The continuous flowing spacetime forms a spacetime group G, one of its fundamental groups is the Poincare group PO(1,3), and the matter and interaction fields are representations of its intrinsic spacetime group. As a kind of quantized space-time unit, space-time group elements generate both space-time manifolds and matter. Matter and fields are aggregates of the quantum space-time within them and determine their type: the Lorentz group SO(1,3) represents a rotating spacetime corresponding to visible matter and the translation group P^1,3 represents a translational spacetime corresponding to dark matter and dark energy. The aggregation mode of space-time degrees of freedom in matter reveals that charge conjugation symmetry is the inverse symmetry of internal time of charged particles, and the external parity breaking of neutrinos is also due to their internal spatial aggregation mode.

Throughout this paper the effects of injuries on athletes are highlighted in different aspects. Exertional compartment syndrome is a specific injury related to athletes that is thoroughly explored in this paper through an analysis of the anatomy, symptoms, diagnosis and treatments of the syndrome. Exertional compartment syndrome is an exercise-induced muscle and nerve condition that causes pain, swelling as well as disability in the affected muscles of the lower leg. This syndrome commonly develops in young athletes involved in sports with excessive running and repetitive impact such as track and field, soccer, basketball and lacrosse. Exertional compartment syndrome is commonly misdiagnosed as other less severe injuries such as shin splints, which is symptomatic of pain along the tibia bone of the lower leg caused by overuse. The misdiagnosis of exertional compartment syndrome allows the syndrome to worsen and intensify resulting in the only effective treatment to be fasciotomy, a surgical procedure to release the pressure within the compartment of the lower leg. There is no definitive protocol developed for patients after fasciotomy is performed. Athletes experiencing similar symptoms after surgery are usually treated for their symptoms rather than the syndrome as a whole, which does not have a high degree of success. The development of a definitive protocol utilizing the techniques of manual therapy, mobility stretching and corrective strength training can improve the adverse effects of exertional compartment syndrome as well as restore functionality to the athlete. Raising awareness of this syndrome in athletics will be effective in treating the athlete early on in order to avoid severe effects and invasive procedures.

The ocean of the planet Earth, which is as thin as a cicada's wings, play a role of catalyst to the evolving of the ancient plates. The ocean and the ancient plates of the planet Earth formed a magic Whirlpool of the Cross “十” shape with double whirl arms. The central core of the Cross “十” shape Ocean-Plate Whirlpool is the Hint Black Hole (HBH) located at the Northwestern Pacific Ocean floor which is decorated with invisible geological age distribution of clam shell. The double whirl arms of ancient plates are distinguished to be left and right at Bering Strait and just formed the ring of fire of the Pacific Ocean.The Cross “十” shape Ocean-Plate Whirlpool of the planet Earth was born at the equatorial area about 66 Ma ago and is rotating anticlockwise and drifting northward by a mini footprint of spiral at s speed of as slow as a snail moves. Obviously, it would come to an end at the North Pole about 100 Ma in the future. So, the lifespan of the Cross “十” shape Ocean-Plate Whirlpool would be about 166 Ma, from birth to death on the planet Earth.What is hidden behind of the evolving of the oceans and the ancient plates is the golden law of geometrical progression of ladder pagoda of attributes evolving of them, which is “1➨2➨4➨2➨1”, including upgrading and downgrading process. It seems to hint that what is happening on the planet Earth, including the top-level species of human race, is actually unique in the Milky Way galaxy in essence.The property roles of expanding and shrinking are existing in the Cross “十” shape Ocean-Plate Whirlpool by face to face and the exchange of property roles took place tens of millions of years ago. And that situation would happen again tens of millions of years in the future. It seems a giant circle of evolving of the exchange of property roles would be drawn by the Cross “十” shape Ocean-Plate Whirlpool in her lifetime.

Background: Smad4, a critical tumor suppressor gene, plays a significant role in pancreatic biology and tumorigenesis. Genetic background and sex are known to influence phenotypic outcomes, but their impact on pancreatic weight in Smad4-deficient mice remains unclear. This study investigates the impact of Smad4 deficiency on pancreatic weight in F1 mice from diverse Collaborative Cross (CC) lines, focusing on the influence of genetic background and sex. Methods: F1 mice were generated by crossbreeding female CC mice with C57BL/6J-Smad4tm1Mak males. Genotyping confirmed the presence of Smad4 knockout alleles. Mice were housed under standard conditions, euthanized at 80 weeks, and their pancreatic weights were measured, adjusted for body weight, and analyzed for effects of Smad4 deficiency, sex, and genetic background. Results: The overall population of F1 mice showed a slight but non-significant increase in adjusted pancreatic weights in heterozygous knockout mice compared to wild-type mice. Sex-specific analysis revealed no significant difference in males but a significant increase in adjusted pancreatic weights in heterozygous knockout females. Genetic background analysis showed that lines CC018 and CC025 substantially increased adjusted pancreatic weights in heterozygous knockout mice. In contrast, other lines showed no significant difference or varied non-significant changes. The interplay between genetic background and sex further influenced these outcomes. Conclusion: Smad4 deficiency affects pancreatic weight in a manner significantly modulated by genetic background and sex. This study highlights the necessity of considering these factors in genetic research and therapeutic development, demonstrating the value of the Collaborative cross-mouse population in dissecting complex genetic interactions.

This study investigates the effects of xylitol, a natural sugar alcohol, on tumor progression in syngeneic mouse cancer models. Xylitol has been known for its dental health benefits, but emerging evidence suggests broader biological roles, including potential anti-cancer properties. We explored xylitol's impact on two mouse cancer models: 4T1 mammary carcinoma and B16F10 melanoma. Xylitol's efficacy in inhibiting cancer cell lines and modulating tumor progression was assessed using immunocompetent female mice. The experiments involved intratumoral and peri-tumoral administration of a 20% xylitol solution in two mouse strains: BALB/c (4T1 mammary carcinoma) and C57BL/6 (B16F10 melanoma). Tumor volume, histopathology, and metabolomic analyses were conducted to gauge xylitol's influence. The study revealed that xylitol administration initially reduced tumor growth in the B16F10 melanoma model, accompanied by alterations in tumor metabolism. However, similar effects were not observed in the 4T1 mammary carcinoma model, and melanoma tumor growth re-commenced after stroma deterioration permitted xylitol solution leakage. These findings suggest that xylitol may have potential as an adjunct therapy in cancer treatment, specifically in melanoma. The differential response between the two cancer models underscores the complexity of cancer biology and the need for further investigation into xylitol's mechanisms of action and its role in cancer therapy.

A change in biological properties of the SARS-CoV-2 virus can enhance its transmissibility and virulence, complicate the disease course, and reduce the effectiveness of anti-viral therapy and vaccination. We have studied 16 genetic lineages of the Omicron variant. The viral reproduction course was analyzed based on plaque morphology in the agar layer and the maximum titer in Vero E6 cells. BALB/c mice and Syrian hamsters were used as animal models. Viral load and infectious SARS-CoV-2 titer were determined in the nasal tissue and lungs. The severity of infectious process was assessed using histological methods. An increased plug size was observed in CH.1.1 and BQ.1.2.1 strains after six passages. This was due to substitutions D614G, H655Y, and N764K in the coronavirus S protein. The same changes in gene variants Gamma and BA.1 were caused by the substitution R682W, which is not present in lineages CH.1.1 and BQ.1.2.1. A similar substitution, namely R682P, was observed in the BA.5.1 strain. We characterized BA.1 (as a reference), BA.5.2, and XBB.3 strains in vivo as representatives of the main circulating genetic lineages. For the BA.1 strain, ID50 was 1.3 and 14 TCD50 in Syrian hamsters and BALB/c mice, respectively. An insignificant increase in the BA.5.2 virulence compared to that of BA.1 was noted (ID50 was 07. and 10 TCD50, respectively). The XBB.3 pathogenicity in laboratory animals is similar to that of BA.1 (ID50 was 1.8 and 15 TCD50, respectively). Experiments showed a consistent decrease in the virulence of Omicron strains compared to previously circulating SARS-CoV-2 variants. A co-evolutionary change in amino acid sequences, affecting the conformation of the coronavirus S protein and its surface epitopes in representatives of different genetic lineages, was noted. The emergence of potential proteolysis sites and alterations of the furin cleavage site have been observed in numerous Omicron coronavirus variants.

This study focuses on mimicking constitutive phosphorylation in the N-terminus of the myosin regulatory light chain (S15D-RLC) as a rescue strategy for the mutation-induced cardiac dysfunction in transgenic (Tg) models of restrictive (RCM) and dilated (DCM) cardiomyopathy caused by mutations in myosin essential (ELC) or regulatory (RLC) light chains. S15D-RLC phosphomimetic was reconstituted in left ventricular papillary muscle (LVPM) fibers from two mouse models of cardiomyopathy, RCM-E143K ELC and DCM-D94A RLC, along with their corresponding Tg-ELC and Tg-RLC wild type (WT) mice. The beneficial effects of S15D-RLC in rescuing cardiac function were manifested by S15D-RLC-induced destabilization of the super-relaxed (SRX) state that was observed in both models of cardiomyopathy. S15D-RLC promoted a shift from the SRX state to the disordered relaxed (DRX) state, increasing the number of heads readily available to interact with actin and produce force. Additionally, S15D-RLC reconstituted fibers demonstrated significantly higher maximal isometric force per cross-section of muscle compared with reconstitution with WT-RLC protein. The effects of the phosphomimetic S15D-RLC were compared to those observed for Omecamtiv Mecarbil (OM), a myosin activator shown to bind to the catalytic site of cardiac myosin and increase myocardial contractility. A similar SRX↔DRX equilibrium shift was observed in OM=treated fibers as in S15D-RLC-reconstituted preparations. Additionally, treatment with OM resulted in significantly higher maximal pCa 4 force per cross-section of muscle fibers in both cardiomyopathy models. Our results suggest that both treatments with S15D-RLC and OM may improve the function of myosin motors and cardiac muscle contraction in RCM-ELC and DCM-RLC mice.

In recent times, the adoption of cloud computing by small and medium-sized 9 enterprises (SMEs) has become a crucial issue. These businesses face substantial difficulties in 10 accessing reliable and affordable IT infrastructure due to economic constraints and technological 11 restrictions. Hybrid cloud computing solutions which incorporate Infrastructure as a Service 12 (IaaS), Platform as a Service (PaaS), and Software as a Service (SaaS) offer a feasible approach to 13overcoming these challenges. This study proposes a systematic literature review of cloud 14 computing's impact on SME performance emphasizing cost-efficiency, reliability, and 15 competitive advantages, using the 2020 Preferred Reporting Items for Systematic Reviews and 16 Meta-Analyses (PRISMA) framework. The inclusion criteria are bounded by (1) publication date 17 between 2014 and 2024, (2) English-language publications, (3) research focused on cloud 18 computing for SMEs, and (4) studies with a clear analytical framework for evaluating SME 19 performance. Following this process, 90 eligible research studies were included. The average 20 total cost for cloud services varies significantly, with operational costs reflecting the scalability 21 of the services and the specific needs of SMEs. This analysis offers valuable guidance for SMEs 22 and stakeholders in optimizing cloud-based strategies for enhanced performance.

Recent developments in microfluidics and biomaterials have enabled the creation of organs-on-chips (OoCs), which provide a controlled and lifelike in vitro microenvironment resembling an actual organ. Organ-on-a-chip technology offers a tremendous opportunity for efficient, cost-effective, and ethical drug testing and research. However, the high throughput and large quantities of data these complex microenvironments produce make it difficult for researchers to effectively analyze the data and draw valuable conclusions. Convolutional Neural Networks (CNNs) are most aptly positioned to address many of OoC’s challenges because of their ability to interpret microscopic images and facilitate the analytical process. Despite the growing field of AI, there have been a limited number of studies summarizing the various applications of CNNs in OoCs. This review aims to provide 1) an overview of the technology involved with CNNs and OoCs 2) an insight into the state-of-the-art applications of CNNs in OoCs including device parameters, predicting and tracking cell trajectories, super-resolution image segmentation, and image classification, and 3) an overview of existing challenges and opportunities ahead for clinical translation of this technology. Various applications of CNNs have been classified by the type of task. Different CNN models such as Faster R-CNNs, fully convolutional networks (FCNs), and Mask R-CNNs are explained and highlighted. This review article can be used as a resource for a better understanding of the potential of CNNs in biomedical research and clinical applications, particularly OoCs.

Due to Motor Neurone Diseases, a large population remains disabled worldwide, negatively impacting their independence and quality of life. This typically involves a weakness in the hand and forearm muscles, making it difficult to perform fine motor tasks such as writing, buttoning a shirt, or gripping objects. This project presents a vision-enabled rehabilitation hand exoskeleton to assist disabled persons in their hand movements. The design goal was to create an accessible tool to help with a simple interface requiring no training. This prototype is built on a commercially available glove where a camera and embedded processor were integrated to help open and close the hand, using air pressure, thus grabbing an object. An accelerometer is also implemented to detect the characteristic hand gesture to release the object when desired. This passive vision-based control differs from active EMG-based designs as it does not require individualized training. Continuing the research will reduce the cost, weight, and power consumption to facilitate mass implementation.

The existence of semantic inaccuracy §2 articles by A. Einstein “On the electrodynamics of moving bodies”, illustrating the principle of the relativity of simultaneity. In a sentence “The observers co-moving with the moving rod would thus find that the two clocks do not run synchronously while the observers in the system at rest would declare them synchronous”, the preposition “not” must be moved and placed before the word “synchronous”, at the end of the sentence. The criterion for synchronism of the clocks on the rod is the time it takes for the beam to travel from clock A to clock B and back, and for observers on the rod it will be the same both when the rod is at rest and when the rod is moving. Otherwise, observers on the rod would have had at their disposal an experiment that would allow them to determine whether the rod is moving or at rest, which contradicts the first postulate of the Special Theory of Relativity. The inaccuracy is found unchanged in modern editions in English and Russian, and can become a source of difficulties when teaching the basics of the Special Theory of Relativity based on primary sources, as well as make it difficult to understand the author’s logic when studying independently. Nobel laureate R. Feynman, having expanded and modified A. Einstein's thought experiment, eliminated the inaccuracy described in the article.

The automotive industry has witnessed a significant push towards increased fuel efficiency and reduced carbon emissions. Among many factors influencing overall vehicle efficiency, aerodynamic drag is a critical consideration, accounting for a substantial portion of fuel consumption. Our investigation focused on the drag coefficients of three prominent 2023 passenger car models – the Toyota Corolla, Hyundai Elantra, and Kia Soul. Using ANSYS Fluent to perform computational fluid dynamics, we demonstrated an inverse correlation between drag force and gas mileage, underlining the significance of aerodynamic design in fuel efficiency. Notably, the Hyundai Elantra emerged as the most aerodynamically efficient of the three vehicles, followed closely by the Toyota Corolla. In contrast, the boxier-designed Kia Soul exhibited significantly higher drag coefficients and drag forces, rendering it the least efficient of the trio. These findings emphasize the importance of environmental factors in car design. Shaping aerodynamic profiles directly impacts fuel efficiency, stability, and overall performance.

The lungs of tuberculosis (TB) patients contain a spectrum of granulomatous lesions ranging from solid and well vascularized cellular granulomas, to avascular caseous granulomas. In solid granulomas, current therapy kills actively replicating (AR) intracellular bacilli, while in low vascularized caseous granulomas the low oxygen tension stimulates aerobic and microaerophilic AR bacilli to transit into non-replicating (NR), drug-tolerant, extracellular stages. These stages, which do not have genetic mutations and are often referred to as persisters, are difficult to eradicate due to low drug penetration inside caseum and mycobacterial cell walls. The sputum of TB patients contains also viable bacilli called differentially detectable (DD) cells that, unlike persisters, grow in liquid, but not in solid media. This review provides a comprehensive update on drug combinations killing in vitro AR and drug-tolerant bacilli (persisters and DD cells), and sterilizing Mycobacterium tuberculosis-infected BALB/c and caseum-forming C3HeB/FeJ mice. These observations have been important for testing new drug combinations in noninferiority clinical trials, in order to shorten duration of current regimens against TB. In 2022, the World Health Organization, based on one of this trial, supported the use of a 4-month regimen for treatment of drug-susceptible TB as a possible alternative to the current 6-month regimen.

Epilepsy is a heterogenous neurological disorder characterized by recurrent unprovoked seizures, mitochondrial stress, and neurodegeneration. Hydrogen sulfide (H2S), a gasotransmitter, promotes mitochondrial function and biogenesis, elicits neuromodulation and neuroprotection, and may acutely suppress seizures. A major gap in knowledge remains in understanding the role of mitochondrial dysfunction and progressive changes in H2S levels following acute seizures and during epileptogenesis. We thus sought to quantify changes in H2S and its methylated metabolite (MeSH) via LC-MS/MS subsequent to acute maximal electroshock and 6 Hz 44 mA seizures in mice, as well as in the corneal kindled mouse model of chronic seizures. Plasma H2S was acutely reduced after a maximal electroshock seizure. H2S or MeSH levels in whole brain homogenate and expression of related genes in corneal kindled mice were not altered. However, plasma H2S and MeSH levels were significantly lower during kindling, but not after established kindling. Morever, we demonstrated a time-dependent increase in expression of mitochondrial membrane integrity-related proteins, Opa1, Mfn2, Drp1, and Mff during kindling, which did not correlate with gene expression. Taken together, short-term reductions in plasma H2S could be a novel biomarker for seizures. Future studies should further define the role of H2S and mitochondrial stress in epilepsy.

Susceptibility to photoimmune suppression and photocarcinogenesis is greater in male than in female humans and mice and is exacerbated in female estrogen receptor-beta knockout (ER-β-/-) mice. We previously reported that the active vitamin D hormone, 1,25-dihydroxyvitamin D3 (1,25(OH)2D) applied topically protects against ultraviolet radiation (UV)-induction of cutaneous cyclobutane pyrimidine dimers (CPDs) and suppression of contact hypersensitivity (CHS) in female mice. Here we compare these responses in female versus male Skh:hr1 mice, in ER-β-/- versus wild type C57BL/6 mice, and in female ER-blockaded Skh:hr1 mice. Induction of CPDs was significantly greater in male than female Skh:hr1 mice and was more effectively reduced by 1,25(OH)2D in female Skh:hr1 and C57BL/6 mice, than in male Skh:hr1 or ER-β-/- mice respectively. This correlated with reduced sunburn inflammation by 1,25(OH)2D in female but not male Skh:hr1 mice. Furthermore, although 1,25(OH)2D alone dose-dependently suppressed basal CHS responses in male Skh:hr1 and ER-β-/- mice, UV-induced immunosuppression was universally observed. In female Skh:hr1 and C57BL/6 mice, the immunosuppression was decreased by 1,25(OH)2D dose-dependently, but not in male Skh:hr1, ER-β-/- or ER-blockaded mice. These results reveal a sex bias in genetic, inflammatory and immune photoprotection by 1,25(OH)2D favoring female mice, that is dependent on the presence of ER-β.

Riemann’s functional equation is valid on the vertical line of s=1/2. Each side is a real-valued function. The Riemann’s Xi function is also a real-valued function along the vertical line of s=1/2. Through the holomorphic extensions of the Riemann zeta function, starting from the real-valued function at s=1/2 into both sides of sigma<1/2 and sigma>1/2, we can get two versions of the zeta functional equation, eq. (45). The key property of the scaling and rotational factors g(s) and g(1-s) behave as multiplicative inverses in the complex plane, eq. (48). It is deduced that the Zeta function also has multiplicative inverses, the symmetric point is at (1/2,0) in the complex plane. The moduli behave as a hyperbola. Especially, along the vertical line sigam=1/2, the amplitudes of both function g(s) and g(1-s) are equal to 1, its arguments have opposite signs. If sigma is not equal to 1/2, the amplitudes of zeta(s) and zeta(1-s) are not equal to each other, because of their multiplicative inversion relationship. It is deduced that the non-trivial zeros can only be on the vertical line of s=1/2. A gamma function vector field is given in Appendix B, and some moduli of gamma function at special points are given. Finally, another variation of the Zeta function is provided in an integral form in Appendix D. The asymptotes behave as a c₈ cyclic group for the large t values.

Sodium valproate is a established antiepileptic drug of first choice, primarily used to treat epilepsy, but also bipolar disorder and prevent migraine headaches. Valproate increases concentrations of gamma-aminobutyric acid in the brain, due to inhibition of enzymes responsible for the catabolism of gamma-aminobutyric acid. Main goal of this research consisted in the optimization and development for a new sensitive spectrophotometric quantitative analysis method of sodium valproate from tablets in the Visible field. Following the quantitative color reaction of sodium valproate with diazonium salt of alpha naphthylamine in alkaline medium, a light yellow azo dye was formed and spectrophotometrically analyzed at the wavelength of 386 nanometers. The amount of pure sodium valproate found on pharmaceutical extended-release tablet was 492.578 miligrams compared to the official declared pure amount of 500 miligrams on prolonged-release tablet. Amount found was assigned to a percentage content of 98.5156 percent pure sodium valproate in a pharmaceutical tablet. Mean average percentage error (deviation) from the officially stated value was about 1.4844 percent, which was included within normal limits, below five percent maximum limit allowed by European and Romanian Pharmacopoeias rules. Spectrophotometric method was subjected to the statistical validation procedure and was successfully validated.

Background. Chronic kidney disease (CKD) is a progressive condition with limited treatment options that often lead to significant morbidity. Recent studies suggest that oxyhydrogen nanobubbles (HHOnb) may offer therapeutic benefits due to their antioxidative and anti-inflammatory properties. This case series examines the effects of intravenous HHOnb therapy on three patients with varying stages of CKD.Methods. Three patients with CKD underwent a series of ten HHOnb infusions over a period of two to three months. The patients, aged 43 to 70, presented with additional comorbidities including hypertension, diabetes mellitus, and polycystic kidney disease. Clinical parameters, including glomerular filtration rate (GFR), serum creatinine, blood pressure, and uric acid levels, were monitored alongside subjective health improvements.Results. Patient A. A 70-year-old woman with CKD grade 3a experienced a reduction in serum creatinine from 0.98 mg/dL to 0.82 mg/dL and an improvement in GFR from 59 mL/min/1.73 m² to 73.2 mL/min/1.73 m². She reported reduced leg swelling and increased vitality. Patient B. A 52-year-old man with CKD grade 4 and class III obesity showed a decrease in serum creatinine from 3.0 mg/dL to 2.86 mg/dL, an increase in GFR from 23 mL/min/1.73 m² to 24.4 mL/min/1.73 m², and improved sleep quality. Blood pressure reduced from 167/82 mmHg to 145/85 mmHg. Patient C. A 43-year-old man with CKD grade 4 and massive polycystic kidney disease reported reduced fatigue and normalized urination. His serum creatinine decreased from 3.26 mg/dL to 3.09 mg/dL, and his GFR improved from 22 mL/min/1.73 m² to 23.6 mL/min/1.73 m².Conclusion. Intravenous HHOnb therapy demonstrated potential benefits in improving renal function and overall health in CKD patients. These findings suggest that HHOnb could be a promising complementary treatment for CKD, though larger, controlled studies are needed to confirm its efficacy and safety.

In the dynamic landscape of the telecommunications industry, understanding and mitigating customer churn is paramount for maintaining competitive advantage and sustaining revenue streams. This comprehensive literature review delves into the intricacies of customer churn prediction, a crucial aspect in fortifying the bond between telecom businesses and their customers. The review methodically analyzes 11 articles published between 2000 and March 2024, spotlighting the strategic role of Customer Relationship Management and the prevalence of high churn rates that necessitate a shift from customer acquisition to retention strategies. Furthermore, the review navigates through the challenges inherent in churn prediction, including the complexities of managing large, imbalanced, and noisy datasets and the intricacies involved in model selection and optimization. Despite these challenges, the paper highlights the superior capability of machine learning techniques in handling complex datasets to provide accurate predictions, albeit acknowledging their practical complexities. The main aim of the study is to provide an overview, serving as a knowledge base for researchers interested in machine learning techniques within the realm of telecommunications.

The classical propositional calculus (zero-order logic, classical propositional logic), is the most fundamental two-valued logical system. In this paper we present a proof of inconsistency of the classical propositional calculus. Then, we get right away the conclusion that the metatheory of the classical propositional calculus is inconsistent.

Introduction: In Part II of this three-part series, we expose techniques that can be used by the U.S. Centers for Disease Control and prevention (CDC) and Food and Drug Administration (FDA) to manipulate and throttle the Vaccine Adverse Event Reporting System (VAERS), a vaccine safety monitoring system open to the public. The U.S. government’s recommendation of COVID-19 vaccines during pregnancy was more a product of propaganda than of science and plagued with conflicts of interest. The extreme breach of COVID-19 vaccine pregnancy complication safety signals documented in VAERS cannot be disregarded or concealed. As a result, CDC/FDA are moving to closed, government captured platforms, including V-safe, Vaccine Safety Datalink (VSD) system, and the Biologics Effectiveness and Safety (BEST) system. Public transparency of adverse events following COVID-19 vaccination in pregnancy should be increased, not thwarted. Methods: In Part I the CDC/FDA Vaccine Adverse Event Reporting System (VAERS) database was queried from January 1, 1990, to April 26, 2024 for adverse events (AEs) involving pregnancy complications following vaccination. In Part II we investigate tactics discovered in VAERS that concealed vaccine injuries and deaths. Conflicts of interest, as well as specific communications and publications from the CDC/FDA and the New England Journal of Medicine (NEJM) are analyzed. Results: Of all VAERS AE reports, 8.47% (138,983) of COVID-19 reports had no vaccination date and thus were missing from the data presented in Part I of this series. We unconcealed data presented in Part I of this series to include VAERS case reports that were excluded when using standard queries because of an “unknown vaccination date”. The unconcealed data in the 37 AE cases reported in this study (Part II) ranged from 0 - 38% with a mean of 8.2% (standard deviation 9.7%) and the significant breaches of VAERS safety signals in Part I of this series were largely underestimated. Another method of concealing vaccine associated AEs is to exclude the specific vaccine type rendering it as an “unknown vaccine type”. “Unknown vaccine type” has logarithmically increased since the rollout of the COVID-19 vaccines in 2021, ranging from 1 to 400 cases between 1990 to 2018 to 11,461 cases in 2021. CDC/FDA granted $67 million via a Cooperative Agreement grant to Massachusetts Department of Public Health (MDPH) between July 1, 2019, to June 30, 2025. MDPH then made subawards under this grant to 21 influential public and private health and civic organizations, including NEJM’s owner, Massachusetts Medical Society (MMS). As one of the subawardees under the grant, MMS as owner of NEJM received over $426,000 in federal HHS/CDC grant money from 2019 to 2020 for “public health and medical emergency preparedness projects”. Conclusions: CDC/FDA has failed to capture and account for a significant number of AE case reports following COVID-19 in VAERS by a variety of techniques in an apparent attempt to sanitize the data. CDC’s Rochelle Walensky and NEJM’s Editor-in-Chief Eric Rubin pushed novel untested COVID-19 vaccines in pregnant women despite clear evidence from multiple sources that safety signals had been breached.

Comprising the largest population cohort on this planet, Gen Z presents a future-oriented consumer segment driven by climate change and food. This study sought to investigate Gen Zs’ perceptions to-ward plant-based foods and diets, and explore the relationship between attitude components, meal preparation involvement, personal and lifestyle factors, and perceived barriers in adopting a plant-based diet with willingness to adopt green-eating practices. Using cross-sectional data from uni-versity students in Greece, India and UK, various tools were employed to determine the factors influ-encing youths’ consumer behavior toward animal-protein substitutes. PCA indicated the underlying dimensions of students’ viewpoints on plant-based foods, whereas hierarchical and k-means clustering provided the cluster structure. An ordered probit model was estimated to delineate Gen Zs’ willingness to adopt plant-based diets and distinguish among mostly unwilling, somewhat willing and mostly willing youths. Our findings identified two consumer segments, namely proponents and opponents toward plant-based foods and diets, with statistically significant differences in the perceived health benefits of plant-based diets, attachment to animal-based proteins, perceived exclusion of ani-mal-based foods, dissatisfaction with plant-based foods attributes and demand for ensuring adequate protein intake. The ordered probit model estimates showed that there is a rather «homogeneity» in the factors influencing youths’ intention to adopt plant-based diets, with attitude components, meal prep-aration indicators, perceived barriers to eating “green” and personal factors, viz. self-assessed knowledge on healthy eating and physical activity, being strongly associated with students’ willingness to switch to plant-based diets in all three countries. Mapping potential obstacles and enablers in terms of shifting to more green-eating behaviors, our findings could add information to better understand the factors affecting food choice and youths’ transition to a more sustainable lifestyle.

Epithelial–mesenchymal transition (EMT) is defined as a cellular process during which epithelial cells acquire mesenchymal phenotypes and behavior following the downregulation of epithelial features. EMT and its reversed process, the mesenchymal-epithelial transition (MET), and the special form of EMT, the endothelial-mesenchymal transition (EndMT), have been thought as a universal dogma controlling developmental and pathological processes. More than half a century of EMT study has made it a large research field and a mainstream concept. However, discrepancies and disputes over EMT and EMT research have also grown over time. Particularly, neither the epithelial and mesenchymal states/properties nor their regulatory networks nor specific markers have been defined, rendering the EMT, MET and EndMT concepts groundless. Moreover, EMT and MET effects should not be a cause, but rather a consequence of or an accompanying effect during developmental and pathological processes. EMT and MET represented by the change in cell shapes or adhesiveness or symbolized by EMT factors are biased interpretation of the overall change in cellular property and regulatory networks during development and cancer progression. The true meaning of EMT effects in some developmental and pathological processes, such as fibrosis, needs re-evaluation. But the core EMT factors are actually a few components of the regulatory networks of neural stemness, which determines tumorigenicity and pluripotency. The EMT effects in cancer progression and neural crest formation are wrong attribution of the role of neural stemness during cancer progression and the cell-intrinsic property of neural crest cells to the unknown mesenchymal state. It is time to reassess the significance of EMT and its related concepts in scientific research.

The weakness of the dispersion-managed link combined with optical phase conjugation to compensate for optical signal distortion caused by chromatic dispersion and nonlinear Kerr effect of standard single mode fiber is its limited structural flexibility. We propose dispersion map that can simultaneously compensate for the distorted wavelength division multiplexed signal while increasing the configurational flexibility. Each residual dispersion per span (RDPS) in the former half of the proposed link is randomly determined, and in the latter half, the arrangement order of RDPS is the same as or inverted in the former half. We confirm that the dispersion maps in which the RDPS distribution pattern in the latter half is opposite to the arrangement order in the former half are more effective in compensation, and rather, the compensation effect is better than in the dispersion map of the conventional scheme. The notable result of this paper is that the increase of flexibility can be achieved through random arrangement of RDPS in the former half, and the compensation improvement can be achieved by through inverse arrangement in the latter half which make the distribution profile of each half link roughly symmetric with respect to the midway optical phase conjugator.

The last 50 years witnessed the emergence of various so called “hyperpolarization technologies” that allow generating large magnetizations of spin ensembles. This Editorial Essay provides a brief overview of the use of these technologies in various fields, including medicine, chemistry, and quantum sensing. It is concluded that critical questions still need to be addressed to harness benefits of nuclear hyperpolarization in clinical medical imaging while interdisciplinary innovation can unlock potential of novel (yet unexplored) methods. My hope is that this Editorial Essay provides valuable insights into the current state and future directions of spin technologies.

We propose an improved earlier described “mirror” method [1] for detecting in cell nuclear extracts mutations that arise in DNA during its replication due to misincorporation of deoxyadenosine-5’-monophosphate (dAMP) opposite 7,8-dihydro-8-oxoguanine (8-oxoG). The method is based on the synthesis of a complementary chain (“mirror”) by nuclear extracts of different mice organs on a template containing 8-oxoG inside and dideoxycytidine residue (ddC) at the 3’-end. The “mirror”was amplified by PCR using primers part of which was non-complementary to the template. It allowed obtaining the “framed mirror” products. The misincorporation of dAMP in “framed mirror” products forms an EcoRI restriction site. The restriction analysis of double-stranded “framed mirror” products allows a quantification of the mutation frequency in nuclear extracts. The data obtained showed that the mutagenic potential of 8-oxoG markedly varied in different organs of adult mice and embryos.

This article discuss the estimation of electrical stresses input that is required to determine lifetime degradation of the HV cables installed within overhead transmission lines (OHTL’s). Abort from lightning effects, these electrical stresses are mainly generated due to repetitive switching operation of the transmission line that produces transient overvoltage (TOV) stress and high frequency stress. The transient overvoltage (TOV) due to switching-off the transmission line at the interface points between the cable and OHTL is estimated using artificial neural network (ANN). PSCAD software is used to build the transmission line model for 749 different case in order to build the required database for ANN training. Two different algorithm input to train ANN with one hidden layer and one output layer using different number of nodes are modeled in MATLAB. The results performance is continuously compared and evaluated till acceptable Regression is achieved to insure the error is less than +/-1.5%. The high frequency due to switching-on the transmission line is also recorded and analyzed. The results show that this new method is efficient, accurate and useful as there is no cable monitoring system is available for each HV cable installed within the transmission line.

A groundbreaking integrated predictive model, termed Cyber Forensics Behavioral Analysis (CFBA), has been developed in an environment characterized by rapidly evolving and increasingly sophisticated cyber threats. This model merges Cyber Behavioral Sciences with Digital Forensics to enhance the prediction accuracy and effectiveness of cyber threats originating from specific Autonomous System Numbers (ASNs). It has been observed that traditional cybersecurity strategies, predominantly focused on technical aspects, must be improved in addressing the complex landscape of cyber threats. Consequently, a novel approach has been proposed in this research, combining technical expertise with insights into the behavior of cybercriminals, thereby addressing a significant gap in existing methodologies. A mixed-methods approach has been employed in the study, integrating quantitative and qualitative research methods. This approach has created a comprehensive framework incorporating digital forensics, cybersecurity, computer science, forensic psychology, and the cyber behavioral sciences which incorporates disciplines scuch as cyberpsychology and forensic cyberpsychology. The study is anchored around four key concepts: (1) Forensic Cyberpsychology, which focuses on understanding psychological aspects of cybercriminal behavior; (2) Digital Forensics, involving the collection and analysis of digital evidence from cyber incidents; (3) Predictive Modeling, which utilizes historical data and patterns to anticipate potential cyber threats; and (4) the Cyber Behavioral Analysis Metric (CBAM) and Cyber Behavioral Score (CBS), tools designed for evaluating and scoring ASNs based on their behavior in terms of cybersecurity threat risks. Challenges encountered in the development of this integration have been significant. Initial setbacks included the misalignment of traditional cyber defense methods with the evolving nature of cyber threats and the absence of a holistic approach in pre-existing models. Through the narrative of these challenges and the subsequent development of the CFBA model, the research highlights the necessity for an interdisciplinary approach to cybersecurity. The outcomes of this study are not merely theoretical but provide practical, actionable tools and frameworks that markedly improve the precision of predicting cyber threats, especially from ASNs. The CFBA model represents a significant shift in cybersecurity strategies, highlighting the importance of integrating behavioral insights with technical knowledge. The study emphasizes the need for ongoing research and collaboration in cybersecurity, advocating for an approach that is as comprehensive and multifaceted as the cyber threats it seeks to mitigate. This research has been conducted to contribute significantly to cybersecurity, offering new perspectives and methodologies in a rapidly changing domain.

The present study examined metabolites in Northern wild rice (WLD), the impact of WLD supplemented high fat (HF) diet on gut microbiota, short chain fatty acids (SCFAs) and correlation with metabolism or inflammation versus HF+white rice (WHR) in mice. C57BL/6J mice received HF diet supplemented with 26g% WHR, 26g% WLD, or 13g% WHR+13g% WLD (WTWD) for 12 weeks. The levels of fasting plasma glucose, total cholesterol, triglycerides, insulin resistance, inflammatory cytokines and monocyte adhesion were lower, and the abundances of fecal Lactobacillus gasseri species bacteria and propionic acid were higher in HF+WLD diet-fed mice compared to HF+WHR diet-fed mice (p<0.05). The anti-inflammatory effects of HF+WTWD diet were weaker than that in HF+WLD diet, but were greater than that in HF+WHR diet-fed mice (p<0.05). Relative abundances of fecal Lactobacillus gasseri and propionic acid in HF+WLD fed-mice were higher than that in HF+WHR fed mice. The abundance of fecal L. gasseri and propionic acid negatively correlated with metabolic and inflammatory markers (p<0.05). The findings suggest that WLD dose-dependently attenuated metabolic and inflammatory disorders in HF diet-fed mice. Interactions between WLD components and gut microbiota may upregulate fecal propionic acid and contribute to metabolic and anti-inflammatory benefits of WLD diet-induced insulin resistant mice.

It is widely recommended to group house male laboratory mice because they are ‘social animals’, but male mice do not naturally share territories and aggression can be a serious welfare problem. Even without aggression, not all animals within a group will be in a state of positive welfare. Rather, many male mice may be negatively affected by the stress of repeated social defeat and subordination, raising concerns about welfare and also research validity. However, individual housing may not be an appropriate solution, given the welfare implications associated with no social contact. An essential question is whether it is in the best welfare interests of male mice to be group- or singly-housed. This review explores the likely impacts, positive and negative, of both housing conditions, presents results of a survey of current practice and awareness of mouse behaviour, and includes recommendations for good practice and future research. We conclude that whether group- or single-housing is better (or less worse) in any situation is highly context-dependent according to several factors including strain, age, social position, life experiences, and housing and husbandry protocols. It is important to recognise this and evaluate what is preferable from animal welfare and ethical perspectives in each case.

The objective of the this study was to reduce the benzo[a]pyrene-induced hepatotoxicity method in herbal medicine products and to give proof that neferine, daidzein, genistein possess antihepa-totoxic effects. B[a]P which classified as a group 1 carcinogen and metabolized to B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) causes mutagenic DNA addition products. The reduc-tion of BPDE-DNA adduct formation by B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) was derived by benzo[a]pyrene (B[a]P). In HepG2 cells, B[a]P exhibited toxicity and substance treatment of the cells with B[a]P with neferine in lotus and daidzein, genistein in soybean reduced the BPDE-DNA ad-ducts level. The level of B[a]P-metabolites in the substance treatment of the cells was presented that BPDE levels were reduced by neferine in lotus and daidzein, genisten in soybean. These results suggest that neferine in lotus and daidzein, genistein in soybean prevent B[a]P-induced hepato-toxicity for BPDE-DNA adduct formation.

BackgroundThe use of antimicrobials to treat food animals may result in antimicrobial residues in foodstuffs of animal origin. The European Medicines Association (EMA) and World Health Organization (WHO) define safe antimicrobial concentrations in food based on acceptable daily intakes (ADIs). It is unknown if ADI doses of antimicrobials in food could influence the antimicrobial susceptibility of human-associated bacteria. ObjectivesThis aim of this study was to evaluate if the consumption of ADI doses of erythromycin could select for erythromycin resistance in a Galleria mellonella model of Streptococcus pneumoniae infection. Methods A chronic model of S. pneumoniae infection in G. mellonella larvae was used for the experiment. Inoculation of larvae with S. pneumoniae was followed by injections of EMA (0.0875 μg/ml) and WHO (0.012 μg/ml) ADI doses of erythromycin proceeded by isolation of S. pneumoniae colonies on selective agar plates. Minimum inhibitory concentrations (MICs) of resistant colonies were measured, and whole genome sequencing (WGS) was performed followed by variant calling to determine the genetic modifications.   Results Exposure to single doses of both EMA and WHO ADI doses of erythromycin resulted in the emergence of erythromycin resistance in S. pneumoniae. Emergent resistance to erythromycin was associated with a mutation in rplA. Conclusion In our in vivo model, even single dose of erythromycin that are classified as acceptable by the WHO and EMA induced significant increases in erythromycin MICs in S. pneumoniae. These results suggest the need to include the induction of antimicrobial resistance (AMR) as a significant criterion for determining ADIs.

Morphine-induced antinociception is partially reduced in interleukin-31 (IL-31) receptor A (IL-31RA)-deficient mice, indicating that IL-31RA is crucial for morphine-induced peripheral antinociception. Herein, we examined the combined effects of IL-31 and morphine on antinociceptive activity and itch-associated scratching behavior (LLS) in mice, and elucidated the regulatory mechanisms. A hot-plate test was used to assess antinociception. LLS was automatically detected and recorded via computer. IL-31RA mRNA expression was assessed using real-time polymerase chain reaction. Repeated pre-treatment with IL-31 resulted in significant antinociceptive activity. Repeated administration of morphine decreased the morphine-induced antinociceptive activity, LLS counts, and regular dose, and inhibited IL-31-induced LLS. These results suggested that repeated administration of morphine depleted inter-neuronal IL-31RA levels, preventing morphine-induced antinociception. Therefore, IL-31 may be helpful as an adjunct analgesic to morphine. To explore the benefits of IL-31, its influence on morphine-induced antinociceptive tolerance in mice was examined. IL-31 and morphine combination increased analgesic action which increased the expression of DRG neuronal IL-31RA, elucidating the site of peripheral antinociception of morphine. This site may induce exocytosis of IL-31RA in the sensory nervous system. Collectively, the suppressive effect of IL-31 on morphine-induced antinociceptive tolerance may result from IL-31RA supplementation in sensory nerves.

The theory that an itch inhibits pain has been refuted; however, previous research did not investigate this theory for interleukin-31 (IL-31)-induced itch. Previously, we have found that morphine-induced antinociception was partially reduced in IL-31 receptor A (IL-31RA)-deficient (IL-31RAKI) mice, indicating that IL-31RA may play an important role in morphine-induced peripheral antinociception. In the present study, we evaluated the effect of IL-31-induced analgesia on a 2,4,6-trinitrochlorobenzene (TNCB)-sensitized mice using a hot-plate test. This test evaluated the antinociceptive activity of morphine, and non-steroidal anti-inflammatory drugs (NSAIDs). Repeated pretreatment with IL-31 showed significant antinociceptive action. Furthermore, its combination with morphine, but not with NSAIDs, increased the analgesic action. In contrast, treatment with TNCB and capsaicin decreased antinociception. Moreover, TNCB increased IL-31RA expression in the dorsal root ganglia at 24 h, whereas capsaicin inhibited it. The comparative action of several analgesics on TNCB or capsaicin was evaluated using a hot-plate test, which revealed that the antinociceptive activity was decreased or disappeared in response to capsaicin-induced pain and in IL-31RAKI mice. These results indicate that the analgesic action of IL-31 involves the peripheral nervous system, which affects sensory nerve. These results provide a basis for developing novel analgesics using this mechanism.

The enormous diversity of hair fibers found in human population is striking, while the basic structure of human fibers is often the same! But why do some fibers curl? Curling is related to the machinery and processes that produce different keratin filament orientation in relation to the axis of hair growth, influenced by developmental and molecular control. It is established that a curly hair shaft is produced by a curved hair follicle that have an angulated dermal implantation, with a bulb bent in the shape of golf club, while the outer root sheath is dissymmetrical; have an outer side that is convex bulging and thin and a concave side in which the cells express alpha-smooth muscle protein reflecting internal mechanical force. Yet, the exact cause of hair curling is not known. All the previous studies were short of impacting curly hair treatment. My hypothesis is that the curling mechanical force is generated by a hypersensitive contracted Arrector Pili muscle (APM) of the hair follicle. In curly hair, each APM fiber is shortened; pulling its attachment spot upward towards the epidermis and obliquely or laterally; curling the outer root sheath to produce the curved follicle described above. This contraction has the influence at a time when the young hair root is being formed and keratin microfibrils are being oriented and packed. APM is a multi-unit muscle wherein each fiber contracts independently to create the enormous diversity of curly hair types. APM contraction can be modulated by oral administration of selective smooth muscle relaxing treatment that relax the curved follicle from within. Further studies are needed to confirm the role of APM in shaping curly hair follicle including AI studies, i.e., computer-aided target identification to demonstrate APM active site that can interact with herbal small molecules.

Maritime surveillance technology faces challenges of astronomical size in this vast ocean world—challenges vital to global security and environmental protection alike. Such as these may be reversible or not. Remotely sensed monitoring also uses photos taken from satellites, synthetic aperture radar (SAR) equipment, and unmanned aerial vehicles (UAVs) to fully monitor maritime activities but also ferret out suspicious behaviour like piracy, bootleg shipments, and illegal fishing. This mixed-method approach--quantitatively and qualitatively——measures the efficiency of difficulties associated with, and legal implications behind aerospace-monitored maritime surveillance. The results show that remote sensing provides a great deal of sea-level situational awareness; however, there are also many complex technical, operational, and legal issues, including information overcrowding, complications in integration, privacy issues, as well as the need for worldwide legal harmonisation. It ends with recommendations on ways to ultimately increase capacity, how to write standard procedures for secondary development and proposals for revising laws to absorb these new technologies. Its goal, therefore, is to benefit the global anti-maritime crime effort. Ultimately, though, it dreams that we might construct an entirely marine environment where all marine activities are conducted both safely and freely, without fear.

Recently, Gohar et al. introduced a novel, local, and well-behaved fractional calculus. It possesses all the classical properties, and Its locality imposes simplicity and accuracy in modeling fractional order systems. In this article, we further develop the definitions and extend the classical properties of Gohar fractional calculus to address some of the open problems in Calculus. The fractional Gronwall's integral inequality, Taylor power series expansion, and Laplace transform are defined and applied to overcome some of the limitations in the classical integer-order calculus. The fractional Laplace transform is applied to solve Bernoulli-type logistic and Bertalanffy nonlinear fractional differential equations, and the criteria under which it can be applied to solve linear differential equations are investigated.

Throughout this paper the impact of anxiety on adolescent athlete’s is highlighted through analyzing neurological and psychological aspects involved in sports performance. The neuroanatomy and neuropsychology of the human brain plays a major role in developing athlete’s that has only begun to be analyzed within recent years. Especially in young athletes, there are numerous factors that affect performance on the field that originate from the environment and training the adolescent athlete is involved in. Sports performance is viewed as a major physical factor such as training and lifting weights, however the psychological aspect of sports performance often goes unnoticed. Athletes can begin to develop mental fatigue and anxiety which inevitably can decrease their ability to perform. The athlete’s internal suffering begins to go unnoticed, as the only tangible factor is watching their performance decrease. This causes the athlete to push themselves further in training resulting in greater mental fatigue. This paper emphasizes the numerous factors neurologically that play a role in athletic performance which should be focused on in adolescent athletes as they navigate the challenges and competition that are apparent within athletics. It is critical to understand the processes and hormonal changes the body undergoes with training and playing a sport, this information can change the way adolescent sports are approached and advanced.

Cancer cells cannot proliferate and survive unless they obtain sufficient levels of the 20 proteinogenic amino acids (AAs). Unlike normal cells, cancer cells have genetic and metabolic alterations that may limit their capacity to obtain adequate levels of the 20 AAs under challenging metabolic environments. However, since normal diets provide all AAs at relatively constant levels and ratios, these potentially lethal genetic and metabolic defects are eventually harmless to cancer cells. If we temporarily replace the normal diet of cancer patients with artificial diets in which the levels of specific AAs are manipulated, cancer cells may be unable to proliferate and survive. This article reviews in vivo studies that have evaluated the antitumor activity of diets restricted or supplemented with the 20 proteinogenic AAs, individually and in combinations. It also reviews our recent studies that show that manipulating the levels of several AAs simultaneously can lead to marked survival improvements in mice with metastatic cancers.

The assessment of welfare and disease progression in animal models is critical. Most tools rely on evaluating individual subjects, whereas social behaviors, also sensitive to acute illness, chronic diseases, or mental health, are scarcely monitored because of their complexity, are invasive, and time-consuming. We propose the evaluation of social nesting, a species-typical behavior naturally occurring in standard housing conditions, for such behavioral monitoring. We provide an example of its use to evaluate social deficits and the long-term effects of neonatal sensorial stimulation in male and female adult 3xTg-AD mice for Alzheimer's disease compared to sex- and age-matched NTg counterparts with normal aging. Social nesting was sensitive to genotype (worse in 3xTg-AD mice), sex (worse in males), profile, and treatment (distinct temporal patterns, time to observe the maximum score and incidence of the perfect nest). Since social nesting can be easily included in housing routines, this neuroethological approach can be useful for animal's welfare, monitoring the disease's progress, and evaluating potential risk factors and effects of preventive/therapeutical strategies. Finally, the non-invasive, painless, simple, short time and low-cost features of this home-cage monitoring are advantages that make social nesting feasible to be successfully implemented in most animal department settings.

The acetylcholinesterase (AChE) inhibitors are the main drugs for symptomatic treatment of neurodegenerative disorders like Alzheimer’s disease. A recently designed, synthesized and tested hybrid compound between the AChE inhibitor galantamine (GAL) and the antioxidant polyphenol curcumin (CU) showed high AChE inhibition in vitro. Here, we describe tests for acute and short-term toxicity in mice as well as antioxidant tests on brain homogenates measured the levels of malondialdehide (MDA) and glutathione (GSH). Haematological and serum biochemical analyses were also performed. In the acute toxicity tests, the novel AChE inhibitor given orally in mice showed LD50 of 49 mg/kg. The short-term administration of 2.5 and 5 mg/kg did not show toxicity. In the ex vivo tests, the GAL-CU hybrid performed better than GAL and CU themselves. In a dose of 5 mg/kg, it demonstrates 25% reduction in AChE activity, 28% and 73% increase in the levels of MDA and GSH, respectively. No significant changes in blood biochemical data were observed. The GAL-CU hybrid is a novel non-toxic AChE inhibitor with high antioxidant activity which makes it a perspective multitarget drug candidate for treatment of Alzheimer’s disease.

Improper lifting measures of long-span spatial steel structures during construction process may delay the construction period and even cause safety accidents. Few studies on long-span spatial steel structures considered time-varying mechanical characteristic during construction process. In order to achieve safe and efficient installation in a long-span spatial steel structure, this research presents a time-varying mechanical analysis of the synchronous and asynchronous integral lifting and a single and interlaced point’s asynchronous integral lifting analysis method of a long-span spatial steel structure. The results showed that in the case of asynchronous lifting of single point, the displacement influence on other members is related to the distance. The closer the distance from the lifting point, the greater the influence. In asynchronous integral lifting, the lifting point with large lifting force is first installed to the specified position, and the lifting point with small lifting force is installed to the specified position.

In our recent publications, based on strong and electroweak interactions, we have developed a completely new formula for estimating nuclear binding energy. With reference to currently believed Semi Empirical Mass Formula (SEMF), we call our formula as ‘Strong and Electroweak Mass Formula’ (SEWMF). Our formula constitutes 4 simple terms and only one energy coefficient of magnitude 10.1 MeV. First term is a volume term, second term seems to be a representation of free nucleons associated with electroweak interaction, third term is a radial term and fourth one is an asymmetry term about the mean stable mass number. In this paper, we make an attempt to understand and estimate the maximum binding energy associated with any mass number. It can be expressed as, for A > 4, $\left(BE\right)_A\cong \left[A-0.000935A^2-A^{1/3}-A^{-1/2}\right]$ MeV. We are working on refining the 4^th term with even-odd corrections, shell corrections and other microscopic corrections. Proceeding further, stable mass numbers and super heavy mass numbers can be understood with a relation of the form, $\left[\textrm{RoundOff}\left(\left(Z+2.9464\right)^{1.2}-1.7165\right)\right]\pm\left[0,1\right]\pm\left(2n\right)$ where $n \cong 0,1,2$. It needs a review with respect to even-odd proton numbers and other microscopic corrections.Very interesting point to be noted is that based on the concept of “binding energy per nucleon”, the most complicated Avogadro number and Unified atomic mass unit can be estimated in a unified approach.

This literature review investigates the morphological and behavioral significance of the horns of Carnotaurus sastrei, a theropod dinosaur from the Late Cretaceous period. Through a comprehensive analysis of fossil specimens, comparative anatomy, and biomechanical modeling, this review explores the evolutionary adaptations and potential functions of these distinctive cranial structures. The horns of Carnotaurus are hypothesized to serve multiple roles, including species recognition, thermoregulation, and intraspecific combat. Our findings suggest that its cranial horns likely served a primary role in species recognition, intimidating rivals and signaling mating readiness. It also could have been used occasionally in head-butting contests, potentially as a display of dominance, but likely did not play a role in thermoregulation. Additionally, we examine the ecological context in which Carnotaurus lived, assessing how environmental factors could have influenced the development of such features. The implications of this study extend to broader discussions on the functional morphology and adaptive strategies of theropod dinosaurs, highlighting the complex relationship between form and function in the evolutionary history of predatory dinosaurs like Carnotaurus sastrei.

Event detection provides a crucial foundation for intelligent text analysis and supports numerous downstream applications. However, existing detection models often fail to meet the high accuracy requirements and typically require a human–machine collaborative detection mode involving “machine detection followed by manual audit and correction.” Analysis reveals that the recall rate of machine detection is a major factor limiting the efficiency of human–machine collaboration. To address this at its root and ensure high recall, an event trigger recommendation task is introduced, and a span-based recommendation model for Chinese, SpETR (Span-based Event Trigger Recommender), is developed. This model integrates confidence information from both trigger identification and event classification stages to recommend candidate triggers and their event types for each event. To enhance recall, a semantic boundary smoothing method is proposed, which assigns soft labels to spans around gold triggers based on semantic completeness and part-of-speech, combined with a modified focal loss function to make the model predictions smoother. Experiments on DuEE and a self-built dataset show that SpETR is most effective when the number of recommendations is set to 3, achieving recall rates of 97.76% and 98.70%, respectively, comprising improvements of 4.30% and 5.22% over the optimal baseline models. In terms of human–machine collaborative detection, SpETR saved 30.6% and 25.8% of time compared to traditional detection models on two datasets, and the average F1 score of the annotation results was also improved by 5.35% and 3.48%, respectively.

Gilbert's syndrome (GS) is a common hereditary condition characterized by mild increases in serum bilirubin levels due to inherited defects in bilirubin metabolism. This review, based on data from peer-reviewed articles and journals spanning from 1977 to January 2024, provides a comprehensive overview of over four decades of research on GS. Early studies primarily focused on defining the clinical and genetic characteristics of the syndrome, laying the foundation for subsequent investigations. More recent research has delved into the genetic mechanisms underlying the reduced expression of bilirubin UDP-glucuronosyltransferase, which has significantly enhanced our understanding of the pathogenesis of GS. Furthermore, recent studies have shed light on the clinical implications of GS, including its association with non-alcoholic fatty liver disease and mortality risk, highlighting the complex interplay between genetic factors, bilirubin metabolism, and clinical outcomes. Despite its generally benign nature, thorough research is essential to fully understand the impact of GS on patients' lives. This review emphasizes the importance of ongoing research to deepen our understanding of GS and its broader implications.

Ballastless track has high smoothness, but the laying requirements are strict. Therefore, the maximum span of cable-stayed bridges laying ballastless tracks is 392m. For laying ballastless track structures over larger spans, the deformation characteristics of long-span cable-stayed Bridges under complex loads are incomplete, and the interaction between long-span bridge-track structures is unclear. The influence of wavelength of cosine wave on the track- bridge mapping of different orbital structures was explored. The wavelength characteristics of vertical deformation under complex loads were investigated. The track-bridge integrated model for the cable-stayed bridge was establish to analyze the mapping relationship between rail and bridge and wavelength characteristics of deformation. Based on mapping relationships and wavelength characteristics of deformation, the Train-Track-Bridge dynamic simulation model was simplified. The results show that when the minimum wavelength of bridge deformation surpasses 6 m, 10 m, and 16 m, the rail deformation in the ballasted track, the longitudinal-connected track, and the unit slab-type ballastless track accurately mirrors the deformation of the bridge. For the span of bridge ranging from 200 m to 600 m, the wavelength of vertical deformation ranges from 21 to 1270 m under complex loads. During local loads, the vertical deformation below the 200 m wavelength constitutes a significant proportion near the pie. Considering the influence of the deformation on train vibration response, the Train-Bridge dynamic coupling model can be employed to treat the track structure as a load to reduce complexity of model and enhance the calculation efficiency.

A large body of evidence reports about the positive effects of physical activity in pathophysiological conditions associated with aging. Physical exercise, alone or in combination with other medical therapies, unquestionably causes reduction of symptoms in chronic non-transmissible diseases often leading to significant amelioration or complete healing. The molecular basis of this exciting outcome, however, remain largely obscure. Epigenetics, exploring at the interface between environmental signals and the remodelling of chromatin structure, promises to shed light on this intriguing matter possibly contributing to the identification of novel therapeutic targets. In this review, we shall focalize on the role of sirtuins (Sirts) a class III histone deacetylases (HDACs) which function has been frequently associated, often with a controversial role, to the pathogenesis of aging-associated pathophysiological conditions including cancer, cardiovascular, muscular, neurodegenerative, bones and respiratory diseases. Numerous studies, in fact, demonstrate that Sirt-dependent pathways are activated upon physical and cognitive exercises linking mitochondrial function, DNA structure remodelling and gene expression regulation to designed medical therapies leading to tangible beneficial outcomes. However, in similar conditions, other studies assign to sirtuins a negative pathophysiological role. In spite of this controversial effect, it is doubtless that studying sirtuins in chronic diseases might lead to an unprecedented improvement of life quality in the elderly.

This case report demonstrates the rare but potentially serious complication of pulmonary vein stenosis (PVS) diagnosed several years after radiofrequency ablation for atrial fibrillation. Pulmonary vein stenosis can remain asymptomatic until significant occlusion occurs, after which it can present with a variety of symptoms, mimicking numerous cardiovascular and pulmonary pathologies. Early diagnosis and treatment rely on consistent follow-up using appropriate diagnostic imaging modalities, which are paramount in preventing severe complications.

Stem cells can be used to treat diabetic mellitus and complications. ω3-docosahexaenoic acid (DHA) derived lipid mediators are inflammation-resolving and protective. This study found novel DHA-derived 7S,14R-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-docosahexaenoic acid (7S,14R-diHDHA), a maresin-1 stereoisomer biosynthesized by leukocytes and related enzymes. Moreover, 7S,14R-diHDHA can enhance mesenchymal stem cell (MSC) functions in the amelioration of diabetic mellitus and retinal pericyte loss in diabetic db/db mice. MSCs treated with 7S,14R-diHDHA were delivered into db/db mice i.v. every 5 days for 35 days. Blood glucose levels in diabetic mice were lowered by 7S,14R-diHDHA-treated MSCs compared to control and untreated MSC groups, accompanied by improved glucose tolerance and higher blood insulin levels. 7S,14R-diHDHA-treated MSCs increased insulin+ β-cell ratio and decreased glucogan+ α-cell ratio in islets, as well as reduced macrophages in pancreas. 7S,14R-diHDHA induced MSC functions in promoting MIN6 β-cell viability and insulin secretion. 7S,14R-diHDHA induced MSC paracrine functions by increasing the generation of hepatocyte growth factor and vascular endothelial growth factor. Furthermore, 7S,14R-diHDHA enhanced MSC functions to ameliorate diabetes-caused pericyte loss in diabetic retinopathy by increasing their density in retina in db/db mice. Our findings provide a novel strategy for improving therapy for diabetes and diabetic retinopathy using 7S,14R-diHDHA-primed MSCs.

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive neuromuscular disease prevalent in 1 in 3500 to 5000 males worldwide. As a result of mutations that interrupt the reading frame of the dystrophin gene (DMD), DMD is characterized by a loss of dystrophin protein which leads to decreased muscle membrane integrity, which increases susceptibility to degeneration. CRISPR/Cas9 technology has garnered interest as an avenue for DMD therapy due to its potential for permanent exon skipping, which can restore the disrupted DMD reading frame in DMD and lead to dystrophin restoration. An RNA-guided DNA endonuclease system, CRISPR/Cas9 allows for the targeted editing of specific sequences in the genome. The efficacy and safety of CRISPR/Cas9 as a therapy for DMD has been evaluated by numerous studies in vitro and in vivo, with varying rates of success. Despite the potential of CRISPR/Cas9-mediated gene editing for the long-term treatment of DMD, its translation into the clinic is currently challenged by issues such as off-targeting, immune response activation, and sub-optimal in vivo delivery. Its nature as being mostly a personalized form of therapy also limits applicability to DMD patients, who exhibit a wide spectrum of mutations. This review summarizes the various CRISPR/Cas9 strategies that have been tested in vitro and in vivo for the treatment of DMD. Perspectives on the approach will be provided, and the challenges faced by CRISPR/Cas9 in its road to the clinic will be briefly discussed.

The document sets out three differentiated proposals for the transport of medicines through RPAS with their respective regulations, adapted to different operational categories: open category, special category and military scope. In the open category, an economical and efficient solution is prioritized for urban and rural areas, complying with weight and height regulations, in addition to guaranteeing the stability and quality of medications during transportation. The special category allows more complex operations and in more adverse conditions, such as densely populated areas and long routes, incorporating advanced security measures and training for personnel. In the military field, RPAS are used in conflict zones and hard-to-reach areas, ensuring the safe and rapid delivery of medical supplies under extreme conditions. Success stories in different countries are highlighted, demonstrating significant improvements in delivery times and risk reduction for health personnel.

We delve into the axion-dilaton model within the supergravity framework, with a specific focus on the intricacies of domain wall construction and stability. Employing holographic vitrification, we unravel the dynamics of domain wall formation in gauge theories featuring periodic vacuum structures. Our model, incorporating a QCD-like axion term and a stabilizing dilaton, undergoes scrutiny for conductivity variations under weak disorder. The investigation reveals the model's resilience, manifesting near-perfect conductivity under mild disorder conditions. However, the rigorous mathematical motivation for the holographic setup demands further elucidation. The scattered nature of our results prompts the necessity for a more systematic interpretation of QCD phenomena and conductivity transitions. This study contributes to the mathematical understanding of the axion-dilaton model's behavior, highlighting the imperative for a refined holographic framework and a more coherent interpretation of observed phenomena.

As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.

Epoxy asphalt (EA) concrete is widely used in constructing long-span steel bridge pavements (SBDPs). This study aims to derive a fatigue damage evolution law, conducting an experimental investigation of SBDP. First, a general theoretical form of the fatigue damage evolution law of materials is established based on the thermal motion of atoms. Then, fatigue experiments demonstrate that this evolution law well represents the known damage–life relationships of SBDP. Taking into account the experimental relationships between damage and fatigue life under symmetrical cyclic loadings with different overload amplitudes and temperature variations, a detailed damage evolution law is deduced. Finally, the role of damage accumulation is discussed on the basis of the proposed damage evolution law for the extreme situation of heavy overload and severe environments. The results show that both heavy loading and falling temperatures increase the fatigue damage of SBDP considerably; therefore, SBDP should avoid heavy loading combined with winter temperatures. EA shows a fatigue life two to three times longer than that of modified matrix asphalt (SMA) or guss asphalt (GA). For the same thickness, EA pavement is demonstrated to be more suitable for an anti-fatigue design of large-span SBDP under high traffic flows and low temperatures.

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (K_d), can be considered as one of the most important characteristics for any antibody-antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC₅₀ approaches the K_d value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to K_d. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols.

Long-span steel structure trusses are widely used in factory buildings, but with the growth of service time and the increase of dynamic load fatigue, a considerable part of the long-span truss with dynamic load appears serious transverse cracks at the bottom of the middle span and oblique deformation of the abdomen in the operation process. The U-shaped cracks at the bottom and belly, as well as the mid-span down deflection of the main truss, reduced the functional function of the factory building truss structure, and had to limit the original crane load, which affected the normal safety and durability of the structure. Therefore, the application principle of the variable axial force cable system in the long-span factory building truss structure and 3D3S software modeling [1] were used. Analyzing and studying the reinforcement method of large-span powerhouse truss can provide practical experience for subsequent similar projects. In view of the above phenomenon, the large-span powerhouse trusses of Hongcheng Powerhouse 1 and No.2 located in Tonglu, Zhejiang Province are used as the research object, and the variable axial force cable method is proposed to strengthen and lift the load. Considering the span of large-span powerhouse truss, the cable system with 22m controlling force of 400kN is proposed to be selected for powerhouse 1, and the cable system with variable axial force of 24m is proposed to be selected for Powerhouse 2. The force model of large-span truss is established by using the finite element method commonly used to analyze the force of truss. Under two working conditions, The influence of reinforcement effect is analyzed and compared from three aspects: stiffness, bearing capacity and stability. And the phenomenon of uneven stress distribution is analyzed. The stress distribution characteristics of each node are understood by simulating the most disadvantageous node plates with the greatest internal force before and after reinforcement.

This study delves into the intricate interplay between cosmology and gravity in dilaton-based models, enhancing our understanding. Exploring boundary theories coupled to gravity, we derive a four-dimensional effective theory from the cosmological constant. Dilaton gravity is then scrutinized, revealing elegant solutions and insights into brane embedding. The analysis extends to probe scalar fields, employing the WKB approximation in both conformal and non-conformal cases. In summary, this work contributes to a nuanced understanding of the complex relationship between cosmology and gravity in dilaton-based frameworks.

We introduce the linear subgroup of volume-preserving diffeomorphism as the underlying symmetry to construct an action within the effective field theory framework and the Schwinger-Keldish formalism. The formulated action is posited to effectively incorporate dissipative effects into the Navier-Stokes equations.