The present study investigates the reliability and validity of the Positive-Negative Relationship Quality (PN-RQ) scale in Turkey. In order to determine the validity and reliability of the scale, two studies were performed. The first was carried out with emerging adults (university students) who were in a romantic relationship (148 females, 43 males, and 2 unkown) and had the main purpose to examine the structure validity of the measurement tool in the Turkish sample with an exploratory analysis. Study 2 was performed online with 513 married adults (359 females, 149 males, and 5 unknown); confirmatory findings and criterion validity studies were added. Exploratory factor analyses revealed that relationship quality had a two-factor structure and that there was also a negative relationship between the factors. Confirmatory factor analyses on the married sample showed that the bi-factor model provided evidence for the multidimensional nature of the scale. Both studies demonstrated high internal consistency.

The development of smart negative electrode materials with high capacitance for use in supercapacitors remains challenging. Although there have been several types of electrode materials with high capacitance used in energy storage, carbon-based materials are the most reliable electrodes due to their high conductivity, high power density and excellent stability. The most common complaint about general carbon materials is that these as-formed electrode materials can hardly ever be used as free-standing electrodes. Free-standing carbon-based electrodes are in high demand and are a passionate topic of energy storage research. Electrospun nanofibers are a potential candidate to fill this gap. However, the as-spun carbon nanofibers (ECNFs) have low capacitance and energy density on their own. To this end, several attempts have been made to improve these characteristics. In this review, we introduce negative electrode materials that have been developed. Moreover, this review places special attention to the advances of electrospun nanofiber-based negative electrode materials and their limitations. Based on the above information, we put forth a future perspective on how these limitations can be overcome to meet the demands of next-generation smart devices.

In this article, we assume that the beginning of the universe was before the Big Bang. In the beginning, all matter in the universe was combined in an infinitesimal spherical shape. This sphere was compressed to an incomprehensible value for a period, and then exploded and expanded time and space. We are referring to the negative time before the Big Bang. The evolution of the universe before the Big Bang, passing through the moment of the explosion to the end of the universe at the Big Rip, has been studied. In this article, we try to answer the questions; did the universe exist before the Big Bang? What is the origin of the universe and how did it arise? What are the stages of the evolution of the universe until the moment of the Big Rip? What is the length of time for the stages of this development?

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were used as positive controls. AA manipulation led to modest improvements in mice survival when the levels or lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Mice fed the artificial diets as monotherapy lived longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.

AI is extraordinarily useful technology but it is becoming increasingly powerful with rapidly growing capabilities to disrupt and harm human society. We call on international and national organizations and individuals to join forces in banning the development of superintelligent AI and introducing regulations to prevent and mitigate AI-caused harm.

Up to now, Schrödinger equation, Klein-Gordon equation (KGE) and Dirac equation are believed the fundamental equations of quantum mechanics. Schrödinger equation has a defect that there is no NKE solutions. Dirac equation has positive kinetic energy (PKE) and negative kinetic energy (NKE) branches. Both branches should have low momentum, or nonrelativistic, approximations: one is Schrödinger equation and the other is NKE Schrödinger equation. KGE has two problems: it is an equation of second time derivative, and calculated density is not definitely positive. To overcome the problems, it should be revised as PKE and NKE decoupled KGEs. The fundamental equations of quantum mechanics after the modification have at least two merits. They are of unitary in that everyone contains the first time derivative and are symmetric with respect to PKE and NKE. This reflects the symmetry of the PKE and NKE matters, as well as matter and dark matter, of our universe. The problems of one-dimensional step potentials are resolved by means of the modified fundamental equations for a nonrelativistic particle.

Triple negative breast cancer (TNBC) is an aggressive subtype of the disease with poor clinical outcomes and limited therapeutic options. Immune checkpoint blockade (CP) has surged to the forefront of cancer therapies with widespread clinical success in a variety of cancer types. However, the percentage of TNBC patients that benefit from CP as a monotherapy is low and clinical trials have shown the need for combined therapeutic modalities. Specifically, there has been interest in combining CP therapy with radiation therapy where clinical studies primarily with external beam have suggested their therapeutic synergy, contributing to the development of anti-tumor immunity. Here, we have developed a therapeutic platform combining radionuclide therapy (RT) and immunotherapy utilizing a radiolabelled biomolecule and CP in an E0771 murine TNBC tumor model. Survival studies show that while neither monotherapy is able to improve therapeutic outcomes, the combination of RT + CP extended overall survival. Histologic analysis showed that RT + CP increased necrotic tissue within the tumor and decreased levels of F4/80+ macrophages. Flow cytometry analysis of the peripheral blood also showed that RT + CP suppressed macrophages and myeloid-derived suppressive cells, both of which actively contribute to immune escape and tumor relapse.

The concept of using special electrical circuit design realize a "cold resistors", that is, an active resistor circuitry with lowered effective noise temperature, was first introduced about 80 years ago. Later on, various kinds of artificial resistors were applied in different research areas, such as gravitational wave detection, photo-amplifiers and quartz oscillators. Their proofs of concepts were experimentally proved. Unfortunately, the complete theory was not found even though several attempts had been published, sometimes with errors. In this paper, we describe a correct and complete circuit theoretical model of a cold resistor system. The results are confirmed by computer simulations. A design tools for this circuit is also shown.

The gravitational charge should be the energy instead of mass. This modification will lead to some different results and the experiments to test are also presented. Especially, we propose a scheme to achieve the negative energy and gravitational repulsive force in the lab.

The first Network Arch Bridge (NAB) was opened to traffic 60 years ago and since then the idea spread around the world. It is a type of a tied arch bridge that combines the benefits of tied arch bridges and trusses in a single system, thus it has a very good stiffness even in the case of extremely slender structures. In a Network Arch the hangers are inclined and some of them intersect each other at least twice. The core of a NAB is the hanger arrangement that minimizes the bending moment in the arch to very small values, leading thus to compression in the arch. This paper reviews the Network Arch idea devised by prof. Tveit and extended by researchers and engineers worldwide. A comprehensive review of the literature about the Network Arch is provided and the situation of NABs around the world from the standpoint of location, span, structural system used for the cross-section, bridge type (road, railway, combined or pedestrian) and opening year is discussed.

Background: We attempted to find if there were gender differences in different types of Negative life events and Suicidal ideation among Chinese adolescents, then analyze the relationship between different types of Negative life events and Suicidal ideation among these young students. Methods: Based on the data from 6 middle-schools and 3 universities in 3 cities of Western China, the gender difference in different types of Negative life events and Suicidal ideation and their related factors were investigated and analyzed in the study. Results: Gender differences were found during different types of Negative life events and Suicidal ideation; Negative life events could predict the intensity of Suicidal ideation by gender, to some specific types. Conclusions: Negative life events were proved to be risk factors of adolescents’ Suicidal ideation regardless of different gender stereotypes, but the specific classification of negative life events which had significant impact on adolescents’ Suicidal ideation also indicated significant gender divisions. For males, negative life events of punishment and adaptation had a significant and boosting impact on their Suicidal ideation, the higher the scores of punishment and adaptation negative life events had, the greater intensity of male adolescents were to have Suicidal ideation. Thus, the above two types of negative life events may be the main stressors predicting male adolescents' Suicidal ideation; For females, in addition to punishment, other types of negative life events all had significant impacts on their Suicidal ideation, which can be treated as the main stressors to trigger female adolescents' Suicidal ideation; Additionally, parents’ marital status of remarriage and divorce were proved to be significant indicators to adolescents’ Suicidal ideation, the age variable was proved to be strongly correlated with Suicidal ideation among female adolescents.

Microalgae are a source of carotenoids, phycocyanin, phenol, amino acids, polyunsaturated fatty acids, sulfated polysaccharides, pigments, and other bioactive molecules with antimicrobial, antioxidant, antiviral, antitumor, anti-inflammatory, and fat-burning properties. The increasing incidence of infectious processes, including tuberculosis, caused by antimicrobial resistant strains of microorganisms necessitates the search for alternative sources of compounds with antimicrobial activity, including microalgae. In this study, the antimicrobial properties of marine and freshwater microalgae extracts were evaluated against Gram-positive (Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pyogenes) and Gram-negative (Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa), Mycobacterium tuberculosis strain H37Rv and Mycobacterium smegmatis. Water, dimethyl sulfoxide, and ethanol were used as extractants. The obtained microalgae extract exhibited cytotoxicity against splenocytes and, to a lesser extent, against peritoneal macrophages of CBA mice. The bacteriostatic effect of the microalgae extracts against bacteria and mycobacteria was demonstrated by MTT test. In addition, activation of bacterial and mycobacterial growth was observed in a number of cases with high levels of microalgae extracts in the medium. In an expression model of tuberculosis in mice, a decrease in mycobacterial load in the lungs and spleen was observed. Thus, microalgae have moderate to weak antimicrobial activity.

Development of targeted therapies for triple-negative breast cancer (TNBC) is an unmet medical need. Cisplatin has demonstrated its promising potential for the treatment of TNBC in clinical trials; however, cisplatin treatment is associated with hypoxia that in turn promotes cancer stem cell (CSC) enrichment and drug resistance. Therapeutic approaches to attenuate this may lead to increased cisplatin efficacy in the clinic for the treatment of TNBC. In this report, we analyzed clinical dataset of TNBC and found that TNBC patients possessed higher levels of EGFR and hypoxia gene expression. A similar expression pattern was also observed in cisplatin-resistant ovarian cancer cells. We thus developed a new therapeutic approach to inhibit EGFR and hypoxia by combination of metformin and gefitinib that sensitized TNBC cells to cisplatin and led to the inhibition of both CD44+/CD24- and ALDH+ CSCs. We demonstrated a similar inhibition efficacy on organotypic cultures of TNBC patient samples ex vivo. Since these drugs have already been used frequently in the clinic, this study illustrates a novel, clinically translatable therapeutic approach to treat patients with TNBC.

The formulation used by the most of studies on an elastic torus are either Reissner mixed formulation or Novozhilov's complex-form one, however, for vibration and some displacement boundary related problem of the torus, application of those formulations has encountered great difficulty. It is highly demanded to have a displacement-type formulation for the torus. In this paper, I will simulate some typical problems and free vibration of the torus. The numerical results are verified by both finite element analysis and H. Reissner's formulation. My investigations show that both deformation and stress response of an elastic torus are sensitive to the radius ratio, and suggest that the analysis of a torus should be done by using the bending theory of a shell, and also reveal that the inner torus is stronger than outer torus due to the property of their Gaussian curvature. Regarding the free vibration of the torus, our analysis indicates that both initial in u and w direction must be included otherwise will cause big errors in eigenfrequency.

By introducing a variable transformation $\xi=\frac{1}{2}(\sin \theta+1)$, a complex-form ordinary differential equation (ODE) for the small symmetrical deformation of an elastic torus is successfully transformed into the well-known Heun's ODE, whose exact solution is obtained in terms of Heun's functions. To overcome the computational difficulties of the complex-form ODE in dealing with boundary conditions, a real-form ODE system is proposed. A general code of numerical solution of the real-form ODE is written by using Maple. Some numerical studies are carried out and verified by both finite element analysis and H. Reissner's formulation. Our investigations show that both deformation and stress response of an elastic torus are sensitive to the radius ratio, and suggest that the analysis of a torus should be done by using the bending theory of a shell.

The Gol'denveizer problem of a torus can be described as follows: a toroidal shell is loaded under axial forces and the outer and inner equators are loaded with opposite balanced forces. Gol'denveizer pointed out that the membrane theory of shells is unable to predict deformation in this problem, as it yields diverging stress near the crowns. Although the problem has been studied by Audoly and Pomeau (2002) with the membrane theory of shells, the problem is still far from resolved within the framework of bending theory of shells. In this paper, the bending theory of shells is applied to formulate the Gol'denveizer problem of a torus. To overcome the computational difficulties of the governing complex-form ordinary differential equation (ODE), the complex-form ODE is converted into a real-form ODE system. Several numerical studies are carried out and verified by finite-element analysis. Investigations reveal that the deformation and stress of an elastic torus are sensitive to the radius ratio, and the Gol'denveizer problem of a torus can only be fully understood based on the bending theory of shells.

A gravitational lens is mass-curved spacetime. Light that propagates freely, locally always on the fastest way, follows curved paths in it. The same applies to all effects propagating with the speed of light, also to gravity itself. They all have to follow the curvature of spacetime. A gravitational lens not only enhances the light from background objects but concurrently also their gravitational effect ! The "Gravitationally Lensed Gravity" (GLG) is a still scarcely noticed peculiar feature of general relativity. In [1] I presented a thought experiment to make the existence of this effect plausible. Here these considerations are described in terms of future and past light cones or null cones commonly used in relativity theory to illustrate the causal structure of spacetime. In the framework of general relativity, the GLG effect can be understood as a consequence of the folding of the past null cone by a gravitational lens. Starting from the basic ideas of the theory, the terms are introduced and applied. The extensive description on textbook level should be understandable also for beginners. In order not to obstruct the view on the essential physical relations, I avoid a mathematical formalism and use instead diagrams and figures, based on realistic numerical calculations, to reinforce my logical argumentation. Experts will recognize many long-known facts, but may still be surprised by the resulting conclusions. First, I present some particular aspects of the historical evolution of the concept of gravitational lensing and give a brief overview of the work of other authors on the subject GLG. I then explain the limitations of the applicability of the "Newtonian Limit" and move on to the key role of the speed of gravity in understanding GLG. Finally, I use a simple example to illustrate the possible significance of the GLG effect. With this work I intend to elicit greater interest in "Gravitationally Lensed Gravity" and to initiate a broader discussion about it.

To explore the impact of parenting styles on the perception of campus non-physical bullying, 492 students in upper elementary school grades were surveyed by using the Delaware Bullying Victimization Scale, the Negative Coping Style Scale, the Negative Affect Scale, and the Egna Minnen Beträffende Uppfostran Questionnaire. The questionnaire survey was conducted in the fifth and sixth grades of eight primary schools in Zhejiang province. The results showed that cyberbullying was not significantly related to an anxious parenting style, but negative affect experiences, negative coping styles, negative family parenting styles, and the perception of campus non-physical bullying were all positively correlated with each other (p < 0.05). The refusal parenting style was shown to be an important factor that affected students’ perception of campus non-physical bullying; it was observed to directly affect students’ perception of campus non-physical bullying and indirectly affect students’ perception of campus non-physical bullying by influencing negative affect experiences and negative coping styles. In conclusion, negative affect experiences and negative coping styles had a chain-like mediating effect between the refusal parenting style and students’ perception of campus verbal bullying. Moreover, negative affect experiences had a partial mediating effect between the refusal parenting style and students’ perceptions of campus cyberbullying, relationship bullying, and non-physical bullying total scores. Implications and suggestions based on these results are also discussed.

COVID-19 may not be a ‘youth disease’ but nevertheless impacts the life of young people dramatically, loneliness and negative mood being an unexpected additional pandemic. Many young people rely on social media for their feeling of connectedness with others. However, social media are suggested to have many negative effects on people’s anxiety. Instead of self-disclosing to others, design may develop alternatives to employ social robots for self-disclosure. In a follow-up on Duan et al. (2021), we report on a lab experiment of self-disclosing negative emotions to a social-media group as compared to writing a conventional diary journal or to talk to an AI-driven social robot after negative mood induction (i.e. viewing shocking earthquake footage). Participants benefitted the most from talking to a robot rather than from writing a journal page or sharing their feelings on social media. Self-disclosure on social media or writing a journal page did not differ significantly. In the design of interventions for mental well-being, human helpers thus far took center stage. Based on our results, we propose design alternatives for an empathic smart-home, featuring social robots and chatbots for alleviating stress and anxiety: a social-media interference chatbot, smart watch plus speaker, and a mirror for self-reflection.

Negative work behavior (NWB) threatens employee well-being. There are numerous constructs that reflect NWBs, such as bullying, aggression, and discrimination and they are often examined in isolation of each other, limiting scientific integration of these studies. We aim to contribute to this research field by developing a diagnostic tool with content validity on the full spectrum of NWBs. First, we provide a full description of how we tapped and organized content from 44 existing NWB measurement instruments and 48 studies. Second, we discussed our results with experts (N = 3) in this research field to check for missing studies and to discuss our integration results. This two-stage process yielded a questionnaire measuring physical, material, psychological, sociocultural, and digital NWB. Furthermore, the questions include a range of potential actors of NWB, namely internal (employees, managers) and external actors (clients, customers, public, family members) at work and their roles (i.e., target, perpetrator, perpetrator's assistant, target's defender, outsider, and witness of NWBs). Finally, the questionnaire measures what type of harm is experienced (i.e., bodily, material, mental, and social harm).

It is quite easy to stochastically distort an original count variable to obtain a new count variable with relatively more variability than in the original variable. Many popular overdispersion models (variance greater than mean) can indeed be obtained by mixtures, compounding or randomlystopped sums. There is no analogous stochastic mechanism for the construction of underdispersed count variables (variance less than mean), starting from an original count distribution of interest. This work proposes a generic method to stochastically distort an original count variable to obtain a new count variable with relatively less variability than in the original variable. The proposed mechanism, termed condensation, attracts probability masses from the quantiles in the tails of the original distribution and redirect them toward quantiles around the expected value. If the original distribution can be simulated, then the simulation of variates from a condensed distribution is straightforward. Moreover, condensed distributions have a simple mean-parametrization, a characteristic useful in a count regression context. An application to the negative binomial distribution resulted in a distribution allowing under, equi and overdispersion. In addition to graphical insights, fields of applications of special cases of condensed Poisson and condensed negative binomial distributions were pointed out as an indication of the potential of condensation for a flexible analysis of count data

To have a better protection, strong toughness and good flexibility, all lives and plants must have skins, similarly, all books should have covers. In this paper, considering interlayer friction as a perturbation, we formulate a hardcover-book-like laminated plates with internal friction. For a quasi-static problem, detail analysis on the bending response and energy dissipation are carried out for a three-point-supported plates. Our numerical investigations show that the hardcover is more essential than the core layers in terms of bending response, and the energy dissipation within per loading-unloading cycle can be made to vary by a considerable amount. The central goal of studying is not only to predict the bending deformation of the book-like-plates, but also as a representative case to help finding some clue on the universal behaviours of multilayered architectures with internal friction.

To realize structural vibration control,a two parameters H2 optimization design was proposed to optimize the tuning ratio and damping ratio for electromagnetic tuned mass damper (EMTMD). The control effect of this two parameters optimization design is better than that of classical tuned mass damper (TMD).For this two parameters optimization,the most important thing is that the inductance of the coil can be set very small and the external load resistance can be positive ,which can avoid the use of complex negative impedance circuit. If Ref.[6] were designed according to the H2 optimization of two parameters, the EMTMD can be used for multi-modal vibration control of structures without connecting negative inductance and negative resistance spontaneously.

In the present trend of constructing taller and longer structures, the application of lightweight aggregate concrete is becoming an increasing important advanced solution in the modern construction industry. In engineering practice, the analysis of lightweight concrete elements is performed using the same algorithms used for normal concrete elements. As an alternative to traditional engineering methods, nonlinear numerical algorithms based on constitutive material models may be used. The paper presents a comparative analysis of curvature calculations for flexural lightweight concrete elements, incorporating analytical code methods EN 1992-1 and ACI 318-14, as well as a numerical analysis using the constitutive model of cracked tensile lightweight concrete recently proposed by the authors. To evaluate the adequacy of the theoretical predictions, experimental data of 51 lightweight concrete beams tested during five different programmes were collected. A comparison of theoretical and experimental results showed that the most accurate predictions are obtained using numerical analysis and the constitutive model proposed by the authors. In the future, the latter algorithm can be used as a reliable tool for improving the design standard methods or numerical modelling of lightweight concrete elements subjected to short-term loading.

Because of an often complicated and difficult-to-access care system, help-seeking for people with suspected dementia can be stressful. Difficulty in help-seeking may contribute to carer burden, in addition to other known stressors in dementia care. This study examined the relationship between perceived help-seeking difficulty and carer burden, and the barriers contributing to perceived difficulty. We interviewed 110 carers accessing a community-based dementia assessment service for suspected dementia of a family member for their perceived difficulty, delays, and barriers in help-seeking, and carers burden in terms of role strain, self-criticism, and negative emotions. Linear regression models showed that perceived help-seeking difficulty is associated with carer self-criticism, while carer role strain and negative emotions are associated with symptom severity of the person with dementia but not help-seeking difficulty. Inadequate knowledge about symptoms, service accessibility, and affordability together explained more than half of the variance in perceived help-seeking difficulty (Nagelkerke R2 = .56). Public awareness about symptoms, support in navigating service, and financial support may reduce perceived difficulty in help-seeking, which in turn may reduce carer self-criticism during the early course of illness.

There are unsolved problems related to inflation, gravity, dark matter, dark energy, missing antimatter, and the birth of the universe. Some of them can be better answered by assuming the existence of aether and hypoatoms. Both were created during the inflation in the very early universe. While aether forms vacuum, hypoatoms, composed of both matter and antimatter and believed to be neutrinos, form all observable matter. In vacuum, aether exists between the particle-antiparticle dark matter form and the dark energy form in a dynamic equilibrium: A + A-bar = gamma + gamma. The same reaction stabilizes hypoatoms and generates a 3-dimensional sink flow of aether that causes gravity. Based on the hypoatom structure, the singularity does not exist inside a black hole; the core of the black hole is a hypoatom star or neutrino star. By gaining enough mass, ca. 3 X 10²² M_sun, to exceed neutrino degeneracy pressure, the black hole collapses or annihilates into the singularity, thus turning itself into a white hole or a Big Bang. The universe is anisotropic. Its center, or where the Big Bang happened, is at 0.66^+0.03_-0.01 times the radius of the observable universe at Galactic coordinates (l, b) = (286⁺¹⁰_-10, -43⁺⁷_-6). If we look from the Local Group to the center of the universe, the universe is rotating clockwise.

Today, air quality is one of the global concerns that governments are facing. One of the main air pollutants is the particulate matter (PM) that affects human health. This article presents the modeling of a purification system by means of negative air ions (NAIs) for air pollutant removal, using computational intelligence methods. The system uses a high voltage booster output to ionize air molecules from stainless steel electrodes; its particle-capturing efficiency reaches up to 97%. With two devices (5 x 2 x 2.5 cm), 2 trillion negative ions are produced per second, and the particulate matter (PM 2.5) can be reduced from 999 to 0 mg / m3 in a period of approximately 5 to 7 minutes (in a 40 x 40 x 40 cm acrylic chamber). This negative ion generator is a viable and sustainable alternative to reduce polluting emissions, with beneficial effects on human health.

Background: We previously found that QNBC tumors are more frequent in African Americans compared to TNBC tumors. To characterize this subtype further, we sought to determine the miRNA-mRNA profile in QNBC patients based on race. Methods: Both miRNA and mRNA expression data were analyzed from TCGA and validated using datasets from the METABRIC, TCGA proteomic, and survival analysis by KMPLOT. Results: miRNA-mRNAs which include FOXA1 and MYC (mir-17/20a targets); GATA3 and CCNG2 (mir-135b targets); CDKN2A, CDK6, and B7-H3 (mir-29c targets); and RUNX3, KLF5, IL1-β, and CTNNB1 (mir-375 targets) were correlated with basal-like and immune subtypes in QNBC patients and associated with a worse survival. Conclusion: Thus, QNBC tumors have an altered gene signature implicated in racial disparity and poor survival.

The aim was to study alterations of bacterial communities in patients undergoing hip or knee arthroplasty to assess the impact of chlorhexidine gluconate soap decolonisation and systemic antibiotic prophylaxis. A Swedish multicentre, prospective collection of samples obtained from elective arthroplasty patients (n=83) by swabbing anterior nares, skin sites in the groin and the site of planned surgery, before and after arthroplasty surgery, was analysed by 16S rRNA (V3-V4) gene sequencing and a complementary targeted tuf gene sequencing approach to comprehensively characterise alterations in staphylococcal communities. Significant reductions in alpha diversity was detected for both bacterial (p=0.04) and staphylococcal (p=0.03) groin communities after arthroplasty surgery with significant reductions in relative Corynebacterium (p=0.001) abundance and S. hominis (p=0.01) relative staphylococcal abundance. In nares, significant reductions occurred for S. hominis (p=0.02), S. haemolyticus (p=0.02), and S. pasteuri (p=0.003) relative to other staphylococci. S. aureus colonised 35% of anterior nares before and 26% after arthroplasty surgery. S. epidermidis was the most abundant staphylococcal species at all sampling sites. No bacterial genus or staphylococcal species increased significantly after arthroplasty surgery. Application of a targeted tuf gene sequencing approach provided auxiliary staphylococcal community profiles and allowed species-level characterisation directly from low biomass clinical samples.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44⁺/CD24^-) and epithelial (ALDH^high) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these populations remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and highlights novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation which may lead to the development of novel therapies to improve TNBC patient prognosis.

The formulation used by most of the studies on an elastic torus are either Reissner mixed formulation or Novozhilov's complex-form one, however, for vibration and some displacement boundary related problem of a torus, those formulations face a great challenge. It is highly demanded to have a displacement-type formulation for the torus. In this paper, I will carry on my previous work [ B.H. Sun, Closed-form solution of axisymmetric slender elastic toroidal shells. J. of Engineering Mechanics, 136 (2010) 1281-1288.], and with the help of my own maple code, I am able to simulate some typical problems and free vibration of the torus. The numerical results are verified by both finite element analysis and H. Reissner's formulation. My investigations show that both deformation and stress response of an elastic torus are sensitive to the radius ratio, and suggest that the analysis of a torus should be done by using the bending theory of a shell, and also reveal that the inner torus is stronger than outer torus due to the property of their Gaussian curvature. Regarding the free vibration of a torus, our analysis indicates that both initial in u and w direction must be included otherwise will cause big errors in eigenfrequency. One of the most intestine discovery is that the crowns of a torus are the turning point of the Gaussian curvature at the crown where the mechanics' response of inner and outer torus is almost separated.

The effect of the negative effective mass emerging in the gravitating core-spring-shell system is considered. The effect appears when the entire system is exerted to the external harmonic force and the frequency of external force approaches to the critical frequency from above. The critical frequency depends on the density of the self-gravitating system only. The scaling law predicting the value of for condensed phases is derived. The generalization of the effect for the Coulomb-like forces is reported

Abstract: Discussed is an expansion of SRT to fourth-order of space-time including any velocities and possible negative kinetic energies by real rest mass in analogy of the model amplitude of enforced damped oscillation. This paper serves an introduction to developed SRT including superluminar translating velocities without tachyons or imaginary restmass. Focused is on those parts, which develop the elaborated lorentz-transformations. Discussed are the problems of this theory.

We report the negative effective mass metamaterials based on the electro-mechanical coupling exploiting plasma oscillations of a free electron gas. The negative mass appears as a result of vibration of a metallic particle with a frequency of ω which is close the frequency of the plasma oscillations of the electron gas m_2 relatively to the ionic lattice m_1. The plasma oscillations are represented with the elastic spring k_2=ω_p^2 m_2, where ω_p is the plasma frequency. Thus, the metallic particle vibrated with the external frequency ω is described by the effective mass m_eff=m_1+(m_2 ω_p^2)/(ω_p^2-ω^2 ) , which is negative when the frequency ω approaches ω_p from above. The idea is exemplified with two conducting metals, namely Au and Li.

The negative binomial regression model (NBRM) is a generalized linear model which relaxes the restrictive assumption by the Poisson regression model when the variance is equal to the mean. The estimation of the parameters of the NBRM is obtained using the maximum likelihood (ML) method. Maximum likelihood estimator becomes unstable when the explanatory variables are linearly dependent, a situation known as multicollinearity. Based on this, we developed a new estimator called modified jackknifed Negative Binomial Kibria-Lukman (MJNBKL) estimator for the radiation of multicollinearity in NBRM using four different biasing (shrinkage) parameters. We establish superiority condition for MJNBKL estimator over the ones. The performance MJNBKL estimator was ascertained by comparing it with the existing ones through a Monte Carlo simulation study and two real life application datasets. The results of the simulation and real life application show that MJNBKL estimator outperformed the other estimators compared with by having the smallest MSE across all sample sizes and for different levels of correlation for the four biasing parameters used and the third biasing parameter is the optimal shrinkage parameter with the lowest MSE.

All vaccines exhibit specific and nonspecific effects. Specific effects are shown by the efficacy against the target pathogen, while nonspecific effects can be detected by the change in all-cause mortality. The real-world non-COVID-19 all-cause mortality (NCACM) data for the population of England between January 2021 and May 2023 was assessed. All vaccines administered were based on the original Wuhan antigen. Each gender and age group, along with COVID-19 variant shows its own unique NCACM vaccination benefit/disbenefit time profile. The efficacy of COVID-19 vaccination against COVID-19 disease/death per se is undisputed, however, the nonspecific outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated. This confirms an earlier study on the unanticipated nonspecific effects of influenza vaccination against all-cause winter mortality. Interestingly, a high proportion of NCACM beneficial effects occurred during the first 21 days following COVID-19 vaccination, while the worst example of increased NCACM occurred during the fourth dose of COVID-19 vaccination in 19–40-year-olds for the interval &gt;21 days post vaccination which led to NCACM 3- to 10-times higher than in the unvaccinated. By the time of the Omicron variant, NCACM outcomes in those aged 90+ are mostly adverse. The beneficial nonspecific effects of COVID-19 vaccination increase with age and reach their maximum effect during the second week post vaccination for age groups below 50 years, rising to during the third week for those aged 70+. Finally, we discuss the mechanisms by which COVID-19 vaccination could induce wider nonspecific effects. Most of these mechanisms seem to depend on gene regulation by noncoding RNAs which also interact with mRNAs. We suggest that further international studies are required to discern the nonspecific NCACM effects of the different COVID-19 variants other than the three variants prevalent in the UK, and different types/manufacturer of COVID-19 vaccines which have been employed around the world. We can only speculate regarding the nonspecific effects of the COVID-19 vaccines administered to persons with an asymptomatic infection, and during vaccine waning. Vaccines not only need to be effective against the target pathogen, as primarily determined by antibody production, but need to minimize any unanticipated adverse nonspecific effects against all-cause mortality.

The Sulfur Dioxide (SO2) compound is a primary environmental pollutant worldwide, whereas elemental Sulfur (S) is a global commodity possessing a variety of industrial as well as commercial functions. The chemical relationship between poisonous SO2 and commercially viable elemental S has motivated this investigation using Density Functional Theory calculation of the relative transition state barriers for the 2-step Dehydro-sulfurization oxidation-reduction reaction. Additionally, doubly-charged nanoscale platelet Molybdenum Disulfide (MoS2), Armchair (6,6) Carbon Nanotube, 28-atom Graphene nanoflake (GR-28), and Fullerene C-60 are utilized as catalysts. The optimal heterogeneous and homogeneous catalysis pathways of the 2-step oxidation-reduction from SO2 to elemental S are further inspired by the biomimicry of the honeybee species multi-step bio-catalysis of pollen conversion to organic honey. Potential applications include environmental depollution, the mining of elemental sulfur, and the functionalization of novel technologies such as the recently patented aerial and amphibious Lynchpin TM drones.

Weaving is an ancient and effective structural forming technique characterized by the ability to convert two-dimensional ribbons to three-dimensional structures. However, most 3D structures woven from straight ribbons have topological defects. Baek et al. proposed a method to weave smoother continuous 3D surface structures using naturally curved (in-plane) ribbons, obtained a new surface structure with relatively continuous variation of Gaussian curvature, and analyzed its geometric properties. We believe that this new 3D surface structure with smooth geometric properties must correspond to new mechanical properties. To this end, we investigated a 3D surface structure using naturally curved (in-plane) ribbon weaving, and the results of calculations and experiments show that such structures have better buckling stability than those woven with straight ribbons. It is observed that the number of ribbons influences the buckling behavior of different types of woven structures.

The nonlinear deformation and stress analysis of a circular torus is a difficult undertaking due to its complicated topology and the variation of the Gauss curvature. A nonlinear deformation (only one term in strain is omitted) of Mindlin torus was formulated in terms of the generalized displacement, and a general Maple code was written for numerical simulations. Numerical investigations show that the results obtained by nonlinear Mindlin, linear Mindlin, nonlinear Kirchhoff-Love, and linear Kirchhoff-Love models are close to each other. The study further reveals that the linear Kirchhoff-Love modeling of the circular torus gives good accuracy and provides assurance that the nonlinear deformation and stress analysis (not dynamics) of a Mindlin torus can be replaced by a simpler formulation, such as a linear Kirchhoff-Love theory of the torus, which has not been reported in the literature.

We work within a Winterberg framework where space, i.e., the vacuum, consists of a two component superfluid/super-solid made up of a vast assembly (sea) of positive and negative mass Planck particles, called planckions. These material particles interact indirectly, and have very strong restoring forces keeping them a finite distance apart from each other within their respective species. Because of their mass compensating effect, the vacuum appears massless, charge-less, without pressure, net energy density or entropy. In addition, we consider two variable models, where, , is Newton’s constant, and, , increases with an increase in cosmological time. We argue that there are at least two competing models for the quantum vacuum within such a framework. The first follows a strict extension of Winterberg’s model. This leads to nonsensible results, if increases, going back in cosmological time, as the length scale inherent in such a model will not scale properly. The second model introduces a different length scale, which does scale properly, but keeps the mass of the Planck particle as, the Planck mass. Moreover we establish a connection between ordinary matter, dark matter, and dark energy, where all three mass densities within the Friedman equation must be interpreted as residual vacuum energies, which only surface, once aggregate matter has formed, at relatively low temperatures. The symmetry of the vacuum will be shown to be broken, because of the different scaling laws, beginning with the formation of elementary particles. Much like waves on an ocean where positive and negative planckion mass densities effectively cancel each other out and form a zero vacuum energy density/ zero vacuum pressure surface, these positive mass densities are very small perturbations (anomalies) about the mean. This greatly alleviates, i.e., minimizes the cosmological constant problem, a long standing problem associated with the vacuum.

Holding an object by clamping force is a fundamental phenomena, layered or laminated architectures with internal sliding features are essential mechanism in natural and man-made structural system. In this paper, we combine the layered architecture and clamping mechanism to form a multilayered clamp and study the clamping force with internal friction. Our investigations show that the clamping force and energy dissipation are very mich depend on the number of layers, its geometry and elasticity, as well as internal friction. The central goal of studying the covered book is not only to predict the clamping force of the clamp, but also as a representative case to help finding some clue on the universal behaviours of multilayered architectures with internal friction.

It is urgent to find new antibiotic classes to replenish the empty development pipeline of antibiotics. Recently, pyrrolobenzodiazepines (PBDs) with a C8-linked aliphatic-heterocycle have been identified as a new broad spectrum antibiotic class with activity against Gram-negative bacteria. The active imine moiety of the reported lead pyrrolobenzodiazepine compounds was replaced with amide to obtain the non-DNA binding and non-cytotoxic dilactam analogues to further understand the structure activity relationship and improve the safety potential of this class. The synthesized compounds were tested against panels of multidrug resistant Gram-positive and Gram-negative bacteria, including WHO priority pathogens. Minimum inhibitory concentrations for the dilactam analogues ranged from 4 – 32 mg/L for MDR Gram-positive bacteria, compared to 0.03 to 2 mg/L for the corresponding imine analogues while they were found to be inactive against MDR Gram-negative bacteria, with an MIC &gt;32 mg/L, compared to an MIC of 0.5 to 32 mg/L. A molecular modelling study suggests the lack of imine functionality also affects the interaction of PBDs with DNA gyrase. This study suggests the presence of N10-C11 imine moiety is crucial for broad spectrum activity of pyrrolobenzodiazepines.

This paper presents an investigation into the influence of drag-reducing polymer (DRP) on the flow of water inside and around U-bends. The DRPs tested were partially hydrolysed polyacrylamide (HPAM) and two different molecular weight polyethylene oxides (PEO). The Reynolds number and in-situ concentration ranges of water and DRP were and respectively. The test section was made up of clear polyvinyl chloride (CPVC) pipes that contained two U-bends with radii of curvature (R) of 100 and 200 mm as well as straight sections of 19-mm ID. Higher pressure gradient was recorded in the under-developed flow section after the bend. Drag reduction (DR) increased with in-situ concentration of the DRP and the flowrate up to some threshold values. The concentration and flowrate thresholds were about 20 ppm and 1.07 m/s respectively. DR differed among the different sections considered with the highest values recorded for developed flows upstream of the bend and the least values recorded in the bend. DR at station 1 (immediately after the bend) was generally lower than that at station 2 (further downstream). P-K Plots showed that, the DR envelop for developed flow in straight pipes did not apply to the bend and the under-developed flow section. DR increased with polymer molecular weight and ionic strength in straight sections. However, molecular weight (and polymer shearing) had limited effect on DR in the bends. DR characteristics at the bend suggested that there was a different or additional mechanism. The effect of bend curvature ratio on DR was predominant after the U-bend. The larger the ratio of pipe diameter to bend diameter, the lower the DR in the redeveloping sections after the bend. For R = 100 mm, the highest DR recorded for fully developed flows before bend, in the bend, at stations 1 and 2 were 57, 31, 36 and 33% respectively while that for R = 200 mm were 64, 28, 42 and 49% respectively.

ABSTRACT. The immunotherapies, as a modern therapeutic approach, get an attention because of theirs’ promise to treat a large number of different medical disorders. Immunomodulation effects of low titres (10 HA/ml) of NDV (Newcastle Disease Virus) ZG1999HDS or La Sota were tested on TLT (Human macrophage cell line) bound to PBMC (Peripheral Blood Mononuclear Cells). During the immunomodulation, the amount of NO, H2O2, lysozym and induced antibacterial activity against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) and against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) were analysed. In addition, the cytokine secretion, IL-1α, IL-2, IL-4, GM-CSF, TNF-α, IFN-α and IFN-α were evaluated. Firstly, the TLT cells are activated through the NDV ZG1999HDS or La Sota binding, followed by the NO “burst” and H2O2 and lysozyme level increase. Secondly, after the binding to the TLT cells and interaction with the PBMCs, the decrease of GM-CSF, and an increase of TNF – α and IFN – γ were found. Simultaneously, the decrease of pro – inflammatory cytokine IFN-α and the differentially increase of IL-1α, IL-2 and IL-4 were recorded. During the induction of the antibacterial response, against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) the effect was one third higher with NDV ZG1999HDS compared to La Sota. Antibacterial response against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) was not so clear. In general, NDV ZG1999HDS or La Sota activated TLT cells, further bound to PBMC; the ZG1999HDS is stronger immunomodulator than La Sota.

This joint experimental-theoretical work focuses on molecular and photophysical properties of the spiropyran-containing amphiphilic molecule in organic and aqueous solutions. Being dissolved in tested organic solvents, the system demonstrates positive photochromism, i.e. upon UV stimulus the colorless spiropyran form is transformed into colorful merocyanine isomer. However, aqueous solution of the amphiphile possesses a negative photochromism: the orange-red merocyanine form turns to be thermodynamically more stable in water, and both UV and vis stimuli lead to the partial or complete photobleaching of the solution. The explanation of this phenomenon is given on the basis of density functional theory calculations and classical modeling including thermodynamic integration. The simulations reveal that stabilization of merocyanine in water proceeds with the energy of ca. 70 kJ mol−1, and that the Helmholtz free energy of hydration of merocyanine form is 100 kJ mol−1 lower as compared to the behavior of SP isomer in water. The explanation of such a difference lies in the molecular properties of the merocyanine: after ring-opening reaction this molecule transforms into a zwitterionic form, as evidenced by the electrostatic potential plotted around the opened form. The presence of three charged groups on the periphery of a flat conjugated backbone stimulates the self-assembly of merocyanine molecules in water, ending up with the formation of elongated associates with stack-like building blocks, as shown in molecular dynamics simulations of the aqueous solution with the concentration above critical micelle concentration. Our quantitative evaluation of the hydrophilicity switching in spiropyran/merocyanine containing surfactants may prompt the search for new systems, including colloidal and polymeric ones, aiming at remote tuning of their morphology, which could give new promising shapes and patterns for the needs of modern nanotechnology.

Traditional dry fermented meat products are obtained artisanally in many countries, where they represent a gastronomic heritage well distinguished from industrial counterparts. This food category is most often obtained from red meat, a food commodity that is under attack because of evidences of increased risk of cancer and degenerative diseases with high consumption. However, traditional fermented meat products are intended for moderate consumption and gastronomic experience and, as such, their production must be continued also to safeguard culture and economy of the geographical areas of origin. In this review, the main risks attributed to these products are considered and how these risks are minimized by following precise production norms, respectful of the ancient manufacturing processes is described. Moreover, results obtained in studies reporting use of autochthonous microbial cultures of lactic acid bacteria (LAB), coagulase negative staphylococci (CNS), Debaryomyces hansenii and Penicillium nalgiovense to improve safety and quality of traditional fermented meats are summarized. The role of these products as a source of microorganisms that can be beneficial to the host are also considered. From the results of the studies reviewed here it appears that the development of autochthonous cultures for these foods ensure safety and stabilize sensory characteristics with possibility to be extended to the large variety of traditional productions.

Group IV phospholipase A₂α (cPLA₂α) regulates the production of prostaglandins and leukotrienes via the formation of arachidonic acid from membrane phospholipids. The targeting and membrane binding of cPLA₂α to the Golgi involves the N-terminal C2 domain whereas the catalytic domain produces arachidonic acid. Although most studies of cPLA₂α concern its catalytic activity, it is also linked to homeostatic processes involving the generation of vesicles that traffic material from the Golgi to the plasma membrane. Here we investigate how membrane curvature influences the homeostatic role of cPLA₂α in vesicular trafficking. The cPLA₂α C2 domain is known to induce changes in positive membrane curvature, a process which is dependent on cPLA₂α membrane penetration. We show that cPLA₂α undergoes C2 domain-dependent oligomerization on membranes in vitro and in A549 cells. We found that the association of the cPLA₂α C2 domain with membranes is limited to membranes with positive curvature, and enhanced C2 domain oligomerization was observed on vesicles ~50 nm in diameter. We demonstrated that the cPLA₂α C2 domain generates cholesterol enriched Golgi-derived vesicles independently of cPLA₂α catalytic activity. Our results therefore provide novel insight into the molecular forces that mediate C2 domain-dependent membrane localization in vitro and in cells.

A new picture of the Josephson effect is devised. The radio-frequency (RF) signal, observed in a Josephson junction, is shown to stem from bound electrons, tunneling periodically through the insulating film. This holds also for the microwave mediated tunneling. The Josephson effect is found to be conditioned by the same prerequisite worked out previously for persistent currents, thermal equilibrium and occurence of superconductivity. The observed negative resistance behaviour is shown to originate from the interplay between the normal and superconducting currents.

The decapod fauna in intertidal rocky shore in continental Chile has high species diversity mainly in northern and central Chile due high productivity of these coast due influence of cold Humboldt stream. One of the abundant species in these ecosystems is decapod Cyclograpsus cinereus Dana, 1851. The aim of the present study was determine the spatial distribution pattern of C. cinereus along rocky shore in Antofagasta bay, north of Chile between spring and summer 2018-2020. Data was obtained counting individuals from random quadrants in intertidal zones, to the obtained data was applied the variance mean ratio for determine if the specimens have random, aggregate or uniform distribution, that are associated to Poisson, negative binomial or positive binomial distributions respectively. Data obtained revealed the existence of associated distribution with respective negative binomial distribution pattern in 16 observations, and uniform distribution for 3 observations. The sites corresponds to rocky shores in urban zones, and in a protected zone, and the density does not have significant differences for both kind of sites. The observed data about aggregated pattern agree with observations for decapods for rocky shore in central and southern Chile, specifically in interpretative probabilistic models.

Triple negative breast cancer (TNBC) has a negative expression of estrogen receptors (ER), progesterone receptors (PR), or human epidermal growth factor receptors (HER2). The survival rate for TNBC is generally worse than other breast cancer subtypes. TNBC treatment has made significant advances, but certain limitations remain. Treatment for TNBC can be challenging since the disease has various subtypes. Individualized therapy is recommended rather than generalized therapy, given the genetic variations among these TNBC subtypes. A precise and effective treatment for TNBC requires identifying prognostic markers. Depending on the type and stage of TNBC, patients are treated with various therapeutic interventions. A variety of treatment options are available, such as chemotherapy, immunotherapy, radiotherapy, and surgery. Chemotherapy is the most common of these options. TNBC is generally treated with systemic chemotherapy using drugs such as anthracyclines and taxanes in the neoadjuvant or adjuvant settings. Developing resistance to anticancer drugs and off target toxicity are the primary hindrances to chemotherapeutic solutions for cancer. It is imperative that researchers, clinicians, and pharmaceutical companies work together to develop effective treatment options for TNBC. Several studies have suggested nanotechnology as a potential solution to the problem of suboptimal TNBC treatment.

Breast cancer stands as the prevailing malignancy across all six Gulf Cooperation Council (GCC) nations. In this literature review, we highlighted the incidence and trend of BC in the GCC. Most of the studies reported a consistent increase in BC incidence over the past decades, which was particularly attributed to the adoption of a westernized lifestyle in the region and the implications of emerging risk factors and other environmental and societal factors, the increase in screening uptake, as well as the improvement in data collection and reporting in the GCC. The data about BC risk factors in GCC was limited. In this geographic region, breast cancer frequently manifests with distinctive characteristics, including an early onset, typically occurring before the age of 50, an advanced stage at presentation, and a higher pathological grade. Additionally, it often exhibits more aggressive features such as human epidermal growth factor receptor 2 (HER2) positivity or the presence of triple-negative (TN) attributes, particularly among younger patients. Despite the growing body of literature on breast cancer in the GCC, data pertaining to survival rates are, regrettably, meager. Reports on breast cancer survival rates emanating from the GCC region are largely confined to Saudi Arabia and the United Arab Emirates (UAE). In the UAE, predictive modeling reveals 2-year and 5-year survival rates of 97% and 89%, respectively, for the same period under scrutiny. These rates, when compared to Western counterparts such as Australia (89.5%) and Canada (88.2%), fall within the expected range. Conversely, Saudi Arabia reports a notably lower 5-year survival rate, standing at 72%. This disparity in survival rates underscores the need for further research directed towards elucidating risk factors and barriers that hinder early detection and screening. Additionally, there is a pressing need for expanded data reporting on survival outcomes within the GCC. In sum, a more comprehensive and nuanced understanding of breast cancer dynamics in this region is imperative to inform effective strategies for prevention, early detection, and improved patient outcomes.

Triple-negative breast cancer (TNBC), characterized by deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotype such as tumor heterogeneity and therapy resistance remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approach, we found 55-up and 9-down regulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration, was positively correlated with status of tumor hypoxia and clustered with stemness-associated genes, as recognized by Parametric Gene Set Enrichment Analysis (PGSEA). Also, enhanced infiltration of immunosuppressive cells was positively correlated with the expression of these 5 genes. Moreover, our experiments showed that depletion of the transcriptional co-factor nucleus accumbens-associated protein 1 (NAC1), which is highly expressed in TNBC, reduced the expressions of these genes. Thus, the five genes signature identified by this study warrants further exploration as a potential new biomarker of TNBC heterogeneity/stemness characterized by high hypoxia, stemness enrichment, and immune-suppressive tumor microenvironment.

Background: Relatively little is known and inconclusive about social inequality in human papillomavirus (HPV) vaccination among teenagers in the United States. This study aims to investigate whether there is a social disparity in HPV vaccination among teenagers and if so, whether it can differ by the source of teen vaccination information (parental reports and provider records). 
Methods: We used the data from the 2019 National Immunization Survey-Teen (NIS-Teen; 42,668 teenagers, aged 13-17) including parental reported vaccination status. Among them, 18,877 teenagers had adequate provider reported vaccination records. Two socioeconomic status (SES) measures were used: mother’s education and annual family income. Multivariate logistic analyses were conducted. 
Results: False negatives of parental reports against provider records were more than two times higher (p < 0.001) in low SES teens than in high SES teens. In both SES measures, the proportion of HPV unvaccinated teenagers were lowest in the highest SES level in analyses with parental reports. However, it was the opposite in analyses with provider records. Interestingly, regardless of vaccination information source, the HPV unvaccinated rate was highest in the middle SES teens (>12 years, non-college graduates; and above poverty level, but not > $75K). 
Conclusion: A significant social inequality in HPV vaccination among teenagers exists in the United States. The pattern of social inequality in HPV vaccination can be distorted when only parent reported vaccination information is used.

CRCMSS/pMMR contain a significantly increased fraction of TREM2+ macrophages (TAMs) and CD66+ neutrophils (TANs) together with decrease of CD4-CD8-CD3+ double negative T lymphocytes (DNTs); no differences were revealed by the analysis of myeloid and plasmacytoid dendritic cell populations. A fraction of tumor-infiltrating T-cells display an exhausted phenotype, co-expressing PD-1 and TIM-3. Remarkably, expression of PD-L1 on fresh tumor cells and TAMs was undetectable even after in vitro stimulation with interferon-γ. These findings confirm the immune suppressive microenvironment of CRCMSS/pMMR characterized by dense infiltration of TAMs, occurrence of TANs, lack of DNTs, T-cell exhaustion and interferon-γ unresponsiveness by host and tumor cells. Appropriate bypass strategies should consider these combinations of immune escape mechanisms in CRCMSS/pMMR.

Hepatocellular carcinoma (HCC) early diagnosis is challenging. Moreover, for patients with al-pha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profile may serve as potential HCC molecular markers. We aimed to assess plasma homo sabines (hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, hsa-miR-199a-5p expression levels, as panel of biomarkers for HCC in chronic hepatitis C virus (CHCV) patients with liver cirrhosis (LC), es-pecially AFP-negative HCC cases, a step toward non-protein coding (nc) RNA precision medicine. Subjects and Methods: 79 patients enrolled with CHCV infection with LC, subclassified into LC group without HCC (n=40) and LC with HCC (n=39) in comparison with 15 apparently healthy control subjects. Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p. Results: Plasma hsa-miR-21-5p and hsa-miR-155-5p demonstrated significant upregulation, while hsa-miR-199a-5p demonstrated significant downregulation in the HCC group (n=39) when compared to LC group (n=40). Hsa-miR-21-5p expression was positively correlated with serum AFP, insulin, and insulin re-sistance (r=0.5, p<0.001, r=0.334, p=0.01, and r=0.303, p=0.02, respectively). According to the ROC curves, for differentiating HCC from LC, combining AFP with each of hsa-miR-21-5p, hsa-miR-155-5p, and miR199a-5p improved the diagnostic sensitivity to 87%, 82%, and 84%, re-spectively, vs 69% for AFP alone, with an acceptable specificity of 77.5%, 77.5%, and 80%, respec-tively, and AUC= 0.89, 0.85, and 0.90, respectively vs. 0.85 for AFP alone. Hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios discriminated HCC from LC at AUC=0.76 and 0.71, respectively, with sensitivities=94% and 92%, and specifici-ties=48% and 53%, respectively. Upregulation of plasma hsa-miR-21-5p was considered as an independent risk factor for HCC development [OR=1.198(1.063–1.329), p=0.002]. Conclusion: Combining each of hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-199a-5p with AFP made possi-ble to identify HCC development in LC patients’ cohort with higher sensitivity than using AFP alone. Hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios are poten-tial HCC molecular markers for AFP-negative HCC patients. Hsa-miR-21-5p was linked to insu-lin metabolism in HCC patients’ group as well as being an upregulated independent risk factor for the emergence of HCC from LC in CHCV patients.

BOLD-100, a ruthenium-based complex, sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (also known as IT-139, NKP1339 or KP1339), is a novel small molecule drug that demonstrated a manageable safety profile at the maximum tolerated dose and modest antitumor activity in a phase I clinical trial. BOLD-100 has been reported to inhibit the upregulation of the endoplasmic reticulum stress sensing protein GRP78. However, response to BOLD-100 varies in different cancer models and the precise mechanism of action in high-response versus low-response cancer cells remains unclear. In vitro studies have indicated that BOLD-100 induces cytostatic rather than cytotoxic effects as a monotherapy. To understand BOLD-100 mediated signaling mechanism in breast cancer cells, we used estrogen receptor positive (ER+) MCF7 breast cancer cells to obtain gene-metabolite integrated models. Particularly, BOLD-100 significantly reduced expression of genes involved in the DNA repair pathway. BOLD-100 also induced reactive oxygen species (ROS) and phosphorylation of histone H2AX, gH2AX (Ser139), suggesting disruption of proper DNA surveillance. In estrogen receptor negative (ER-) breast cancer cells, combination of BOLD-100 with a PARP inhibitor, olaparib, induced significant inhibition of cell growth and xenografts and increased gH2AX. Thus, BOLD-100 is a novel DNA repair pathway targeting agent and can be used with other chemotherapies in ER- breast cancer.

The modulation instability of surface capillary-gravity water waves is analysed in a shear flow model with a tangential discontinuity of velocity. It is assumed that air blows along the surface of the water with a uniform profile in the vertical direction. Such a model, despite its simplicity, plays an important role in hydrodynamics as the reference model for investigating basic physical phenomena of wave-current interactions and acquiring insights into a series of complex phenomena. In certain cases where the wavelength of interfacial perturbations is much bigger than the width of the shear fow profile, the model with the tangential discontinuity in the velocity is adequate for describing physical phenomena at least within limited spatial and temporal frameworks. A detailed analysis of the air-flow conditions under which modulation instability sets in is presented. It is also shown that the interfacial waves are subject to dissipative or radiative instability when negativeenergy waves appear at the interface.

This interdisciplinary work presents a novel patent pending method of inertial electrostatic confinement (IEC) fusion called the Nuclear Electromagnetic Shaping Accelerator Reactor (NESAR) that addresses all of the major failure problems with currently known methods of IEC fusion. A brief background of previous IEC methods that generate a negative potential well to accelerate ions for fusion will be reviewed and compared to the NESAR method of magnetic confinement. In addition, a direct comparison will be presented between the NESAR and the tokamak method of fusion. The NESAR method of fusion obtains the plasma oscillation and compression capabilities of a tokamak without producing the catastrophic magnetic reconnection disruptions that currently plague tokamaks. Since the NESAR can oscillate charged particles comparable to the tokamak, this work will briefly review the history of the tokamak, how sawtooth magnetic reconnection occurs, and how the NESAR precludes the occurrence of magnetic reconnection. This work will also review the beginnings of a novel theory that has obtained interest from the Defense Advanced Research Projects Agency (DARPA) which is currently interested in possibly supporting further research into the NESAR to explore this new theoretical concept. This novel theory is a unified field theory based upon the trajectory of charged particle movements within the NESAR. The NESAR is the only concept of magnetic confinement in the world that may have the capability to allow charge particles to collectively interact relatively to a solitary location. Due to this possible capability, there is a probability that the confined particles may experience curved trajectories that could allow them to experience the effects of curvature deviation. If curvature deviation occurs with these magnetically confined charged particles; then the deviated acceleration would allow for the electromagnet field to be propelled to a higher dimension that could influence spacetime. Finally, this work will review another theory that explains how pole reversals are observed by the National Aeronautics and Space Administration’s (NASA) coiled magnetic field detectors. This theory requires little to no postulations to be framed and it is purely based upon the trajectory of charged particles within the NESAR, Michael Faraday’s law of induction, and experimental observations of rotating plasmas.

In the modern construction industry, lightweight aggregate concrete (LWAC) is often used in the production of load-bearing structural members. LWAC can be up to 40% lighter by volume in comparison to normal strength concrete. On the other hand, the lack of adequate numerical models often limits the practical application of innovative building materials, such as lightweight concrete, in real projects. This trend is due to the uncertainties in design standard methods and calculation errors, the level of which is generally unacceptable to civil engineers in terms of safety and reliability. In the present paper, a comparative numerical deformation analysis of a full-scale bridge deck slab and girder has been carried out. Using the physical model proposed by the authors and the finite element software ATENA, the deformations of full–scale lightweight and traditional reinforced concrete elements under short-term effects of permanent and variable loads was compared. Depending on the safety and serviceability limit requirements, it was found that the amount of longitudinal reinforcement in lightweight reinforced concrete elements can be reduced compared to normal reinforced concrete elements with the same parameters. The results of the numerical analysis show that the deformation analysis model proposed by the authors can be a reliable tool for the design of lightweight concrete flexural members by selecting the optimum geometrical and reinforcement parameters limited by the stiffness condition.

The negative energy solutions of the Klein-Gordon and Dirac equations have been used to define the antiparticle with the positive energy from the Feynman - Stueckelberg interpretation in the standard model based on the 4-D Minkowski space with the relative time. The negative energy solutions of the Klein-Gordon and Dirac equations are used to define the antiparticles with the negative energy in the present 3-D quantized space model. Note that all the present results are based on the 4-D Euclidean space with the absolute time (t) and relative time (t_l). Then the particle with the positive energy and antiparticle with the negative energy have the 4-D P₄ = TCP = T_cP symmetry. The continuity equations are derived from the Klein-Gordon, Dirac and Schrodinger equations. The Klein-Gordon and Schrodinger equations with the potential barriers are solved. The Klein paradox is explained by using the pair production of the electron with the positive energy and positron with the negative energy under the P₄ = _TcP symmetry, The effective velocity ( c_eff=√2 " c " ) and effective energy ("Etl =" √2 E ) along the relative time axis (ctl) give the relative time momentum of "p_tl"=E_tl/c_eff =(√2 E)/(√2 c)=E/c=p_t=p_x. This indicates that the photons with the energy of E have the constant photon velocity of c and the constant photon momentum of "ptl"=E_tl/c_eff =(√2 E)/(√2 c)=E/c=p_t=p_x. For the negative energy particles, the space momentum directions are opposite to the particle velocity directions because the energy is negative. And the matter collapse to the photons at the very high particle velocity is discussed from the length expansion. It is, for the first time, proposed that the gamma ray burst is originated from the matter collapse to the photons near the black hole. Also, the wave function collapse is explained from the length expansion. The wave function collapse takes place when the measurement makes the particle velocity to be zero. It is concluded that the negative energy solutions of the Klein-Gordon and Dirac equations support the existence of the partner antimatter universe with the negative energy and negative time direction. Our matter universe has the positive energy and the positive time direction.

In the framework of 2D circular membrane Micro-Electric-Mechanical-Systems (MEMS), a new non-linear second-order differential model with singularity in the steady-state case is presented in this paper. In particular, starting from the fact that the electric field magnitude is locally proportional to the curvature of the membrane, the problem is formalized in terms of the mean curvature. Then, a result of existence of at least one solution is achieved. Finally, two different approaches prove that the uniqueness of the solutions is not ensured.

Triple-negative breast cancer (TNBC) is characterized by an active immune response. We evalu-ated intratumoral interrelation between FOXP3+ tumor-infiltrating lymphocytes and other cy-tokines in TNBC. Network analysis refined cytokines significantly correlate with FOPX3 in TNBC. Treatment response and prognosis imformation of patients and survival data from the TGCA and METABRIC databases were analyzed according to refined cytokines. Interleukin (IL)-33 was sig-nificantly expressed by TNBC cell lines than luminal cell lines (log2 fold change: 5.31, p <0.001) and IL-33 and TGFB2 showed a strong correlation with FOXP3 in the TNBC cell line. Immunohisto-chemistry demonstrated IL-33 high group was a significant predictor of complete response of neoadjuvant chemotherapy (odds ratio (OR) 4.12, p<0.05) and a favorable survival compared to IL-33 low group (OR 6.48, p<0.05) in TNBC. Survival data from TGCA and METABRIC revealed that FOXP3 was a significantly favorable marker in IL-33 high group com-pared to the low IL-33 low group (hazard ratio (HR) 2.1, p=0.02), and IL-33 high/TGFB2 high subgroup showed significant favorable prognosis in the FOXP3 high group compared to the FOPX3 low group in TNBC (HR 3.5, p=0.01). IL-33 and TGFB2 were key cytokines of intratumoral interrelation among FOXP3 in TNBC.

Alcohol use disorder (AUD) represents major public and socioeconomic issues. Alcohol exerts its phar-macological effects by altering different neurotransmitter systems, such as g-aminobutyric acid (GABA), glutamate, opioids, etc. Recent evidence suggests that the dynorphin (DYN)/kappa opioid receptor (KOR) system mediates the negative affective states associated with alcohol withdrawal. This system is also in-volved in stress-mediated alcohol intake in alcohol-dependent subjects. The DYN/KOR system probably exerts its action in the central nucleus of the amygdala (CeA) to mediate the negative affective states as-sociated with alcohol withdrawal. This article aims to review the current literature regarding the role of the DYN/KOR system in the actions of alcohol. We first review the literature regarding the effect of alcohol on the level of the peptide and its receptor, and the role of the endogenous DYN/KOR system in alcohol reward and negative affective states associated with alcohol withdrawal is then discussed. We also review the literature regarding the effects of KOR ligands on these processes.

Assuming a geometrically closed universe, we predict a value for the cosmic curvature, , a value within current observational bounds. We also propose a thermodynamic heat engine model for the universe, which bypasses the need for an inflaton field. Our model is based on a Carnot Cycle where we have isothermal expansion, followed by adiabatic expansion, followed by isothermal contraction, followed by adiabatic contraction, bringing us back to our original starting point. For the working substance, we focus specifically on the CMB radiation filling the collective voids in the universe. Using this construct, we identify cosmic inflation as the isothermal expansion phase, which lasts just under, . The collective CMB volume we see today only increases by a factor of 5.65 times during this process, and homogeneity and perturbations in the CMB are explained. The singularity problem is avoided and we have a clear mechanism for the work done by the cosmos in causing expansion, and later contraction. For scaling laws with respect to the density parameters in Friedmann’s equations, we will assume a susceptibility model for space, where, , the smeared cosmic susceptibility, decreases with increasing cosmic scale parameter, . Within this framework, we can predict a maximum Hubble volume with minimum CMB temperature for the voids before contraction begins, as well as a minimum volume with maximum CMB temperature when expansion starts. The thermodynamic heat cycle deviates from efficiency in converting heat energy into mechanical energy (expansion) by a minuscule amount, namely, . The significance of this number is not known.

Residual stresses in fiber metal laminates (FML) inevitably develop during the manufacturing process. The main contributor to these stresses is the difference in the coefficients of thermal expansion (CTE) between fibers and metal in combination with high process temperatures. To quantify these stresses, the use of specimens with an asymmetric layup is an easily adaptable method. The curvature that develops after the manufacturing of flat laminates with an asymmetrical layer stack is a measure of the level of residual stresses evolving during cure. However, the accuracy of the curvature evaluation is highly dependent on specimen design and other influencing parameters. In this work a large set of FML specimens is investigated to identify relevant influencing parameters and derive conclusions about specimen design and evaluation techniques. For certain layups and process parameters, there is a good correlation between the curvature and the stress-free temperature, which is further covered by analytical solutions for bimetals. This correlation is the basis to transfer curvature into a stress-free temperature that can consequently be used for the quantification of residual stress levels in more complex FMLs. The transfer is validated by in-situ strain measurements during cure using a strain gage technique. Based on the results, the application of asymmetric specimens for residual stress characterization in more complex laminates is presented in the form of a workflow.

Gol'denveizer's problem of a torus has been analyzed by Audoly and Pomeau (2002) and Sun (2021). However, all of the investigations of Gol'denveizer's problem of an elastic torus have been linear. In this paper, the finite element method is used to more accurately address this problem. Furthermore, Sun (2021) cannot be solved by nonlinear analysis. We research the nonlinear mechanical properties of Gol'denveizer's problem of circular and elliptic tori, and relevant nephograms are given. We study the buckling of Gol'denveizer's problem of an elastic torus, and propose failure patterns and force-displacement curves of tori in the nonlinear range. Investigations reveal that circular tori have more rich buckling phenomena as the parameter a increases. Gol'denveizer's problem of the buckling of an elliptic torus is analyzed, and we find a new buckling phenomenon called a "skirt." As a/b increases, the collapse load of an elliptic torus of the Gol'denveizer problem is enhanced gradually.

We studied the prognostic impact of tumor immunoglobulin kappa C (IGKC) mRNA expression as a marker of the humoral immune system in the FinHer trial patient population, where 1,010 patients with early breast cancer were randomly allocated to either docetaxel-containing or vinorelbine-containing adjuvant chemotherapy. HER2-positive patients were additionally allocated to either trastuzumab or no trastuzumab. Hormone receptor-positive patients received tamoxifen. IGKC was evaluated in 909 tumors using quantitative real-time polymerase chain reaction, and the influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates. Interactions were analyzed using Cox regression. IGKC expression, included as continuous variable, was independently associated with DDFS in a multivariable analysis including also age, molecular subtype, grade, and pT and pN stage (HR 0.930, 95% CI 0.870 – 0.995, P = 0.034). An independent association with DDFS was also found in a subset analysis of triple-negative breast cancers (TNBC) (HR 0.843, 95% CI 0.724 – 0.983, P = 0.029), but not in luminal (HR 0.957, 95% CI 0.867 – 1.056, P = 0.383) or HER2-positive (HR 0.933, 95% CI 0.826 – 1.055, P = 0.271) cancers. No significant interaction between IGKC and chemotherapy or trastuzumab administration was detected (Pinteraction = 0.855 and 0.684, respectively). These results show that humoral immunity beneficially influences the DDFS of patients with early TNBC.

The Sulfur Dioxide (SO2) compound is a primary environmental pollutant worldwide, whereas elemental Sulfur (S) is a global commodity possessing a variety of industrial as well as commercial functions. The chemical relationship between poisonous SO2 and commercially viable elemental S has motivated this investigation using Density Functional Theory calculation of the relative transition state barriers for the 2-step Dehydro-sulfurization oxidation-reduction reaction. Additionally, doubly-charged nanoscale platelet Molybdenum Disulfide (MoS2), Armchair (6,6) Carbon Nanotube, 28-atom Graphene nanoflake (GR-28), and Fullerene C-60 are utilized as catalysts. The optimal heterogeneous and homogeneous catalysis pathways of the 2-step oxidation-reduction from SO2 to elemental S are further inspired by the biomimicry of the honeybee species multi-step bio-catalysis of pollen conversion to organic honey. Potential applications include environmental depollution, the mining of elemental sulfur, and the functionalization of novel technologies such as the recently patented aerial and amphibious Lynchpin TM drones.

The cytoplasmic membrane is the fundamental component of all living cells, which participates in various physiological processes, such as material exchange, stress response, cell recognition, signal transduction, cellular immunity, apoptosis, pathogenicity, etc. The normal function of a cytoplasmic membrane requires stable organization of transmembrane protein-lipid microdomains, transmembrane protein-cell wall microdomains, and cytoskeleton-transmembrane protein microdomains. Here, we review the mechanisms and functions of various membrane lipid components, fatty acid content and saturation, membrane curvature, and cell wall and cytoskeleton in plasma membrane homeostasis affecting the pathogenicity of pathogenic fungi. Pathogenic fungi maintains plasma membrane homeostasis and contributes to fungal virulence by maintaining plasma membrane assembly, structural and functional integrity of pathogenic fungi at various stages of cell development through interactions among lipid components of cytoplasmic membranes, transmembrane proteins, cytoskeleton and cell wall components, etc.

The leaves and stems of Bauhinia guianensis Aubl. are used in traditional Amazonian phytotherapy for the treatment of pain and inflammation. This study investigates the anti-inflammatory and antinociceptive effects of hydroethanolic extracts from B. guianensis Aubl. leaves and stems (HELBg and HESBg, respectively) in in vivo models of inflammation and hyperalgesia. Danio rerio experimental animals were submitted to the acute inflammation test, induced by intraperitoneal (ip.) administration of carrageenan 20 μg / animal (abdominal edema), the groups were previously treated orally with saline solution 2 μl / animal (SS), Dimethyl sulfoxide 2 μl / animal (DMSO), Indomethacin 10 mg/Kg, HELBg 100 mg/Kg and HESBg 100 mg/Kg, n = 12 per experimental group, to evaluate inhibition of edema and alterations histopathology of the liver, intestine and kidney of these animals. The antinociceptive effect was observed from the body curvature index and the behavioral responses of Danio rerio, after an experimental protocol for the induction of hyperalgesia, by ip administration. of 10 μl / animal of 2.5% acetic acid, the animals were previously orally treated with saline solution 2 μl/animal (SS), dimethyl sulfoxide 2 μl/animal (DMSO), morphine 2.5 mg/Kg, HELBg 100 mg/Kg and HESBg 100 mg/Kg, n = 5 per experimental group. In carrageenan-induced edema, the group treated with HESBg inhibited edema formation over the 3 hours of the experiment. Maximum edema was inhibited by 54% (p &lt; 0.05) when compared to the control group. Both HELBg and HESBg prevented body curvature index changes (t (df = 3 8) =, 6.96 and t (df = 3, 8) = 6.61, respectively, both p &lt; 0.0001). In the behavioral parameters sensitive to antinociceptive pharmacological modulation, due to the abdominal constriction induced by acetic acid, the administration of HELBg and HESBg resulted in an improvement in swimming activity, by increasing the distance covered (F (df = 3, 16) = 6.50 and F (df = 3, 16)  = 7.72, respectively, both p &lt; 0.0001), decrease in freezing time (F (df = 3, 16)  = 2.04 and F (df = 3, 16)  = 1.28, respectively, both p &lt; 0.0059), increase in the number of ascents to the upper area of the tank (F (df = 3, 16)  = 33.02 and F (df = 3, 16)  = 35.62, respectively, both p &lt; 0.0009 ) and decreased time spent in that area (F (df = 3, 16)  = 101.19 and F (df = 3, 16)  = 103.59, respectively, both p &lt; 0.0038). It is reasonable to suppose that both extracts modulated the variations induced by carrageenan and acetic acid through the inhibition of prostaglandin biosynthesis, decreasing the release of inflammatory mediators and the sensitization of peripheral nociceptors and, consequently, the perception of pain. These results suggest that HELBg and HESBg have anti-inflammatory and antinociceptive activities, probably of peripheral origin and linked to the inhibition of prosta-glandin biosynthesis

In this paper, we will consider an autonomous two-dimensional ODE Kolmogorov type 1 system with three parameters, which is a particular system of the general predator–prey systems with 2 a Holling type II. By reformulating this system as a set of two second order differential equations, we 3 will investigate the nonlinear dynamics of the system from the Jacobi stability point of view, using 4 the Kosambi-Cartan-Chern (KCC) geometric theory. We will determine the nonlinear connection, the 5 Berwald connection and the five KCC-invariants which express the intrinsic geometric properties 6 of the system, including the deviation curvature tensor. Furthermore, we will obtain necessary and 7 sufficient conditions on the parameters of the system in order to have the Jacobi stability near the 8 equilibrium points and we will point out these on a few examples.

3D measurement is a high-throughput method that can record a large amount of information. In this study, we have developed new methods that could be used for morphological analysis of plants from the information contained in 3D data. Specifically, we investigated characteristics that can be measured by scale (dimension) and/or visual assessment by humans. The characteristics that can be measured on a scale-related dimension were tested based on the bounding box, convex hull, column solid, and voxel. Furthermore, for characteristics that can be evaluated by visual assessment, we propose a new method using normal vectors and local curvature (LC) data. For these examinations, we used our highly accurate all-around 3D plant modelling system. The correlation coefficients between manual measurements and the scale-related methods were all above 0.9. In particular, the differences in LC calculated from the normal vector data allowed us to visualize and quantify the concavity and convexity of leaves. Furthermore, we also found a difference in the time point at which leaf blistering began to develop among the cultivars. The precise 3D model made it possible to perform quantitative measurements of lettuce size and morphological characteristics. In addition, the newly proposed LC-based analysis method made it possible to quantify the characteristics that rely on visual assessment.

We present a new interpretation of the Higgs field as a composite particle made up of a positive, with, a negative mass Planck particle. According to the Winterberg hypothesis, space, i.e., the vacuum, consists of both positive and negative physical massive particles, which he called planckions, interacting through strong superfluid forces. In our composite model for the Higgs boson, there is an intrinsic length scale associated with the vacuum, different from the one introduced by Winterberg, where, when the vacuum is in a perfectly balanced state, the number density of positive Planck particles equals the number density of negative Planck particles. Due to the mass compensating effect, the vacuum thus appears massless, charge-less, without pressure, energy density, or entropy. However, a situation can arise where there is an effective mass density imbalance due to the two species of Planck particle not matching in terms of populations, within their respective excited energy states. This does not require the physical addition or removal of either positive or negative Planck particles, within a given region of space, as originally thought. Ordinary matter, dark matter, and dark energy can thus be given a new interpretation as residual vacuum energies within the context of a greater vacuum, where the populations of the positive and negative energy states exactly balance. In the present epoch, it is estimated that the dark energy number density imbalance amounts to, , per cubic meter, when cosmic distance scales in excess of, , are considered. Compared to a strictly balanced vacuum, where we estimate that the positive, and the negative Planck number density, is of the order, particles per cubic meter, the above is a very small perturbation. This slight imbalance, we argue, would dramatically alleviate, if not altogether eliminate, the long standing cosmological constant problem.

46 patients with a newly diagnosed, histologically verified glioma that was visually classified as [18F]FET-negative were included. Tumor volumes were defined using routine T2/FLAIR MRI data and applied to extract information from dynamic [18F]FET PET data, i.e. early and late tu-mor-to-background (TBR5-15, TBR20-40) images and time-to-peak (TTP) images. Radiomic features of healthy background were calculated from the tumor volume-of-interest mirrored to the con-tralateral hemisphere. Differences between tumor and healthy tissue features were compared us-ing Wilcoxon test. Additionally, the ability to distinguish tumor from healthy tissue was assessed using logistic regression. 5 % of features derived from TBR20-40 images were significantly differ-ent; 16 % of features derived from TBR5-15 images and 69 % of features derived from TTP images. The high number of significantly different features derived from TTP images was even found in isometabolic gliomas (after exclusion of photopenic gliomas) with visually normal [18F]FET up-take in static images. However, the differences did not reach satisfactory predictability for ma-chine learning based identification of tumor tissue. In conclusion, radiomic features derived from dynamic [18F]FET PET data may extract additional information even in [18F]FET-negative glio-mas, which should be investigated in larger cohorts and correlated with histological and out-come features in future studies.

(1) Background: This article reviews the available scientific literature on drug-related problems and negative outcomes associated with medications identified by medication review with follow-up for end-stage renal disease and discussed with the physicians; (2) Methods: A systematic review was conducted of the scientific literature retrieved from the following databases: MEDLINE (via PubMed), Web of Science, SCOPUS, Cochrane Library: The Cochrane Central Register and Control Trials (CENTRAL) and Literatura Latinoamericana y del Caribe (LILACS), Medicina en Español (MEDES), and the SciELO bibliographic database (collection of scientific journals). The following terms were used as descriptors and searched in free text: "end-stage renal disease", "medication review", and "drug-related problems” and “negative outcomes associated with medication". The following limits were applied: "humans" and "adults (more than 18 years)”; (3) Results: A total of 59 references were recovered and after applying inclusion/exclusion criteria, 16 articles were selected. Of these selected articles, 15 provided information on drug-related problems and only 1 on negative outcomes associated with medications; (4) Conclusions: It can be concluded that drug-related problems and negative outcomes associated with medication affect patients with end-stage renal disease, mainly those receiving renal replacement therapy. More evidence is needed, especially on negative outcomes associated with medication.

Standard of care for triple negative breast cancer (TNBC) involves the use of microtubule poisons like paclitaxel, which are proposed to work by inducing lethal levels of aneuploidy in tumor cells. While these drugs are initially effective in treating cancer, dose-limiting peripheral neuropathies are common. Unfortunately, patients often relapse with drug resistant tumors. Identifying agents against targets that limit aneuploidy may be a valuable approach for therapeutic development. One potential target is the microtubule depolymerizing kinesin, MCAK, which limits aneuploidy by regulating microtubule dynamics during mitosis. Using publicly available datasets, we found that MCAK is upregulated in triple negative breast cancer and is associated with poorer prognoses. Knockdown of MCAK in tumor-derived cell lines caused a two- to five-fold reduction in the IC50 for paclitaxel, without affecting normal cells. Using FRET and image-based assays, we screened compounds from the ChemBridge 50k library and discovered three putative MCAK inhibitors. These compounds reproduced the aneuploidy-inducing phenotype of MCAK loss, reduced clonogenic survival of TNBC cells regardless of taxane-resistance, and the most potent of the three, C4, sensitized TNBC cells to paclitaxel. Collectively, our work shows promise that MCAK may serve as both a biomarker of prognosis and as a therapeutic target.

Abstract: A prevalence boundary (PB) marks the point in prevalence where the false omission rate, RFO=FN/(TN+FN), exceeds the tolerance limit for missed diagnoses. Objectives were to mathematically analyze rapid antigen test (RAgT) performance, determine why PBs are breeched, and evaluate the merits of testing three times over five days, now required by the US Food and Drug Administration for asymptomatic persons. Equations were derived to compare test performance patterns, calculate PBs, and perform recursive computations. An independent July 2023 FDA-university-commercial evaluation of RAgTs provided performance data used in theoretical calculations. Tiered sensitivity/specificity comprise: Tier-1) 90%, 95%; Tier-2) 95%, 97.5%; and Tier-3) 100%, ≥99%, respectively. Repeating a T2 test improves the PB from 44.6% to 95.2% (RFO 5%). In the FDA-university-commercial evaluation, RAgTs generated sensitivity of 34.4%, which improved to 55.3% when repeated, then 68.5% with the third test. With RFO=5%, PBs were 7.37/10.46/14.22%, respectively. PB analysis suggests RAgTs should achieve clinically proven sensitivity of 91.0-91.4%. When prevalence exceeds PBs, missed diagnoses can perpetuate virus transmission. Repeating low-sensitivity RAgTs delays diagnosis. In homes, high-risk settings, and hotspots, PB breaches may prolong contagion, defeat mitigation, facilitate new variants, and transform outbreaks into endemic disease. Molecular diagnostics can help avoid these potential vicious cycles

Buckground: Although ceftazidime/avibactam (CAZ/AVI) has become important option for treating adults and children, no recommendations exist for neonates. We report a neonatal sepsis case due to CAZ/AVI-resistant KPC-2 producing-Klebsiella pneumoniae carrying blaVEB-25 and the use of a customized active surveillance program in conjunction to infection control measures. Methods: The index case was an extremely premature neonate hospitalized for 110 days that had been previously treated with multiple antibiotics. Customized molecular surveillance was implemented at hospital level and enhanced infection control measures were taken for early recognition and prevention of outbreak. Detection and identification of blaVEB-25 was performed by next-generation sequencing. Results: That was the first case of a bloodstream infection caused by KPC producing K. pneumoniae that was resistant to CAZ/AVI without the presence of a metalo-β-lactamase in the multiplex PCR platform in a neonate. All 36 additional patients tested (12 in the same NICU and 24 from other hospital departments) carried wild-type blaVEB-1 but they did not harbor blaVEB-25. Conclusion: The emergence of VEB-25 is signal for horizontal transfer of plasmids at hospital facilities and it is of greatest concern for maintaining a sharp vigilance for surveillance of novel resistance mechanisms. Molecular diagnostics can guide appropriate antimicrobial therapy and early implementation of infection control measures against antimicrobial resistance.

The study examines n-balls, regular n-simplices, and n-orthoplices in real dimensions using novel recurrence relations that removed indefiniteness present in known formulas. They show that in the negative, integer dimensions volumes of n-balls are zero if n is even, positive if n = -4k - 1, and negative if n = -4k - 3, for natural k. Volumes and surfaces of n-cubes inscribed in n-balls in negative dimensions are complex, wherein for negative, integer dimensions they are associated with integral powers of the imaginary unit. The relations are continuous for n Î ℝ and show that the constant of π is absent for 0 ≤ n < 2. For n < -1 self-dual n-simplices are undefined in the negative, integer dimensions, and their volumes and surfaces are imaginary in the negative, fractional ones, and divergent with decreasing n. In negative, integer dimensions n-orthoplices reduce to the empty set, and their real volumes and imaginary surfaces are divergent in negative, fractional ones with decreasing n. Out of three regular, convex polytopes present in all natural dimensions, only n-orthoplices, n-cubes (and n-balls) are defined in the negative, integer dimensions.

Obesity is one of the most prevalent chronic diseases and has become a global epidemic. Obesity leads to a greater risk of breast cancer (BC), metastases, recurrence, and decreased survival. For sustained weight loss, bariatric surgery is effective as a long-term solution. Bariatric surgery is associated with improved outcomes of several cancers including BC, although the mechanisms mediating this protection are unknown. We hypothesized that elevated bile acid pools detected after bariatric surgery may be factors that contribute to improved BC outcomes. Indeed, patients with greater expression of the bile acid receptor FXR displayed improved survival in specific BC subtypes. Patients with tumors that are estrogen receptor negative (ER-) displayed significantly elevated survival with higher FXR (NR1H4) expression compared to lower expression. FXR is a nuclear hormone receptor activated by bile acids. Therefore, we posited that activating FXR using an established FDA-approved agonist would display anticancer effects. Indeed, FXR agonism by the bile acid mimetic known commercially as OCALIVA (“OCA”), or Obeticholic acid (INT-747), significantly reduced BC progression and overall tumor burden in a pre-clinical model. In human and murine BC analyses in vitro, agonism of FXR significantly and dose-dependently inhibited proliferation, migration, and viability. In contrast, synthetic agonism of another common bile acid receptor, the G protein-coupled bile acid receptor (GPBAR1, TGR5) which is mainly activated by secondary bile acids, failed to significantly alter cancer cell dynamics. In conclusion, agonism of FXR by primary bile acid memetic OCA yields potent anti-tumor effects potentially through inhibition of proliferation and migration and reduced cell viability. Findings suggest that FXR is a tumor suppressor gene with high potential for personalized therapeutic strategies for individuals with BC.

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature data concerning the immunogenicity of breast cancer have been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune re-sponse in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ sub-types where increased TIL levels have been linked to better response to neoadjuvant chemotherapy and with improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes . In detail, TNBC shows the highest percentages of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0-10% of cases) in hormone-receptor positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points and scoring systems have been utilized across published studies. In the present paper an extensive review on the current knowledge of immune landscape of BC is provided. In detail TILS and PD-L1 expression across different BC subtypes is discussed also providing a guide for their pathological assessment and reporting.

This research work deals with the formulation of numerical scheme with algorithm to compute singularly perturbed partial differential equations(SP-PDEs) involving a significant negative shift. The problem involves small parameter which causes a rapidly changing boundary layers in the vicinity of a body, and the negative shift term causes interior layer. Such appearance of an abruptly varying layers causes difficulties to find the exact solution and it is not adequate to employ classical numerical methods. The technique presented in this research work simplifies these challenges and yields accurate numerical solution.The stability and convergence analyses of the methods are examined and proven. To test the developed technique, numerical experiments are carried out and confirmed with theoretical analysis.

Hydrogen-bond (H-bond) energies in 310-helices of short alanine peptides were systematically examined by precise DFT calculations with the negative fragmentation approach (NFA), a modified method based on the molecular tailoring approach. The contribution of each H-bond was evaluated in detail from the 310-helical conformation of total energies (whole helical model; WH3-10 model), and the results were compared with the property of H-bond in a-helix from our previous study. The H-bond energies of the WH3-10 model exhibited tendencies different from those exhibited by the -helix, in that they depended on the helical position of the relevant H-bond pair. H-bond pairs adjacent to the terminal H-bond pairs were observed to be strongly destabilized. The analysis of electronic structures indicated that structural characteristics cause the destabilization of the H-bond in 310-helices. We also found that the longer the helix length, the more stable the H-bond in the terminal pairs of the WH3-10 model, suggesting the action of H-bond cooperativity.

Pregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tumor heterogeneity, is least responsive to standard treatments and has the poorest clinical outcomes. There is a critical need to address the lack of effective targeted therapeutic options available. PAPP-A is a protein that is highly elevated during pregnancy. Frequently, higher PAPP-A expression is detected in tumors than in healthy tissues. The increase in expression coincides with increased rates of aggressive cancers. In BC, PAPP-A has been demonstrated to play a role in tumor initiation, progression, metastasis including epithelial-mesenchymal transition (EMT), as well as acting as a biomarker for predicting patient outcomes. In this review, we present the role of PAPP-A, with specific focus on TNBC. The structure and function of PAPP-A, belonging to the pappalysin subfamily, and its proteolytic activity are assessed. We highlight the link of BC and PAPP-A with respect to the IGFBP/IGF axis, EMT, the window of susceptibility and the impact of pregnancy. Importantly, the relevance of PAPP-A as a TNBC clinical marker is reviewed and its influence on immune-related pathways are explored. The relationship and mechanisms involving PAPP-A reveal the potential for more treatment options that can lead to successful immunotherapeutic targets and the ability to assist with better predicting clinical outcomes in TNBC.

Sepsis is a life-threatening condition caused by the body's overwhelming response to an infection, such as pneumonia or urinary tract infection. It occurs when the immune system releases cytokines into the bloodstream, triggering widespread inflammation. If not treated, it can lead to organ failure and death. Unfortunately, sepsis has a high mortality rate, with studies reporting rates ranging from 20% to over 50%, depending on the severity and promptness of treatment. According to the World Health Organization (WHO), the annual death toll in the world is about 11 million. One of the main toxins responsible for inflammation induction are lipopolysaccharides (LPS, endotoxin) from Gram-negative bacteria, which ranks among the most potent immunostimulants found in nature. Antibiotics are consistently prescribed as a part of anti-sepsis-therapy. However, antibiotic therapy (i) is increasingly ineffective due to resistance development and (ii) most antibiotics are unable to bind and neutralize LPS, a prerequisite to inhibit the interaction of endotoxin with its cellular receptor complex, namely Toll-like receptor 4 (TLR4)/MD-2, responsible for the intracellular cascade leading to pro-inflammatory cytokine secretion. The pandemic virus SARS-CoV-2 has infected hundreds of millions of humans worldwide since its emergence in 2019. The COVID-19 (Coronavirus disease-19) caused by this virus is associated with high lethality, particularly for elderly and immunocompromised people. As of August 2023, nearly 7 million deaths were reported worldwide due to this disease. According to some reported studies, upregulation of TLR4 and the subsequent inflammatory signaling detected in COVID-19 patients “mimics bacterial sepsis”. Furthermore, the immune response to SARS-CoV-2 was described by others as “mirror image of sepsis”. Similarly, the cytokine profile in sera from severe COVID-19 patients was very similar to those suffering from the acute respiratory distress syndrome (ARDS) and sepsis. Finally, the severe COVID-19 infection was frequently accompanied by bacterial co-infections, as well as by the presence of significant LPS concentrations. These data indicate similarity and interdependences of both syndromes, but also significant differences which will be discussed in the present review.

Bone metastasis detection and quantification on bone scintigraphy is challenging and clinical important for treatment and patient’s life quality. To develop a CNN based diagnostic system for automated segmentation on bone metastasis regions is non-trivial, especially for a small dataset. A dataset in house comprising 100 breast cancer patients and 100 prostate cancer patients is utilized for this research. The Double U-Net model is adapted through the integration of background removal, adding negative samples, and transfer learning methods for bone metastasis detection. The performance is investigated via 10-fold cross-validation and computed in pixel-wise scale. The best model we achieved has precision of 63.08%, sensitivity of 70.82%, and F1-score of 66.72%. The developed system has the potential to provide pre-diagnostic reports for physicians in final decisions and the calculation of the bone scan index (BSI) with the combination with bone skeleton segmentation.

An interesting physical phenomenon was recently observed when a fresh-water basin is covered by a thin ice film that has properties similar to that of a rubber membrane. Surface waves can be generated under the action of wind on the air-water interface that contains an ice film. The modulation property of hydro-elastic waves (HEWs) in deep water covered by thin ice film blown by the wind with a uniform vertical profile is studied here in terms of the air-flow velocity versus a wavenumber. The modulation instability of HEWs is studied through the analysis of coefficients of the nonlinear Schrödinger (NLS) equation with the help of the Lighthill criterion. The NLS equation is derived using the multiple scale method in the presence of airflow. It is demonstrated that the potentially unstable hydro-elastic waves with negative energy appear for relatively small wind speeds, whereas the Kelvin–Helmholtz instability arises when the wind speed becomes fairly strong. Estimates of parameters of modulated waves for the typical conditions are given.

When generalized noncommutative Heisenberg algebra accommodating impacts of finite gravitational fields as specified by loop quantum gravity, doubly–special relativity, and string theory, for instance, is thoughtfully applied to the eight-dimensional manifold (M8), the generalization of the Riemannian manifold becomes imminent. By constructing the deformed affine connections on a four-dimensional Riemannian manifold, we have determined the minimal length deformation of Riemann curvature tensor and its contractions, the Ricci curvature tensor, and Ricci scalar. Consequently, we have been able to construct the deformed Einstein tensor. As in Einstein’s classical theory of general relativity, we have proved that the covariant derivative of the deformed Einstein tensor vanishes, as well. We conclude that the minimal length correction suggests a correction to the spacetime curvature which is manifest in the additional curvature terms of the corrected Riemann tensor and its contractions. Accordingly, the spacetime curvature endows additional curvature and geometrical structure.

The study shows that the volumes and surfaces of $n$-balls, $n$-simplices, and $n$-orthoplices are holomorphic functions of $n$, which makes those objects omnidimensional, that is well defined in any complex dimension. Applications of these formulas to the omnidimensional polytopes inscribed in and circumscribed about $n$-balls reveal previously unknown properties of these geometric objects. In particular, for $0 < n < 1$, the volumes of the omnidimensional polytopes are larger than those of circumscribing $n$-balls, and both their volumes and surfaces are smaller than those of inscribed $n$-balls. The surface of an $n$-simplex circumscribing unit diameter $n$-ball is spirally convergent to zero with real $n$ approaching negative infinity but first has a local maximum at $n=-3.5$. The surface of an $n$-orthoplex circumscribing unit diameter $n$-ball is spirally divergent with real $n$ approaching negative infinity but first has a local minimum at $n=-1.5$, where its real and imaginary parts are equal to each other; similarly, as its volume, where the similar local minimum occurs at $n=-3.5$. Reflection functions for volumes and surfaces of these polytopes inscribed in and circumscribed about $n$-balls are proposed. symmetries of products and quotients of volumes in complex dimensions $n$ and $-n$ and of surfaces in complex dimensions $n$ and $2-n$ are shown to be independent of the metric factor and the gamma function. Specific symmetries also hold between volumes and surfaces in dimensions $n = -1/2$ and $n = 1/2$.

B and T lymphocytes demonstrate important alterations in patients with Systemic Lupus Erythematous (SLE), with significant up-regulation of Double Negative (DN) B cells. Aim of this study was to evaluate correlation of T cell immunity changes with the distinct B cell-pattern SLE. In the present study, Flow cytometry was performed in 30 patients with SLE, on remission, and 31 healthy controls, to detect DN B cells (CD19+IgD-CD27-) and a wide range of T lymphocyte subpopulations, based on the presence of CD45RA, CCR7, CD31, CD28, CD57, defined as naive, memory and advanced differentiated/senescent T cells. Both B and T lymphocytes were significantly reduced in SLE patients. However, the percentage of DN B cells were increased, compared to HC, 12.9(2.3-74.2) vs. 8(1.7-35), p=0.04. Distribution of CD4 and CD8 lymphocytes demonstrated a shift to advanced differentiated subsets. The population of DN B cells had significant positive correlation with most of early differentiated T lymphocytes, CD4CD31+, CD4CD45RA+CD28+, CD4CD45RA+CD57-, CD4CD45RA-CD57-, CD4CD28+CD57-, CD4CD28+CD57+, CD4 CM, CD8 CD31+, CD8 NAÏVE, CD8CD45RA-CD57-, CD8CD28+CD57-, CD8CD28+CD57+. Multiple Regression analysis revealed CD4CD31+, CD8CD45RA-CD57- and CD8CD28+CD57- cells as independent parameters contributing to DN B cells, adjusted R2=0.534, p<0.0001. The predominance of DN B cells in patients with SLE is closely associated with early differentiated T lymphocyte subsets, indicating a potential causality role of DN B cells in T lymphocyte activation.

We tested the possibility of using “adverse events count” (AEC) as a drug-risk indicator and side-effect severity indicator. Data from 3938 adverse event (AE) reports for COVID-19 vaccines (Comirnaty, Moderna, Vaxzevria, and Janssen) and 6869 AE reports for other medicines were collected from the Bulgarian Drug Agency database (01.01.2018–31.03.2022). AEC was modeled with zero-adjusted negative binomial (ZANBI) and zero-adjusted Poisson inverse Gaussian (ZAPIG) regression models, which account for zero absence and overdispersion. The models’ fit was checked with residual diagnostic plots and parametric correspondence to normality. Explanatory variables were: age, sex, sequence number (order of submission), severity of AE, and vaccine type. Average AEC was higher in severe vs. non-severe AE, and in females vs. males; it decreased with age and was lower in Comirnaty than other vaccines. Variability of AEC for COVID-19 data decreased with sequence number in severe AE and increased in non-severe AE. Full ZANBI models had greater sensitivity than parametric ZANBI or ZAPIG models. Results showed correlation between AEC and AE severity, suggesting AEC as a simple and reliable measure of drug-risk and side-effect severity for clinicians and regulators, especially for COVID-19 vaccines.

Ventricina del Vastese is a traditional dry fermented sausage from Central Italy not yet charac-terized for occurrence, identity and safety of coagulase negative staphylococci (CNS), a bacterial group technologically important for this kind of products. Therefore, in this study, 98 CNS isolates from four manufacturers were differentiated by Repetitive element palindromic PCR (Rep-PCR) and identified by 16S rRNA gene sequencing. These were examined for genes encoding biogenic amine (BA) production, resistance to aminoglycosides, β-lactams and tetracyclines and staphylococcal enterotoxins (SEs). Staphylococcus succinus (55%) predominated, followed by S. xylosus (30%), S. epidermidis (7.4%), S. equorum (3.1%), S. saprophyticus (3.1%) and S. warneri (1%). One S. succinus subsp. casei isolate was slightly β-hemolytic. SEs and the histidine decarboxylase gene hdcA were not detected, while the tyrosine decarboxylase gene tdcA was detected in four S. xylosus isolates. A blaZ beta-lactamase gene and tetracycline resistance genes tetK (six isolates) and tetA (one isolate also bearing tetK) were found, respectively. However, fewer hazardous and AR traits compared to CNS examined in other studies were found, as a probable consequence of using meat from animals reared in conditions that allow to minimize pathogen circulation and antibiotic use. Therefore, appropriate production conditions can reduce these threats.

Sarcosine (N-methylglycine), a glutamatergic modulator, reduces the primary negative symp-toms of schizophrenia. These beneficial changes might be mediated by trophic factors such as ep-idermal growth factor (EGF). We assessed associations between initial serum EGF levels or changes in serum EGF levels and symptom severity during the addition of sarcosine to stable an-tipsychotic treatment and thereby evaluate the associations between glutamatergic modulation, clinical changes and peripheral EGF concentrations. 58 subjects with a diagnosis of chronic schizophrenia with dominant negative symptoms, stably treated with antipsychotics completed a prospective 6-month, randomized, double-blind, placebo-controlled study. Subjects received orally 2 grams of sarcosine (n=28) or placebo (n=30) daily. Serum EGF levels and symptom se-verity (using Positive and Negative Syndrome Scale - PANSS and Calgary Depression Scale for Schizophrenia - CDSS) were assessed at baseline, 6 weeks, and 6 months follow-up. Augmenta-tion antipsychotic treatment with sarcosine had no effect on EGF serum levels at any time-points. Only the sarcosine group showed a significant improvement in negative symptoms, general psy-chopathology subscales, and the overall PANSS score. We found reduction of serum EGF levels in the placebo group, but levels in the sarcosine remained stable during the study. Our data indicate that improvement in negative symptoms due to sarcosine augmentation is not mediated by EGF, but effective treatment may induce the production or block the decrease in EGF concentrations, which indicates the neuroprotective effect of treatment and confirms the relationship between neuroprotection and EGF levels.

The structure and phenomena arising from charge transfer in cold field emission modus in a single closed carbon nanotube under cold field emission conditions were studied. By studying microphotographs in various microscopes - AFM, SEM, TEM it was found inhomogeneities in the form of two types of superlattices. The conductivity of the emitter section of a nanodiode circuit with an emitter made of an individual closed carbon nanotube (CNT) and arrays of closed CNTs was studied. High values of cold field emission were observed, as well as nonlinearity and anomalies of the current-voltage characteristic (I-V characteristics), which manifested themselves in the form of peaks at low and high current values. Peaks in the CVC have distinct areas of negative differential conductivity. It is argued, that the anomalously high currents in the I–V characteristics of cold field emission of electrons from a nanoemitter made of closed CNTs can be associated with a sharp increase in the density of electron states at energies near the van Hove singularity.

Background: Skin and soft tissue infections (SSTI) are common presentations to the emergency department. However, this is less common after contact with contaminated water, both salt or fresh. This review presents the diagnosis and the management of water-related soft tissue sepsis in this vulnerable and difficult to treat subgroup of necrotizing soft tissue sepsis. Methods: A summative literature overview regarding bacterial and fungal SSTI after contact with contaminated water, with practical diagnostic and management aspects addressed. Results: The literature indicates that these remain difficult to treat wounds and organisms. An approach using appropriate diagnostic tools with both medical and surgical management strategies is provided. Conclusion: SSTI due to water contamination of wounds involve unusual organisms with unusual resistance patterns and require a nuanced and directed diagnostic approach with adaptation of the normal antibiotic or antifungal selection to achieve cure, along with aggressive debridement and wound care.

The present studies were undertaken to address the role of fetuin-A in the growth and invasion potential in a triple negative breast cancer (TNBC) cell line, MDA-MB-468. Basal like TNBC that express high levels of ectopic fetuin-A have poorer prognosis for the patients compared to those that express low levels of the protein. We overexpressed fetuin-A in MDA-MB-468 and then determined the invasive potential of fetuin-A overexpressing cells vs controls transfected with empty vector. We also determined the adhesion and growth potential of the cells in the presence of only fetuin-A in serum free medium and also in complete medium. Our data suggest that fetuin-A overexpression significantly enhances the invasive potential of the cells and also the expression of Toll like receptor 4 (TLR4) on these cells. More importantly, the cells rely on fetuin-A-TLR4 signaling network for growth and invasion because the specific TLR4 inhibitor CLI-095 (resatorvid) abrogates fetuin-A mediated growth and invasion. Taken together, the data suggest that fetuin-A-TLR4 signaling network plays a significant role in the growth and invasion potential of TNBC.

Bacterial resistance to antibiotics is a public health menace that needs urgent efforts to mitigate and forestall their transmission in the general environment. Plasmid-mediated metallo beta-lactamase (MBL) gives bacteria an exceptional ability to transmit resistance genes. This study investigated plasmid-mediated resistance in MBL P. aeruginosa isolates from poultry food chain settings. Cloacal swab samples (n=120) were bacteriologically analyzed for the isolation of P. aeruginosa isolates. Susceptibility studies were performed by the CLSI guideline using selected antibiotics. MBL was phenotypically detected using modified Hodges test, and confirmed using PCR technique. Plasmid curing studies detected the presence of plasmids in the isolates. P. aeruginosa isolates (n=48) showed high levels of reduced susceptibility to cefoxitin (93.8%), imipenem (81.3%), gentamicin (85.4%), amikacin (85.4%), nitrofurantoin (83.3%), ofloxacin (72.9%) and cefotaxime (77.1%). MBL was phenotypically detected in 7 (14%) isolates of P. aeruginosa. The presence of blaIMP-1 and blaIMP-2 MBL genes in P. aeruginosa (n=5) isolates was confirmed by PCR. The PCR did not detect blaVIM-1 and blaVIM-2 MBL genes. The P. aeruginosa isolates were multidrug resistant, with about 50% of the isolates showing multidrug resistance (MDR) to the antibiotics. The genes for MDR in the P. aeruginosa isolates were borne on plasmids, indicating a high possibility of community transmission of MBL resistance genes. Finally, the P. aeruginosa isolates from poultry food chain milieus are multidrug resistant, produce MBL, and harbour their resistance genes on plasmids. Since many antibiotic resistance genes in bacteria are associated with mobile genetic elements (MGEs) like plasmids, it is important to step up actions to mitigate incessant use of antibiotics in poultry and other agricultural practices in Nigeria in order to diminish the evolution and spread of plasmid-mediated resistance which is capable of initiating community acquired infections that may prove difficult to treat in our hospitals with the available antibiotics.

We introduce a special vector field ω on a Riemannian manifold (N^m, g), such that the Lie derivative of the metric g with respect to ω is equal to ρRic, where Ric is the Ricci curvature of (N^m, g) and ρ is a smooth function on N^{m} and call this vector field a ρ-Ricci vector field. We use ρ-Ricci vector field on a Riemannian manifold (N^m, g) and find two characterizations of m-sphere S^m(α). In first result, we show that an m-dimensional compact and connected Riemannian manifold (N^m, g) with nonzero scalar curvature admits a ρ-Ricci vector field ω such that ρ is nonconstant function and the integral of Ric(ω,ω) has a suitable lower bound is necessary and sufficient for (N^m, g) to be isometric to m-sphere S^m(α). In second result, we show that an m-dimensional complete and simply connected Riemannian manifold (N^m, g) of positive scalar curvature admits a ρ-Ricci vector field ω such that ρ is a nontrivial solution of Fischer-Marsden equation and the squared length of the covariant derivative of ω has an appropriate upper bound, if and only if, (N^m, g) to be isometric to m-sphere S^m(α).

Auger electrons (AEs) represent an intriguing topic in the field of radionuclide therapy. They are emitted by several radionuclides commonly used in nuclear medicine (indium-111, iodine-123, iodine-125), allowing for highly localized energy deposition and thus exerting a radiotoxic effect on specific cellular and sub-cellular targets. However, due to their short range in matter, AEs have had limited use in therapeutic applications so far. In recent years, the synthesis of various radiopharmaceuticals capable of binding to the enzyme poly(ADP-ribose) polymerase 1 has reignited interest in this type of therapy, laying the groundwork for a theranostic approach based on radionuclides emitting AEs. The enzyme PARP-1 operates enzymatically in close proximity to DNA that represents the prime target of radionuclide therapies. Following this trend, several PARP-targeted radiopharmaceuticals for AE-based theranostics have been developed. We provide an updated overview of preclinical studies focused on the applications of this new theranostic approach in glioblastoma, breast, prostate and ovarian carcinoma, and pancreatic adenocarcinoma.

The incidence of multidrug-resistant (MDR) bloodstream infections (BSI) is associated with high morbidity and mortality. Little evidence exists regarding the epidemiology of BSIs and the use of appropriate empirical antimicrobial therapy in endemic regions. Novel diagnostic tests (RDTs) may facilitate and improve patient management. Data from patients with MDR GNB bacteremia at a university tertiary hospital were assessed over a 12-month period. 157 episodes of MDR GNB BSI were included in the study. Overall mortality rate was 50,3 percent. Rapid molecular diagnostic tests were used in 94% of BSI episodes. In univariate analysis, age (OR 1.05 (95% CI 1.03, 1.08) p<0.001), Charlson Comorbidity Index (OR 1.51 (95% CI 1.25, 1.83) p<0.001), Procalcitonin≥1(OR 3.67 (CI 95% 1.73, 7.79) p<0.001) and monotherapy with tigecycline (OR 3.64 (95% CI 1.13, 11.73) p=0.030) were the only factors associated with increased overall mortality. Surprisingly, time to appropriate antimicrobial treatment had no impact on mortality. MDR pathogen isolation, other than Klebsiella pneumoniae and Acinetobacter baumanii was associated with decreased mortality (OR 0.35 (95% CI 0.16, 0.79) p=0.011). In multivariate analysis though the only significant factor for mortality was Procalcitonin≥1(OR 2.84 (95% CI 1.13, 7.11) p=0.025). In conclusion, in an endemic area, mortality rates in MDR BSI remain high. High procalcitonin was the only variable that predicted death. The use of rapid diagnostics did not improve mortality rate.