Every day around 93% of children under the age of 15 (1.8 billion children) breathe outdoor air that is so polluted it puts their health and development at serious risk. Due to the pandemic, however, ventilation of buildings using outdoor air has become an important safety technique to prevent the spread of COVID-19. With the mounting ev-idence suggesting that air pollution is impactful to human health and educational out-comes, this contradictory guidance may be problematic in schools with higher air pol-lution levels, but keeping kids COVID-19 free and in school to receive their education is now more pressing than ever. To understand if all schools in an urban area are ex-posed to similar outdoor air quality and if school infrastructure protects children equally indoors, we installed research grade sensors to observe PM2.5 concentrations in indoor and outdoor settings to understand how unequal exposure to indoor and out-door air pollution impacts indoor air quality among high- and low-income schools in Salt Lake City, Utah. Based on this approach, we found that during atmospheric inver-sions and dust events, there was a lag ranging between 35 to 73 minutes for the out-door PM2.5 concentrations to follow a similar temporal pattern as the indoor PM2.5. This lag has policy and health implications and may help to explain the rising concerns re-garding reduced educational outcomes related to air pollution in urban areas. These data and resulting analysis show that poor air quality may impact school settings, and the potential implications with respect to environmental inequality.

Observing air quality from sensors onboard light rail cars in Salt Lake County, Utah began as a pilot study in 2014 and has now evolved into a five-year state-funded program. This metropolitan region suffers from both elevated ozone levels during summer and high PM2.5 events during winter. Pollution episodes result predominantly from local anthropogenic emissions but are also impacted by regional transport of dust, chemical precursors to ozone, and wildfire smoke as well as being exacerbated by the topographical features surrounding the city. Two electric light-rail train cars from the Utah Transit Authority light-rail Transit Express (“TRAX”) system were outfitted with PM2.5 and ozone sensors to measure air quality at high spatial and temporal resolution in this region. Pollutant concentration data underwent quality control procedures to determine whether the train motion affected the readings and how the sensors compared against regulatory sensors. Quality assurance results from data obtained over the past year show that TRAX Observation Project sensors are reliable, which corroborates earlier preliminary validation work. Two case studies from summer 2019 are presented to illustrate the strength of the finely-resolved air quality observations: 1) an elevated ozone event and 2) elevated particulate pollution resulting from 4th of July fireworks. The mobile observations were able to capture spatial gradients as well as pollutant hotspots during both of these episodes. Sensors have been recently added to a third light rail train car, which travels on a north-south oriented rail line along which we were unable to monitor air quality previously. The TRAX Observation Project is currently being used to provide reliable pollutant data for health studies and inform urban planning efforts. Links to real-time data displays and updated information on the quality-controlled data from this study are available at https://atmos.utah.edu/air_quality/trax/.

In insects, Adipokinetic hormone is the primary hormone responsible for the mobilization of stored energy. While a growing body of evidence has solidified role of Adipokinetic hormone (AKH) in modulating the physiological and behavioral responses to metabolic stress, little is known about the upstream endocrine circuit that directly regulates AKH release. We evaluated the AKH-producing cell (APC) transcriptome to identify potential regulatory elements controlling APC activity, and found that a number of receptors show consistent expression levels, including all known dopamine receptors and the Pigment Dispersing Factor receptor (PDFR). We tested the consequences of targeted genetic knockdown and found that AKH expression of RNAi elements corresponding to each dopamine receptor caused a significant reduction in survival under starvation. In contrast, PDFR knockdown significantly extended lifespan under starvation whereas expression of a tethered PDF in APCs resulted in a significantly shorter lifespan. These manipulations caused various changes in locomotor activity under starvation. We used live-cell imaging to evaluate the acute effects of the ligands for these receptors on APC activation. Dopamine application led to a transient increase in intracellular calcium in a sugar-dependent manner. Furthermore, co-application of dopamine and ecdysone led to a complete loss of this response, suggesting that these two hormones act antagonistically. We also found that PDF application led to an increase in cAMP in APCs, and that this response was dependent on expression of the PDFR in APCs. Together these results suggest a complex circuit in which multiple hormones act on APCs to modulate metabolic state.

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

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

This article discusses the implementation of the Water Framework Directive (WFD) in the Netherlands and intends to show how law and politics combine in river basin management. Initially, the implementation of the WFD in the Netherlands was approached as a technical and administrative issue, handled by water quality and ecology experts, but in 2003 this approach was broken open by the agricultural sector, who were worried about stricter regulation. Subsequently, the environmental objectives of the WFD were set as low as possible and they are not used in authorising individual projects. Yet, in 2015 of the European Court of Justice determined that the environmental objectives have binding effect and that Member States have to refuse authorisation for projects that endanger the achievement of these objectives. In the future, the European Court of Justice and national courts may force the Dutch government to change its approach. They may only do so because and as long as they enjoy sufficient social and political support and function relatively independently. The article concludes that, to understand river basin management fully, one has to open up the black box of water law and become a kind of water lawyer.

Polar Mesospheric Summer Echoes (PMSEs) are radar echoes that are observed in the mesosphere during the Arctic summer months in the polar regions. By studying PMSE, researchers can gain insights into physical and chemical processes that occur in the upper atmosphere specifically in the 80 to 90 km altitude range. In this paper, we employ fully convolutional networks such as UNET and UNET++ for the purposes of segmenting PMSE from the EISCAT VHF dataset. First, experiments are performed to find suitable weights and hyperparameters for UNET and UNET++. Second, different loss functions are tested to find one suitable for our task. Third, as the number of PMSE samples used is relatively small that can lead to poor generalization. To address this, image-level and object-level augmentation methods are employed. Four, we briefly explain our findings by employing layerwise relevance propagation.

In December 2012, DOAJ’s parent company, IS4OA, announced they would introduce new criteria for inclusion in DOAJ [1] and that DOAJ would collect vastly more information from journals as part of the accreditation process – and that journals already included, would need to reapply in order to be kept in the registry. My hypothesis was that the journals removed from DOAJ on May 9th 2016 would chiefly be journals from small publishers (mostly single journal publishers) and that DOAJ journal metadata information would reveal that they were journals with a lower level of publishing competence than those that would remain in the DOAJ. Among indicators of publishing competence could be the use of APCs, permanent article identifiers, journal licenses, article level metadata deposited with DOAJ, archiving policy/solutions and/or having a policy in SHERPA/RoMEO. The analysis shows my concerns to be correct.

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

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

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

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

Biofilms are congregations of bacteria on a surface, and they grow into obstacles for the functionalities of any device or machinery involves anything biological. Biofilms are developed through a biochemical system known as ‘Quorum Sensing’ that accounts for the chemical signaling that direct either biofilm formation or inhibition. Computational models that relate chemical and structural features of compounds to their performance properties have been used to aide in the discovery of active small molecules for many decades. These quantitative structure-activity relationship (QSAR) models are also important for predicting the activity of molecules that can have a range of effectiveness in biological systems. This study uses QSAR methodologies combined with and different machine learning algorithms to predict and assess the performance of several different compounds acting in Quorum Sensing. Through computational probing of the quorum sensing molecular interaction, new design rules can be elucidated for countering biofilms.

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

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

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

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

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

Subseasonal-to-seasonal (S2S) weather forecasting has improved in recent years, thanks partly to better representation of physical variables in models. For instance, realistic initializations of snow and soil moisture in models yield enhanced predictability on S2S time scales. Snow depth and soil moisture also mediate month-to-month persistence of near-surface air temperature. Here the role of snow depth as predictor of temperature one month ahead in the Northern Hemisphere is probed via two causal pathways. Through the first pathway, snow depth anomalies in month 1 cause snow depth anomalies in month 2, which then cause temperature anomalies in month 2. This pathway represents the snow–albedo feedback, as well as cooling due to insulation, emissivity and heat loss. It is active from fall to summer, and its effect peaks in March/April in the midlatitudes and in May/June at high latitudes. A complementary second pathway, where snow depth anomalies in month 1 cause soil moisture anomalies in month 2, which then cause temperature anomalies in month 2 through soil moisture–temperature feedbacks, is only active in spring and summer. Its effect peaks later in the warm season than the effect of the first pathway. Geographically, snow depth mediates north of, and soil moisture south of, the areas with the highest temperature predictability from snow depth. These results indicate that the two pathways describe complementary physical mechanisms. The first pathway embodies month-to-month persistence of snow depth, and the second pathway represents melting of snow from one month to the next.

Marine cold air outbreaks (MCAOs) are large-scale events in which cold air masses are advected over open ocean. It is well-known that these events are linked to the formation of polar lows and other mesoscale phenomena associated with high wind speeds, and that they therefore in some cases represent a hazard to maritime activities. However, it is still unknown whether MCAOs are generally conducive to higher wind speeds than normal. Here this is investigated by comparing ocean near-surface wind speeds during MCAOs in atmospheric reanalysis products with different horizontal grid spacings, along with two case studies using a convection-permitting numerical weather prediction model. The study regions are the Labrador Sea and the Greenland–Iceland–Norwegian (GIN) Seas, where MCAOs have been shown to be important for air–sea interaction and deep water formation. One of the main findings is that wind speeds during the strongest MCAO events are higher than normal and higher than wind speeds during less severe events. Limited evidence from the case studies suggests that reanalyses with grid spacings of more than 50 km underestimate winds driven by the large ocean–atmosphere energy fluxes during MCAOs. The peak times of MCAO usually occur when baroclinic waves pass over the regions. Therefore, the strong wind episodes during MCAOs generally last for just a few days. However, MCAOs can persist for 50 days or more.

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

In this review article will be described the (wide) variety of approaches that I envisaged to develop a specific therapy of viral infections: (i) interferon and its inducers, (ii) HSV, VZV and CMV inhibitors, (iii) NRTIs (nucleoside reverse transcriptase inhibitors), NtRTIs (nucleotide reverse transcriptase inhibitors) and NNRTIs (non-nucleoside reverse transcriptase inhibitors) as HIV inhibitors, (iv) NtRTIs as HBV inhibitors and finally, (v) the transition of an HIV inhibitor to a stem cell mobilizer, as exemplified by AMD-3100 (Mozobil®).

Keywords: coagulation parameters, procoagulant factors, anticoagulant factors, chronic hepatitis C infection, direct-acting antivirals therapy, sustained virological response, liver cirrhosis

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

Myoelectric control is the cornerstone of many assistive technologies used in clinical practice, such as prosthetics and orthoses, and human-computer interaction, such as virtual reality control. Although the performance of such devices exceeds 90\% in controlled environments, myoelectric devices still face challenges in robustness to variability of daily living conditions. Within this survey, the intrisic physiological mechanisms limiting practical implementations of myoelectric devices were explored: the limb position effect and the contraction intensity effect. The degradation of electromyography (EMG) pattern recognition in the presence of these factors was demonstrated on six datasets, where performance was 13% and 20% lower in realistic environments compared to controlled environments for the limb position and contraction intensity effect, respectively. The experimental designs of limb position and contraction intensity literature were surveyed. Current state-of-the-art training strategies and robust algorithms for both effects were compiled and presented. Recommendations for future limb position effect studies include: the collection protocol providing exemplars of 6 positions (four limb positions and three forearm orientations), three-dimensional space experimental designs, transfer learning approaches, and multi-modal sensor configurations. Recommendations for future contraction intensity effect studies include: the collection of dynamic contractions, nonlinear complexity features, and proportional control.

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

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

The ability of thermoresponsive polymers to respond to temperature with a reversible conformational change makes them promising ‘smart’ materials for solutions in medical and biotechnological applications. In this work, two such polymers and structural isomers were studied: poly(N-isopropyl acrylamide) (PNiPAm) and poly(2-isopropyl-2-oxazoline) (PiPOx). We compare the critical solution temperatures (CST) of these polymers in D2O and H2O in the presence of Hofmeister series salts, as results obtained under these different solvent conditions are often compared. D2O has a higher dipole moment and electronegativity than H2O, which could significantly alter the CST transition. We used two complementary methods to measure the CST, dynamic light scattering (DLS) and differential scanning calorimetry (DSC), and found that the CST decreased significantly in D2O compared to H2O. In the presence of highly concentrated kosmotropes, the CST of both polymers decreased in both solvents. The influence of the kosmotropic anions was smaller than the water isotope effect at low ionic strengths but considerably higher at physiological ionic strengths. However, the Hofmeister anion effect was quantitatively different in H2O than in D2O, with the largest relative differences observed for Cl-, where the CSTs in D2O decreased more than in H2O measured by DLS but less by DSC. PiPOx was more sensitive than PNiPAm to the presence of chaotropes. It exhibited much higher transition enthalpies and multistep transitions, especially in aqueous solutions. Our results highlight that measurements of thermoresponsive polymer properties in D2O cannot be compared directly or quantitatively to application conditions or even measurements performed in H2O.

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

The current disruptive innovation model has a limitation in incorporating customers’ demands while the customer can be a co-creator of value on performance, design, and price innovation. Thus, this research attempted to explore the disruptive innovation model which can include both the incumbent’s innovation trajectory and customer’s demand, and how incumbents behave to enable disruptive innovation in the smartphone market. Based on the Apple iPhone case study, this study verified that the current disruptive innovation model can incorporate customers’ demand by reflecting their demand in the direction of innovating the performance, design, or price of smartphones with the price-adjusted innovation trajectory. The secondary innovation trajectory which was found uniquely in this study is meaningful since it can be a creative solution for the innovator’s dilemma. Besides, Apple, as an incumbent, has behaved to innovate iPhone performance and design demands of customers creating significant papers and patents as outcomes of innovation activities. This study has practical implications for incumbents’ managers as well as customers to enable disruptive innovation in the smartphone market.

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

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

Anthelmintic drugs are the major line of defense against parasitic nematode infections, but the arsenal is limited and resistance threatens sustained efficacy of the available drugs. Discoveries of the modes of action of these drugs and mechanisms of resistance have predominantly come from studies of a related non-parasitic nematode species, Caenorhabditis elegans, and the parasitic nematode Haemonchus contortus. Here, we discuss how our understanding of anthelmintic resistance and modes of action came from the interplay of results from each of these species. We argue that this “cycle of discovery”, where results from one species inform the design of experiments in the other, can use the complementary strengths of both to understand anthelmintic modes of action and mechanisms of resistance.

We specify basic definitions of the Chern-Simons current in cohomology theory, then we calculate its value by using a model of quantum machine learning, the so-called supersymmetric support Dirac machine. The supercurrent is generated from the coupling between three states of a quantum flux of modified Wilson loop of the Cooper pairs. We use Holo-Hilbert spectrum in frequency modulation to visualize the network as a coupling behavior of convolutional neuron network in superstatistical theory with the application to the theory of a superconductor. We also calculate the number of carbon atoms in the stable support spinor network structure of a graphene wormhole to produce a supercurrent of Cooper pairs as graviphoton states by using the Holo-Hilbert spectral analysis.

Currently available data are consistent with increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at temperatures encountered in the upper airways (25–33°C when breathing room temperature air, 25°C) compared to those in the lower airways (37°C). One factor that may contribute to more rapid viral growth in the upper airways is the exponential increase in SARS-CoV-2 stability that occurs with reductions in temperature, as measured in vitro. Because SARS-CoV-2 frequently initiates infection in the upper airways before spreading through the body, increased upper airway viral growth early in the disease course may result in more rapid progression of disease and potentially contribute to more severe outcomes. Similarly, higher SARS-CoV-2 viral titer in the upper airways likely supports more efficient transmission. Conversely, the possible significance of air temperature to upper airway viral growth suggests that prolonged delivery of heated air might represent a preventative measure and prophylactic treatment for coronavirus disease 2019.

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

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

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

Objective: On March 11, 2020 the WHO declared that COVID-19 is pandemic. Among the risk factors for many infectious diseases, a role of the ABO blood group system is reported in the literature. We argue whether it is necessary to investigate the relationship between ABO blood groups and susceptibility to SARS-CoV-2 infection and if we should consider some blood groups as potential risk factors for COVID-19. Results: Based on the scientific evidence reported in this letter, we believe that further studies are needed to investigate how the ABO polymorphism influences the host susceptibility, individual response and clinical risk for SARS-CoV-2 infection.

The subject of the research is the investigation of the behavior of railway tracks in locations with a significant change in the stiffness of the track. These locations can be designed from various structural elements and their materials, and this mainly results in a height change of the track level during its operation. These transition zones are monitored and expertly examined in order to detect undesirable deformations of the geometrical position of the track caused by the trains running. The transition zones are at the points where the fixed track transitions to the classic track bed, in our case it is their combination with bridge structures, especially at their supports. In Slovakia, under the conditions of the Railways of the Slovak Republic, the issue is topical within the framework of the modernization of trans-European railway corridors. The results of experimental measurements and their analysis will provide relevant data for subsequent research solutions for their new numerical modeling, which will ensure a smooth passage through these points of change without height fluctuations, vibrations, and shocks from the wheels of train sets.

Both globally and in Hungary, agriculture is one of the industries that is most vulnerable to weather and climate extremes. Intense temperature rises, spatial and temporal variations in precipitation, and significant changes in extreme climatological and weather parameters have contributed to changes in the conditions of cropland, crop losses, and impacts on crop quality in recent years. This paper depicts the transformation of the domestic agricultural sector due to the extreme drought shock of 2022, as well exploring the adaptation strategies applied. The research is based on official agro-climate database and crop data, and the temperature, precipitation, and radiation during the growing season are all examined. The agro-meteorological properties in Hungary had to be investigated for the entire year and all four of its seasons, with indicator analysis projected onto the ever-increasing and dormant seasons. Long-term climate analysis is necessary to understand the historic drought of 2022 and the success of future adaptation and mitigation techniques. The results can help smallholders effectively reduce the adverse impacts of drought conditions, thereby increasing their adaptation to similar shocks.

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

Boolean functions and networks are commonly used in the modeling and analysis of complex biological systems, and this paradigm is highly relevant in other important areas in data science and decision making, such as in the medical field and in the finance industry. In a Boolean model, the truth state of a variable is either 0 or 1 at a given time. Despite its apparent simplicity, Boolean networks are surprisingly relevant in many areas of application such as in bioinformatics to model gene expressions and interactions. In the latter case, a gene is either ``on" or ``off" depending on its expression level. Despite the promising utility of Boolean modeling, in most practical applications the Boolean network is not known. Automated learning of a Boolean network and Boolean functions, from data, is a challenging task due in part to the large number of unknowns (including both the structure of the network and the functions) to be estimated, for which a brute force approach would be exponentially complex. In this paper we develop a new information theoretic methodology that we show to be significantly more efficient than previous approaches. Building on the recently developed optimal causation entropy principle (oCSE), that we proved can correctly infer networks distinguishing between direct versus indirect connections, we develop here an efficient algorithm that furthermore infers a Boolean network (including both its structure and function) based on data observed from the evolving states at nodes. We call this new inference method, Boolean optimal causation entropy (BoCSE), which we will show that our method is both computationally efficient and also resilient to noise. Furthermore, it allows for selection of a set of features that best explains the process, a statement that can be described as a networked Boolean function reduced order model. We highlight our method to the feature selection in several real-world examples: (1) diagnosis of urinary diseases, (2) Cardiac SPECT diagnosis, (3) informative positions in the game Tic-Tac-Toe, and (4) risk causality analysis of loans in default status. Our proposed method is effective and efficient in all examples.

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

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

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

Fokker-Planck PDEs (incl. diffusions) for stable Lévy processes (incl. Wiener processes) on the joint space of positions and orientations play a major role in mechanics, robotics, image analysis, directional statistics and probability theory. Exact analytic designs and solutions are known in the 2D case, where they have been obtained using Fourier transform on $SE(2)$. Here we extend these approaches to 3D using Fourier transform on the Lie group $SE(3)$ of rigid body motions. More precisely, we define the homogeneous space of 3D positions and orientations $\mathbb{R}^{3}\rtimes S^{2}:=SE(3)/(\{\mathbf{0}\} \times SO(2))$ as the quotient in $SE(3)$. In our construction, two group elements are equivalent if they are equal up to a rotation around the reference axis. On this quotient we design a specific Fourier transform. We apply this Fourier transform to derive new exact solutions to Fokker-Planck PDEs of $\alpha$-stable Lévy processes on $\mathbb{R}^{3}\rtimes S^{2}$. This reduces classical analysis computations and provides an explicit algebraic spectral decomposition of the solutions. We compare the exact probability kernel for $\alpha = 1$ (the diffusion kernel) to the kernel for $\alpha=\frac12$ (the Poisson kernel). We set up SDEs for the Lévy processes on the quotient and derive corresponding Monte-Carlo methods. We verify that the exact probability kernels arise as the limit of the Monte-Carlo approximations.

A data-driven analysis method known as dynamic mode decomposition (DMD) approximates the linear Koopman operator on projected space. In the spirit of Johnson-Lindenstrauss Lemma, we will use random projection to estimate the DMD modes in reduced dimensional space. In practical applications, snapshots are in high dimensional observable space and the DMD operator matrix is massive. Hence, computing DMD with the full spectrum is infeasible, so our main computational goal is estimating the eigenvalue and eigenvectors of the DMD operator in a projected domain. We will generalize the current algorithm to estimate a projected DMD operator. We focus on a powerful and simple random projection algorithm that will reduce the computational and storage cost. While clearly, a random projection simplifies the algorithmic complexity of a detailed optimal projection, as we will show, generally the results can be excellent nonetheless, and quality understood through a well-developed theory of random projections. We will demonstrate that modes can be calculated for a low cost by the projected data with sufficient dimension.

The subject of this article is the dynamics of water in a soil pedostructure sample whose internal environment is subjected to a potential gradient created by the departure of water through surface evaporation. This work refers entirely to the results and conclusions of a fundamental theoretical study focused on the molecular thermodynamic equilibrium of the two aqueous phases of the soil pedostructure. The new concepts and descriptive variables of the hydro-thermodynamic equilibrium state of the soil medium, which have been established at the molecular level of the fluid phases of the pedostructure (water and air) in a previous article, are recalled here in the systemic paradigm of hydrostructural pedology. They allow access to the molecular description of water migration in the soil and go beyond the classical mono-scale description of soil water dynamics. We obtain a hydro-thermodynamic description of the soil's pedostructure at different hydro-functional scale levels including those relating to the water molecule and its atoms. The experimental results show a perfect agreement with the theory, validating at the same time the systemic approach which was the framework.

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

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

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

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

The mantle mass flow interconnected with the process of Glacial Isostatic Adjustment (GIA) and the reformation of the Earth’s crust constantly perturbs the observed gravity field towards a hypothetic isostatic state. We analyse the temporal changes of the gravity field from the GRACE data, using different mathematical and/or statistical methods to detect the GIA amidst other gravity signals. A number of gravimetric post-glacial land uplift rate (LUR) modelling methods are investigated and compared with the data from a total number of 515 GPS stations and preferred GIA forward models in Fennoscandia and North America. We investigate three mathematical methods, namely regression, principal component, and independent component analysis (ICA) to extracting the GIA signal from the GRACE monthly geoid heights. We use some regularization techniques to exploit the GRACE monthly data to their maximum spatial resolution and to increase the Signal to Noise Ratio of their short wavelengths. Near the centres of the study areas the gravimetric LUR model using the fast-ICA algorithm of Hyvärinen and Oja (2000) is shown to be in a complete agreement with the GPS data and the predictions of the GIA forward models, and for the whole areas, subject to epeirogeny movement of the two regions, their discrepancies reach to the extrema at -1.8 and +3.3, and -4.5 and +7.5 mm/a, respectively. We show that the largest discrepancies between the gravimetric model using the ICA method and the GIA forward model, occur for the sub-regions likely collocated with strong ice mass change signals.

Much of the debate on Plan S seems to concentrate on how to make toll access journals open access, taking for granted that existing open access journals are Plan S compliant. We suspected this was not so, and set out to explore this using DOAJ's journal metadata. We conclude that an overwhelmingly large majority of open access journals are not Plan S compliant, and that it is small HSS publishers not charging APCs that are least compliant and will face major challenges with becoming compliant. Plan S need to give special considerations to smaller publishers and/or non-APC-based journals.

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

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

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

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

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

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

Suspended and deposited sediments in streams can interfere with filter-feeding caddisfly larvae by reducing feeding sites and feeding efficiency, potentially lowering densities, growth rates, and secondary production of an important trout prey. We conducted field studies at multiple stream sites with differing suspended sediment loads, and a laboratory study conducted under controlled conditions, together designed to examine the role of suspended sediments in the population dynamics and behavior of Brachycentrus occidentalis (Trichoptera: Brachycentridae) larvae in a Minnesota, USA, trout stream. Stream sites that had elevated turbidities and suspended sediments also had significantly more fine bottom substrates and higher substrate embeddedness. In addition, Brachycentrus densities were reduced, growth rates were slower, secondary production was reduced, and overall benthic macroinvertebrate taxa richness was lowest at the site with the highest suspended sediment loading. Colder water temperatures at one site also influenced Brachycentrus production. In 24-hour laboratory studies conducted in recirculating aquaria, the feeding activities of Brachycentrus larvae were reduced and positioning altered under high turbidities (500 nephelometric turbidity units, NTU) relative to low turbidities (50 NTU or lower). High suspended sediment loads have adversely affected filter-feeding caddisfly larvae by embedding and burying preferred coarse feeding substrates, altering their feeding positions and movements during highest flows, and ultimately impacting densities, growth rates, and secondary production.

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

The crystals, C11H4BrF5N2S, (I), 1-((4-bromothiophen-2-yl)methylene)-2-(perfluorophenyl)hydrazine and C12H6BrF5N2S, (II), 1-((4-bromo-5-methylthiophen-2-yl)methylene)-2-(perfluorophenyl)hydrazine are molecules with two rings and hydrazone part like a centre of the molecule. The compounds have been synthesized and characterized by elemental, spectroscopic (¹H-NMR) analysis. The crystal structures of the solid phase were determined by single crystal X-ray diffraction method. They crystallize in the monoclinic space group with Z = 4 and Z = 2 molecules per unit-cell. The compound (I) crystallizes as a racemate in the centrosymmetric space group and the compound (II) crystallizes as a non-racemate in the non-centrosymmetric space group. The “absolute configuration and conformation for bond values” were derived from the anomalous dispersion (ad) for (II). The crystal structures are revealed diverse non-covalent interactions such as intra- and interhydrogen bonding, π-ring···π-ring, C-H···π-ring and they were investigated. The expected stereochemistry of hydrazones atoms C7, N2 and N1 were confirmed for (I) and (II). The hole molecule of the (I), and (II) possesses “a boat conformation” like a 6-membered ring. The results of the single crystal studies are reproduced with the help of Hirshfeld surface study and Gaussian software.

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

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

Spontaneous, unwilled subjective imagery and symbols often emerge in psychotherapy that can appear baffling and confound interpretation. Moreover, early psychoanalytic theories seemed to diverge as often as they agreed on the meaning of such content. Nevertheless, reviewing key findings in the empirical science of spontaneous thought, as well as insights gleaned from neurosciences and especially embodied cognition, it is now possible to construct a more coherent theory of interpretation that is clinically useful. Given that thought is so thoroughly embodied, it is possible to demonstrate that universalities in human physiology yield universalities in thought. Such universalities can then be demonstrated to form a kind of biologically directed universal “code” for understanding spontaneous symbolic expressions that emerge in psychotherapy. An example is given that illustrates how this can be applied to clinical encounters.

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

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

The World Meteorological Organization (WMO) recommends that the most recent 30-year period, i.e. 1991-2020, shall be used to compute climate normals of geophysical variables. A unique aspect this recent 30-year period is that the satellite-based observations of many different essential climate variables are available during this period, thus opening up new possibilities to provide a robust, global basis for the 30-year reference period in order to allow climate monitoring and climate change studies. Here, using the satellite-based climate data record of cloud and radiation properties, CLARA-A3, for the month of January between 1981 to 2020, we illustrate the difference between climate normal, as defined by guidelines from WMO on calculations of 30-yr climate normals, and climatology. It is shown that this difference is strongly dependent on the climate variable in question. We discuss the impacts of the nature and availability of satellite observations, variable definition, retrieval algorithm and programmatic configuration. It is shown that the satellite-based climate data records show enormous promise in providing climate normal for the recent 30-year period (1991-2020) globally. We finally argue that the holistic perspectives from the global satellite community should be increasingly considered while formulating the future WMO guidelines on computing climate normals.

This study investigates the use of programming language Python to analyse and model chemical engineering processes. Using municipal sewage sludge (MSS) drying as an example, the study demonstrates how Python can support analyses and model drying data. The drying process was performed on a flat plate while maintaining a uniform, parallel drying air speed of 1.15 m s-1. The Python program helped to analyse the digitalised weight measurements from each sample. The program enables sorting input data, determining the drying critical point and evaluating the first and second drying periods.

In-cloud ice mass accretion on wind turbines is a common challenge faced by energy companies operating in cold climates. On-shore wind farms in Scandinavia are often located in regions near patches of forest, the heterogeneity length scales of which are often less than the resolution of many numerical weather prediction (NWP) models. The representation of these forests--including the cloud water response to surface roughness and albedo effects related to them--must therefore be parameterized in NWP models used as meteorological input in ice prediction systems, resulting in an uncertainty that is poorly understood and to present date not quantified. The sensitivity of ice accretion forecasts to the subgrid representation of forests is examined in this study. A single column version of the HARMONIE-AROME 3D NWP model is used to determine the sensitivity of the forecast of ice accretion on wind turbines to the subgrid forest fraction. Single column simulations of a variety of icing cases at a location in northern Sweden were examined in order to investigate the impact of vegetation cover on ice accretion in varying levels of solar insulation and wind magnitudes. In mid-winter cases, the wind speed response to surface roughness was the primary driver of the vegetation effect on ice accretion. In early season cases, the cloud water response to surface albedo effects plays a secondary role in the impact of in-cloud ice accretion, with the wind response to surface roughness remaining the primary driver for the surface vegetation impact on icing. Two different surface boundary layer (SBL) forest canopy subgrid parameterizations were tested in this study that feature different methods for calculating near-surface profiles of wind, temperature, and moisture, with the ice mass accretion again following the wind response to surface vegetation between both of these schemes.

Syntrophic acetate oxidation operates close to the thermodynamic equilibrium and very little is known about the participating organisms and their metabolism. Clostridium ultunense is one of the most abundant syntrophic acetate-oxidising bacteria (SAOB) found in engineered biogas processes operating with high ammonia concentrations. It has been proven to oxidise acetate in cooperation with hydrogenotrophic methanogens. There is evidence that the Wood-Ljungdahl (WL) pathway plays an important role in acetate oxidation. In this study we analysed the physiological and metabolic capacities of C. ultunense on genome scale and conducted a comparative study of all known characterised SAOB, namely Syntrophaceticus schinkii, Thermacetogenium phaeum, Tepidanaerobacter acetatoxydans and Pseudothermotoga lettingae. The results clearly indicated physiological robustness beneficial for anaerobic digestion environments and revealed unexpected metabolic diversity with respect to acetate oxidation and energy conservation systems., Unlike S. schinkii and Th. phaeum, C. ultunense clearly does not employ the oxidative WL pathway for acetate oxidation, as its genome (and that of P. lettingae) lack important key genes. In both those species, a proton motive force is likely formed by chemical protons involving putative electron-bifurcating [Fe-Fe] hydrogenases rather than proton pumps. No genes encoding a respiratory Ech hydrogenase, as involved in energy conservation in Th. phaeum and S. schinkii, were identified in C. ultunense and P. lettingae. Moreover, two respiratory complexes sharing similarities to the proton-translocating ferredoxin:NAD⁺ oxidoreductase (Rnf) and the Na+ pumping NADH:quinone hydrogenase (NQR) were predicted. These might form a respiratory chain involved in reduction of electron acceptors other than protons. However, involvement of these complexes in acetate oxidation in C. ultunense and P. lettingae needs further study. This genome-based comparison provides a solid platform for future meta-proteomics and meta-transcriptomics studies and for metabolic engineering, control and monitoring of SAOB.

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

Integrated information theory (IIT) proposes a measure of integrated information (Φ) to capture the level of consciousness for a physical system in a given state. Unfortunately, calculating Φ itself is currently only possible for very small model systems, and far from computable for the kinds of systems typically associated with consciousness (brains). Here, we consider several proposed measures and computational approximations, some of which can be applied to larger systems, and test if they correlate well with Φ. While these measures and approximations capture intuitions underlying IIT and some have had success in practical applications, it has not been shown that they actually quantify the type of integrated information specified by the latest version of IIT. In this study, we evaluated these approximations and heuristic measures, based not on practical or clinical considerations, but rather based on how well they estimate the Φ values of model systems. To do this, we simulated networks consisting of 3–6 binary linear threshold nodes randomly connected with excitatory and inhibitory connections. For each system, we then constructed the system’s state transition probability matrix (TPM), as well as its state transition matrix (STM) over time for all possible initial states. From these matrices, we calculated, approximations to Φ, and measures based on state differentiation, state entropy, state uniqueness, and integrated information. All measures were correlated with Φ in a state dependent and state independent manner. Our findings suggest that Φ can be approximated closely in small binary systems by using one or more of the readily available approximations (r > 0.95), but without major reductions in computational demands. Furthermore, Φ correlated strongly with measures of signal complexity (LZ, r_s = 0.722), decoder based integrated information (Φ*, r_s = 0.816), and state differentiation (D1, r_s = 0.827), on the system level (state independent). These measures could allow for efficient estimation of Φ on a group level, or as accurate predictors of low, but not high, Φ systems. While it’s uncertain whether the results extend to larger systems or systems with other dynamics, we stress the importance that measures aimed at being practical alternatives to Φ are at a minimum rigorously tested in an environment where the ground truth can be established.

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

Managing a portfolio whose value closely tracks an index by trading only in a subset of the index constituents involves an NP-hard optimisation problem. In the prior literature, it has been suggested to solve this problem using sequential Monte Carlo (SMC, a.k.a. particle filter) methods. However, this literature does not take transaction costs into account, although transaction costs are the primary motivation for attempting to replicate the index by trading in a subset, rather than the full set of index constituents. This paper extends the SMC approach to index tracking to allow for proportional transaction costs and implements this extended method on empirical data for a variety stock indices. In addition to providing a more practically useful tracking strategy by allowing for transaction costs, we find that including a penalty for transaction costs in the optimisation objective can actually lead to better tracking performance.

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

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

The rapid development of three-dimensional (3D) acquisition technology based on 3D sensors provides a large volume of data, which is often represented in the form of point clouds. Point cloud representation can preserve the original geometric information along with associated attributes in a 3D space. Therefore, it has been widely adopted in many scene-understanding-related applications such as virtual reality (VR) and autonomous driving. However, the massive amount of point cloud data aggregated from distributed 3D sensors also poses challenges for secure data collection, management, storage, and sharing. Thanks to the characteristics of decentralization and security nature, Blockchain has a great potential to improve point cloud services and enhance security and privacy preservation. Inspired by the rationales behind Software Defined Network (SDN) technology, this paper envisions SAUSA, a blockchain-based authentication network that is capable of recording, tracking, and auditing the access, usage, and storage of 3D point cloud data sets in their life-cycle in a decentralized manner. SAUSA adopts an SDN-enabled point cloud service architecture which allows for efficient data processing and delivery to satisfy diverse Quality-of-Service (QoS) requirements. A blockchain-based authentication framework is proposed to ensure security and privacy preservation in point cloud data acquisition, storage, and analytics. Leveraging smart contracts for digitizing access control policies and point cloud data on the blockchain, data owners have full control of their 3D sensors and point clouds. In addition, anyone can verify the authenticity and integrity of point clouds in use without relying on a third party. Moreover, SAUSA integrates a decentralized storage platform to store encrypted point clouds while recording references of raw data on the distributed ledger. Such a hybrid on-chain and off-chain storage strategy not only improves robustness and availability but also ensures privacy preservation for sensitive information in point cloud applications. A proof-of-concept prototype is implemented and tested on a physical network. The experimental evaluation validates the feasibility and effectiveness of the proposed SAUSA solution.

Graphene oxide (GO), nanographene oxide (nGO) and partially reduced graphene oxide (rGO) have been studied as possible foam stabilizing agents for CO₂ based enhanced oil recovery (EOR). GO was able to stabilize CO₂/synthetic sea water foams. rGO was not able to stabilize foams likely due to the high reduction degree of the material. Particle size had a strong influence on foamability and stability. GO hydrophilicity increased as the particle size decreased and no foams were created when particle size was below 1 µm (nGO). GO brine dispersions showed immediate gel formation, which improved foam stability. Particle growth due to layer stacking was also observed. This mechanism was detrimental for foam formation and stabilization. nGO dispersed in synthetic sea water rapidly formed hydrogels and was not filterable. This work indicates that the particles studied are not suitable for CO₂ EOR purposes.

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

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

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

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

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

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

Mutations in the calcium channel gene Transient Receptor Potential cation channel subfamily V member 4 (TRPV4) cause autosomal dominant skeletal dysplasia, with phenotypes ranging from mild to perinatal lethality. A recent report detailed murine thrombocytosis in the absence of functional TRPV4, but no prior reports have described platelet count abnormalities in the context of human TRPV4 disease. Here, we report a case of prolonged thrombocytosis in the context of TRPV4-associated metatropic dysplasia that was lethal in the infantile period.

Conditional Independence (CI) testing is fundamental in statistical analysis. For example, CI testing helps validate causal graphs or longitudinal data analysis with repeated measures in causal inference. CI testing is difficult, especially when testing involves categorical variables conditioned on a mixture of continuous and categorical variables. Current parametric and non-parametric testing methods designed for continuous variables and can quickly fall short in the categorical case. This paper presents a computational approach for CI testing for categorical data types, which we call computational conditional independence (CCI) testing. The test procedure is based on permutation and combines machine learning prediction algorithms and Monte Carlo Cross-Validation. We evaluated the approach through simulation studies and assessed the performance against alternative methods; the generalized covariance measure (GCM) test, the kernel conditional independence (KCI) test, and testing with multinomial regression. We find that the computational approach to testing has utility over the alternative methods, and we can achieve better control over type-I-error rates. We hope this work can expand the toolkit for CI testing for practitioners and researchers.

We extended our model of the S1 tubular segment to address the mechanisms by which SGLT1 interacts with lateral Na/K pumps and tight junctional complexes to generate isosmotic fluid reabsorption via tubular segment S3. The strategy applied allowed simulation of laboratory experiments. Reproducing known experimental results constrained the range of acceptable model outputs and contributed to minimizing the free parameter space. 1. In experimental conditions, published Na and K concentrations of proximal kidney cells were found to deviate substantially from their normal physiological levels. Analysis of the mechanisms involved suggested insufficient oxygen supply as the cause and indirectly, that a main function of the Na/H exchanger (NHE3) is to extrude protons stemming from mitochondrial energy metabolism. 2. The water path from the lumen to the peritubular space is through aquaporins on the cell membrane and claudin-2 at paracellular tight junctions, with a smaller additional contribution to water transport by the coupling of 1 glucose:2 Na:200 H2O in SGLT1. 3. A Na+-uptake component passed through paracellular junctions by solvent drag in Na- and water-permeable claudin-2, thus bypassing the Na/K-pump, in agreement with the findings of early studies. 4. Electrical cross talk between apical rheogenic SGLT1 and lateral rheogenic Na/K pumps results in tight coupling of luminal glucose uptake and transepithelial water flow. 5. Isosmotic transport is achieved by Na-mediated ion recirculation at the peritubular membrane.

Many neuropsychological theories agree that the brain maintains a relatively persistent representation of one’s own body, as indicated by vivid “phantom” experiences. It remains unclear how the loss of sensory and motor information contributes to the presence of this representation. Here, we focus on new empirical and theoretical evidence of phantom sensations following damage to or an anesthetic block of the brachial plexus. We suggest a crucial role of this structure in understanding the interaction between peripheral and central mechanisms in health and in pathology. Studies of brachial plexus function have shed new light on how neuroplasticity enables “somatotopic interferences,” including pain and body awareness. Understanding the relations among clinical disorders, their neural substrate, and behavioral outcomes may enhance methods of sensory rehabilitation for phantom limbs.

This study introduces a novel computational approach for testing conditional independence (BB CI test) within causal Directed Acyclic Graphs (DAGs), leveraging Bayesian non-parametric bootstrap and machine learning techniques. Our method offers an alternative for validating the assumptions underpinning causal DAGs. Through simulation studies and an industrial case analysis, we demonstrate the test procedure in accurately assessing conditional independence, comparing it with the Generalized Covariance Measure (GCM) test. Our findings suggest that the BB CI test is advantageous in scenarios where existing methods may falter due to violations of model assumptions. This research contributes to the causal inference literature by providing a computational tool for researchers and practitioners to validate causal models.

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

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

Wang et al. (Nature 623, 340—350; 2023)¹ used satellite observations and phenological signatures to estimate the extent of planted rubber (Hevea brasiliensis Müll.Arg.) and associated deforestation for eight Southeast Asian countries. Their map implies that planted rubber has caused more than 4 Mha of deforestation since 1993 — a value greater than previously assumed. Unfortunately, their approach was flawed. Our assessment indicates that the actual extent of planted rubber is approximately half that reported by Wang et al., while the extent of associated deforestation is approximately one quarter.

Powder metallurgy is a preferred manufacturing method in various industries because it offers design flexibility, material efficiency and a cost-effective production. In this work, we study the effects of different compaction directions on the strength of parts produced by powder metallurgy. Al–4wt.%Cu alloys are used due to their recyclability, and three distinctive compaction pressures are applied, resulting in two sample groups. One group is air-cooled after sintering, while the other is water-quenched and naturally aged (T4 temper). Both the compressive and tensile strengths are measured and analyzed. The study reveals that both heat treatments and compaction directions significantly influence anisotropic strengths. The novelty of this research lies in the use of powders that can be reused from machining, turning, or foundry rejection. By omitting or reducing the melting stage and employing simple powder metallurgy, the cost-effective and environmentally friendly processes are achieved. The planning of compaction load, compaction direction, and heat treatments is found to play a crucial role in determining the final mechanical performance. Notably, this approach aligns with the environmental, social and governance (ESG) practices that have been increasingly adopted by industry.

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

Electric vehicles offer a means to reduce greenhouse gas emissions in passenger transport. The availability of reliable charging infrastructure is crucial for the successful uptake of electric vehicles in dense urban areas. In a pilot project in the city of Hamburg, Germany, public charging infrastructure is equipped with a reservation option providing exclusive access for local residents and businesses. The present paper combines quantitative and qualitative methods to investigate the effects of the newly introduced neighborhood charging concept. We use a methodology combining a quantitative questionnaire survey and qualitative focus group discussions as well as the analyses of charging infrastructure utilization data. Results show that inner-city charging and parking options are of key importance for (potential) users of electric vehicles. Hence, the neighborhood concept is rated very positively. Providing guaranteed charging and parking facilities are therefore likely to increase the stock of EVs. On the other hand, these could to a large extent be additional cars with consequential disadvantages. The study shows that openly accessible infrastructure is presently utilized much more intense than the exclusive option. Consequentially, the concept evaluated should be part of an integrated approach managing parking and supporting efficient concepts like car sharing.

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

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