory failure (26). Although the risk of acute coronary syndromes (ACS) was greater in acute-phase of COVID-19, there were lower rates of hospitalization for ACS, due to patient’s hesitation for presenting at the hospital (22). Hospitalized ACS patients with COVID-19 infection, had a prolonged symptom-to-first medical contact time, and longer door-to-balloon time. The mechanisms of myocardial injurie in COVID -19 patients are not still not clear, most often is incriminated: the down-regulation of ACE2 inhibitors, endothelial disfunction, pro-coagulant status, increased levels of pro-inflammatory cytokines. The aim of this paper is to evaluate the long-term outcomes of COVID-19 survivors that presented an acute myocardial infarction by reviewing existing data.

Most natural language processing (NLP) tasks operate an input sentence as a sequence with token-level embeddings and features, despite its clausal structures. Taking Abstract Meaning Representation (AMR) parsing as an example, recent parsers are empowered by Transformers and pre-trained language models, but long-distance dependencies (LDDs) introduced by long sequences are still open problems. We argue that LDDs are not superficially blamed on the sequence length but are essentially related to the internal clause hierarchy. Typically, non-verb words in a clause cannot depend on words outside, and verbs from different but related clauses have much longer dependencies than those in the same clause. With this intuition, we introduce a type of clausal feature, hierarchical clause annotation (HCA), into AMR parsing and propose two HCA-based approaches, HCA-based self-attention (HCA-SA) and HCA-based curriculum learning (HCA-CL), to integrate HCA trees of complex sentences for addressing LDDs. We conduct extensive experiments on two in-distribution (ID) AMR datasets (AMR 2.0 and AMR 3.0) and three out-of-distribution (OOD) ones (TLP, New3, and Bio). Experimental results show that our HCA-based approaches achieve significant and explainable improvements against the baseline model and outperform the state-of-the-art (SOTA) model when encountering sentences with complex clausal structures that introduce most LDD cases.

This study investigates the long-term impact of soil tillage systems and crop residue incorporation on agrophysical properties. A long-term field experiment has been conducted since 1999 at the Ex-perimental Station of Vytautas Magnus University Agriculture Academy. According to the latest edition of the International Soil Classification System, the soil in the experimental field was classified as Planosol, with a silty medium loam texture at a depth of 0–20 cm and a silty light loam at a depth of 20–40 cm. This investigation aimed to assess the long-term impact of reduced tillage systems, straw, and green manure combinations on soil physical properties, including soil shear strength, and soil aggregate stability. Studies were carried out on winter wheat crops in 2014, 2017, and 2023. The treatments were arranged using a split-plot design. In a two-factor field experiment, one part of the experimental field had straw removed, while the other part had the entire straw yield chopped and spread at harvest (Factor A). The subplot factor (Factor B) included three different tillage sys-tems: conventional deep ploughing, cover cropping for green manure with no-till, and no-tillage. Soil samples were analysed in the Laboratory of Agrobiology at Vytautas Magnus University Ag-riculture Academy. The findings indicate that long-term application of reduced tillage significantly increases soil shear strength. Shallower tillage depths lead to higher soil shear strength, while the effect of spreading plant residues is relatively lower. Long-term tillage of different intensities, spreading plant residues, and catch crop cultivation for green manure did not significantly affect soil structure. However, soil structural stability was found to be highly dependent on soil tillage. Cover cropping for green manure with no-till and no-tillage positively affected soil aggregate sta-bility in the upper (0–10 cm) and 10–25 cm layers.