Sacroiliac (SI) joint dysfunction can lead to debilitating pain but can be treated with minimally invasive sacroiliac joint fusion (SIJF). This treatment is commonly performed using 2D fluoroscopic guidance. This makes placing the implants without damaging surrounding neural structures challenging. Virtual surgical planning (VSP) using simulated fluoroscopic images may improve perioperative guidance. This article describes a workflow with VSP in SIJF using simulated fluoroscopic images and evaluates achieved implant placement accuracy. Routinely collected survey data on the added value of VSP were also evaluated. Ten interventions were performed on 10 patients by the same surgeon, comprising 30 implants; the median age was 39 years, and all patients were female. The overall mean implant placement accuracy was 4.9 ± 1.26 mm and 4.0 ± 1.44°. There were no malpositioning complications. The VSP helped the surgeon understand the anatomy and determine the optimal position and length of the implants. The average Likert scale score of the survey was 4.7, suggesting a positive role of VSP for SIJF. Planned positions of the implants could be reproduced in surgery with clinically acceptable accuracy and VSP was a valuable asset for the surgeon.

Amidst the rapid urbanization of cities worldwide, there is a pressing need for practical tools to manage and preserve the invaluable architectural heritage contained within them. This research introduces a systematic methodology for digitalizing and interpreting architectural heritage through augmented Reality (AR). The primary goal is to enhance the documentation, preservation, and accessibility of cultural assets, addressing both educational and touristic needs. Focusing on the historic district of Pelourinho in Salvador, Bahia, Brazil, the study showcases how 3D digitalization combined with AR can provide users with an interactive experience with historical structures, bridging the temporal divide. By integrating the digital replicas of historic buildings into a real-time environment, users gain enriched insights into these structures’ history, architecture, and cultural significance. Though the preliminary results underscore the potential of this approach, comprehensive user testing remains an area for future exploration. This paper thus highlights the potential of AR in historical and cultural preservation, suggesting its broader implications for education, tourism, and heritage management.

Psychological readiness following Anterior Cruciate ligament Reconstruction (ACLR) correlates with different return to sport outcomes. However, the relationship between strength and power and psychological readiness remains unexplored. The aim of this study was to investigate the relationship between the Anterior Cruciate Ligament Return to Sport After Injury (ACL-RSI) scores and various hamstrings and quadriceps strength and power variables. Twelve participants (20.7±2.5 years old; 174.2±7.5 cm; 70.2±8.5 kg; 18.2±8.3% of body fat) who had an ACLR nine months or more before the study completed the ACL-RSI questionnaire and isokinetic strength testing of the hamstrings and quadriceps (60°.s-1 and 180°.s-1). Based on ACL-RSI scores, they were divided into “cases” and “controls”, deemed not psychologically ready and psychologically ready to return to previous sport performance (PILOS), respectively. The main findings are that quadriceps’ and hamstrings’ rate of torque development (RTD) and time since surgery were determinants of psychological readiness following ACLR. Furthermore, compared to controls cases showed significantly lower angle-specific quadriceps and hamstrings torque close to extension and lower RTD, but no difference in peak torque. These results suggest that physiotherapists should facilitate athletes’ RTS by focusing on the restoration of RTD and strength at angles close to full knee extension.

Interactions between proteins and ions are essential for various biological functions like structural stability, metabolism, and signal transport. Given that more than half of all proteins bind to ions, it becomes crucial to identify ion-binding sites. Accurate identification of protein-ion binding sites helps us to understand proteins’ biological functions and plays a significant role in drug discovery. While several computational approaches have been proposed, this remains a challenging problem due to the small size and high versatility of metals and acid radicals. In this study, we propose IonPred, a sequence-based approach that employs ELECTRA (Efficiently Learning an Encoder that Classifies Token Replacements Accurately) to predict ion binding sites using only raw protein sequences. We successfully fine-tuned our pretrained model to predict the binding sites for nine metal ions (Zn2+, Cu2+, Fe2+, Fe3+, Ca2+, Mg2+, Mn2+, Na+, and K+) and four acid radical ion ligands (CO32−, SO42−, PO43−, NO2−). IonPred surpassed six current state-of-the-art tools by over 44.65% and 28.46% respectively in F1 score and MCC when compared on an independent test dataset. Our method is more computationally efficient than existing tools producing prediction results for a hundred sequences for a specific ion in under ten minutes.

Genetic engineering technology offers opportunities to improve many important agronomic traits in crops, including insect-resistance. However, genetically modified (GM) exogenous proteins in edible tissues of transgenic crops has become an issue of intense public concern. To advance the application of GM techniques in maize, a Cre/loxP-based strategy was developed for manipulating the transgenes in green tissues while locking it in non-green tissues. In the strategy, the site-specific excision can be used to switch on or off the expression of transgenes at specific tissues. In this work, two basic transgenic maize named KEY carrying the Cre gene and LOCK containing the Vip3A gene with a blocked element, were obtained based on their separate fusion gene cassettes. The expression level and concentration of Vip3A were observed with high specific accumulation in green tissues (leaf and stem), and only a small amount in root and kernel tissues in the KEY × LOCK hybrids. The insect-resistance of transgenic maize against two common lepidopteran pests, Ostrinia furnacalis and Spodoptera frugiperda, was assessed in the laboratory and field. The results indicated that the hybrids possessed high resistance levels against the two pests, with mortality rates above 73.6% and damage scales below 2.4 compared with the control group. Our results suggested that the Cre/loxP-mediated genetic engineering approach has a competitive advantage in GM maize. Overall, findings from this study are significant for providing a feasible strategy for transgenes avoiding expression in edible parts and exploring novel techniques toward the biosafety of GM plants.

Obtaining a proper position for THA’s components is a crucial aspect for the implant perfor-mance and consequently patient outcomes. Patient specific kinematic seems to be a key factor to reach the optimal implant positioning. The aim of this study was to assess the accuracy and safety of a computed dynamic analysis system which through patient specific guides tries to improve implant positioning and functional orientation according to patient’s spinopelvic mobility and anatomy.A total of 100 consecutive patients were prospectively enrolled. All patients received an OPS dynamic hip preoperative planning. A TC scan protocol follow up analysis has done at 6 month after surgery.The mean deviation from the planned acetabular inclination and anteversion was 4.3° e 3.8° respectively. The 98% of cases was within +/- 10° of Lewinnek safe zone both for inclination and anterversion. The height of osteotomy deviated on the average of 1.6mm. The 100% cases were included within 4mm of osteotomy. Patient specific and laser guided instru-mentation is safe and accurately reproduce the dynamic planning in terms of components orien-tation, osteotomy level, leg length and offset.

Although tourism seasonality significantly influences the livelihood activities of rural tourism households, limited research has explored how they adapt their livelihood strategies to achieve optimal outcomes. Employing an exploratory sequential mixed-methods design that combines thematic analysis and fuzzy-set Qualitative Comparative Analysis (fsQCA), we investigated the relationship between the livelihood strategies and outcomes of rural tourism households under the influence of tourism seasonality at the Guilin Karst World Heritage Site. The results indicate that livelihood strategies adopted by rural tourism households include "Tourism Persistence,” "Seasonal Employment,” and “Seasonal Farming” during the off-season, and “Extending Working Hours,” “Increasing Staffing Input,” and “Increasing Capital Input” during the peak season. Furthermore, these strategies form flexible combinations to realize livelihood outcomes, with “Extending Working Hours” being a necessary condition. The findings also revealed that the four configurations of seasonal livelihood strategies in the two patterns significantly contributed to high livelihood outcomes. One is named “Peak-Season Driven Pattern,” where “Extending Working Hours” and “Increasing Staffing Input” are the core conditions; the other is named “Peak-Off Blend-Driven Pattern,” where “Extending Working Hours,” “Increasing Capital Input,” and the absence of “Tourism Persistence” are the core conditions. These findings provide theoretical and practical insights for sustainable livelihood research.

Modeling and assessing the sustainability of machining systems has been considered to be a crucial approach to improving the environmental performance of the machining processes. As the most common machining system, the computer numerical control (CNC) milling system is a typical man-machine cooperative system where the activities of the machine tool and operator generate material and energy consumption. However, the energy consumption of the operator in the CNC milling system has often been ignored in most existing research. Therefore, existing methods fail to provide a comprehensive understanding of the sustainability of the CNC milling system. To fill this gap, an exergy loss assessment method is proposed to investigate the sustainability of the CNC milling system, where the energy consumption of the operator, the energy consumption of the machine tool, and material consumption are taken into consideration. The key performance indexes of the energy consumption of the operator, the energy consumption of the machine tool, the exergy loss, and the specific exergy loss (SEL) are analyzed and modeled. To demonstrate the feasibility of the proposed method, a case study was carried out on a three-axis machining center (XH714D), in which SEL was found to be 88.04J/mm3. The proposed method is effective to assess the sustainability of the CNC milling system, and the established exergy loss models build a good basis for exergy efficiency optimization.

Plasminogen (Plg) is the inactive form of plasmin (Plm) that exists in two major glycoforms, referred to as glycoforms I and II (GI and GII). In the circulation, Plg assumes an activation-resistant 'closed' conformation via interdomain interactions and is mediated by the lysine binding site (LBS) on the kringle (KR) domains. These inter-domain interactions can be readily disrupted when Plg binds to lysine/arginine residues on protein targets or free L-lysine and analogues. This causes Plg to convert into an 'open' form which is crucial for activation by host activators. In this study, we investigated how various ligands affect the kinetics of Plg conformational change using small-angle X-ray scattering (SAXS). We began by examining the open and closed conformations of Plg using size-exclusion chromatography (SEC) coupled with SAXS. Next, we developed a high throughput (HTP) 96-well SAXS assay setup. This method enables us to determine the Kopen value, which is used to compare ligands’ effect on Plg conformation directly. Based on our analysis using Plg GII, we have found that the Kopen for ε-aminocaproic acid (EACA) is approximately three times greater than that of Tranexamic acid (TXA), which is widely recognized as a highly effective ligand. We demonstrated further that Plg undergoes a conformational change when it binds to the C-terminal peptides of the inhibitor α2-antiplasmin and receptor Plg‑RKT. Our findings suggest that, besides the C-terminal lysine, internal lysine(s) are also necessary for the formation of open Plg. Finally, we compared the conformational changes of Plg GI and GII directly and found that the closed form of GI, which has an N-linked glycosylation, is less stable. To summarize, we have successfully determined the response of Plg to various ligand/receptor peptides by directly measuring the kinetics of its conformational changes.

With the development of information technology and the wide application of building information modelling technology, the construction industry continues to make digital changes. Managers are trying to apply smart construction site management to promote the upgrading of production modes. We used CiteSpace software to analyze 1707 articles from China National Knowledge Infrastructure, Web of Science and Scopus to understand the current research hotspots of global scholars in this field. Results show that: (1) The number of studies on smart construction sites increases rapidly by year. Researchers from China, America and the UK have the most influential studies. (2) The cooperation between researchers and institutions is not close enough. In addition, the directions of research in the field are still scattered; (3) Chinese scholars are good at building intelligent platforms and evaluating intelligent systems from multiple perspectives. International scholars are willing to pursue technological innovation, allowing the continuous development of intelligent construction technology. (4) The applications in this field have not been popularized despite relatively perfect technology and typical cases. Future scholars should gradually improve the theoretical basis and industry standards of smart construction sites, promote the development of intelligent construction technology and establish the evaluation standards of qualified smart sites. This study will provide scholars in this field with the theoretical basis and research directions for further in-depth research, help construction companies to understand the development status and trend of smart construction sites and accelerate the intelligent transformation of construction companies.

Ubiquitin-Specific-peptidase 22 (Usp22) cleaves ubiquitin moieties from numerous proteins, in particular transcription factors. Recently, it was reported that Usp22 acts as negative regulator of interferon-dependent responses. In the current study, we investigated the role of Usp22 deficiency upon acute viral infection with lymphocytic choriomeningitis (LCMV) virus. We found that lack of Usp22 on bone marrow derived cells (Usp22 fl/fl Vav1-Cre mice) reduced induction of type I and II interferons. Limited type I interferon response did not influence virus replication. However, restricted expression of PD-L1 led to increased frequencies of functional virus-specific CD8+ T cells and rapid death of Usp22 deficient mice. CD8+ T cell depletion experiments revealed that accelerated CD8+ T cells were responsible for enhanced lethality in Usp22 deficient mice. In conclusion, we found that the lack of Usp22 generated a pathological CD8+ T cell response, which gave rise to severe disease in mice.

The fishmeal production industry is essential for providing protein for animal feed in the aquaculture sector. However, the industry faces challenges related to energy consumption and environmental sustainability. This study evaluates the energy efficiency and environmental benefits of waste heat recovery (WHR) technologies in a fishmeal production plant in Vietnam. Data were collected from the plant between 2016 and 2022, and a specific energy consumption (SEC) indicator and a comprehensive methodology were utilized. Implementing an economizer as a WHR technology resulted in a 55.5% decrease in SEC compared to the state before installation. The enhanced energy efficiency also translated to reduced energy consumption per output unit. Moreover, the economizer contributed to annual energy savings of 4,537.57 GJ/year and cost savings of $26,474.49. Additionally, carbon dioxide (CO2) emissions associated with producing one ton of fishmeal decreased by 58.37%. These findings highlight the potential for WHR technologies to improve energy efficiency and reduce the environmental footprint of fishmeal production. The study's results provide valuable insights for practitioners and policymakers in promoting energy efficiency practices and reducing environmental impact in the industry.

In recent years, the number of open preservation surgeries for treatment of laryngeal Cancer has increased. The purpose of this surgery is to avoid the highly mutilating intervention of a total laryngectomy (TL) and to maintain laryngeal function while ensuring oncological radicality. The aim of this study was to assess the oncologic results of OPHL I and II and to identify prognostic factors that could impact patient survival and local failure rates. This study was conducted on 182 patients with laryngeal squamous cell carcinoma treated with OPHLs between 2005 and 2015. The survival rates of a group of patients treated with TL between 2004 and 2014 were taken into con-sideration to compare survival outcomes. The DSS in pT2 and pT3 tumors in relation to the type of surgery showed no statistically significant difference between OPHLs and TL (p=0.54 and p=0.63 respectively). The 5-years T-recurrence free survival showed that pT4 tumors, perineural/vascular positive invasion and OPHL IIb + ARY treated tumors were associated with a higher risk of tumor recurrence (p<0.0001, p=0.0005 and p=0.016 respectively). OPHLs represent an excellent alterna-tive to TL considering the characteristics of the tumor and the general conditions of the patient.

High prevalence of allergic disorders in Indian pediatric patients demands early diagnosis of allergens so that appropriate allergen avoidance methods, pharmacotherapy or immunotherapy can be provided in time to avoid the worsening of symptoms due to triggers. In this context, identification of the most prevalent aeroallergens in a given area is critical for diagnosis and treatment of various allergic reactions especially in case of rhino-conjunctivitis and asthma. The specific diagnosis of IgE mediated allergy is usually based on the correlation between the clinical history and signs and symptoms endorsed by the diagnostic tests. Skin prick tests are the gold standard however has some limitation. In view of this, the aim of this study was to assess the significance of ImmunoCAP assay for assessing serum specific IgE levels, available in India, against skin prick test by standardized allergens, for the diagnosis of allergic sensitization. A single-center observational study was conducted at tertiary care corporate hospitals in North India from 2017-2020. Patients with self-reported allergic symptoms or whose symptoms were suspected for allergies were tested for the type of sensitization using skin prick test (SPT) after their consents followed by ImmunoCAP based quantification of serum specific IgE levels. A total of 256 (95.9%) pediatric patients were analyzed in the study and were analysed. The patients were most commonly (30% patients) sensitized to D. farinae (173 [67.6%]), D. pteronyssinus (174 [68.0%]), Acarus siro (93 [36.3%]), Lepidoglyphus destructor (96 [37.5%]), Plantago lanceolata (Engl.). The ROC curve of Bermuda grass shows that the AUC of serum-specific IgE is larger than that of SPT (1.000 / 0.881). The receiver operating characteristic (ROC) analysis of serum-specific IgE reference method resulted in the largest AUC of all the allergens taken into consideration (0.711 / 1.000) compared to those of SPT (0.589 / 1.000). These results revealed that serum-specific IgE is more reliable method over prick test for accessing the sensitivity of patient for various allergens. This study may be helpful in performing early diagnosis of allergies as well as in taking appropriate preventive measures for managing life threatening allergic reactions

Sedimentation processes have negative socioeconomic and environmental consequences, ranging from eutrophication phenomena, loss of water quality in surface water bodies, effects on the potential for hydroelectric generation, etc. Frequently, anthropic activity is the main cause that enhances these processes through changes in land use that can lead to landscape modifications. Therefore, it is relevant to evaluate this phenomenon and to be able to discriminate the influence of different land uses on the contributions to sediment loads at different scales. The novel Compound Specific Stable Isotopes technique allows the evaluation of sediment inputs associated with different land use changes in a study region. In the present work this technique was used in the Alhajuela Lake sub-basin, within the Panama Canal Watershed. The contribution levels of three (3) representative land uses (forest, pasture and sediment) in the study area were evaluated for the sediments present in sixteen (16) selected mixing points. The main contributions of the sources to the sediments present in the main rivers and tributaries flowing into Alhajuela Lake, in the sub-basin of the same name, were identified. The results obtained are consistent with observations and measurements of sedimentation in the study area.

Parasite control strategies such as blanket anthelmintic treatment of all horses in a herd or interval treatment regimen based on egg reappearance remain widely followed practices for the last several decades. These practices have resulted in the fast emergence of resistance in equine strongyles to all major classes of drugs on the market. In this regard, the guidelines set by the American Association of Equine Practitioners advocate evidence-based strongyle control in horses. It recommends targeted treatment of all heavy egg shedders [&gt; 500 eggs per gram (EPG) of feces] while the low shedders (0-200 EPG) are left untreated to maintain susceptible parasite refugia in a herd. As 50-75% of adult horses in a herd are low shedders, preventing them from unnecessary anthelmintic exposure is critical to tackling resistance. There are various fecal egg count (FEC) techniques with many modifications and variations in use, but none is identified as a gold standard and methods comparison studies are lacking. We hypothesized that the diagnostic performance of commonly used quantitation methodologies differs and the FEC methods must be evaluated to determine the gold standard. In this regard, we performed methods comparison studies using polystyrene beads with size and specific gravity comparable to strongyle eggs, as proxy. The linearity of 12 commonly used FEC methodologies (3 techniques with 4 different solutions) was studied using bead standards in the clinically applicable range (63 to 1,000) to determine their suitability for strongyle egg counts. Deming regression analysis identified Mini-FLOTAC with sugar (specific gravity 1.33) as the test with the greatest coefficient of determination. All tests underestimated the true bead count, and we determined a correction factor (CF) for each test to estimate the true count. CF negates the preference for a gold standard test. Finally, we analyzed the validity of CF for 5 tests with R2&gt;0.95 to accurately quantify strongyle eggs from 40 different horses. Overall, this study identified methodologies with the highest diagnostic performance and the limitations to standardizing routine FEC tests to promote uniformity in implementing AAEP parasite control guidelines.

A reduced ability to work with information contained in a text is usually registered in low-achieving students. One important internal factor influencing reading comprehension concerns the child’s executive functioning. The current study investigated whether the domain-specific intervention ExeFun-READ targeting language abilities related to reading comprehension and executive functioning in primary school children would be effective in improving their scholastic performance in their reading domain and executive functioning. ExeFun-READ is designed to address the relations between domain-specific versus thinking-skill-oriented (domain-general) instruction. A child’s active learning is focused on semantic, phonetic, morphological and syntactical comprehension of linguistic material. In total, 151 students attending grade four from seven elementary schools took part in the project. The study concerned a pretest-intervention-posttest experimental design with three conditions: the experimental condition, an active, and a passive control group. To assess the children’s level of EF, the Delis–Kaplan Executive Function System test battery was used; to assess children’s language ability in reading domain, the Cognitive Abilities Test (the verbal battery, Thorndike &amp; Hagan, 1986 [1]), was used. In the current study, the intervention led to improved language abilities related to reading comprehension, but in terms of executive functioning the improvement only extended to switching fluency. Regarding the effects of the ExeFun-READ intervention on children’s reading abilities, specified as language abilities related to reading comprehension, significant improvements were found in vocabulary, completion of sentences, and classification of terms in the group of children that received the ExeFun-READ intervention.

Waste management is an unavoidable technological operation in the process of raw material extraction. The main characteristic of this technological operation is the handling of large quantities of waste material, which can amount to several hundred million cubic metres. Working with this amount of material usually requires high-capacity systems for excavation and loading, a large fleet of trucks for haulage, construction, and maintenance of a complex roads network, use of a significant area of land in order to achieve the required capacities, etc. At the same time, this operation must comply with all administrative and environmental standards. Therefore, optimising waste rock management (particularly haulage and dumping) has the potential to significantly improve the overall value of the project. This paper presents a hybrid model for the optimisation of waste dump design and site selection. The model is based on different mathematical methods (genetic algorithm, analytic hierarchy process and heuristic methods) adapted to different aspects of the problem. The main objective of the model is to provide a solution (in analytical and graphical form) for the draft waste dump design, on the basis of which the final waste dump design can be defined.

Initially introduced almost thirty years ago for the express purpose of providing electronic warfare systems the capabilities to detect, characterize, and identify radar emitters, Specific Emitter Identification (SEI) has recently received a lot of attention within the research community as a physical layer technique for securing Internet of Things (IoT) deployments. This attention is due in large part to SEI’s demonstrated success in passively and uniquely identifying wireless emitters using traditional machine learning and the success of Deep Learning (DL) within the natural language processing and computer vision areas. SEI exploits distinct and unintentional features present within an emitter’s transmitted signals. The existence of these distinctive and unintentional features is attributed to slight manufacturing and assembly variations that exist within and between the components, sub-systems, and systems that comprise an emitter’s Radio Frequency (RF) front end. Although sufficient to facilitate SEI, these features do not hinder normal operations such as detection, channel estimation, timing, and demodulation. However, despite the plethora of SEI publications, it has remained largely a focus of academic endeavors that primarily focus on proof-of-concept demonstration and little to no use in operational networks for various reasons. The focus of this survey is a review of SEI publications from the perspective of its use as a practical, effective, and usable IoT security mechanism, thus we use IoT requirements and constraints (e.g., wireless standard, nature of their deployment) as a lens through which each reviewed paper is analyzed. Previous surveys have not taken such an approach and have only used IoT as motivation, a setting, or a context. In this survey, we consider operating conditions, SEI threats, SEI at scale, publicly available data sets, and SEI considerations that are dictated by the fact that it is to be employed by IoT devices or IoT infrastructure.

Important first phases in the process of implementing CO2 subsurface and ocean storage projects include selecting of best possible location(s) for CO2 storage, site selection evaluation. Sites must fulfil a number of criteria that boil down to the following basics: they must be able to accept the desired volume of CO2 at the rate at which it is supplied from the CO2 source(s); they must as well be safe and reliable; and must comply with regulatory and other societal requirements. They also must have at least public acceptance and be based on sound financial analysis. Site geology; hydrogeological, pressure, and geothermal regimes; land features; location, climate, and access, etc. can all be refined from these basic criteria. In addition to aiding in site selection, site characterization is essential for other purposes, such as foreseeing the fate and impacts of the injected CO2, and informing subsequent phases of site development, including design, permitting, operation, monitoring, and eventual abandonment. According to data from the IEA, in 2022, emissions from Africa and Asia's emerging markets and developing economies, excluding China's, increased by 4.2%, which is equivalent to 206 million tonnes of CO2 and were higher than those from developed economies. Coal-fired power generation was responsible for more than half of the rise in emissions that were recorded in the region. The difficulty of achieving sustainable socio-economic progress in the developing countries is entwined with the work of reducing CO2 emissions, which is a demanding project for the economy. Organisations from developing countries, such as Bangladesh, Cameroon, India, and Nigeria, have formed partnerships with organisations in other countries for lessons learn and investment within the climate change arena. The basaltic rocks, coal seams, depleted oil and gas reservoirs, soils, deep saline aquifers, and sedimentary basins that developing countries (Bangladesh, Cameroon, India, and Nigeria etc) possesses all contribute to the individual country's significant geological sequestration potential. There are limited or no carbon capture and storage or clean development mechanism projects running in these countries at this time. The site selection and characterization procedure are not complete without an estimate of the storage capacity of a storage location. Estimating storage capacity relies on volumetric estimates because a site must accept the planned volume of CO2 during the active injection period. As more and more applications make use of site characterization, so too does the body of written material on the topic. As the science of CO2 storage develops, regulatory requirements are implemented, field experience grows, and the economics of CO2 capture and storage improve, so too will site selection and characterisation change.

Contrary to the long-held belief that the effects of vaccines are specific for the disease they were created; compelling evidence has demonstrated that vaccines can exert positive or deleterious non-specific effects (NSEs). In this review, we compiled research reports from the last 40 years, showing that live vaccines induce positive NSEs, whereas non-live vaccines induce several negative NSEs, including increased female mortality associated with enhanced susceptibility to other infectious diseases, especially in developing countries. These negative NSEs are determined by the vaccination sequence, the antigen concentration in vaccines, the type of vaccine used (live vs. non-live), and also by repeated vaccination. We do not recommend stopping using non-live vaccines, as they have demonstrated to protect against their target disease, so the suggestion is that their detrimental NSEs can be minimized simply by changing the current vaccination sequence. High IgG4 antibody levels generated in response to repeated inoculation with mRNA COVID-19 vaccines could be associated with a higher mortality rate from unrelated diseases and infections by suppressing the immune system. Since most COVID-19 vaccinated countries are reporting high percentages of excess mortality not directly attributable to deaths from such disease, the NSEs of mRNA vaccines on overall mortality should be studied in depth.

There was no significant difference in bacterial adhesion between the 3 bone graft types tested, regardless of the bacterial strain used (p &gt; 0.22). After 72 hours of culture, there was no significant difference between the Fresh and Frozen bone groups, while the number of CFU in the Decellularised group was significantly lower (p &lt; 0.01), averaging -0.72 +/- 0.08 lg, -0.20 +/- 0.01 lg and -0.78 +/- 0.48 lg with S. epidermidis, S. aureus and E. coli respectively. Absolute values differences are low, and considering fresh bone (equivalent to autograft) as the gold standard due to its low infection rates in clinical studies, we can conclude that adhesion and biolfilm development characteristics are similar between Fresh, Frozen and Decellularised bone grafts..

Rare-earth tetraborides RB4 are of great interest due to the occurrence of geometric magnetic frustration and corresponding unusual magnetic properties. While the Gd3+ spins in GdB4 align along the ab plane, Er3+ spins in the isomorphic ErB4 are confined to the c–axis. The magnetization in the latter exhibits a plateau at the midpoint of the saturation magnetization. Therefore, solid solutions of (Gd, Er)B4 provide an excellent playground for exploring the intricate magnetic behavior in these compounds. Single crystals of Gd(1-x)Erx B4 (x = 0, 0.2, and 0.4) were grown in aluminum flux. X-ray diffraction scans revealed single phase materials, and a drop in the unit cell volume with increasing Er content, suggesting the partial substitution of Er at the Gd sites. Heat capacity measurements indicated a systematic decrease of the Néel temperature (TN) with increasing Er content. The effective magnetic moment determined from the magnetization measurement agreed with the calculated free-ion values for Gd3+ and Er3+, providing further evidence for the successful substitution of Er for Gd. The partial substitution resulted in an anomalous ferromagnetic phase below TN, exhibiting significant anisotropy, predominantly along the c-axis. This intriguing behavior merits further studies of the magnetism in the Gd(1-x)ErxB4 borides.

Profitability is an underestimated concept in precision agriculture. In this research, a new module is developed within a pre-existing farm management system to assess the profitability of precision agriculture applications in extended crops. The module is regulated on a 5-meter spatial resolution, thus allowing scaling up of original and processed data on a zone-, field-, cultivar-, and farm-scale. A bottom-up approach, taking advantage of the full functionality of the farm management system, together with a flexible architecture and an easy-to-use interface, renders the new module an innovative commercial application.

Prostate-specific membrane antigen (PSMA) has been identified as a target for the development of theranostic agents. In our current work, we describe the design and synthesis of novel N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-L-lysine (DCL) urea-based PSMA inhibitors with a chlorine-substituted aromatic fragment at the lysine ε-nitrogen atom, a dipeptide as peptide fragment of the linker, including two phenylalanine residues in the L-configuration, and 3- or 4-(tributylstannyl)benzoic acid as prosthetic group in their structures for radiolabeling. The standard compounds ([127I]PSMA-m-IB and [127I]PSMA-p-IB) for comparative and characterization studies were firstly synthesized using two alternative synthetic approaches. An important advantage of the alternative synthetic approach in which the prosthetic group (NHS-activated esters of compounds) is first conjugated with the polypeptide sequence, followed by replacement of the Sn(Bu)3 group with radioiodine, is that the radionuclide is introduced in the final step of synthesis, thereby minimizing operating time with iodine-123 during the radiolabeling process. The obtained DCL urea-based PSMA inhibitors were radiolabeled with iodine-123. The radiolabeling optimization results showed that the radiochemical yield of [123I]PSMA-p-IB was higher than those of [123I]PSMA-m-IB, which were 74.9± 1.0% and 49.4 ± 1.2%, respectively. The radiochemical purity of [123I]PSMA-p-IB after purification was greater than 99.50%. The initial preclinical evaluation of [123I]PSMA-p-IB demonstrated a considerable affinity and specific binding to PC-3 PIP (PSMA-expressing cells) in vitro. The in vivo biodistribution of this new radioligand [123I]PSMA-p-IB showed less accumulation than [177Lu]Lu-PSMA-617 in several normal organs (liver, kidney and bone). These results warrants further preclinical development including toxicology evaluation and experiments in tumor-bearing mice.

Antibody-mediated targeting is an efficient strategy to enhance the specificity and selectivity of polymer nanomedicines towards the target site, typically a tumor. However, direct covalent coupling of an antibody with a polymer usually results in a partial damage of the antibody binding site accompanied with a compromised biological activity. Here, an original solution based on well-defined non-covalent interactions between tris-nitrilotriacetic acid (trisNTA) and hexahistidine (His-tag) groups, purposefully introduced to the structure of each macromolecule, is described. Specifically, trisNTA groups were attached along the chains of a hydrophilic statistical copolymer based on N-(2-hydroxypropyl)methacrylamide (HPMA), and at the end or along the chains of thermo-responsive di-block copolymers based on N-isopropylmethacrylamide (NIPMAM) and HPMA; His-tag was incorporated to the structure of a recombinant single chain fragment of an anti-GD2 monoclonal antibody (scFv-GD2). Static and dynamic light scattering analyses confirmed that mixing of polymer with scFv-GD2 led to the formation of polymer/scFv-GD2 complexes; those prepared from thermo-responsive polymers formed stable micelles at 37 °C. Flow cytometry and fluorescence microscopy clearly demonstrated antigen-specific binding of the prepared complexes to GD2 positive murine T-cell lymphoma cells EL-4 and human neuroblastoma cells UKF-NB3, while no interaction with GD2 negative murine fibroblast cells NIH-3T3 was observed. These non-covalent polymer protein complexes represent a new generation of highly specific actively targeted polymer therapeutics or diagnostics.

Soil erosion due to soil erosion is an important ecological impact factor. In order to further explore the impact and contribution of soil and water conservation measures on sand production and transport in the watershed, and also to provide a reference for soil erosion control, soil and water conservation and ecological environmental protection in the Yellow River Basin. In this paper, based on the measured data from the Henan Soil and Water Conservation Observatory in the Yellow River Basin, we select appropriate equations for quantifying soil erosion factor to calculate the rainfall erosion, topography, soil, vegetation and soil conservation measures in the basin, and then analyse the changes in soil erosion factor and the actual benefits of soil conservation measures in the basin. The results show that there is an increasing trend in the rainfall erosion force factor R in the Yellow River Basin; Soil erosion can be K value made the vertical loess > yellow clunamon soil, the overall change shows a decreasing trend, indicating that erosion control has produced results and that attention should be paid to erosion control in the lithosol region in the future; Since the slope lengths of the runoff plots are laid out consistently with the same LS values for both topographic factors, soil erosion is severely increased when the slope exceeds 20°. The C value of natural vegetation is small, while the C value of bare land is large. The authorities should continue to promote the return of farmland to forests and grasses and pay attention to the self-regulation and restoration of ecosystems; There is an overall decreasing trend in the P value of the soil and water conservation measures factor, the soil and water conservation measures have been effective in providing good protection.

Background. Green spaces contribute to a significant life quality and maintain the sustainability of cities. In Benin, despite the political greening willingness, municipalities are experiencing technical issues in finding suitable spaces to achieve this goal. This study should serve many other towns. It aims at identifying suitable areas for green spaces to integrate landscaping into urban planning in Abomey-Calavi district. Methods. The multi-criteria analysis combining GIS and the hierarchical classification approach were performed. Six factors (land use, altitude, slope, distance from main roads, proximity to urban centres and distance from flood zones, water bodies) were combined using the ArcGIS "Spatial Analysis" extension to generate a map of green space suitability. Results. large areas of land, of which 23.27% are very suitable and 26.06% are suitable for landscaping in this municipality. The ranking of the factors revealed altitude, proximity to road networks, large conurbations and distance from wetlands accounting for 18%, compared with 14% for the other factors regarding the study environment. However, the use of these results must take into account the existing inhabited areas for a good site selection. Conclusion. These outputs guidance to decision-makers in choosing suitable sites for green spaces there and integrating them into sustainable development.

Electroencephalography (EEG) signals are the primary source for discriminating the preictal from the interictal stage, enabling early warnings before the seizure onset. The epileptic seizure prediction models face significant challenges due to data scarcity, diversity, and privacy. This paper proposes a three-tier architecture for epileptic seizure prediction associated with the Federated Learning (FL) model that enhances the capability by utilizing the significant amount of seizure patterns from globally distributed patients with data privacy. The determination of the preictal state is influenced by global and local model-assisted decision-making by modeling the two-level edge layer. Integrating the Spiking Encoder (SE) with Graph Convolutional Neural Network (Spiking-GCNN) works as the local model trained using the bi-timescale approach. Each local model utilizes the aggregated seizure knowledge from the different medical centers through FL and determines the preictal probability in the coarse-grained personalization. The Adaptive Neuro-Fuzzy Inference System (ANFIS) is utilized in fine-grained personalization to recognize epileptic seizure patients by examining the outcomes of the FL model, heart rate variability features, and patient-specific clinical features. The proposed seizure prediction is evaluated using benchmark datasets by comparing them with the existing works to demonstrate the potential results.

Health services research is a multidisciplinary discipline that aims to improve population health by studying healthcare services' organization, delivery, and financing. Over time, the field has worked to define its boundaries and establish a set of core research topics and methods addressing population wellbeing, access, quality, and cost. Although the influence of health technology is significant, our literature survey on health services research showed that SCs in general—containing their management, cost, and policy—had received little attention. Importantly, our assessment also showed that the system’s readiness to handle supply policy and supply device deficiencies like those encountered during pandemic was hardly ever mentioned. Reduced open areas and water bodies, deteriorating infrastructure, and changes in the biological morphology all affect cities’ uncontrollable and unplanned growth. Urban amenities, facilities, and healthcare services were unevenly distributed due to this unchecked urban population development. In light of this, this research suggests two reliable models for site selection issues for one of Hong Kong’s main hospitals. Levels of uncertainty, infeasibility tolerance, and reliability are taken into consideration. Then, two categories of uncertainty—symmetric and bound-ed—were examined. As a result, the challenge of scheduling in uncertainty has been considered, and potential solutions have been presented using a specified probability distribution function. The paper concludes by introducing the specific justice and health problems and outlining four typical strategies. In order to ensure that medications and other healthcare supplies are produced, distributed, and given to patients, a vast network of systems, components, and procedures must be effectively managed. This research contributes in this regard. Also, its grantee fairness in health systems and the populations health locally, nationally, and globally. It highlights health inequity, advances the measurement of health inequity, and promotes public dialogues on health inequity.

Aiming at the prediction of environmental vibrations induced by elevated high-speed railway, a machine-learning method is developed by combining random forest algorithm and Bayesian optimization, which using the dataset from on-site experiments . When it comes to achieving a rapid and effective prediction of environmental vibration, there is few research on com-parisons and verifications of different algorithms, and neither on parameter tuning and optimi-zation of machine learning algorithms. In this paper, a field experiment is firstly carried out to measure the ground vibrations caused by high-speed trains running on bridge, and then the en-vironmental vibration characteristics are analyzed in view of ground accelerations and weighted vibration levels. Subsequently, three machine-learning algorithms of linear regression, support vector machine and random forest are developed by using experimental database, and their prediction performance are discussed. Finally, two optimization models for the hyperparameter set of random forest algorithm are further compared. It turns out that the integrated random forest algorithm has higher accuracy in predicting environmental vibration than linear regression and support vector machine; the Bayesian optimization has excellent performance and high efficiency in achieving efficient and in-depth optimization of parameters, and can be combined with the RF machine learning algorithm to effectively predict the environmental vibrations induced by the high-speed railway.

Expanding previous efforts to survey the visual opsin repertoires of the Hemiptera, this study confirms that homologs of the UV- and LW-opsin subfamilies are conserved in all Hemiptera, while the B-opsin subfamily is missing from the Heteroptera and subgroups of the Sternorrhyncha and Auchenorrhyncha, i.e. aphids (Aphidoidea) and planthoppers (Fulgoroidea), respectively. Unlike in the Heteroptera, which are characterized by multiple expansions of the LW-opsin subfamily, the lack of B-opsin correlates with the presence of tandem-duplicated UV-opsins in aphids and planthoppers. Available data on organismal wavelength sensitivities and retinal gene expression patterns lead to the conclusion that, in both groups, one UV-opsin paralog shifted from ancestral UV peak sensitivity to derived blue sensitivity, thereby compensating for the lost B-opsin. Two parallel bona fide tuning site substitutions compare to 18 non-corresponding amino acid replacements in the blue-shifted UV-opsin paralogs of aphids and planthoppers. Most notably, while the aphid blue-shifted UV-opsin clade is characterized by a replacement substitution at one of the best-documented UV/blue tuning sites (Rhodopsin site 90), the planthopper blue-shifted UV-opsin paralogs retained the ancestral lysine at this position. The combined findings identify aphid and planthopper UV-opsins as a new valuable data sample for studying adaptive opsin evolution.

Background: Exclusively breastfeeding your newborn while in the hospital is imperative for suc-cessful breastfeeding at home. This study will investigate if having a nurse on-site during rooming-in can enhance the proportion of exclusive breastfeeding. Methods: We carried out a prospective cohort study to assess exclusive breastfeeding in the first three months of life among two Neona-tology Units in Southern Italy with different hospital settings. The Ente Ecclesiastico Miulli of Ac-quaviva delle Fonti had on-site nurses available 24/7 (on-site group), while the Policlinico of Bari had nurses available on call 24/7 from the Neonatology Unit (on-call group). Results: Between January 3rd and March 31st, 2018, a total of 564 sets of mothers and babies were admitted - 299 on-site and 265 on-call. The exclusive breastfeeding rate for the entire group was 76.4% at 90 days, demonstrating the positive impact of rooming-in and nursing, regardless of the setting. Infants delivered via ce-sarean section in the on-site group demonstrated higher rates of exclusive breastfeeding at both 30 and 90 days of life. Conclusions: Our research indicates that having a nurse available at all times is crucial for promptly identifying any problems with breastfeeding. We highly suggest having an on-site nurse present during rooming-in for mothers who have had a caesarean delivery. This nurse should continuously promote exclusive breastfeeding until the baby is three months old.

For Convolutional Neural Network (CNN), Depthwise Separable CNN (DSCNN) is a preferred architecture for Application Specific Integrated Circuit (ASIC) implementation on edge devices. It can benefit from a multi-mode approximate multiplier proposed in this work. The proposed approximate multiplier uses two 4-bit multiplication operations to implement a 12-bit multiplication operation by reusing the same multiplier array. With this approximate multiplier, sequential multiplication operations are pipelined in a modified DSCNN to fully utilize the PE array in the convolutional layer. This Approximate (A-DSCNN) was implemented on TSMC 40-nm CMOS process with a supply voltage of 0.9 V. At the clock frequency of 200 MHz, the design achieves 4.78 GOPs/mW while occupying 1.24 mm x 1.24 mm silicon area. Compared to conventional DSCNN implemented in a similar process node, the chip area and power consumption were reduced by 53% and 25%, while the throughput was improved by 17%.

The environmental legacy of post-closure mine sites poses a significant risk to the sustainability of mining operations and natural resource development. This study aims to advance the understanding of sustainable mine site reclamation behavior in Canada by using multi-temporal Landsat satellite images to examine the long-term land cover changes at post-closure mine sites. Six representative post-closure mine sites were selected for the evaluation and comparison. The Normalized Difference Vegetation Index (NDVI) analysis, Landsat image classification, post-classification change detection, and Regrowth Index (RI) analysis were conducted to assess the speed and extent of landscape and vegetation recovery at the target mine sites. A significant vegetation recovery was quantified for the mine sites that have experienced active reclamation activities. In contrast, the post-closure mine area undergoing only the passive revegetation typically demonstrated a slow and minor increase in vegetation over time. The actively revegetated mine sites can typically be restored to a level that equals or better than the pre-mining situation. This work confirms that active reclamation and revegetation at post-closure mine sites is critically important in sustainable mining. The quantified mine site reclamation behavior and the relevant sustainable practices would be useful for evidence-based sustainable resource management in Canada.

Since 2017 Cartagena UNESCO World Heritage has threatened to be categorized as "in Danger" by UNESCO. This research analyzes two main critical aspects, Governance and Current state of the Site. Regarding Governance, the study aims to identify strengths, weaknesses, opportunities and treats in the UNESCO Site. Exemplary heritage management systems are studied to propose an adaptable management approach specifically for Cartagena. On the other hand, a comprehensive analysis is conducted utilizing a photographic report that highlights the major issues arising from inadequate heritage management. Hyperspectral images obtained from a previous study are employed to identify vegetation and asbestos-cement roofs within the cultural heritage Site. The study reveals that the ambiguity surrounding decision-making authority for heritage management, distributed between the Mayor's Office and the Ministry of Culture, is a primary challenge. This fragmentation has resulted in duplicated efforts and a lack of coordinated action, significantly compromising the conservation and protection of the cultural heritage Site. Moreover, twelve current shortcomings of cultural heritage in Cartagena are identified through authors' five-year on-site regular visits, photographic reports and observation. To address the prevailing concerns, a new line of command for cultural heritage management is proposed as the most effective means of tackling these challenges. Additionally, general recommendations are presented to mitigate the existing problems and prevent the classification of Cartagena's heritage as "at risk" by UNESCO in the near future. This research provides a scientific perspective, drawing upon years of experience studying heritage and residing in the city, devoid of political influences or conflicts of interest.

Prostate-specific membrane antigen (PSMA) is a well validated prostate cancer marker, but reported PSMA-targeted tracers derived from the Lys-urea-Glu pharmacophore including the clinically validated [99mTc]Tc-EDDA/HYNIC-iPSMA have high off-target uptake in kidneys, spleen and salivary glands. In this study, we synthesized and evaluated three novel 99mTc-labeled PSMA-targeted tracers and investigated if the tracers derived from the Lys-urea-Aad pharmacophore could have minimized uptake in off-target organs/tissues. In vitro competition binding assays showed that compared with HYNIC-iPSMA, the three novel ligands had slightly weaker PSMA binding affinity (average Ki = 3.11 vs 8.96 - 11.6 nM). Imaging and ex vivo biodistribution studies in LNCaP tumor-bearing mice showed that [99mTc]Tc-EDDA/HYNIC-iPSMA and the three novel tracers successfully visualized LNCaP tumor xenografts in SPECT images and were excreted mainly via the renal pathway. The average tumor uptake at 1 h post-injection varied from 5.40 to 18.8 %ID/g, and the tracers derived from the Lys-urea-Aad pharmacophore had much lower uptake in spleen and salivary glands. Compared with the clinical tracer [99mTc]Tc-EDDA/HYNIC-iPSMA, the Lys-urea-Aad derived [99mTc]Tc-EDDA-KL01127 had lower background uptake and superior tumor-to-background contrast ratios, and is therefore promising for clinical translation to detect prostate cancer lesions with SPECT.

This paper addresses the grammatical challenges associated with the development of clause complexity, focusing on the performance of a group of monolingual Spanish-speaking schoolchildren with Specific Language Impairment/Developmental Language Disorder (SLI/DLD) in a longitudinal corpus of oral narrative samples. The study examines the presence of interclause relations of subordination and equivalence (hypotaxis and parataxis) in language samples of two groups: an experimental group made up of 24 schoolchildren with SLI/DLD and a control group made up of 24 schoolchildren with typical development (TD). The results show that while both groups use parataxis as the most common relation between clauses in all school grades, there is a significant decrease in paratactic relations and a significant increase in hypotactic relations from first to fourth grade of primary education. Although the development patterns are highly similar, the SLI/DLD group shows greater difficulties in mastering more complex (hypotactic) relations in fourth grade compared to the control group, indicating that they are less sophisticated in the use of these types of complex relations. These findings suggest that focused support on the most complex structures is needed towards the fourth grade of primary education, given the demands of the school academic register from 6 and 7 years of age, and the potential problems that the development of clause complexity can cause in school-age children.

Autistic spectrum disease (ASD) is an increasingly common diagnosis nowadays with a prevalence of 1-2% in most countries. Its complex causality – a combination of genetic, immune, metabolic and environmental factors - is translated into pleiomorphic developmental disorders of various severity, which have in common two main aspects: repetitive, restrictive behaviors, and difficulties in social interaction varying from awkward habits and verbalization to complete lack of interest from the ASD child for the outside world. The wide variety of ASD causes also makes it very difficult to find a common denominator – a disease biomarker and medication – and currently there is no commonly used diagnostic and therapeutic strategy besides clinical evaluation and psychotherapy.It is known that inflammation is present in a majority of ASD children, and blood inflammatory markers, together with metabolic, electrophysiological markers and imagistics are useful for ASD diagnostic validation and treatment; however, they tend to leave out a sizeable proportion of ASD kids who do not have such modifications. Genetic testing – whole exome sequencing or targeted profiling on about 500 ASD-linked genes- may also provide good insight into pathophysiology, however many times its results are more restrictive rather than offering additional therapeutic options.Here we describe a new biomarker for ASD - the neuron-specific enolase (NSE) - which was elevated above the normal clinical range (less than 16.3 ng/mL) in the vast majority of ASD kids tested in our study (40 of 41, or 97.5%). This finding opens up a new direction for diagnostic confirmation, dynamic evaluation and therapeutic intervention for ASD kids.

Abstract: Presence in a recipient of antibodies directed against donor specific antigens represent a major obstacle in transplanting such patients. Removal of these antibodies represents a challenge for physicians dealing with kidney transplantation. Several strategies, techniques and old and new drugs are to date used to desensitize these patients. Desensitization may occur before transplantation or at the time of transplantation or after transplantation according whether physicians deal with living or deceased donors. Different techniques may be used to reveal the presence of antibodies in the recipients; each technique has different sensitivity and specificity, different advantages and disadvantages. The target of the drugs used to desensitize are B cells, Plasma cells, the antibodies themselves and finally, the complement that is the final actor causing tissue disruption. If B cells are relatively easy to be targeted, more difficult are the plasma cell. Indeed, several new drugs are used in randomized trials also to defeat plasma cells. Antibodies may be removed rather easily, but often their removal is followed by a rebound. Complement is not easy to be defeated and new drugs are to date used to be successful in this action. However is to date possible to desensitize many patients and to obtain successful transplantation.

Hubei, Hunan and Henan Provinces are located in Central China, a region with extensive transport networks and trade. Bursaphelenchus xylophilus, the causative agent of pine wilt disease, is spreads mainly through human activities. In order to further understand the genetic structure of PWN in Central China, we studied the genetic information of PWN populations in this region and compared the genetic relationship with strains from Guangdong and Jiangsu provinces. We found that the HB (Hubei) 15, HEN (Henan) 20, HN (Hunan) 07, HN08 and HN10 had significantly more SNPs and homozygotes than other strains from Central China, and their most frequent mutant genotypes also differed from other strains. The clustering results indicated that HB15, HEN 20, HN07, HN08 and HN10 were genetically distinct from other strains and closely related to Guangdong strains. We also observed significant genetic variation among strains in Henan province, suggesting that some of them might have different transmission sources than those from Hubei and Hunan provinces. The results provide a basis for tracing the origin and spread of PWD in China.

To increase the prediction accuracy of positive oral food challenge (OFC) outcome during stepwise slow oral immunotherapy (SS-OIT) in children with hen’s egg (HE) allergy, we evaluated the predictive value of the combination of antigen-specific IgE (sIgE) with antigen binding-avidity and sIgG4 values. Sixty-three children with HE allergy undergoing SS-OIT were subjected to repeated OFC with HE. We measured the ovomucoid (OVM)-sIgE by ImmunoCAP or densely carboxylated protein (DCP) microarray, sIgG4 by DCP microarray, and the binding-avidity of OVM-sIgE defined as the level of 1/ IC50 (nM) measured by competitive binding inhibition assays. The OFC was positive in 37 (59%) patients undergoing SS-OIT. Significant differences in DCP-OVM-sIgE, CAP-OVM-sIgE, I/ IC50, DCP-OVM-sIgG4, the multiplication products of DCP-OVM-sIgE and binding-avidity of DCP-OVM-sIgE (DCP-OVM-sIgE/IC50) and DCP-OVM-sIgE/sIgG4 were compared between the negative and positive groups (p<0.01). Among them, the variable with greatest area under the receiver operating characteristic curve was DCP-OVM-sIgE/IC50 (0.84), followed by DCP-OVM-sIgE/sIgG4 (0.81). DCP-OVM-sIgE/IC50 and DCP-OVM-sIgE/sIgG4 are potentially useful markers for the prediction of positive OFC during HE-SS-OIT and may allow proper evaluation of the current allergic status in the healing process during HE-SS-OIT

The main issues of accounting reporting regarding goodwill are whether a firm’s management reliably conveys their private information about future earnings, and whether they disclose value-relevant and useful information to accounting users. In the current International Financial Reporting Standards (IFRS) regulations, the goodwill impairment test is based on management’s discretionary assessments. This study examines how goodwill impairment is reported under IFRS considering company- and industry-specific economic factors, proxies for earnings management, and macroeconomic crisis years. We extend previous research using Tobit and Logit regression, by employing a fixed-effects model. This approach is possible because of a panel data set comprising 449 of 600 active companies sampled from the STOXX Europe 600 index from 2005 to 2018. We find that goodwill impairments are largely concentrated in certain companies, industries, and years. The regression models show a significant negative correlation between companies’ return on total assets and goodwill impairments. Moreover, we discover that goodwill impairments have a significant positive correlation with goodwill intensity, debt ratio, and the proxy for reporting a one-off big bath charge. In addition, we find that the global financial crisis in 2008-2009 and the European debt crisis in 2011 differ significantly from other fiscal years

Production of lumpfish (Cyclopterus lumpus) has become crucial in controlling sea lice levels in salmonid aquaculture. To improve their breeding, there is a need for early sex identification. The genomic region containing anti-Müllerian hormone (amh) gene was suggested as the candidate sex-determining gene in lumpfish. However, the genome of lumpfish contains three copies of amh with ambiguous sex specificity, designated amh1, amh2, and amh3. The study aims to analyse the male-specific region between these amh paralogues, for its application as a sex marker. In this study, we utilised polymerase chain reaction (PCR)-based assays to identify the male-specific amh markers in lumpfish and estimate the length of the male-specific region in the lumpfish genome. Our results suggest that a region of approximately 26 kilobase (kb) region containing amh1 and amh2 is male-specific, while both sexes share amh3. The developed PCR-based genetic sex identification assays targeting amh1 and amh2 exhibited more than 97% accuracy. Further experiments in other members of the Cyclopteridae: Aptocyclus ventricosus, Eumicrotremus taranetzi, and E. asperrimus revealed male-specific amh fragments only in A. ventricosus. Phylogenetic analyses using the available Cyclopteridae amh sequences suggest that male-specific amh arose early in the Cyclopteridae lineage. These findings and development of the PCR test will be of service to lumpfish aquaculture as well as to future studies attempting to further elucidate the sex-determination system and sex chromosome evolution in lumpfish.

MultiCal is an affordable, high-precision measuring device designed for the on-site calibration of industrial robots. Its design features a long measuring rod with a spherical tip that is attached to the robot. By restricting the rod’s tip to multiple fixed points under different rod orientations, the relative positions of these points are accurately measured beforehand. A common issue with MultiCal is the gravity deformation of the long measuring rod, which introduces measurement errors into the system. This problem becomes especially serious when calibrating large robots, as the length of the measuring rod needs to be increased to enable the robot to move in a sufficient space. To address this issue, we propose two improvements in this paper. Firstly, we suggest the use of a new design of the measuring rod that is lightweight yet has high rigidity. Secondly, we propose a deformation compensation algorithm. Experimental results have shown that the new measuring rod improves calibration accuracy by 20% to 39%, while by using the deformation compensation algorithm, the accuracy increases by 6% to 16%. In the best configuration, the calibration accuracy is similar to that of a measuring arm with a laser scanner, producing an average positioning error of 0.274 mm and a maximum positioning error of 0.838 mm. The improved design is cost-affordable, robust, and has sufficient accuracy, making MultiCal a more reliable tool for industrial robot calibration.

The length of stay (LOS) in the hospital emergency department (ED) is a crucial key performance indicator that is used to track and manage the performance of the ED as a whole. Our study had two objectives. Firstly, we aimed to evaluate the association between LOS and the most common primary ICD-10 diagnoses. To achieve this, we examined LOS in groups with specific (internal, surgical, neurological, and traumatic diseases) and non-specific diagnoses in adult ED visits at a tertiary referral hospital between 2017 and 2019 (134,675 visits in total). Our secondary objective was to measure LOS by age, day of the week, time of day, and season. The mean LOS was 254 minutes and was the shortest in the traumatic group (160 minutes), while in other groups it was significantly longer: neurological by 185 minutes, internal medicine by 158 minutes, surgical by 36 minutes, and non-specific by 24 minutes. In conclusion, non-specific diagnoses accounted for 21% of all ICD-10 primary diagnoses. In this group of patients, the percentage of hospitalizations was the highest. Other significant determinants of LOS were the patients’ age, the day of the week, the time of arrival, and repeated visits.

Cross-species investigations on cancer invasiveness are a new approach that identified new biomarkers potentially useful for improving tumor diagnosis and prognosis in clinical medicine and veterinary science. In this study, we combined proteomic analysis of four experimental rat malignant mesothelioma (MM) tumors with analysis of ten patient-derived cell lines to identify common features associated to mitochondrial proteome rewiring. The comparison of significant abundance changes between invasive and non-invasive rat tumors rat tumors gave a list of 433 proteins, including twenty-six proteins reported to be exclusively located in mitochondria. Next, we analyzed the differential expression of genes encoding the mitochondrial proteins of interest in five primary epithelioid and five primary sarcomatoid human MM cell lines, and the most impressive increase was observed in the expression of the long-chain acyl coenzyme A dehydrogenase (ACADL). To evaluate the role of this enzyme in the migration/invasiveness, two epithelioid and two sarcomatoid human MM cell lines derived from patients with the highest and lowest overall survival were studied. Interestingly, sarcomatoid vs epithelioid cell lines were characterized by higher migration and fatty oxidation rates, in agreement with ACADL findings. These results suggest that evaluating mitochondrial proteins in MM specimens might identify tumors with higher invasiveness.

Pharmaceutically active compounds (PhACs) enter soil with organic substrates such as manure. Such complex substrates differently affect PhACs’ soil sorption. To elucidate the effects, batch experiments were conducted using five selected chemicals as model constituents. Urea, KH2PO4, acetic acid, phenol and nonadecanoic acid (C:19) altered the sorption strength and/or nonlinearity of sulfadiazine, caffeine and atenolol in a topsoil. The nonlinear Freundlich model best described sorption. Overall, the PhACs’ sorption coefficients increased in the sequence urea&lt;phosphate&lt;phenol&lt;C:19&lt;acetic acid. The sorption nonlinearity also increased in most cases. The effects on sulfadiazine and caffeine were rather similar, but in many cases different from atenolol. Phosphate mobilized sulfadiazine and caffeine and urea mobilized sulfadiazine, which was explained by sorption competition resulting from specific preference of similar sorption sites. Soil sorbed phenol strongly increased the sorption of all three PhACs; phenolic functional groups are preferred sorption sites of PhACs in soil. The large increase in sorption of all PhACs by acetic acid was attributed to a loosening of the soil organic matter and thus the creation of additional sorption sites. The effect of C:19 fatty acid, however, was inconsistent. These results help to better understand the sorption of PhACs in mixtures of soil and manure.

Knowledge of the biological effects of molecular hydrogen (H2), hydrogen gas, is constantly expanding giving a reason for optimism for several healthcare practitioners regarding management of multiple diseases, including socially significant ones. However, mechanisms underlying the biological effects of H2 are still being actively argued. In this review, we focus on mast cells as a potential target for H2 at the level of a specific tissue microenvironment. H2 regulates processing of pro-inflammatory components of the mast cell secretome and their entry into the extracellular matrix; this can significantly affect the state of the integrated-buffer metabolic environment and the structure of the immune landscape of the local tissue microenvironment. The analysis performed highlights several potential mechanisms for developing the biological effects of H2 and offers great opportunities for translating the obtained findings into clinical practice.

Kidney fibrosis is a complex polyetiological progressive disease manifesting as an intraorgan proliferation of the connective tissue with the appearance of cicatricial changes. However, pathogenetic mechanisms of renal fibrosis remain poorly understood. The paper highlights features of the protease phenotype and histotopography of mast cells (MCs) found in the kidney, as the key players in extracellular matrix remodeling in nephrofibrosis, detected in a patient diagnosed with "nephrosclerosis with the non-functioning upper pole of the duplex right kidney in the junction of refluxing megaureter of the upper pole of the duplex right kidney". The highest content of MCs was found in the kidney areas with fibrotic changes. MCs were actively involved in the development of inflammatory and fibrotic changes in limited loci of the specific tissue microenvironment of the kidney through targeted secretion of tryptase, chymase, and carboxypeptidase A3 to the vascular endothelium, nephron epithelium, interstitium cells, and components of the intercellular substance. The formation of a profibrotic environment in the kidney interstitium was facilitated by epigenetic effects of tryptase promoting epithelial-mesenchymal transition (EMT) of the nephron epithelium. A selectively increased number and targeted secretory activity of MCs in limited loci of the kidney parenchyma without visible pathological changes evidence a trigger pathogenetic role of specific proteases in the formation of a local microenvironment with a profibrogenic metabolic profile. Thus, MCs are actively involved in the mechanisms of formation and evolution of fibrogenic niches in the kidney; this fact can be used to develop new strategies for therapeutic options of tubulointerstitial fibrosis resulted from chronic kidney injury. Further study of the molecular phenotype of mast cells reveals new fundamental mechanisms of fibrosis pathogenesis being a significant tool for personalized therapy in nephrology.

Whole genome duplication (WGD) or polyploidization can occur at the cellular, tissue, and organismal levels. At the cellular level, tetraploidization has been proposed as a driver of aneuploidy and genome instability, and correlates strongly with cancer progression, metastasis, and development of drugs resistance[1–6]. WGD is also a key developmental strategy for regulating cell size, metabolism, and cellular function[1,7–10]. In specific tissues, WGD is involved in normal development (e.g. organogenesis), tissue homeostasis, wound healing, and regeneration[10–17]. At the organismal level, WGD propels evolutionary processes such as adaptation[18], speciation[19], and crop domestication[20]. An essential strategy to further our understanding of the mechanisms promoting WGD and its effects is to compare isogenic strains that differ only in their ploidy. Caenorhabditis elegans (C. elegans) is emerging as an animal model for these comparisons, in part because relatively stable and fertile tetraploid strains can be produced rapidly from nearly any diploid strain[7]. Here we review the use of Caenorhabditis polyploids as tools to understand important developmental processes (e.g. sex determination, dosage compensation, and allometric relationships)[21–27] and cellular processes (e.g. cell cycle regulation, chromosome dynamics during meiosis)[28–32]. We also discuss how the unique characteristics of the C. elegans WGD model will enable significant advances in our understanding of mechanisms of polyploidization and its role in development and disease.

Environmental degradation is one of the most visible problems in Hargeisa. Currently, solid waste is disposed of at two dumping sites within the city limits causing nuisance and unsanitary conditions. Moreover, the existing dumpsites are on the verge of closure, therefore necessitating a dire need to be addressed. This research paper is aimed to integrate multicriteria decision analysis and GIS for evaluating the site suitability for the landfill in Hargeisa, Somaliland. For this purpose, eleven significant parameters were selected: proximity from built-up areas, surface water, groundwater well points, sensitive sites (Airports), land use/land cover, geology, soil type, elevation, slopes, roads, and distance to existing dumpsites. These were then integrated using an analytical hierarchy process (AHP). Subsequently, restriction buffer analysis was performed on the seven parameters to obtain better and more accurate results, and restricted zones were omitted. Furthermore, the pair-wise comparison used to obtain priorities between the selected criteria showed that the land uses land cover is the most significant criterion in the model with a relative weight of 0.1829, followed by the habitations, 0.1506. The overall result reveals that about 68.96% (21060.9 ha) of the study area is unsuitable, while 24.36% (7441.53 ha) and 6.68% accounted for the less and highly appropriate zone, respectively. Following the results of this study, Hargeisa City's municipal council must reconsider the waste management and landfill sites to solve the problems observed in the area before it is overdue. Furthermore, this systematic research approach will assist regional and global researchers, policymakers, and municipal governments.

Magnetic nanoparticles (MNPs) have attracted a great interest in nanomedical research. MNPs exhibit many important properties, particularly, magnetic hyperthermia for selective killing of cancer cells is one of them. In hyperthermia treatment, MNPs act as nano-heaters when they are under the influence of an alternating magnetic field (AMF). In this work, micromagnetic simulations have been used to investigate the magnetization dynamics of a single-domain nanoparticle of magnetite in an external AMF. Special attention is paid to the circumstances dealing with a dynamic phase transition (DPT). Besides, we focus on the influence of the orientation of the magnetic easy-axis of the MNP on the dynamic magnetic properties. For amplitudes of the external AMF above certain critical value, the system is not able to follow the magnetic field and it is found in a dynamically ordered phase; whereas for larger amplitudes, the state corresponds to a dynamically disordered phase and the magnetization follows the external AMF. Our results suggest that the way how the order-disorder DPT takes place, and both the metastable lifetime as well as the specific loss power (SLP), are strongly dependent on the interplay between the orientation of the magnetic easy-axis and the amplitude of the external AMF.

In implantology, among the key choices, to obtain predictable results, it is essential to establish, on the basis of radiographic examinations, the bone site where to insert the implants; these selected locations must be identified first on the mucosa and then on the cortical bone. Surgical guides represent a valid aid especially in complex cases with more than 3 or 4 implants, whereas in single implant cases they are rarely used. This study evaluates the clinical precision with which the implant sites, on the patient's mucosa, are identified in surgical procedures planned without any templates. The verification of this precision is carried out through thermo-printed templates with radiopaque references which could however help the clinician to identify these sites in a simple, rapid and economical way.

Malignancy is a fatal disease with an increasing incidence with each passing year, and the early diagnosis of malignancy can significantly improve the cure rate of patients, which has profound implications for saving patients' lives. The changes of miRNA are closely related to the occurrence of malignant tumors. The expression of miRNA in many malignant tumors is obviously different and unique from that in normal tissues. In this study, a strategy for amplifying microRNA (miRNA) signal was designed using duplex specific nuclease (DSN), which was then combined with Peptide nucleic acid (PNA) probe hybridization technology to prepare a sensitive and efficient paper-based lateral flow biosensor (LFB) for the detection of pancreatic cancer (PC) associated microRNA-10b. The performance evaluation results of the LFB showed that the detection limit of miR-NA-10b is 5 nM/mL, and carries demonstrated well specificity, stability, reproducibility. The biosensor prepared in this paper can provide accurate and rapid detection of miRNA-10b. The detection results play a guiding role in the early diagnosis of PC. Meeting the clinical need for largescale screening of individuals at high risk of PC. Providing new avenues to achieve early mass screening in individuals at high risk of PC.

Over the past few decades, the quantity of construction waste has steadily risen in tandem with the expansion of construction activities and the rapid pace of development and urbanization. This problem is rooted in the practice of delivering materials to construction sites without totally using them for their intended purpose. The primary aim of the JIT tactic is to ensure that the precise materials required for production are available at the precise location, exact time, and appropriate quantity, thereby facilitating timely production. Presently, the use of ready-mix concrete is the most typical instance of a just-in-time construction process Developed countries have benefitted immensely from the use. However, the reverse is the case in developing countries like Nigeria, where indigenous contractors still employ traditional in-situ concreting even when faced with restrictive site space. This study focuses on investigating Ready-mix concrete, to project its immense benefits and effectiveness in minimizing lean construction waste. A survey research design and case study were adopted for this study, with the population being the management staff of construction firms in Lagos State, Nigeria. The questionnaire was used to collect data and the targeted respondents were purposively selected from the population. A total number of 112 questionnaires were administered with a response rate of 51%. Percentage, mean, standard deviation, and ANOVA were used to analyze the data. The mean value is above 3 on a Likert Scale of 5, while faster construction speed and uniform quality of concrete are the topmost benefits derived from adopting Ready-mix Concrete in Nigeria. The Case study also revealed the effectiveness of Ready-mix concrete in minimizing the two lean construction wastes that were examined, namely; waste of overproduction and waste of waiting. It is recommended Just-in-Time technique should be extended to other construction materials aside from concrete to improve waste minimization through the adoption of an overall JIT policy for the construction process.

The endomembrane system in plant cells enables the cell to manage and coordinate a variety of membranous compartments so that they and their contents arrive at the right location. The secretory pathway takes part in this complex network and has its gateway at the Endoplasmic Reticulum. Therefore, alterations at the Endoplasmic reticulum level could condition how protein trafficking takes place or, at least, influence how such cargo leaves this organelle. With this work, we intended to assess how abnormalities at the Endoplasmic Reticulum would interfere with protein sorting and trafficking. Thus, we used a novel Arabidopsis mutant - leb-2 GFP-h -, presenting ER morphology alterations. Our results show that alterations in the leb-2 GFP-h mutant did not disrupt PSI A/B–mCherry transport to the vacuole but influences the expression of endogenous aspartic proteinases. Furthermore, the study of key-endomembrane genes expression revealed an upregulation of the SNAREs AtVAMP722 and AtVAMP723. As a whole, the leb-2 mutant seems not to interfere with vacuolar routes but may be implicated in secretion events.

Laboratory experiments and natural phenomena investigations in this research series experimentally revealed the existence of gravitational repulsion force dependent on thermal energy content, pervading our surroundings both microscopically and macroscopically. This paper presents an alternative mathematical model of both gravitational repulsion and attraction forces between two gaseous molecules, validated by experimental data. The model is self-standing and independent of existing models built on idealistic assumptions. While existing models considered gravitational interaction as a single force, the presented experimental model considers it the resultant of two distinct forces: gravitational repulsion and attraction. When established experimental data on nitrogen, hydrogen, oxygen, water vapor, carbon monoxide and carbon dioxide were applied, the model performed, both analytically and experimentally: (1) confirming the existence of both gravitational repulsion and attraction forces among gas molecules, (2) demonstrating that the two forces follow Inverse-Cube relationship with the distance between molecules, (3) revealing that repulsion force is linearly proportional to the absolute temperature, thus filling the critical gap between energy and fundamental forces. Orders of magnitude of gravitational repulsion and attraction forces are very large compared to the gravitational force between gas molecules calculated according to the classical theory, enabling manipulation to achieve hitherto unknown outcomes and developments.

In the last decade, we have witnessed an upsurge in nuclei-based studies, particularly coupled with next-generation sequencing. Such studies aim at understanding the molecular states that exist in heterogeneous cell populations by applying increasingly more affordable sequencing approaches, in addition to optimized methodologies developed to isolate and select nuclei. Although these powerful new methods promise unprecedented insights, it is important to understand and critically consider the associated challenges. Here, we provide a comprehensive overview of the rise of nuclei-based studies and elaborate on their advantages and disadvantages. Improved designs and appropriate use of the various experimental strategies will result in acquiring biologically accurate and meaningful information.

In this study, a numerical simulation of fluid flow through railway ballast in the time domain is presented, providing a model for unsteady-state flow. It is demonstrated that the position of the free surface with respect to time can also be used to solve the steady flow case. The effect of ballast fouling is included in the model to capture the realistic behavior of railway ballast, which is critical to understanding the impact of flooding. A thorough comparison with a range of previous studies, including theoretical and experimental approaches, is made and very close agreement is obtained. The significant impact of ballast fouling on fluid flow and its potential consequences for railway infrastructure are highlighted by the simulation. Valuable insights into the behavior of water flow through porous media and its relevance to railway ballast management are offered by this study.

The mutation databases have vital importance in detecting genetic mutation and their corresponding phenotypes. The emergence of next generation sequencing genetic technologies has accelerated this process, and the growth of genetic disease identification has created a need for quality control and documentation of mutation-related information. Ethnic-specific mutation databases offer valuable information for researchers, and the article evaluates the homogeneity and effectiveness of these databases. The aim to raise awareness of NEMDBs to healthcare professionals, the general public, and researchers studying genetic disorders. The article also recommendations to improve the effectiveness of these databases.

The investigation by the integrated approach newly introduced for this study indicates that insulin resistance (IR) would develop first preferentially in the muscle tissue with a relatively low cell turnover and then progress in sequence to the subcutaneous adipose tissue, to the visceral adipose tissue, and to the liver with higher cell turnovers. Moreover, metabolic disruptions due to IR vary widely from tissue to tissue, contrary to the conventional notion that IR merely impairs glucose uptake in the whole body. This warrants that IR be divided better into four distinct tissue specific IRs: muscle insulin resistance (MIR), subcutaneous adipose insulin resistance (s-AIR), visceral adipose insulin resistance (v-AIR), and hepatic insulin resistance (HIR). Tissue-specific IRs developing in the order of MIR, s-AIR, v-AIR, and HIR – producing tissue specific metabolic disruptions – would amount to nothing but the whole body insulin resistance (WBIR) evolving in four distinctively insulin resistant stages. The four stage metabolic evolution from rapid weight gain to visceral obesity to rapid weight loss to full blown diabetes not only complies well with the natural development history of diabetes but also resolves most of the controversies regarding obesity or diabetes, including visceral obesity, obesity paradox, and dawn phenomenon that have long remained metabolic puzzles. In addition, the four-stage WBIR evolution model refutes the entrenched notion of the lipid-induced insulin resistance (LIIR) but supports instead the glycation-induced insulin resistance (GIIR) proposed in this study. A speculation is that the glycation reaction activated ever more with WBIR evolving may serve as the common thread connecting each other a cluster of disorders or diseases that are often collectively referred to as the metabolic syndrome, such as obesity, diabetes, cardio/cerebral vasculopathy, nephropathy, neuropathy, and retinopathy.

A separate group consists of compounds that are able to simultaneously interact with both orthosteric and allosteric sites, which are classified as bitopic GPCR ligands [74, 76-81]. They have two pharmacophores, one of which binds with high affinity to the orthosteric site, while the other, with lower affinity, binds to the allosteric site. If these sites are spatially separated in the receptor, then the pharmacophores in the bitopic ligand must be connected with a flexible linker, the length of which exactly corresponds to the distance between the orthosteric and allosteric sites. At the same time, it is important that the linker does not significantly affect the conformational rearrangements in the receptor caused by its activation by orthosteric and (or) allosteric agonists [74, 79].

COVID-19 is one of the deadliest respiratory diseases, and its emergence caught the pharmaceutical industry off guard. While vaccines have been rapidly developed, treatment options for infected people remain scarce, and COVID-19 poses a substantial global threat. This study presents a novel workflow to predict robust druggable targets against emerging RNA viruses using metabolic networks and information of the viral structure and its genome sequence. For this purpose, we implemented pymCADRE and PREDICATE to create tissue-specific metabolic models, construct viral biomass functions and predict host-based antiviral targets from more than one genome. We observed that pymCADRE reduces the computational time of flux variability analysis for internal optimizations. We applied these tools to create a new metabolic network of primary bronchial epithelial cells infected with SARS-CoV-2 and identified enzymatic reactions with inhibitory effects. The most promising reported targets were from the purine metabolism, while targeting the pyrimidine and carbohydrate metabolisms seemed to be promising approaches to enhance viral inhibition. Finally, we computationally tested the robustness of our targets in all known variants of concern, verifying our targets’ inhibitory effects. Since laboratory tests are time-consuming and involve complex readouts to track processes, our workflow focuses on metabolic fluxes within infected cells and is applicable for rapid hypothesis-driven identification of potentially exploitable antivirals concerning various viruses and host cell types.

Background: The currently advised follow-up scheme of PSA-testing after robot-assisted radical prostatectomy (RARP) is strict and might pose a burden to our healthcare system. We aimed to optimize the 1-year follow-up scheme for patients who undergo RARP. Methods: All patients with histologically-proven prostate cancer (PCa) who underwent RARP between 2018 and August 2022 in the Prostate Cancer Network the Netherlands were retrospectively evaluated. We excluded patients who underwent salvage RARP and patients who had &lt;1 year of PSA follow-up. Postoperative PSA-values were collected. Biochemical persistence (BCP) was defined as PSA-level &gt;0.10 ng/mL at 0-4 months after RARP, whereas biochemical recurrence (BCR) was defined as PSA-level &gt;0.2 ng/mL at any time point after RARP. We aimed to identify a group of patients who had a very low risk of BCR at different time-points after surgery. Results: Of all 1155 patients, BCP was observed in 151 (13%), of whom 79 (6.8%) had PSA ≥0.2 ng/mL. BCR further developed in 51 (4.7%), and 37 (3.4%) patients at 5-8 and 9-12 months after RARP, respectively. In 12 patients, BCR was found at 5-8 months after RARP in absence of BCP. These patients represented 1.2% (12/1004) of the entire group. In other words, 98.8% (992/1004) of patients who had an unmeasurable PSA-level at 0-4 months after RARP also had unmeasurable PSA-level 5-8 months after surgery. Limitations are the retrospective design and incomplete follow-up. Conclusions: Patients with an unmeasurable PSA-level at 3-4 months after RARP may not need to be retested until 12 months of follow-up as almost 100% of patients will not have biochemically recurrent disease at 5-8 months of follow-up. This will reduce PSA-testing substantially at the costs of hardly any missed patients with recurrent disease.

The purpose of this study was to clarify the attachment types of the tibialis anterior tendon (TAT) in Japanese fixed cadavers and to determine the attachment site area in three dimensions. We examined 100 feet from 50 Japanese cadavers. The TAT was classified according to differences in the number of fiber bundles as: Type I, with one fiber bundle; Type II, with two fiber bundles; and Type III, with three fiber bundles. The attachment site area of the TAT was measured using a three-dimensional scanner. Cases were Type II in 95% and Type III in 5%, with no cases of Type I identified. In Type II, mean attachment site areas were 85.2 ± 18.2 mm2 for the medial cuneiform bone (MCB) and 72.4 ± 19.0 mm2 for the first metatarsal bone (1MB), showing a significantly larger area for MCB than for 1MB. These findings suggest the possibility of ethnic differences in TAT attachment types and suggest that TAT attachments in Japanese individuals are highly likely to be Type II, with rare cases of Type III. Accurate measurement of attachment site areas is possible with appropriate three-dimensional measurements.

To create normative scores for all CrossFit® Open (CFO) workouts and compare male and female performances, official scores were collected from the official competition leaderboard for all competitors of the 2011-2022 CFO competitions. Percentiles were calculated in athletes (18 – 54 years) who completed all workouts within a single year ‘as prescribed’ and met minimum scoring thresholds. Independent t-tests revealed significant (p &lt; 0.05) sex differences for 56 of 60 workouts. In workouts scored by repetitions completed, men completed more repetitions in 18 workouts by small-to-large differences (d = 0.22-0.81), whereas women completed more repetitions in 6 workouts by small-to-medium differences (d = 0.36-0.77). When workouts were scored by time-to-completion, men were faster in 10 workouts by small-to-large differences (d = 0.23-1.12), while women were faster in three workouts by small differences (d = 0.46). In three workouts scored by load lifted, men lifted more weight by large differences (d = 2.00-2.98). All other differences were either trivial or not significant. Despite adjusted programming for men and women, the persistence of performances differences across all CFO workouts suggest resultant challenges are not the same. These normative values may be useful to training and research in male and female CrossFit® athletes.

SARS-CoV-2 breakthrough infections, associated with waning immunity, increase systemic antibody levels. In this study, we analyzed the impact of the infection timing on the magnitude of the systemic humoral response and whether breakthrough infections also boost antibody levels in the salivary compartment. We observed that the combination of infection plus vaccination, regardless of infection timing, produced a sharp increase of systemic antibodies, being higher in subjects infected after third doses. Moreover, despite high systemic antibody levels, breakthrough infections after dose 3 occurred and boosted antibody levels in the salivary compartment. These results lead to rethink the current vaccination strategies against COVID-19 and the use of salivary anti-SARS-CoV-2 antibodies for disease surveillance and vaccination follow-up.

(1) Background: This work aimed to conduct the first comparative study providing long-term data about patient reported outcome measures as well as donor-site scar assessment and aesthetic evaluation of the reconstructed breasts in patients with DIEP versus PAP flap breast reconstruction. (2) Methods: This prospective, single-center, matched cohort study included a total of 36 patients after DIEP and PAP flap breast reconstruction. Evaluation was done using the Breast-Q and POSAS questionnaire as well as the Breast Aesthetic Scale for cosmetic analysis by four plastic surgeons. (3) Results: Post-operative Breast-Q evaluation revealed no significant differences between both patient groups for the categories physical well-being donor-site, physical well-being breast and satisfaction with the breast. Scar evaluation of the donor-site region showed equivalent results for the thigh and the abdomen concerning the overall opinion of patients and observers. There was no significant difference between both methods of reconstruction for all aspects of breast aesthetics. (4) Conclusions: Similar results of donor-site morbidity, scar quality and aesthetic outcome of the breast in both the DIEP and PAP patient group have been demonstrated. Hence, in cases suitable for both types of reconstruction, the decision can be based on factors such as patients’ lifestyle, leisure activities and preferences.

Structure–function relationships in proteins have been one of the crucial scientific topics. Heme proteins have diverse and pivotal biological functions. Therefore, clarifying their structure–function correlation is significant to understand their functional mechanism and is informative for various fields of science. In this study, we constructed convolutional neural network models for predicting protein functions from the tertiary structures of heme-binding sites (active sites) of heme proteins to examine the structure–function correlation. As a result, we succeeded in the classification of oxygen-binding protein (OB), oxidoreductase (OR), proteins with both functions (OB–OR), and electron transport protein (ET) with high accuracy. Although the misclassification rate for OR and ET was high, the rates between OB and ET and between OB and OR were almost zero, indicating that the prediction model works well between protein groups with very different functions. However, predicting the function of proteins modified with amino acid mutation(s) remains a challenge. Our findings indicate a structure–function correlation in the active site of heme proteins. This study is expected to be applied to the prediction of more detailed protein functions such as catalytic reactions.

Transgender (TG) describes individuals whose gender identity differs from the social norms. Some TG people undergo gender-affirming hormone therapy (HT) and may be considered as a sub-group of population susceptible to environmental contaminants for their targets and modes of action. Aim of the work is to set appropriate HT doses and identify specific biomarkers to implement TG animal models. Four adult rats/group/sex are subcutaneously exposed to 3 doses of HT (plus control) selected starting from available data. Demasculinizing-feminizing model (dMF): β-estradiol plus cyproterone acetate: 0.09+0.33, 0.09+0.93 and 0.18+0.33 mg, 5 times/week. Defeminizing-masculinizing model (dFM): testosterone 0.45, 0.95 and 2.05 mg, 2 times/week. Clitoral gain and sperm count, histophatological analysis of reproductive organs and liver, hormone serum levels and gene expression of sex-dimorphic CYP450 are evaluated. In dMF model, the selected doses, leading to T serum levels at the range of the corresponding cisgender, induced strong general toxicity and cannot be used in long-term studies. In dFM model, 0.45 mg of testosterone represents the correct dose. In addition, the endpoints selected are considered suitable and reliable to implement the animal model. The sex-specific CYP expression is a suita-ble biomarker to set proper (de)masculinizing/(de)feminizing HT and to implement TG animal models.

During the past few years unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking ad-vantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss emerging clinical relevance of advanced diagnostics for cardiovascular diseases - includ-ing those associated with COVID-19 - with a focus on the role of inflammation in cardiomyopa-thies and arrhythmias. Second, we consider newly identified immunological interactions at or-gan and systems level which affect cardiovascular pathogenesis. Thus, studies into immune in-fluences arising from the intestinal system are moving towards therapeutic exploitation. Fur-ther, powerful new research tools have enabled novel insight into brain – immune system inter-actions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress - acting through defined brain regions - upon viral and cardiovas-cular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena.

Most existing cancer therapies negatively affect normal tissue as well as cancerous tissue. A potentially effective strategy for treating cancer that precludes off-target damage and could be an option for most patients would involve targeting one or more mutations that are ubiquitous in the given patient’s tumor(s). To effect this strategy, one would employ multi-region sequencing of a patient’s primary tumor and metastases to seek out mutations that are shared between all or at least most regions. Once the target or targets are known, one would ideally rapidly generate a molecular switch for at least one of said ubiquitous mutations that can distinguish the mutated DNA, RNA, or protein from the wild-type version and subsequently trigger a therapeutic response. I propose that the therapeutic response involve the replication of an oncolytic virus or intracellular bacterium, as any mutation can theoretically be detected by a vector that enters the cell - and automatic propagation could be very helpful. Moreover, the mutation “signal” can be easily enhanced through transcriptional and translational (if the target is an intracellular protein) enhancement. Importantly, RNA may make the best target for the molecular switches in terms of amplification of the signal and ease of targeting.

Labelling techniques such as electron paramagnetic resonance spectroscopy and single-molecule fluorescence resonance energy transfer, allow access to distances in the range of tens of angstroms, corresponding to the size of proteins and small to medium-sized protein complexes. Such measurements do not require long-range ordering and are therefore applicable to systems with partial disorder. Data from spin-label-based measurements can be processed into distance distributions that provide information about the extent of such disorder. Using such information in modelling presents several challenges, including a small number of restraints, the influence of the label itself on the measured distance and distribution width, and balancing the fitting quality of the long-range restraints with the fitting quality of other restraint subsets. Starting with general considerations about integrative and hybrid structural modelling, this review provides an overview of recent approaches to these problems and identifies where further progress is needed.

A calibrated mathematical model of antiviral immune response to SARS-CoV-2 infection is developed. The model considers the innate and antigen-specific responses to SARS-CoV-2 infection. Recently published data sets from human challenge studies with SARS-CoV-2 were used for parameter estimation. Understanding the regulation of multiple intertwined reaction components of the immune system is necessary for linking the clinical phenotypes of COVID-19 with the kinetics of immune responses. Consideration of multiple immune reaction components in a single calibrated mathematical model allowed us to address some fundamental issues related to pathogenesis of COVID-19, i.e. sensitivity of the peak viral load to parameters characterizing the specific response components, the kinetic coordination of the individual responses, and the factors favoring a prolonged viral persistence. The model provides a tool for predicting the infectivity of patients, i.e. the amount of virus which is transmitted via droplets from the person infected with SARS-CoV-2, depending on the time of infection. The thresholds in the relative unbalance between innate and adaptive response parameters which lead to a prolonged persistence of SARS-CoV-2 due to the loss of a kinetic response synchrony/coordination were identified.

The structural transitions RNAs undergo during trafficking are not well-understood. Here, we used the well-developed yeast Ty1 retrotransposon to provide the first structural model of genome (g) RNA in the nucleus from a retrovirus-like transposon. Through a detailed comparison of nuclear Ty1 gRNA structure with those established in the cytoplasm, virus-like particles (VLPs), and synthesized in vitro, we detected Ty1 gRNA structural alternations that occur during retrotransposition. Full-length Ty1 gRNA serves as the mRNA for Gag and Gag-Pol proteins and as the genome that is reverse transcribed within VLPs. We show that about 60% of base pairs predicted for the nuclear Ty1 gRNA appear in the cytoplasm, and active translation does not account for such structural differences. Most of the shared base pairs are represented by short-range interactions, while the long-distance pairings seem unique for each compartment. Highly structured motifs tend to be preserved after nuclear export of Ty1 gRNA. In addition, our study highlights the important role of Ty1 Gag in mediating critical RNA:RNA interactions required for retrotransposition.

Optical networks offer a wide range of benefits to the telecommunication sector world- wide with its provision of higher bandwidth which leads to faster data speed, longer transmission distance, and improved latency. Currently, the complexity associated with advancements in optical networks poses problems to network flexibility, reliability, and quality of service. Over the years, many reviews and proposals have been implemented by several literatures to provide solutions for optical networks using software-defined networks and network service orchestrators. This paper reviews the significant challenges in current optical network applications, the various solutions rendered by software-defined networks as well as network service orchestration, the impediments, and gaps in these software – defined networks. This paper will go a step further to look into the various improvements and implementations of software-defined networks tailored to solve specific optical network problems. This paper further proposes a flexible orchestration architecture for software-defined networks for solving flexibility and scalability problems in optical networks. This proposal uses Open Network System (ONOS) SDN controller, leveraging on dockerisation as well as kubernetes clusterisation and orchestration. This solution presents a more flexible, reliable, customable, and higher quality of service which is an improvement upon current solutions in literature.

The Musa textilis var. Abuab has high fiber quality (FQ) but has low resistance against abaca bunchy top virus (AbBTV); the Musa balbisiana var. Pacol, has low FQ but high resistance against AbBTV. Their backcrosses (BC2 and BC3) possess both desirable traits. Analysis using RNA-seq showed that the regulatory divergence of Abuab and Pacol is largely explained by cis differences with 27.4% and 22.3% if we are to assess it using BC2 and BC3, respectively. Cis differences between the two genotypes are significantly reduced from BC2 to BC3 due to changes in genomic constitution. Trans, on the other hand, is robust to changes in allelic composition. All these are attributed to the loss of heterozygosity in the BC3 relative to BC2. Further analysis showed that both backcrosses exhibited genome-wide preferential expression of Pacol- over Abuab-specific alleles, despite the wider genetic presence of the latter in the hybrids. The ratio of the two genotype-specific expressed transcripts and the ratio of their corresponding genetic make-up are significantly disproportionate, a phenomenon which we refer here as “genome–transcriptome incongruence”. We also observed preferential expression switching in which several genes prefer Abuab- (or Pacol-) specific allele in the BC2 but switched to Pacol- (or Abuab-) specific allele in the BC3 genome.

ABSTRACT Background Ubiquitination plays an important role in protein post-translational processes and has been found to be involved in a number of regulatory functions including proteasome degradation, DNA repair, transcription, signal transduction, endocytosis, and sorting. As the identification of ubiquitination site is critical to furthering our understanding of the mechanism of ubiquitination, various experimental and machine learning methods have been used to conduct this task. It has been an important but challenging task to improve the accuracy of ubiquitination site prediction. In this research, we explore the possibility of improving the prediction performance of machine learning by incorporating grid search in the training process. Method We developed grid search procedures for each of six widely used machine learning methods including NB, LR, DT, SVM, LASSO, and KNN, and applied them to ubiquitination site prediction using the six PCP datasets that were previously developed. For each of the ML methods, we developed a set of values for each of the tunable hyperparameters available to the method. These sets of values then can be combined to form a large grid of hyperparameter settings, and each of these settings is used in the grid search. We integrated 5-fold cross-validation in grid search to train and test ML models and applied an additional independent validation procedure by conducting a pre-training 80-20 sample split. We evaluated the performance of the six methods by comparing them side by side for each of the six datasets. We also compared the grid search results with the results that were previously published without doing grid search. To optimize the prediction performance, we trained 1.1 million ML models in total through grid search. Results We compared the overall prediction performance of these six methods, as well as their prediction performance when working with balanced vs. imbalanced data, and large-scale vs. small-scale data. From the perspective of dataset, we find that the overall performance of every PCP dataset has been significantly improved in this study compared to the previous study, with the percentage increase of the average AUC of all six datasets ranging from 7.9% (PCP-4) up to 17.0% (PCP-1). From the perspective of method, we find that three out of four methods significantly benefit from grid search comparing to their previously published non-grid search results, with the maximum AUC improvement as high as 47% (LASSO on PCP-5), 43.3% (NB on PCP-1), and 33.7% (SVM on PCP-6). SVM overall ranks number one, followed by KNN as the number two performer based on their average AUCs on all datasets. But these two also ranked the top two (KNN 76 days and SVM 15 days) in terms of the total running time that they need to do grid search. We also find that SVM, KNN, and DT tend to handle small-scale and imbalanced datasets better, while LR, and LASSO are doing well with large-scale and balanced datasets. NB is more sensitive to data imbalance while less sensitive to the size of a dataset. Conclusions Our results show that using grid search has improved the performance of ubiquitination prediction significantly. We find that the performance of a method is closely related to its hyperparameter setting and the type of data it handles. Even though SVM is on average an outperformer, none of the methods can provide the best performance for all datasets. When sufficient computing resources are well accessible, grid search is an effective way to identify both a top performing model for a machine learning method and a suitable machine learning method for a particular dataset.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Its treatment includes antiarrhythmic drugs (AADs) to modulate the function of cardiac ion channels. However, AADs have been limited by proarrhythmic effects, non-cardiovascular toxicities as well as often modest antiarrhythmic efficacy. Theoretical models showed that combined blockade of Nav1.5 (and its current INa) and Kv1.5 (and its current, IKur) ion channels yield a synergistic anti-arrhythmic effect without effect on ventricles. We focused on Kv1.5 and Nav1.5 to search for structural similarities in their binding site (BS) for flecainide (a common blocker and widely prescribed AAD), as a first step for prospective rational multi-target directed ligand (MTDL) design strategies. We presented a computational workflow for flecainide BS comparison in a flecainide-Kv1.5 docking model and a solved structure of flecainide-Nav1.5 complex. The workflow includes docking, molecular dynamics, BS characterization and pattern matching. We identified a common structural pattern in flecainide BS for these channels. The latter belongs to the inner cavity and consist of a hydrophobic patch and a polar region, involving residues from S6 helix and P-loop. Since the rational MTDL design for AF is still incipient, our findings could advance multi-target atrial-selective strategies for AF treatment.

Buildings can generate heats which are mostly generated from the machinery using inside the buildings, and these heats generally released to the atmosphere. Buildings can also block the wind flow by their canopies and trap the heat by using low albedo materials. These causes pointedly contribute to urban heat island and greenhouse effects. Likewise, urban development and building construction in Cambodia are growing rapidly. The construction has been recognized as a key development sector while thousands of buildings are being built and have been operated in the main cities. However, those buildings mostly have not been considered to incorporate sustainability concepts while the major final energy consumers in the country are buildings. The buildings’ energy consumption is also projected to increase more than double until 2040. Hence, sustainable building promotion in Cambodia is necessary, and sustainable building criteria are completely required. This research aims to find out significant sustainable building criteria for Cambodia and focused on planning and design criteria because having proper planning and design is a smart start leading to achieving building sustainability in all stages. This research used the Delphi methods to validate the relevant sustainable building criteria available in the literature and then select the significant ones for Cambodia based on the Delphi consensus. The results showed that ninety-nine consensus planning and design criteria were found to be significant for sustainable buildings in Cambodia.

Abstract: Ambulatory cancer centers face fluctuating patient demand and deploy specialized personnel who have variable availability. This undermines operational stability through misa-lignment of resources to patient needs, resulting in overscheduled clinics, budget deficits, and wait times exceeding provincial targets. We describe deployment of a Learning Health System framework for operational improvements within the entire ambulatory center. Known methods of value stream mapping, operations research and statistical process control were applied to achieve organizational high performance that is data-informed, agile and adaptive. We transitioned from a fixed template model by individual physician to a caseload management by disease site model that is realigned quarterly. We adapted a block schedule model for the ambulatory oncology clinic to align the regional demand for specialized services with optimized human and physical resources. We demonstrated improved utilization of clinical space, increased weekly consistency and im-proved distribution of activity across the workweek. Increased value, represented as the ratio of monthly encounters per nursing worked hours, and increased percentage of services delivered by full-time nurses were benefits realized in our cancer system. The creation of a data-informed demand capacity model enables application of predictive analytics and business intelligence tools that will further enhance clinical responsiveness..

The effects of photon inertia on the determination of its trajectory were verified and the representation of a displacement mass characterized by the flow of the number of wavefronts and the decomposition of photon inertia into parts associated with translation and rotation motions was considered. It was found that with the relativistic increase of the photon's resistance to change its directional properties, it inhibits the relativistic trajectory of the second torque, of Minkowski, in an angular range of incidence. After synchronizations, in the OAM inversions, there are reductions of the inertia associated to the translational part that assumes classical predominance, where the relativistic trajectory is allowed while the photon offers less resistance to changes in its directional properties. The classical-relativistic variability of the photon inertia characterizes the classical or relativistic profile of the energy distribution in forms of motion, where adjustments of the rotational and translational parts can be performed as a function of the refractive index rate, temperature and angle of incidence. It was found that with increasing temperature of the refringent medium, the synchronizations displacement in the sense of the normal incidence. A specific vacuum temperature for the refringent medium was characterized, where the photon exhibits a classical-relativistic synchronization under all angles of incidence, characteristic of its immaterial state in vacuum.

Long-term, multi-decade research on planted tree survival in urban settings is sparse. One understudied urban environment is highway rights-of-way (ROW), lands adjacent to high-speed, unsignalized roadways. We conducted a re-inventory of tree planting cohort in northern Illinois, U.S. on a 48 km-long highway near Chicago which were 10-, 21-, and 30-years old to evaluate long-term patterns of survival and diversity. Using each randomly selected planting site along the highway as a unit of observation and analysis, we compared the number of trees documented in record drawing to the number of trees currently alive to determine percent survival. We evaluated 224 planting sites which originally contained 2,944 trees and collected data about the planting site location. For the oldest cohort, 26% of trees were still alive in 2018 (median survival by species = 16%, Q1 = 0%, Q3 = 48%), while 31% of the 21-year-old cohort (med. = 6%, Q1 = 0%, Q3 = 47%) and 86% of the 10-year-old cohort were still alive (med. = 85%, Q1 = 74%, Q3 = 96%). The survival of the 21- and 30-year-old cohort matches urban tree survival estimates by other researchers, while the 10-year-old survival is higher than expected. The only planting location characteristic that significantly affected survival was traffic islands (areas between the highway and entrance/exit ramps). Species with low drought tolerance were less likely to be alive for the 10-year-old cohort. Waterlogging tolerant species were more likely to be alive in the 10-year-old cohort. Since some species in the 21- and 30-year-old cohorts had very low survival, the tree species richness and diversity s in study areas declined between the initial record drawings and reinventory. This study demonstrates the challenges of maintaining long-term survival and diversity in the highway ROW and emphasizes the importance of species selection.

Illicit drug consumption is posing critical concerns in our society causing health issues, crime-related activities, and the disruption of border trade. The smuggling of illicit drugs urges the development of new tools for rapid on-site identification in cargos. Current methods used by law enforcement officers rely on presumptive color tests and portable spectroscopic techniques. However, these methods sometimes exhibit inaccurate results due to commonly used cutting agents, the colorful nature of the sample or because the drugs are smuggled (hidden or mixed) in common goods. Interestingly, electrochemical sensors can deal with these specific problems. Herein, an electrochemical device is presented that uses affordable screen-printed electrodes for the electrochemical profiling of illicit drugs by square-wave voltammetry (SWV). The identification of the illicit compound is based on the oxidation potential of the analyte. Hence, a library of electrochemical profiles is built upon the analysis of illicit drugs and common cutting agents. This library allows the design of a tailor-made script that enables the identification of each drug through a user-friendly interface (laptop or mobile phone). Importantly, the electrochemical test is compared by analyzing 48 confiscated samples with other portable devices based on Raman and FTIR spectroscopy as well as a laboratory standard method (i.e. gas chromatography – mass spectrometry). Overall, the electrochemical results obtained through the analysis of different samples from confiscated cargos at an end-user site, present a promising alternative to current methods, offering low-cost and rapid testing in the field.

Until recently, the classic approach to mineral exploration studies is to bring the field samples/drill cores collected during field studies to the laboratory followed by laborious analysis procedures to generate the analytical data. This is very expensive, time consuming and difficult for exploring vast areas. But rapid technological advances in field portable analytical instruments such as portable ultraviolet–visible and near-infrared spectrophotometers, gamma ray spectrometer, pXRF, pXRD, pLIBS, and µRaman spectrometer have changed this scenario completely and increased their on-site applications in mineral exploration studies. These instruments are currently providing direct, rapid, on-site, real-time, non-destructive, cost-effective identification, and determination of target elements, indicator minerals and pathfinder elements in rock, soil, and sediment samples. These portable analytical instruments are currently helping to obtain accurate chemical and mineralogical information directly in field with minimal or no sample preparation, and providing decision-making support during field work as well as during drilling operations in several successful mineral exploration programs. In this article, the developments in these portable devices, and their contributions in the platinum group elements (PGE), rare earth elements (REE), gold, base metals, and lithium exploration studies both on land and on ocean bed have been summarized with examples.

Thyroid hormones regulate tissue metabolism establishing an energy balance in the cell, in particular by affecting oxidative phosphorylation. Their long-term impact is mainly associated with changes in gene expression, while the short-term effects may differ in mechanism. Our work is devoted to short-term effects of hormones T2, T3, and T4 on mitochondrial cytochrome c oxidase (CcO) mediated by a direct contact with the enzyme. The data obtained indicate the existence of two separate sites of CcO interaction with thyroid hormones differing in location, affinity and specificity to hormone binding. It is shown that T3 and T4 but not T2 inhibit oxidase activity of CcO in solution and on membrane preparations with Кi≈100–200 M. In solution, T3 and T4 compete in a 1:1 ratio with the detergent dodecyl-maltoside for binding to the enzyme. Peroxidase and catalase partial activities of CcO are not sensitive to hormones while electron transfer from heme a to the oxidized binuclear center is affected. We believe that T3 and T4 are ligands of the Bile Acid Binding Site found in the 3D structure of CсO by Ferguson-Miller’s group, and hormone induced inhibition is associated with dysfunction of the K- proton channel. Similar conclusion we made recently with regard to steroid-like compounds. It is found that T2, T3, and T4 inhibit superoxide generation by oxidized CcO in the presence of excess Н2О2. Inhibition is characterized by Ki values of 0.3 – 5 M and apparently affects the formation of О2• at the protein surface. The second binding site for thyroid hormones presumably coincides with the point of tight T2 binding on the Va subunit described in the literature.

Podoplanin (PDPN) is a cell-surface mucin-like glycoprotein that plays a critical role in tumor development and normal development of the lung, kidney, and lymphatic vascular systems. PDPN is overexpressed in several tumors and is involved in their malignancy. PDPN induces platelet aggregation through binding to platelet receptor C-type lectin-like receptor 2. Furthermore, PDPN modulates signal transductions that regulate cell proliferation, differentiation, migration, invasion, epithelial to mesenchymal transition, and stemness, all of which are crucial for the malignant progression of tumor. In the tumor microenvironment (TME), PDPN expression is up-regulated in the tumor stroma, including cancer-associated fibroblasts (CAFs) and immune cells. CAFs play significant roles in the extracellular matrix remodeling and the development of immunosuppressive TME. Additionally, PDPN functions as a co-inhibitory molecule on T cells, indicating the involvement with immune evasion. In this review, we describe the mechanistic basis and diverse roles of PDPN in malignant progression of tumor and discuss the possibility of the clinical application of PDPN-targeted cancer therapy, including cancer-specific monoclonal antibodies, and chimeric antigen receptor T technologies.

: Using line × tester analysis, the current research analyses parental genotypes and their combinations in normal conditions and identifies the genes influencing yield characteristics. In the present study, 15 diverse genotypes, including 10 lines, 5 testers, and 50 F1s hybrids, were evaluated for 13 morphological and 2 biochemical traits. A suitable location was taken to study the effect of 15 characters. The results exposed that ability mean squares were significant for all studied additive and non-additive components. In this direction, the general combining ability of PBW-343, DBW-39, K-402, K-1317, KRL-210, and K-68 were higher than the remaining parents. For morphological traits like yield, the top five crosses were described based on SCA effects, namely, HD-3086 × HD-3171, K-402 × K-9107, K-1317 × K-9107, HD-2967 × K-0307 and K-402 × K-68 in F1 generation. In addition, the high value of heritability was estimated for plant height (77.32%), spike length (32.26%), biological yield/plant (59.52%), and grain yield/plant (68.76%). However, the moderate values of heritability were estimated for days to maturity (22.78%) and phenol color reaction (18.00%). The higher genetic advance was not found for recorded characters; however, a moderate genetic advance was recorded for grain yield per plant (13.15%) and harvest index (11.72%). High heritability coupled with moderate genetic advance was recorded for two characters grain yield per plant and harvest index in F1 and F2 generations.

The cardiac sodium ion channel (NaV1.5) is a protein with four domains (DI-DIV), each with six transmembrane segments. Its opening and subsequent inactivation results in the brief rapid influx of Na+ ions resulting in the depolarization of cardiomyocytes. The neurotoxin veratridine (VTD) inhibits NaV1.5 inactivation resulting in longer channel opening times, and potentially fatal action potential prolongation. VTD is predicted to bind at the channel pore, but alternative binding sites have not been ruled out. To determine the binding site of VTD on NaV1.5, we performed docking calculations and high-throughput electrophysiology experiments. The docking calculations identified two distinct binding regions. The first site was in the pore, close to the binding site of NaV1.4 and NaV1.5 blocking drugs in experimental structures. The second site was at the “mouth” of the pore at the cytosolic side, partly solvent-exposed. Mutations at this site (L409, E417, and I1466) had large effects on VTD binding, while residues deeper in the pore had no effect, consistent with VTD binding at the mouth site. Overall, our results suggest a VTD binding site close to the cytoplasmic mouth of the channel pore. Binding at this alternative site might indicate an allosteric inactivation mechanism for VTD at NaV1.5.

Published data or available literature on sustainable building plan-design, construction, performance, and renovation criteria have covered some stages or some parts of each stage. These data usually have been published partially in many different papers―there have not been any papers that published these data together. Hence, this paper aims to collectively review these data and publish them together. The collection and review of these data were carried out by our twenty-five team members who specialized in sustainable urban, architectural, and civil engineering and construction management. The gathered and reviewed outputs were combined and validated based on a general group consensus. This consensus decision-making proceeded through two major group meetings with several follow-up meetings. The first major meeting was to combine and improve the gathered reviewed sustainable building criteria for Cambodia. The second major meeting was to validate the improved reviewed sustainable building criteria for Cambodia. The several follow-up meetings were to discuss the relevance and importance of the validated data “criteria and their classifications and descriptions” in all stages and more focused on their importance and applicability to Cambodia. The collective reviewed data in this paper would be useful to researchers in the fields. They could also be useful collective knowledge and information for policymakers from governmental agencies and development partners, particularly for sustainable building and construction companies.

The most effective method of treating allergic diseases, aimed not at relieving symptoms, but at eliminating the cause of the disease, is allergen-specific immunotherapy (AIT). To reduce the risk of side effects and improve the delivery of allergens to the mucosa, various delivery systems, such as liposomes, dendrimers, nanoparticles, etc., can be used. To date, there are data on the creation of delivery systems based on glycyrrhizic acid (GA) and its derivatives, but such a delivery system has not been used for allergen-specific therapy until now. At the same time, it is known that GA has an anti-inflammatory effect, shifts the balance towards Th1, and increases the number of Treg cells, which means that in the future it can enhance the anti-allergic effect of AIT and reduce the risk of unwanted side effects. Thus, the study of the immunomodulatory effect of supramolecular complexes (micelles) of GA with extracts of allergens seems to be very promising for the development of new drugs for AIT.

Pituitary adenylyl cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal polypeptide (VIP)/secretin/glucagon superfamily. PACAP is present in two forms, PACAP-38 and PACAP-27, and binds to three guanine-regulatory (G) protein-coupled receptors (PAC1, VPAC1, and VPAC2). PACAP is expressed in the central and peripheral nervous systems with high PACAP levels found in the hypothalamus, a brain region involved in feeding and energy homeostasis. PAC1 receptors are high-affinity and PACAP-selective receptors, while VPAC1 and VPAC2 receptors show a comparable affinity to PACAP and VIP. PACAP and its receptors are expressed in the central and peripheral nervous systems, with moderate to high expression in the hypothalamus, amygdala, and other limbic structures. Consistent with their expression, PACAP is involved in several physiological responses and pathological states. A growing body of literature suggests that PACAP regulates food intake in laboratory animals. However, there is no comprehensive review of the literature on this topic. Thus, the purpose of this article is to review the literature regarding the role of PACAP and its receptors in food intake regulation and to synthesize how PACAP exerts its anorexic effects in different brain regions. To achieve this goal, we searched PubMed and reviewed 68 articles regarding the regulatory action of PACAP on food intake. Here, we present the literature regarding the effect of exogenous PACAP on feeding and the role of endogenous PACAP in this process. We also provide evidence regarding the effect of PACAP on the homeostatic and hedonic aspects of food intake, the neuroanatomical sites where PACAP exerts its regulatory action, which PACAP receptors may be involved, and the role of various signaling pathways and neurotransmitters in hypophagic effects of PACAP.

This paper aims to provide an overview of the complete process in the development of a Domain-Specific Language (DSL). It explains the construction steps such as preliminary research, language implementation, and evaluation. Moreover, it provides details for different key components which are commonly found in the DSLs such as the abstraction layer, DSL metamodel, and the applications. It also explains the general limitations related to the Domain-Specific Languages for Workflows.

Background: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC. Methods: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from Surveillance Epidemiology and End Results database with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general US population. Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM. Results: A total of 563298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during study period. While age and surgery positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, more recent year (2001-2015) of diagnosis as well as multiple primary or distant tumors experienced a lower risk of CVSM. Interpretation: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM, which may be helpful for risk stratification and therapeutic optimization of cerebrovascular-specific diseases in CRC patients.

We continue in this paper to illustrate the implications of the Dual Model of Liquids (DML) by deriving the expression for the isochoric specific heat as function of the collective degrees of freedom available at a given temperature and analyzing its dependence on temperature. Two main tasks will be accomplished. First, we show that the expression obtained for the isochoric specific heat in the DML is in line with the experimental results. Second, the expression will be compared with the analogous one obtained in another theoretical dual model of the liquid state, the Phonon Theory of Liquid Thermodynamics. This comparison will allow to get interesting insights about the number of collective degrees of freedom available in a liquid and on the value of the isobaric thermal expansion coefficient, two quantities that are related to each other in this framework.

As is known, the construction industry has one of the highest occupational accidents incidence rates among all economic sectors. Currently, Building Information Modeling (BIM) appears as a tool that addresses occupational safety issues throughout the construction life cycle projects, avoiding hazards and risks and, consequently, increasing safety. This work investigates BIM methodology and related technologies application for building safety planning in construction and demonstrates the potential of this technology for the integrated implementation of safety measures during the design phase and the construction site management. The first step consisted of a literature review on the application of BIM in safety in the design and planning phases. Following, to show the potentialities of construction simulation, a case study based on BIM 4D to prevent falls from height was developed. With BIM 4D, it is possible to follow the construction process over time, giving the construction safety technicians’, designers, supervisors and managers the capability to analyse, in each phase, the potential risks and which safety measures should be implemented. BIM can effectively integrate safety measures from the design phase to the construction and use phase and do integrated safety planning within construction planning, leading to reliable safety management throughout the construction process.

The Lewis basicity of selected organic bases, modeled by the enthalpies of adduct formation between gaseous BF3 and the bases in dichloromethane (DCM) solution, is critically examined. Although experimental enthalpies for a large number of molecules have been reported in the literature, it may be desirable to estimate missing or uncertain data for important Lewis bases. We have decided to use high-level ab initio procedures, combined with a polarized continuum solvation model, in which the solvated species are the clusters formed by specific hydrogen bonding of DCM with the Lewis base and the Lewis base/BF3 adduct. This mode of interaction with DCM corresponds to a specific solvation model (SSM). The results actually show that the enthalpy of BF3 adduct formation in DCM solution is clearly influenced by specific interactions, DCM acting as hydrogen-bonding donor (HBD) molecule in two ways: base/DCM and adduct/DCM, confirming that specific solvation is an important contribution to experimentally determined Lewis basicity scales. This analysis allows us to conclude that there are reasons to suspect some gas-phase values to be in error by more than the stated experimental uncertainty. Some experimental values in DCM solution that were uncertain because of identified reasons can be complemented by the computed values.

Cytosine (C) to uracil (U) RNA editing is one of the most important post-transcriptional processes, however exploring C-to-U editing events efficiently within the crop mitochondrial genome remains a challenge. An improving predictive RNA editor for crop mitochondrial genomes, iPReditor-CMG, was proposed, which was based on SVM, three common crop mitochondrial genomes and self-sequenced tobacco mitochondrial ATPase. After multi-combination feature extracting, high-dimension feature screening and multi-test independent predicting, the results showed that the average accuracy of intraspecific prediction was 0.85, and the highest value even up to 0.91, which outperformed the previous reference models. While the prediction accuracies were 0.78 between dicotyledons and no more than 0.56 between dicotyledons and monocotyledons, implying a possible similarity in C-to-U editing mechanisms among close relatives. The best model was finally identified with an independent test accuracy of 0.91 and an area under the curve of 0.88, and further suggested that five unreported feature sequences TGACA, ACAAC, GTAGA, CCGTT and TAACA were closely associated with the editing phenomenon. Multiple evaluation findings supported that the iPReditor-CMG could be effectively applied to predict crop mitochondrial editing sites, which may contribute to insight into their recognition mechanisms and even other post-transcriptional events in crop mitochondria.

The SARS-CoV-2 polybasic furin cleavage site is still a missing link. Remarkably, the two arginine residues of this protease recognition site are encoded by the CGG codon, which is rare in Betacoronavirus. However, the arginine pair is common at viral furin cleavage sites, but are not CGG-CGG encoded. The question is: Is this genetic footprint unique to the SARS-CoV-2? To address the issue, using Perl scripts, here I dissect in detail the NCBI Virus database in order to report the arginine dimers of the Betacoronavirus proteins. The main result reveals that a group of Middle East respiratory syndrome-related coronavirus (MERS-CoV) (isolates: camel/Nigeria/NVx/2016, host: Camelus dromedarius) also have the CGG-CGG arginine pair in the spike protein polybasic furin cleavage region. In addition, CGG-CGG encoded arginine pairs were found in the orf1ab polyprotein from HKU9 and HKU14 Betacoronavirus, as well as, in the nucleocapsid phosphoprotein from few SARS-CoV-2 isolates. To quantify the probability of finding the arginine CGG-CGG codon pair in Betacoronavirus, the likelihood ratio (LR) and a Markov model were defined. In conclusion, it is highly unlikely to find this genetic marker in betacoronaviruses wildlife, but they are there. Collectively, results shed light on recombination as origin of the virus CGG-CGG arginine pair in the S1/S2 cleavage site.