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.

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.

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.

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

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 to 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 embedded into various matrices. The one-dimensional lattice built of the identical metallic micro-elements m_eff connected by ideal springs k_1 representing various media such as polydimethylsiloxane and soda-lime glass is treated. The optical and acoustical branches of longitudinal modes propagating through the lattice are elucidated for various ratios ω_1/ω_p . The 1D lattice built of the thin metallic wires giving rise to the low frequency plasmons is treated. The possibility of the anti-resonant propagation, strengthening the effect of the negative mass occurring under  = p = 1 is addressed.

It has been theorized that black holes are surrounded by firewalls, although there is not universal agreement concerning this. We first review basic concepts pertaining to Schwarzschild black holes and Hawking radiation. Then we discuss the anticipation of Hawking radiation—albeit from non-black holes—initially by R. C. Tolman and shortly thereafter with P. Ehrenfest. We compare evaporation into a vacuum at absolute zero (0 K) of black holes with that of non-black holes, and show that not only black holes but also non-black holes evaporate within a finite time. The times required for evaporation of black holes and non-black holes are compared. Next, we show that (i) if firewalls exist, they can originate via Hawking radiation at the minimum possible ruler distance (the Planck length) beyond the Schwarzschild horizon, where it has not suffered any gravitational redshift, or, alternatively, suffered maximal gravitational blueshift and (ii) the firewall temperature is on the order of the Planck temperature, independently of the mass and hence also of the Schwarzschild radius of a Schwarzschild black hole. We then explain the exponential nature of the gravitational frequency shift as a function of the gravitational potential. Next, we consider the firewall-mass problem, and provide an at least prima facie tentative resolution thereto based on: (i) the mass of a firewall being canceled by the negative gravitational mass = (negative gravitational energy)/c² accompanying its formation, (ii) the unchanged observations of a distant observer upon formation of a firewall, and (iii) Birkhoff's Theorem (actually first discovered by Jørg Tofte Jebsen). We then consider one aspect of thermodynamics in gravitational fields, showing that equilibrium relativistic gravitational temperature gradients cannot be exploited to violate the Second Law of Thermodynamics.

This research paper explores the framework of Extended Classical Mechanics, with a focus on the Equivalence Principle, Mass, and Gravitational Dynamics. Volume 1 of this study re-examines the classical equivalence principle, which maintains the equivalence of inertial mass and gravitational mass (also referred to as gravitating mass) and extends this concept to incorporate new findings related to both illuminating (baryonic) matter and dark matter. The paper provides a comprehensive analysis of Matter Mass (Mᴍ) and Gravitating Mass (Mɢ) and their roles within the extended framework. It introduces the concept of Apparent Mass (Mᵃᵖᵖ), a negative mass component that influences Effective Mass (Mᵉᶠᶠ), in alignment with the research by A.D. Chernin et al. on dark energy and the structure of the Coma Cluster of Galaxies. Additionally, the paper reinterprets Newton's Law of Universal Gravitation by integrating Apparent Mass, leading to a revised understanding of gravitational potential. The study demonstrates how the interaction between Matter Mass and Negative Apparent Mass contributes to a redefined concept of Gravitating Mass. These extensions enhance classical mechanics by incorporating modern scientific insights, including the gravitational effects of dark matter and the alignment of Apparent Mass with the negative effective mass of dark energy.

One-dimensional chain of core-shell pairs connected by ideal springs enables design of the metamaterial demonstrating the negative effective density and negative specific thermal capacity. We assume that the molar thermal capacity of the reported metamaterial is governed by the Dulong-Petit law in its high temperature limit. The specific thermal capacity depends of the density of the metamaterial; thus, it is expected to be negative, when the effective density of the chain is negative. The range of the frequencies enabling the effect of the negative thermal capacity is established. Dependence of the effective thermal capacity on the exciting frequency for various core/shell mass ratios is elucidated. The effective thermal capacity becomes negative in the vicinity of the local resonance frequency ω0 in the situation when the frequency ω approaches ω0 from above. The effect of the negative effective thermal capacity is expected in metals in the vicinity of the plasma frequency.

The system of non-interacting electrically charged core-massless spring-shell mechanical units, demonstrating negative effective mass, is considered, seen as a Drude-Lorentz gas. When such an ideal gas is exposed to the external harmonic field, it demonstrates as the certain conditions the negative frequency-dependent electrical conductivity. The negative value of the electrical conductivity implies that the electrical current will flow against the direction of the electric field and correspondingly the direction of the electrical force. Low- and high-frequency asymptotic behavior of the electrical conductivity is addressed. The same system demonstrates at low frequencies the negative asymptotic refraction. Experimental realization of the introduced model system, based on the exploitation of plasma oscillations of the free electron gas is suggested.

Assuming a two component, positive and negative mass, superfluid/supersolid for space (the Winterberg model), we model the Higgs field as a condensate made up of a positive and a negative mass, planckion pair. The connection is shown to be consistent (compatible) with the underlying field equations for each field, and the continuity equation is satisfied for both species of planckions, as well as for the Higgs field. An inherent length scale for space (the vacuum) emerges, which we estimate from previous work to be of the order of,

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 purpose of the present study is to explore the linkage between Hazardous Road Locations-based crash counts and a variety of geometric characteristics, roadway characteristics, traffic flow characteristics and spatial features in the region of Sousse, Tunisia. For this purpose, collision data was collected from at 52 hazardous road sections including 1397 crash records for a 11-year monitoring period from January 1, 2004 to December 31, 2014 obtained from National Observatory for Information, Training, Documentation and Studies on Road Safety in Tunisia (NOITDRS). The matrix of Pearson correlation was used in order to avoid inclusion of both variables, which were highly correlated. Both the Random Effects Negative Binomial model and the Negative Binomial model were estimated. To evaluate the models, the Random Effect Negative Binomial model improves the goodness-of-fit compared to the Negative Binomial model. Average Daily Traffic volume, Curved alignment, Presence of public lighting, Visibility, Number of lane, Presence of vertical/horizontal sign, Presence of rural segment, Presence of drainage system, Roadway surface condition, Presence of paved shoulder and presence of major road were found as significant variables influencing accident occurrences. Overall, the current research contributes to the literature from empirical, modeling methodological standpoints since it was the first study conducted in Tunisia to use crash prediction models for hazardous road locations, and that portrays Tunisian reality. The research findings present advantageous insights on hazardous road locations in the region of Sousse, Tunisia and present useful planning tools for public authorities in Tunisia.

The implementation of green logistics can reduce the increasingly serious environmental damage and improve the operating efficiency of logistics enterprises. In this paper, through quantitative calculation of logistics negative external costs, including traffic accidents, atmospheric pollution, noise pollution, and pollution caused by packaging, we build accounting standards to calculate the negative external cost of logistics enterprises that mainly generate pollution from transportation and packaging. Then, assuming the impetus provided by government implementing incentive mechanisms in a free market economy, we establish a ‘Logistics Negative External Cost Internalizing’ model, which quantitatively analyzes the relationships among freight rate, freight volume, investment of enterprise for implementing green logistics, and the subsidy given by government, under the comparison of the two modes ‘enterprise operates first’ and ‘government subsidizes first’. The results show that the introduction of ‘government subsidizes first’ incentive mechanism and increasing freight rate are helpful in promoting the process of logistics market greening.

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.

Here, we report a simple and effective method for separation of gram-negative bacteria using aptamer-modified microbeads and acoustophoresis. As acoustophoresis allows for simultaneous washing and size-dependent separation in continuous flow mode, we efficiently obtained gram-negative bacteria that showed high affinity without any additional washing steps. The proposed device has a simple and efficient channel design, utilizing a long, square-shaped microchannel that shows excellent separation performance in terms of the purity, recovery, and concentration factor. Microbeads (10 µm) coated with the GN6 aptamer can specifically bind gram-negative bacteria. Using acoustophoresis, gram-negative bacteria-bound microbeads and other unbound/contaminants can be separated by size with high purity and recovery. The device demonstrated excellent separation performance, with high recovery (up to 98%), high purity (up to 99%), and a high volume rate (500 µL/min), and a concentration factor of up to 20×. The acoustophoresis microfluidic device also showed binding affinity to multiple strains of gram-negative bacteria, but not to gram-positive bacteria. This study presents a new paradigm for early diagnosis of bacterial infectious diseases. In addition to detecting living bacteria or bacteria-derived biomarkers, this protocol can be extended to monitoring the contamination of water resources, and may aid quick responses to bioterrorism and pathogenic bacterial infections.

(1) Background: Violence against each other via social media has increased and caused cyberbullying that can happen anytime through electronic communication tools that everyone can access easily. So, this study aims to investigate causal factors contributing to youth cyberbullying in Thailand's three Southern border provinces. (2) Methods: The subject group consisted of 340 youths and the data were analyzed with structural equation modeling (SEM). (3) Results: The study found that the model of the causal factors resulting in youth cyberbullying in the three Southern border provinces was consistent with the empirical data (the relative chi-square (χ2/df) was 1.77. The goodness-of-fit index (GFI) was 0.95. The root-mean-square-error of approximate (RMSEA) was 0.049). Cyberbullying was positively influenced directly and indirectly by negative upbringing, the influence of personal violence, and the influence of media violence at a statistically significant level of 0.001, with total effect sizes of 1.13, 0.74, and 0.64, respectively. Additionally, cyberbullying was positively influenced directly by negative mental traits with a statistically significant level of 0.05 and a total effect size of 0.17. (4) Conclusions: The study results could be beneficial in concretely forming policies and strategies to prevent and mitigate the problem of youth cyberbullying.

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.

Intrinsic subtype of triple-negative breast cancer (TNBC) is based on genomic evaluation. In this study, we report the survival and pathological complete response (pCR) rates of TNBC patients subtyped by IHC and treated with neoadjuvant chemotherapy (NACT). A retrospective cohort of 187 TNBC patients who received NACT between 2008 and 2017 was used, and IHC subtyping was performed on biopsy specimens before chemotherapy. The subtyping revealed predominant basal-like tumors (IHC-BL, 61%), followed by basal-like immune-suppressed (IHC-BLIS, 31%), mesenchymal tumors (12.5%), luminal androgen receptor tumors (IHC-LAR, 12%) and basal-like immune-activated (IHC-BLIA, 10.9%). The pathological complete response (pCR) rate varied among subtypes, with IHC-BLIA showing the highest (30.0%) and IHC-LAR showing the lowest (4.5%). IHC-BLIS led in recurrence sites. Overall and disease-free survival analyses did not show significant differences among subtypes. Although, IHC-BLIA demonstrated a trend toward better survival and IHC-mesenchymal worse. Patients who achieved pCR exhibited significantly better disease-free survival and overall survival than non-responders. This study underscores the potential of IHC-based subtyping in TNBC management, highlighting distinct response patterns to neoadjuvant chemotherapy and potential implications for treatment strategies. Further research is warranted to validate these findings and explore tailored therapeutic approaches for specific TNBC subtypes.

Breast cancer represents the most common neoplasm worldwide. Viral infections are involved with carcinogenesis, especially those caused by oncogenic Human Papillomavirus (HPV) genotypes. The relationship between HPV and various types of cancer, such as breast and lung, still requires further studies. After infection with HPV, there is a remodeling of the tumor microenvironment, providing a post-infection alteration with immunosuppressive characteristics. This study evaluated the role of HPV in breast adenocarcinoma cell lineage (MDA-MB-231), transfected with the HPV16 E5, E6, and E7 oncogenes and co-cultured with PBMCs. Immunophenotyping was performed. There was an increase in CD4+ T cells number when compared with non-transfected and transfected MDA-MB-231, especially the Treg profile. Moreover, proinflammatory intracellular cytokines, such as IFN-γ, TNF-α, and IL-17 were impaired by transfected cells and a decrease in the cytolytic ac-tivity of the CD8+ and CD56+ lymphocytes was also observed in the presence of HPV oncogenes, mainly with E6 and E7 in NK and TCD8+ cells. In conclusion, MDA-MB-231 breast cell lineage transfected with HPV oncogenes can downregulate the number and function of lymphocytes and monocytes.

Bromodomain-containing protein 4 (BRD4) is an intracellular protein that regulates expression of various cellular functions. This study investigated whether BRD4 inhibition can alter the immunomodulatory and antitumor effects of radiation therapy (RT). A murine breast cancer cell line was implanted into BALB/c mice. The dual-tumor model was used to evaluate the abscopal effects of RT. A total of 24 Gy was delivered and BRD4 inhibitor was injected intravenously. Tumor size was measured and in vivo imaging was performed to evaluate tumor growth. Flow cytometry and immunohistochemistry were performed to examine immunologic changes upon treatment. The combination of BRD4 inhibitor and RT significantly suppressed tumor growth compared to RT alone. BRD4 inhibitor reduced the size of the unirradiated tumor indicating that it may induce systemic immune responses. Expression of HIF-1α and PD-L1 in tumor was significantly downregulated by the BRD4 inhibitor. Proportion of M1 tumor-associated macrophages (TAMs) increased, and proportion of M2 TAMs decreased upon BRD4 inhibition. BRD4 inhibitor expanded CD4+ and CD8+ T cell populations and reduced the population of monocytic myeloid-derived suppressor cells (M-MDSCs). RT-induced splenic M-MDSCs decreased upon addition of BRD4 inhibitor. Therefore, addition of BRD4 inhibition significantly enhanced the systemic antitumor responses of local RT.

The article deals with auxetic structures made on the basis of suitably connected rigid rotating squares (from Grima and Evans), with axes of rotation on the squares’ surface. The geometric model and the resulting relationships that allow for the determination of Poisson’s ratio are considered in detail. It is demonstrated that changing the rotation axis position does not affect the negative Poisson’s ratio, equal to -1. The models built confirm the initial considerations and can offer new application possibilities.

Background: Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with poor outcomes. The molecular basis of TNBC remains poorly understood. The objective of this study was to explore the relationship between obesity and TNBC in premenopausal and postmenopausal Caucasian women using whole genome transcription profiling. Methods: We compared gene expression levels of tumor samples drawn from normal weight, overweight and obese in pre and postmenopausal women diagnosed with TNBC. We performed hierarchical clustering to assess similarity in patterns of gene expression profiles, and conducted network and pathway analysis to identify molecular networks and biological pathways. Results: We discovered gene signatures distinguishing normal weight from obese, normal weight from overweight and overweight from obese individuals in both premenopausal and postmenopausal women. The analysis revealed molecular networks and biological pathways dysregulated in response to obesity. Among the discovered pathways included the unfolded protein response, endoplasmatic reticulum stress, B cell receptor and the autophagy signaling pathways in obese premenopausal women and the integrin, axonal guidance, ERK/MAPK and Glutathione biosynthesis signaling pathways obese postmenopausal women. Conclusions: The results suggest that both overweight and obesity are associated with TNBC, highlighting the need for conformation of these results in independent studies.

We manufacture different Carbon Negative fuels at out manufacturing facilities. We manufacture fuel Butanol, fuel Isobutanol, fuel Diacetyl alcohol, and fuel Mesityl oxide. All said fuels are manufactured from the air CO2. Mixtures of our Carbon Negative fuels are great to fuel both Gasoline and Diesel fuel cars and trucks. The fuel mileage we can gather using said mixtures exceeds both either the Gasoline mileage aor the Diesel fuel mileage using respective cars / trucks. We publish herein the fuel mileage which always exceeds the gas and diesel fuel mileages for said fuels manufactured by the international petroleum corporations.

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.

The present article aims at investigating the role of social support in the emotional well-being of young offenders. We hypothesized that perceived social support would be positively related to the emotional well-being of juvenile offenders. The methods were worked out to study perceived and received social support, psychological well-being and emotional state of the juvenile offenders. The entire sample consisted of 56 males aged from 15 to 18 years old (M = 16.5; SD = 0.8). 32 subjects (57%) were in pretrial detention and 24 participants (43%) were in a correctional camp located in the central region of Russia. The study detected that the level of psychological well-being of the respondents from the camp was correlated neither with perceived social support nor with the frequency of seeking assistance from the different sources of support. For the respondents in the pretrial detention, the level of psychological well-being was directly connected to the degree of the perceived support from the friends. The obtained differences might be associated with the influence of social environment in the pretrial detention and in the camps.

Studies have shown that vehicle trajectory data are effective for calibrating microsimulation mod-els. Light Detection and Ranging (LiDAR) technology offers high-resolution 3-D data, allowing for detailed mapping of the surrounding environment, including road geometry, roadside infrastruc-tures, and moving objects such as vehicles, cyclists, and pedestrians. This research presents a comprehensive framework for integrating LiDAR sensor data into simulation models and accu-rately calibrating for proactive safety analysis. Vehicle trajectory data were extracted from LiDAR point cloud collected at six urban signalized intersections in Lubbock, Texas in USA. Each study intersection was modelled with PTV VISSIM and calibrated to replicate the observed field scenarios. The Directed Brute Force method was used to calibrate two car-following and two lane-change parameters of Wiedemann 1999 model in VISSIM, resulting in an average accuracy of 92.7%. Rear-end conflicts extracted from the calibrated models combined with a ten-year historical crash dataset were fitted into a Negative Binomial (NB) model to estimate the model's parameters. In all the six intersections, rear-end conflict count is a statistically significant predictor (p-value < 0.05) of observed rear-end crash frequency. The outcome of this study provides a framework for the com-bined use of LiDAR-based vehicle trajectory data, microsimulation and surrogate safety assessment tools to transportation professionals for proactive safety evaluation.

This critical review delves into the often-overlooked aspect of early childhood language development: the potential impact of exposure to foreign languages. While multilingualism is widely celebrated for its cognitive and cultural benefits, emerging research suggests that early exposure to foreign languages may pose challenges for young children's linguistic development. The review synthesizes findings from 17 studies to explore the complexities surrounding this issue, including linguistic confusion, language delay, reduced vocabulary growth, impaired language processing, and socio-emotional implications. Additionally, mitigating factors and future directions for research and intervention are discussed. By shedding light on this topic, the review aims to inform educators, parents, and policymakers about the nuances of bilingual language acquisition and the importance of providing tailored support to optimize early childhood language development in multilingual contexts.

This article presents multiple novel and compelling arguments to systematically disprove two widely accepted notions: one is that entropy is a measure of disorder, and the other is Schrödinger's notion of negative entropy (negentropy). These two notions have been cited hundreds of times annually in scientific literature for decades. To mathematically describe the second law of thermodynamics, the concept of entropy was created and defined in the 1860s as heat energy divided by thermodynamic temperature, and the entropy of an object increases when it absorbs heat. This is the uncontroversial and fundamental nature of entropy, which is pivotal to current thermodynamics and from which multiple facts are deduced. These facts consistently disprove the above two notions. Some biological facts, such as the one that life orderliness is encoded and provided by inherited genes rather than entropy decline, can also disprove Schrödinger's negentropy notion. Moreover, this article further clarifies the reasoning errors of the two notions. It also shows that the tendency of many natural or social systems to become more disordered over time does not result from the second law of thermodynamics.

This study investigates the effects of ambient illumination and negatively polarized text color on visual fatigue, exploring the issue of visual fatigue when using visual display terminals in low-illumination environments. The research methodology utilized an experimental design to collect data on changes in pupil accommodation and blink rate through an eye tracker. Partici-pants completed a reading task while exposed to various text colors and ambient light conditions to evaluate visual fatigue and cognitive performance. The study's findings suggest that text color significantly affects visual fatigue, with red text causing the highest level of visual fatigue and yellow text causing the lowest level of visual fatigue. Improvements in ambient lighting reduce visual fatigue, but the degree of improvement varies depending on the text color. Additionally, cognitive performance is better when using yellow and white text but worse when using red text. Yellow text is the most effective choice for reducing visual fatigue under negative polarity. In-creasing ambient lighting can also improve visual fatigue in low-illumination conditions. These findings will offer valuable guidance for designing visual terminal device interfaces, especially for low-illumination or night environments, to minimize visual fatigue and improve the user ex-perience.

This study aims to spatially analyze the distribution characteristics of vacant homes in Asan-si, Chungcheongnam-do, and understand the differences in factors causing vacant homes by type. We use a variety of statistical methods to examine these factors and identify key influencing factors such as the number of vacant stores, changes in overall population, land use complexity, and physical characteristics of land and buildings. The findings reveal that the factors contributing to the occurrence of vacant homes vary significantly by region and property type, highlighting the need for region-specific policies. For instance, in old town areas, small lot ratios and land use complexity are significant, while in rural village, the average number of floors and land use complexity play a major role. This study underscores the diversity of factors influencing vacant homes, suggesting that policies should be tailored to the unique characteristics of different regions to effectively address this issue.

ABSTRACT Background: To date, the COVID-19 pandemic has been the foremost health concern for humankind in the new millennia. This paper aims to describe the related hospitalizations in Italy during the first two years of the health emergency. Design and methods: This is a retrospective, population-based study of Italian hospitalizations for patients diagnosed with COVID-19 during the 2020-2021 period, extracted from the National Hospital Discharge Registry. The outcome variables considered include hospital admissions, costs, and length of stay, among other hospitalization-level variables. Costs were estimated through the charges associated with the Diagnosis-Related Group and Major Diagnostic Categories coding system, plus an additional cost attributed to COVID-19 admissions. To these charges was added an extra cost defined by the ministry of health. Results: In Italy, there were 357,354 hospitalizations for COVID-19 attributed to 298,856 patients in 2020 and 399,043 hospitalizations for COVID-19 attributed to 333,447 patients in 2021. COVID-19 patients faced a transfer rate thrice that of other patients. Hospitalizations were concentrated predominantly in the northern regions, particularly in the first year. Hospitalization rates varied by age in a sine wave pattern, peaking in the youngest and oldest age groups, with mortality rates escalating with age— tending to remain below 3% for those under 44 but surging to 40% in individuals over 75. The financial impact of COVID-19 hospitalizations was substantial, with total costs reaching €3.97 billion in 2020 and €4.99 billion in 2021. Costs per admission and per day also rose, from €11,112 and €807 in 2020 to €12,503 and €844 in 2021, respectively. Excluding the added financial burden of COVID-19, costs would have been notably lower. Hospitalizations involving continuous invasive mechanical ventilation were particularly costly (about 24.000 euros x admission), reflecting the significant resources required for these treatments. Conclusion: Implementing a protective pad around the entire health system that leverages networks of family doctors and nurses, connected in real time to the entire health system, can be crucial. Such a network, tasked with monitoring the local epidemiological situation, protecting vulnerable individuals also through telehealth visits, and establishing a triage system for infections in the initial phase, may effectively help in managing virus spread and protecting hospitals from unpredictable waves of admission demand. Strengthening primary health care could be a decisive factor for the future and enhance the system's resilience in facing new challenges.

We have successfully synthesized a series of Bi doped BaFe2As2 high quality single crystals for the first time. The x-ray diffraction (XRD) patterns show an expansion of lattice parameter c with Bi doping, indicating a negative pressure effect. By investigating the resistivity, a Fermi liquid (FL) to non-Fermi liquid (NFL) crossover is observed from normal state to antiferromagnetic order state, accompanied by three superconducting transitions labeled as SC I, SC II and SC III which are supposed to be induced from three superconducting realms with various Bi concentration. Thus, the NFL behavior is proposed to be closely related with the presence of superconductivity. The magnetic susceptibility measurements further speculates that the SC I and SC III phases should be filamentary superconductivity while the SC II be a possible bulk superconductivity with TC 7 K.

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.

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.

Sphingomonas paucimobilis is an opportunist pathogen bacillus gram-negative aerobic with a rare occurrence. We present a case in an immunocompetent man successfully treated by surgical debridement, purulent drainage and with an associated course of antibiotics. A large necrotic infection, approximately 5 cm x 3 cm, in a 74-year-old man was identified. Empirical antibiotic therapy with ciprofloxacin 400mg EV 12/12 hours, associated with clindamycin 600mg EV 6/6 hours and pain control was done through dipyrone 1gr, tramadol 400 mg. Deep venous thrombosis was prevented through the prescription of enoxaparin 40mg subcutaneous once a day during hospitalization. The case was well illustrated with pictures throughout treatment. Complete healing was achieved after 90 days. Herein, we present a case of cutaneous contamination. The presented case is the third cutaneous contamination case reported in the literature and the first reported case in the Amazonia region in Brazil.

The high transmissibility, rapid evolution, and immune escape of SARS-CoV-2 variants can influence the course of infection and, in turn, morbidity and mortality in COVID-19, posing a challenge in controlling transmission rates and contributing to the emergence and spread of new variants. The factors that shape viral genetic variation are consequently essential for understanding the evolution and transmission of SARS-CoV-2, especially in vaccinated individuals where immune response plays a role in the progression and spread of this disease. This study assessed. In this context, we evaluated the impact of immunity induced by the CoronaVac vaccine (Butantan/Sinovac) on intra-host genetic diversity, analyzing 118 whole-genome sequences of SARS-CoV-2 from unvaccinated and vaccinated patients infected with the Gamma variant. Vaccination with CoronaVac favors negative selection at the intra-host level in different genomic regions and prevent greater genetic diversity of SARS-CoV-2, which may help reduce the emergence of new mutations, reinforcing the importance of vaccination in reducing virus transmission.

Objective: To explore the functions that physical activity (PA), life satisfaction, and self-efficacy have in the process of coping with anxiety among Chinese college students, and to explore the mediating role of life satisfaction and self-efficacy in this process. Methods: Participants were 358 college students (186 males, 172 females, mean age 20.88, SD=±1.80). Psychosocial tests including the Physical Activity Rating Scale (PARS-3), College Student Life Satisfaction Scale (CSLSS), General Self-Efficacy Scale (GSES), and Generalized Anxiety Disorder Scale (GAD-7) were completed. Correlations between variables were calculated using Pearson's test. The mediation model was tested using the SPSS 26.0 PROCESS macro and regression bootstrap. Results: Physical activity showed a negative correlation with anxiety (β= -0.1617, p < 0.001), life satisfaction and self-efficacy played a role in the relationship between physical activity and anxiety, and, more importantly, physical activity affected anxiety through the parallel mediating effects of life satisfaction and self-efficacy, with a total mediating effect of 55.34%. Conclusion: By increasing college students' participation in physical activity, it helps to promote the growth of their life satisfaction and self-efficacy, which is the key to reducing anxiety and promoting college students' mental health.

Background: Metastatic triple-negative breast cancer (TNBC) is aggressive with a poor median overall survival (OS), ranging from 8 to 13 months. There exists considerable heterogeneity in the survival at the individual patient level. To better understand the survival heterogeneity and improve risk stratification, our study aims to identify the factors influencing survival utilizing a large patient sample in the National Cancer Database (NCDB). Methods: Women diagnosed with metastatic TNBC from 2010 to 2020 in the NCDB were included. Demographic, clinic-pathological, treatment data, and overall survival (OS) outcomes were collected. Kaplan-Meier curves were used to estimate OS. The log-rank test was used to identify OS differences between groups for each variable in the univariate analysis. For the multivariate analysis, the Cox proportional hazard model with backward elimination was used to identify factors affecting OS. Adjusted hazard ratios and 95% confidence intervals are presented. Results: 2,273 women had a median overall survival of 13.6 months. Factors associated with statistically significantly worse OS included older age, higher comorbidity scores, specific histologies, higher number of metastatic sites, presence of liver or other site metastases in those with only one metastatic site (excluding brain metastases), presence of cranial and extra-cranial metastases, lack of chemotherapy, lack of immunotherapy, lack of surgery to distant sites, lack of radiation to distant sites, and receipt of palliative treatment to alleviate symptoms. In the multivariate analysis, comorbidity score, histology, number of metastatic sites, immunotherapy, and chemotherapy had a statistically significant effect on the OS. Conclusions: Through NCDB analysis, we have identified prognostic factors for metastatic TNBC. These findings will help improve prognostication at diagnosis, optimize treatment strategies, and facilitate patient stratification in future clinical trials.

When asked to estimate the carbon footprint of a bundle of relatively low carbon footprint items and relatively high carbon footprint items, people typically report a lower value compared to estimating the high carbon footprint items alone. This finding is called the negative footprint illusion and suggests people report the average rather than sum of the combined items’ carbon footprint. In a recent paper by Gorissen et al. (2024), the authors claimed that people are immune to this illusion if the question is framed differently. Specifically, they found that estimates of the environmental friendliness of a set comprising a burger (high carbon footprint) and an organic apple (low carbon footprint) was higher than for a set comprising the burger alone, whereas no difference was found between the two sets when participants were asked to estimate how environmentally damaging they were. Using larger item categories wherein the degree of the items’ environmental impact is clearly communicated, here we show it does not matter whether participants are required to estimate how friendly or damaging the items are. The roles of attribute substitution, dependent variables, and independent variables (stimulus characteristics) in modulating the negative footprint illusion is discussed.

Background: As the most invasive breast cancer (BrCa), triple-negative BrCa (TNBC) has the worst survival. The use of dexmedetomidine potentially affected BrCa surgery and dexmedetomidine was reported to have direct effects on TNBC cells. The objective of this study is to explore the mechanisms underlying the effect of dexmedetomidine on TNBC. Methods: Dexmedetomidine targets were predicted using The Cancer Genome Atlas data SwissTargetPrediction. Cell lines MDA-MB-231, MCF7, and MCF10A were used to validate the targets in TNBC with both clinical samples and cell lines. Cancer cell lines and normal breast cell lines were grouped in cancer and normal groups respectively. Both groups were exposed to dexmedetomidine treatment. Cell Counting Kit-8 was used to determine the effect of dexmedetomidine on cells with target silencing. The binding model of the candidate targets was docked and critical amino acids were mutated to validate the binding model. Results: Dexmedetomidine selectively inhibits cancer cells. Catalytic subunit of the DNA-dependent protein kinase (PRKDC), indoleamine 2,3-dioxygenase 1 (IDO1), opioid receptor kappa 1 (OPRK1), glutaminyl-peptide cyclotransferase (QPCT), macrophage migration inhibitory factor (MIF), potassium voltage-gated channel, subfamily H (Eag-related), member 2 (KCNH2), cholinergic receptor, muscarinic 3 (CHRM3), and potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4 (KCNN4) were identified as dexmedetomidine targets in TNBC. The expression levels of PRKDC, IDO1, MIF, KCNH2, CHRM3, and KCNN4 were found to be upregulated in TNBC tissues compared to non-TNBC tissues(p<0.05). Silencing of these genes was found to reduce the sensitivity of TNBC cells to dexmedetomidine(p<0.05). This effect was counteracted when the silenced genes were overexpressed, resulting in an increase in the sensitivity of cells to dexmedetomidine (p<0.05). Furthermore, a direct interaction between dexmedetomidine and IDO1 and CHRM3 was observed, which regulated the sensitivity of cells to dexmedetomidine(p<0.05).Conclusion: IDO1 and CHRM3 are direct targets of dexmedetomidine in TNBC.

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.

Abstract Background. There is an inherent limit in the accuracy of our measurements, set by nature itself and predicted by Heisenberg's uncertainty principle, which defines the properties of nature in the microcosmos. There is a fundamental limit to the accuracy with which complementary phys-ical quantities of a particle can be predicted from their initial conditions. As classical physics is essentially considered at borderline of quantum mechanics, so the power of uncertainty princi-ple is limited in describing everyday life perceived or managed phenomena. Method. In this study, we apply Heisenberg's uncertainty principle to children under diagnostic uncertainty re-garding appendicitis. We analyze this phenomenon in clinical practice. Results. Medical practice is full of uncertainty. False negative decisions correlate with delays in treatment and adverse outcomes in children with atypical appendicitis. On the other hand, false-positive surgery deci-sions result in negative appendectomies. With improvement of technology, the incidence of complicated appendicitis or negative appendectomies due to diagnostic uncertainty has de-creased but cannot be ignored or eliminated. Conclusion. According to the principle, there is a fundamental limit to the accuracy with which the complementary variables of negative appen-dectomy and complicated appendicitis can be observed or measured simultaneously. What does all this mean for the physician?

Prosthetics have come a long way since their inception, and recent advancements in materials science have enabled the development of prosthetic devices with improved functionality and comfort. One promising area of research is the use of auxetic metamaterials in prosthetics. Auxetic materials have a negative Poisson's ratio, which means that they expand laterally when stretched, unlike conventional materials, which contract laterally. This unique property allows for the creation of prosthetic devices that can better conform to the contours of the human body and provide a more natural feel. In this review article, we provide an overview of the current state of the art in the development of prosthetics using auxetic metamaterials. We discuss the mechanical properties of these materials, including their negative Poisson's ratio and other properties that make them suitable for use in prosthetic devices. We also explore the limitations that currently exist in implementing these materials in prosthetic devices, including challenges in manufacturing and cost. Despite these challenges, the future prospects for the development of prosthetic devices using auxetic metamaterials are promising. Continued research and development in this field could lead to the creation of more comfortable, functional, and natural-feeling prosthetic devices. Overall, the use of auxetic metamaterials in prosthetics represents a promising area of research with the potential to improve the lives of millions of people around the world who rely on prosthetic devices.

It is proven that the Clapeyron-Mendeleev equation, originally discovered for gases with large entropy, describes the state of dark matter and energy due to enormous self-gravitation. It is shown that the dark matter exists as compact cold neutrino stars at positive temperature with size twice the Schwarzschild radius. In contrast, the dark energy is dark matter at temperature below the absolute zero, which is locked entirely in black holes, where the pressure is negative as required for the Universe intrinsic expansion. The derived dark phase diagram predicts negative critical temperatures for the Big Bang and the Big Rip of black holes.

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.

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.

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.

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.

Metabolite transport across cellular membranes is a key feature of living organisms. Specialized proteins or protein complexes mediate such transport processes and are accessible to genetic engineering approaches. This special issue will reflect on the different transport between cellular compartments. It will provide an overview about different transporter classes and metabolic engineering approaches in different organisms ranging from Bacteria to Eukarya. The transport mechanisms energetics of these compounds were thought little of, and most consideration was given to the designing of metabolic pathways. Gram-negative microbes discharge a wide scope of proteins whose capacities incorporate biogenesis of organelles, for example, pilli and flagella, supplement securing, destructiveness, and efflux of medications and different poisons. Six particular emission frameworks have been appeared to intervene protein send out through the inward and external layers of Gram-negative microbes. These pathways are exceptionally monitored all through the Gram-negative bacterial species. In Gram-positive microscopic organisms, discharged proteins are usually moved across the single layer by the Sec pathway or the two-arginine (Tat) pathway. Recently efforts focused on transporter and metabolite engineering, visualize the improvement and enhancement of microbial cell to pass such metabolites these metabolite carrier proteins are inserted into the inner membrane of mitochondria across the inner membrane, specialized carrier proteins are necessary that mediate the transport into and out of the mitochondrial matrix. Two main strategies for metabolic engineering in plants: the introduction of genes encoding new enzymes and the use of TFs controlling specialized metabolic pathways

A deep relationship is identified between the Coulomb Force and Gravity. A gravitational constant for strong gravity is calculated from the relationship. The equivalence between mass and charge is explored. Implications are given for the expansion of Einstein's Field Equations to include vector gravity.

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 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.

Schizophrenia comprises various symptom domains, including positive and negative symptoms. Machine learning showed that a) negative symptoms are significantly interrelated with PHEM (psychosis, hostility, excitation, and mannerism) symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR); and b) stable phase schizophrenia comprises two distinct classes, namely Major Neuro-Cognitive Psychosis (MNP, largely overlapping with deficit schizophrenia) and Simple NP (SNP). In this study, we recruited 120 MNP patients and 54 healthy subjects and measured the above-mentioned symptom domains. In MNP, there were significant associations between negative and PHEM symptoms, FTD and PMR. A single latent trait, which is essentially unidimensional, underlies these key domains of schizophrenia and MNP and additionally shows excellent internal consistency reliability, convergent validity, and predictive relevance. Confirmatory Tedrad Analysis indicates that this latent vector fits a reflective model. The lack of discriminant validity shows that PHEM and negative symptoms greatly overlap and probably measure the same construct. Soft Independent Modeling of Class Analogy (SIMCA) shows that MNP (diagnosis based on negative symptoms) is better modeled using PHEM symptoms, FTD, and PMR than negative symptoms. In conclusion, in stable phase MNP, a restricted sample of the schizophrenia population, negative and PHEM symptoms, FTD and PMR belong to one underlying latent vector reflecting overall severity of schizophrenia (OSOS). The bi-dimensional concept of “positive” and “negative” symptoms cannot be validated and, therefore, future research in stable phase schizophrenia should consider that the latent phenomenon OSOS as well as its 8 reflective manifestations are the key factors of schizophrenia phenomenology.

This is a review of efforts to discover action principles for Hydrodynamics and Thermodynamics. The work began with a determined attempt to create sources for Einstein's equations that describe continuous matter - as opposed to point particles. This requires a relativistic action principle. This report is mainly about (non relativistic) Adiabatic Thermodynamics, non equilibrium thermodynamics based on the method of Gibbs. The main relations of classical thermodynamics can be derived from an action principle, in the classical global form and in the local form advocated by Callen. The entropy is defined as the negative derivative of the free energy (free energy density) with respect to the volume (density). This is integrated with an action principle for hydrodynamics that was known to Lagrange in 1760. It is strongly limited to irrotational velocity fields, nevertheless it provides the needed Lagrangian for a large part of thermodynamics. This is the subject of the first 3 sections. It includes a brief review of a new theory of mixtures. The most difficult part of the program has been the discovery of Conservative Hydrodynamics with the required four independent degrees of freedom, with general flows. We give an account of the genesis and the structure of this theory, then a tour of recent applications.

Mitochondria are dynamic organelles ubiquitously present in nucleated eukaryotic cells, subserving multiple metabolic functions, including cellular ATP generation by oxidative phosphorylation (OXPHOS). The OXPHOS machinery comprises five transmembrane respiratory chain enzyme complexes (RC). Defective OXPHOS gives rise to mitochondrial diseases (mtD). The incredible phenotypic and genetic diversity of mtD can be attributed at least in part to the RC dual genetic control (nuclear DNA [nDNA] and mitochondrial DNA [mtDNA]) and the complex interaction between the two genomes. Despite the increasing use of next-generation-sequencing (NGS) and various -omics platforms in unraveling novel mtD genes and pathomechanisms, current clinical practice for investigating mtD essentially involves a multipronged approach including clinical assessment, metabolic screening, imaging, pathological, biochemical and functional testing to guide molecular genetic analysis. This review addresses the broad muscle pathology landscape including genotype-phenotype correlations in adult and paediatric mtD, the role of immunodiagnostics in understanding some of the pathomechanisms underpinning the canonical features of mtD, and recent diagnostic advances in the field.

We describe a new approach for integrating multiple views of data into a common latent space using non-negative tensor factorization (NTF). This approach, which we refer to as the "Integrated Sources Model" (ISM), consists of two main steps: embedding and analysis. In the embedding step, each view is transformed into a matrix with common non-negative components. In the analysis step, the transformed views are combined into a tensor and decomposed using NTF. Noteworthy, ISM can be extended to process multi-view data sets with missing views. We illustrate the new approach using two examples: the UCI digit dataset and a public cell type gene signatures dataset, to show that multi-view clustering of digits or marker genes by their respective cell type is better achieved with ISM than with other latent space approaches. We also show how the non-negativity and sparsity of the ISM model components enable straightforward interpretations, in contrast to latent factors of mixed signs. Finally, we present potential applications to single-cell multi-omics and spatial mapping, including spatial imaging and spatial transcriptomics, and computational biology, which are currently under evaluation. ISM relies on state-of-the-art algorithms invoked via a simple workflow implemented in a Jupyter Python notebook.

This study explores the relationship between positive and negative habits and their rewards over time. Using a bibliographic and documentary approach, we analyze how the temporality of rewards influences the formation and maintenance of habits. We developed the "habit chart", which shows that positive habits, such as reading, healthy eating, physical exercise, meditation and personal relationships, offer incremental and lasting rewards. In contrast, negative habits such as sugar consumption, excessive use of social media and a sedentary lifestyle provide immediate gratification followed by a sharp decline. The analysis was based on studies such as those by Warburton et al. (2006), Lally et al. (2010), and Hu (2003) for positive habits, and Malik et al. (2010) and Kross et al. (2013) for negative habits. We conclude that practical strategies, such as financial incentives and creating enabling environments, can make long-term rewards more tangible, promoting the adoption of healthy behaviors. This study reinforces the importance of the temporality of rewards in habit formation and suggests evidence-based interventions to improve quality of life and general well-being.

Within the field of nanomedicine, which is revolutionizing cancer treatment, solid lipid nanoparticles (SLNs) have shown advantages over conventional chemotherapy when tested on cancer cells in preclinical studies. SLNs have proven to be an innovative strategy for the treatment of tri-ple-negative breast cancer cells, providing greater efficiency than existing treatments in various studies. The encapsulation of antineoplastic drugs in SLNs has facilitated a sustained, controlled, and targeted release, which enhances therapeutic efficiency and reduces adverse effects. Moreover, the surface of SLNs can be modified to increase efficiency. For instance, the coating of these particles with polyethylene glycol (PEG) decreases their opsonization, resulting in a longer life in the circulatory system. The creation of positively charged cationic SLNs (cSLNs), achieved by the utilization of surfactants or ionic lipids with positively charged structural groups, increases their affinity for cell membranes and plasma proteins. Hyaluronic acid has been added to SLNs, so that the distinct pH of tumor cells, would stimulate the release of the drug and/or genetic materi-al. The current revision summarizes the recent research on SLNs, focusing on the encapsulation and transport of therapeutic agents with a cytotoxic effect on triple-negative breast cancer.

Abstract: (1) Background: We determined the prevalence of hepatitis B virus (HBV) amongst people without human immunodeficiency virus (HIV) in rural and peri-urban areas in Botswana. (2) Methods: We screened hepatitis B surface antigen (HBsAg) from archived plasma samples of people without HIV (n=2135) randomly selected from the Botswana Combination Prevention Program (BCPP) (2013–2018). We sequenced 415 bp of the surface region using BigDye sequencing chemistry. (3) Results: The median age of participants was 31 (IQR: 24–46) and 64% (1360/2135) were female. HBsAg prevalence was 4.0% (86/2135) [95% CI: 3.3 – 4.9]) and ranged between 0%–9.2%. Older participants (>35 years) had increased odds of HBsAg positivity (OR: 1.94; 95% CI: [1.32–2.86]; p = 0.001. Thirteen samples were sequenced and 7 (53.8%) were genotype A, 3 (23.1%) were genotype D and genotype E each. Clinically significant mutations were identified in the surface region, but no classic drug resistance mutations were identified. (4) Conclusions: We report an HBV prevalence of 4.0% (95% CI 3.3 – 4.9) among people without HIV in rural and pe-ri-urban communities in Botswana with varying rates in different communities. A comprehen-sive national HBV program is required in Botswana to guide HBV prevention, testing and management.

PIEZO1 plays a crucial role in the human body as a mechanosensory ion channel. It has been demonstrated that PIEZO1 is important in tissue development and regulating many essential physiological processes. Studies have suggested that the PIEZO1 ion channel plays a role in invasion and progression in cancer; elevated levels of PIEZO1 have been correlated with increased migration in breast cancer cells, chemo-resistance and invasion in gastric cancer cells, and increased invasion of osteosarcoma cells. In addition, high PIEZO1 expression levels were correlated with a worse prognosis in glioma patients. On the other hand, studies in lung cancer have attributed high PIEZO1 levels to better patient outcomes. However, the clinical impact of PIEZO1 in breast cancer is not well characterized. Therefore, our goal was to determine the clinical relevance of PIEZO1 in breast cancer. Analysis of breast cancer data from The Cancer Genome Atlas (TCGA) was conducted to investigate PIEZO1 expression levels and correlation to survival, followed by validation in an independent dataset, GSE3494. We also performed gene set enrichment analysis (GSEA) and analyzed immune cell levels in breast tumors from TCGA through a CIBERSORT algorithm. Our results demonstrated that PIEZO1 expression levels are higher in hormone receptor (HR) negative than HR positive cohorts. High PIEZO1 expression is correlated with a significant decrease in survival in HR negative cohorts, suggesting that PIEZO1 could be utilized as a prognostic biomarker in HR negative breast cancer. GSEA showed that various signaling pathways associated with more invasive phenotypes and resistance to treatments, including epithelial-mesenchymal transition (EMT), hypoxia, and multiple signaling pathways, are enriched in high PIEZO1 HR negative tumors. Our results also demonstrated a decrease in CD8+ and CD4+ T cell infiltration in high PIEZO1 HR negative tumors. Further investigations are necessary to elucidate the mechanistic roles of PIEZO1 in HR negative breast cancer.

Coagulase-Negative Staphylococci (CoNS) are commensal on human body surfaces and for years, they were not considered a cause of bloodstream infection and were often regardered as contamination. However, the association of CoNS with nosocomial infection is increasingly recognized. The insertion of cannulas and intravascular catheters represents the first source of CoNS entry into the bloodstream, causing bacteremia and sepsis. They owe their pathogenic power to their ability to produce biofilms on surfaces, such as medical devices. In this study, we evaluate the adhesive capacity of CoNS isolated from blood cultures by comparing spectrophotometric phenotypic assay with genotypic analysis based on the evidence of the ica operon. We retrospectively reviewed the database of CoNS isolated from blood cultures, that were considered to be responsible for 361 bloodstream infections. Among them, we selected 89 ones who had full records. Our data show that S. epidermidis was the predominant species isolated, and with greater adhesive capacities, especially those with the complete operon. Knowing the adhesive capabilities of a microorganism responsible for sepsis can be useful in implementing appropriate corrective and preventive measures, as conventional antibiotic therapy cannot effectively eradicate biofilms.

Negative thermal quenching (NTQ) denotes that the integral emission spectral intensity of a given phosphor increases continuously with increasing temperature up to a certain elevated temperature. NTQ has been a subject of intensive investigation in recent years and a large number of phosphors were reportedly to have exhibited NTQ. In this paper, a collection of results in the archival literature about NTQ of specific phosphors are discussed from a macroscopic viewpoint in the following three aspects:1) Could NTQ of a given phosphor be reproducible?2) Could the associated data for a given phosphor exhibited NTQ be in line with the law of conservation of energy?3) Could NTQ of a given phosphor be demonstrated in a prototype WLED device? By analyzing typical cases based on common sense, it is hoped to increase the awareness for the issues with the papers reporting NTQ of the specific phosphors based on spectral intensity along with for the importance of keeping stability and consistency of the measurement conditions in temperature-dependent spectral intensity measurement which is a prerequisite for the validity of the measurement results.

Shared micromobility has gained significant attention in the field of transportation engineering in recent years as an environmentally friendly, convenient, and easily accessible transportation mode. Like other medium-sized cities, Birmingham, Alabama implemented a shared micromobility pilot program in 2021 that captured the attention of local travelers. This study examined shared e-scooter usage and associated travel patterns in Birmingham using 2021-2022 field data. From these data, ArcGIS maps were used to showcase trip origins and destinations. To gain a further understanding of e-scooter travel patterns in the study area, zip code and block group densities were calculated. Additionally, a negative binomial regression model was constructed to identify determinants of shared e-scooter trips. The analysis results showed that the usage of shared e-scooters was the highest during the nighttime, on weekends, and in the fall season. Furthermore, the research findings indicated that shared e-scooters experienced their highest utilization rates in areas with a higher proportion of educated and higher-income individuals. These findings suggest that travelers’ mode choice related to the use of micromobility modes is influenced by environmental and demographic factors. Overall, this case study offers valuable contributions to the understanding of the role of shared e-scooters in Birmingham's transportation landscape and can guide transportation authorities in other medium-sized cities in their efforts to plan for micromobility options.

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.

Eating disorders are a global burden and present personal, family, and societal costs. Most evidence in the literature is based on the relationship between a poor family environment and eating disorders, and the evidence of gender interaction in eating disorders is inconsistent. This study aimed to investigate the relationship between family functioning and disordered eating patterns, the mediating role of negative automatic thoughts, and the moderating role of gender. A sample of 440 (70.9% females, aged 18–21) participated in this study. They completed the Eating Attitudes Test (EAT-26), the Automatic Thoughts Questionnaire (ATQ negative), and the Brief Family Relationship Scale (BFRS). PROCESS MACRO was used to study these relationships. The main findings revealed that family functioning was negatively associated with eating disorders, and that this relationship was negatively mediated by automatic thoughts. Moreover, gender moderated those relationships, and more intensely in females. The results of this study postulate that the prevention of eating disorders should be directed at training individuals to challenge negative thoughts and encourage healthy individuals to be gender mindful.

Wellness is a multidimensional concept that touches upon the various physical, mental, emotional, spiritual, social and environmental facets of health. Interest towards and importance of wellness have been growing constantly for the past two decades and thus makes it crucial to understand which factors affect public engagement with wellness information for multiple stakeholders. The Instagram account of New York Times (NYT) specifically for sharing wellness content with the handle nyt_well was selected as the object of study. 773 posts from this account between March of 2019 and December of 2022 were collected and analyzed to answer the research question of which factors are most influential to public engagement with wellness content. Two negative binomial regressions were run on features including the type of post, length, word count, sentiment score and topic with number of likes and comments as the dependent variables for each of those regression models. Results indicated that the type of post and its sentiment score were the two most influential determinants of public engagement with p-values smaller than 0.05. While the effects of some of these factors aligned with findings from previous studies conducted on social media content not related to wellness (e.g., marketing), some others affected the two separate public engagement metrics in opposite directions, warranting future studies to investigate further on the cause of this phenomenon.

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.

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.

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.

Tilapia lake virus (TiLV) is the main tilapia-infecting virus worldwide, causing serious economic losses. However, there is no vaccine for this viral disease. Here, TiLV ORF10 (TiLV-ORF10) encoding a protein with abundant epitopes was constructed into the eukaryotic expression vector pcDNA3.1, and used to evaluate the immune protective effects in Nile tilapia (Oreochromis niloticus). RT-PCR and western blot analyses confirmed vaccine plasmid expression in tilapia muscle tissues. Moreover, the transcription levels of immunoglobulin M, toll-like receptor 2, myeloid differentiation factor 88, interleukin 8, tumor necrosis factor alpha, gamma-IFN, and nuclear factor κB immune-related genes were statistically significantly upregulated in the spleen, liver, and kidney of vaccinated tilapias (P < 0.05). TiLV challenge experiments showed that relative percent survival (RPS) was significantly enhanced in fish by this DNA vaccine. Moreover, RPS was enhanced further when using a higher amount of the DNA vaccine (85.72% RPS at a DNA dose of 45 μg pcDNA3.1–ORF10). Vaccination with pcDNA3.1–ORF10 significantly reduced virus replication, as evidenced by the low amount of virus in the spleen, liver, and kidney of vaccinated tilapias after TiLV challenge. Thus, pcDNA3.1–ORF10 could induce protective immunity in tilapia and may be a potential vaccine candidate for controlling diseases caused by TiLV.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the lack of estrogen receptors (ER), progesterone receptors, and HER-2 receptors. Thus, TNBC tumours do not benefit from the current therapies targeting ER or HER-2. Therefore, there is an urgent need to develop novel treatment for this subtype of breast cancer. Marijuana is a common name given to Cannabis plants, a group of plants in the Cannabis genus of the Cannabaceae family. Cannabis plants are among the oldest cultivated crops, traced back at least 12,000 years and are well known for their multi-purpose usage, including medicinal purposes. The main active compounds extracted from Cannabis plants are 21-carbon-containing terpenophenolics, which are referred to as phytocannabinoids. Of these, the tetrahydrocannabinol (THC) group contains highly potent cannabinoids, including delta-9-tetrahydrocannabinol (∆9-THC) and delta-8-tetrahydrocannabinol (∆8-THC), which are the most abundant THCs and are largely responsible for psychological and physiological effects of marijuana. The use of Cannabis plants for medicinal purposes was first recorded in 2337 BC in China, where Cannabis plants were used to treat pains, rheumatism, and gout. Recently, several cannabinoids have been approved for a number of treatments, one of which is the treatment of nausea and vomiting caused by chemotherapy in cancer patients. Furthermore, increasing evidence shows that cannabinoids not only attenuate side effects due to cancer treatment, but might also potentially possess direct antitumor effects in several cancer types, including breast cancer. However, anti-tumour activity of marijuana has been variable in different studies and even promoted tumour growth in some cases. In addition, the mechanisms of cannabinoid action in cancer remain unclear. This review summarizes evidence about the mixed actions of cannabinoids in cancer in general and triple-negative breast cancer in particular.

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?

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.

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.

Plasmodium vivax malaria is a neglected tropical disease, despite being more geographically widespread than any other form of malaria. The documentation of P. vivax infections in different parts of Africa where Duffy-negative individuals are predominant suggested that there are alternative pathways for P. vivax to invade human erythrocytes. Duffy-negative individuals may be just as fit as Duffy-positive individuals and are no longer resistant to P. vivax malaria. In this review, we describe the complexity of P. vivax malaria, characterize pathogenesis and candidate invasion genes of P. vivax, and host immune responses to P. vivax infections. We provide a comprehensive review on parasite ligands in several Plasmodium species that further justify candidate genes in P. vivax. We also summarize previous genomic and transcriptomic studies related to the identification of ligand and receptor proteins in P. vivax erythrocyte invasion. Finally, we identify topics that remain unclear and propose future studies that will greatly contribute to our knowledge of P. vivax.

Triple negative breast cancers (TNBCs) are molecularly heterogeneous, and the link between their aggressiveness with African ancestry is not established. We investigated primary TNBCs for gene expression among self-reported race (SRR) groups of African American (AA, n=42) and European American (EA, n=33) women. Using The Cancer Genome Atlas (TCGA) approaches, we analyzed RNA sequencing data to measure changes in genome-wide expression and used logistic regressions to identify ancestry-associated gene expression signatures. To determine global ancestry, GATK best practices were followed for variant calling, and used the 1000 Genomes Project as reference data. We identified >150 African ancestry-associated genes and found that, compared to SRR, quantitative genetic analysis was a more robust method to identify racial/ethnic-specific genes that were differentially expressed. A subset of African ancestry-specific genes that were upregulated in TNBCs of our AA patients were validated in TCGA data. In AA patients, there was a higher incidence of basal-like 2 tumors and altered TP53, NFB1, and AKT pathways. The distinct distribution of TNBC subtypes and altered oncologic pathways show that the ethnic variations in TNBCs are driven by shared genetic ancestry. Thus, to appreciate the molecular diversity of TNBCs, tumors from patients of various ancestral origins should be evaluated.

This study investigated the trends of registered Death and Birth in Nigeria using Generalized Linear Models. Annual data on Death and Birth was collected from National Population Commission for the period of 2004 to 2017. The Natural increase calculated revealed a positive trend in the natural increase in Nigeria from 2004 to 2017. Evidence from summary statistics revealed some level of over dispersion (variance > mean). This study explored Poisson Regression Models and Negative Binomial Regression Models using two links (identity and log). The results revealed a positive increase in registration of birth and death rates in Nigeria and among the competing the models, Negative Binomial regression model with identity link emerged as the best model for modeling birth and death rates registration in Nigeria. Data on numbers of deaths and causes of death are essential if countries are to determine priorities, formulate and monitor policies for public health care as well as other government policies that may be based on such data

In this paper, we examine the performance of several classifiers in the process of searching for very negative opinions. More precisely, we do an empirical study that analyzes the influence of three types of linguistic features (n-grams, word embeddings, and polarity lexicons) and their combinations when they are used to feed different supervised machine learning classifiers: Support Vector Machine (SVM), Naive Bayes (NB), and Decision Tree (DT).

Leishmaniasis is the third most common vector-borne disease and a very important protozoan infection. Cutaneous leishmaniasis is one of the most common types of leishmaniasis infectious diseases with up to 2 million occurrences of new cases each year worldwide. A dynamic transmission multivariate time series model was applied to the data to account for overdispersion and evaluate the effects of three environmental layers as well as seasonality in the data. Furthermore, ecological niche modeling was used to investigate the geographical suitable conditions for cutaneous leishmaniasis using temperature, precipitation and altitude as environmental layers, together with the leishmaniasis presence data. A retrospective analysis of the cutaneous leishmaniasis spatial data in Afghanistan between 2003 and 2009 indicates a steady increase from 2003 to 2007, a small decrease in 2008, then another increase in 2009. An upward trend and regularly repeating patterns of highs and lows was observed related to the months of the year which suggests seasonality effect in the data. Two peaks were observed in the disease occurrence-- January to March and September to December -- which coincide with the cold period. Ecological niche modelling indicates that precipitation has the greatest contribution to the potential distribution of leishmaniasis.

There is limited real-world data from India examining the treatment characteristics, safety, and efficacy of ceftazidime-avibactam against Gram-negative organisms especially multidrug-resistant pathogens including Carbapenem-Resistant Enterobacterales and Carbapenem-Resistant Pseudomonas. In this retrospective study, the real-world treatment patterns, effectiveness, and safety of ceftazidime-avibactam in treating Gram- negative infections were assessed. Data was extracted from electronic health records of adult patients admitted to the hospital with documented Gram-negative infection who had received treatment for at least 48 hours with ceftazidime-avibactam as a part of routine clinical management. Among the 189 patients, on day 3, clinical symptoms improvement was recorded in 79.6% of patients. Clinical success was achieved in 79.5% and 76.3% of assessed patients on day 7 and day 14/End-of-treatment, respectively. Microbiological success was reported in 76% of patients on day 7 and in 60.3% of patients on day 14 or EOT. The mean treatment duration of ceftazidime-avibactam therapy was 6.92 (± 4.1) days. No new safety concerns were identified. In conclusion, this study provides real-world evidence on treatment patterns and clinical outcomes associated with ceftazidime-avibactam in India, complementing the previously reported literature. The results suggest ceftazidime-avibactam is an effective and tolerable option for the management of Gram-negative infections in critically ill patients.

Culture-positive (CP) and culture-negative (CN) periprosthetic joint infections (PJI) remain a crucial area of research; however, current studies comparing these infections rely on unstandardized outcome reporting tools. Our study aimed to compare the outcomes of CP and CN PJI using the standardized Musculoskeletal Infection Society (MSIS) outcome reporting tool. We retrospectively reviewed 138 patients who were diagnosed with PJI and indicated for two-stage revision total knee arthroplasty (rTKA). The majority of patients in both CP and CN cohorts achieved infection control without the need for reoperation (54.1% and 62.5%, respectively). There was a significant difference in the overall distribution of MSIS outcomes (p=0.043), with a significantly greater rate of CN patients falling into Tier 1 (infection control without the use of suppressive antibiotics) (52.5% versus 29.6%, p=0.011). There was also a significant difference in the distribution of septic versus aseptic reoperations after 2nd stage (p=0.013), with more CP reoperations being septic and more CN reoperations being aseptic. The duration from 1st to 2nd stage was significantly shorter in the CN cohort (p=0.002). While overall infection control was similar between cohorts, these data suggest that the outcomes of two-stage rTKA are favorable in cases of CN PJI.

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.

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.

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.

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.

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).

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.

The triple-negative breast cancer (TNBC) subtype is one of the most aggressive forms of breast cancer that has poor clinical outcome and still remains as an unmet clinical challenge. Accumulating evidence suggests that intratumoral heterogeneity or the presence of phenotypically heterogeneous cell populations within a tumor plays a crucial role in chemoresistance, tumor progression and metastasis. Increased understanding of the molecular regulators of intratumoral heterogeneity will enable the development of effective therapeutic strategies in TNBC. We have identified a molecular mediator involved in intratumoral heterogeneity in breast cancer using an unbiased approach. We isolated two heterogeneous tumor cell populations from the 4T1 TNBC tumor model and phenotypic characterization revealed that the cells are distinct in terms of their morphology, proliferation and self-renewal ability in vitro; as well as primary tumor formation and metastatic potential in vivo. Further, RNA sequencing on both cell populations was performed to identify the molecular mediators underlying this heterogeneity. Bioinformatic analysis performed on the differentially expressed genes along with the Kaplan-Meier survival analysis in TNBC patients identified Metastasis associated colon cancer 1 (Macc1) as the top candidate gene mediating the aggressive phenotype. The role of Macc1 in regulating the proliferative phenotype was validated using siRNA mediated gene knockdown. The role of Macc1 in the aggressive cancer cell phenotypes and disease progression is being studied further using a small molecule transcriptional inhibitor of Macc1 in cell line and animal models, thus increasing our understanding of the molecular underpinnings of intratumoral heterogeneity in breast cancer that is critical to the improvement in the treatment of women currently living with the highly aggressive TNBC subtype.

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.

AbstractBaraton University dairy farm is an environment that attracts a microbiologist to inquire the composition of bacteria that exist there in. The knowledge of bacteria has in time and again amazed the life scientist community that have invested to acquire more information in this microbiology world.The study engages fundamental tests such as gram stain, endospore stain, and assays for specific microbial activities & enzymes, susceptibility on disinfectant and antibiotic, utilization of specific substrate and culture characteristics. The two organisms (gram negative and positive) tested positive for sucrose & lactose fermentation, Indole & Methly red, catalase & Oxidase, were both facultative and motile. On contrary, gram positive bacteria had spores and had a gamma haemolysis on Blood Agar, while gram negative bacteria haemolysed beta haemolysis. To draw a conclusion on the identity of the two organisms is that, the gram positive is a Bacillus ........ while gram negative is Escherichia coli.

We provide a detailed analysis of the electronic properties of graphene-like materials with charge carriers living on a curved substrate, focusing in particular on constant negative-curvature spacetime. An explicit parametrization is also worked out in the remarkable case of Beltrami geometry, with an analytic solution for the pseudoparticles modes living on the curved bidimensional surface. We will then exploit the correspondent massless Dirac description, to determine how it affects the sample local density of states.

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 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.

From the perspective of individual resource and social capital, this paper aims to explain how employees’ political skill affect their job satisfaction and turnover intention, through the mediating role of popularity. Using a sample of 237 dyad surveys from supervisors and employees in the Yangtze River Delta of China, we found that: 1) political skill is positively correlated with job satisfaction and negatively correlated with turnover intention, and that these correlations are partially mediated by individual popularity; 2) positive affect (PA) moderates the relationship between political skill and job satisfaction, and negative affect (NA) moderates the relationship between political skill and turnover intention. The implications of our findings and future research directions are discussed.

We study impact of geometry on leakage loss in negative curvature fibers made with As₂Se₃ chalcogenide and As₂Se₃ chalcogenide glasses for carbon dioxide (CO₂) laser transmission. The minimum leakage loss decreases when the core diameter increases both for fibers with six and for fibers with eight cladding tubes. The optimum gap corresponding to the minimum loss increases when the core diameter increases for negative curvature fibers with six cladding tubes. For negative curvature fibers with eight cladding tubes, the optimum gap is always less than 20 μm when the core diameter ranges from 300 μm to 500 μm. The influence of material loss on fiber loss is also studied. When material loss exceeds 10² dB/m, it dominates the fiber leakage loss for negative curvature fiber at a wavelength of 10.6 μm.

For the first time, we describe phylogenomic signatures of an epidemic lineage of vesicular stomatitis Indiana virus (VSIV). We applied multiple evolutionary analyses to a dataset of full-length genome sequences representing the circulation of an epidemic VSIV lineage in the US between 2019 and 2020. Based on phylogenetic analyses, we predicted the ancestral relationship of this lineage with a specific group of isolates circulating in the endemic zone of Chiapas, Mexico. Subsequently, our findings indicate that the lineage diversified into at least four different subpopulations during its circulation in the US. We identified single nucleotide polymorphisms (SNPs) that differentiate viral subpopulations and assessed their potential relevance using comparative phylogenetic methods, highlighting the preponderance of synonymous mutations during the differentiation of these populations. Purifying selection was the main evolutionary force favoring the conservation of this epidemic phenotype, with P and G genes as the main drivers of the evolution of this lineage. Our analyses identified multiple codon sites under positive selection and the association of these sites with specific functional domains at P, M, G, and L proteins. Based on ancestral reconstruction analyses, we showed the potential relevance of some of the sites identified under positive selection to the adaptation of the epidemic lineage at the population level. Finally, using a representative group of viruses from Colorado, we established a positive correlation between genetic and geographical distances, suggesting that positive selection on specific codon positions might have favored the adaptation of different subpopulations to circulation in specific geographical settings. Collectively, our study reveals the complex dynamics that accompany the evolution of an epidemic lineage of VSIV in nature. Our analytical framework provides a model for conducting future evolutionary analyses. The ultimate goal is to support the implementation of an early warning system for vesicular stomatitis virus in the US, enabling early detection of epidemic precursors from Mexico.

Introduction: One of the key strategies to achieve sustainable development goal by reduce preventable maternal deaths below 70 per 100,000 is increasing awareness about major obstetrics danger sign. Mother's awareness of obstetric danger signs in developing country is relatively low regardless of attempts trough many local and national program. It is crucial to increase women’s knowledge of obstetric danger signs through education and awareness-raising efforts. Despite its importance to reduce maternal deaths, Studies are limited only to the Northern Ethiopia. Objective: This study aimed to assess prevalence of knowledge of obstetric danger signs and associated factors among women who delivered in the last 12 months in Sidama region, Ethiopia. Methods: We conducted a community-based cross-sectional study from October to November, 2022. A multi-stage sampling procedure was utilized to select study participants. A structured and pretested questionnaire was utilized to collect data. A multilevel mixed-effects negative binomial regression model was used to control effects of clusters and confounders.Results: Out of 1,140 study participants, only 1,130 study participants took part in the study making a response rate of 99.12%. The overall prevalence of knowledge of obstetrics danger sign was estimated as 22.3% (95%CI: 18.7, 25.9). Government employed women (AIRR = 1.37; 95% CI: 1.2, 1.6), women who had access to mass media (AIRR = 1.16; 95% CI: 1.08, 1.25), women who had received model family training (AIRR = 1.15; 95% CI: 1.1, 1.25), autonomous women (AIRR = 1.15; 95% CI: 1.04, 1.25), women who had faced health problems during pregnancy (APR = 1.21; 95% CI: 1.11, 1.32) and urban women (APR = 1.22; 95% CI: 1.09, 1.62) were factors associated positively with knowledge of obstetrics danger sign. Conclusion: The prevalence of knowledge of obstetrics danger sign is found to be lower compared with the national average. Residence, mass-media exposure, model family planning, problem faced during pregnancy and women autonomy are the main predictors of knowledge of obstetrics danger sign. Public health policy makers should enhance health literacy at for focused on rural community. Awareness creation should be improved through mass media. Health providers should educate women during maternity health services to empower women for decision making process.

Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptors, human epidermal growth factor receptor 2, and progesterone receptors (PR). TNBC has the poorest prognosis among breast cancer subtypes and is more likely to respond to immunotherapy due to its higher expression of PD-L1 and a greater percentage of tumor-infiltrating lymphocytes. Immunotherapy has revolutionized TNBC treatment, especially with the FDA's approval of pembrolizumab (Keytruda) combined with chemotherapy for advanced cases, opening new avenues for treating this deadly disease. Although, immunotherapy can significantly improve patient outcomes in a subset of patients, achieving the desired response rate for all remains an unmet clinical goal. Strategies that improve responses to immune checkpoint blockade, including combining immunotherapy with chemotherapy, molecularly targeted therapy, or radiotherapy may improve response rates and clinical outcomes.  In this review, we provide a short background on TNBC and immunotherapy and explore the different types of immunotherapy strategies that are currently being evaluated in TNBC. Additionally, we review why combination strategies may be beneficial, provide an overview of the combination strategies, and discuss the novel immunotherapeutic opportunities that may be approved in the near future for TNBC.

This review focuses on social play, a complex behavior that is often difficult to categorize. Although play has been typically associated with positive emotions, emerging research indicates that it relates to various emotional systems, ranging from attachment to conflict. Play oscillates between compe-tition and cooperation, and includes a spectrum in-between, thus quantitatively identifying and demonstrating the emotional nature of play remains challenging. We examined some examples from human and non-human animal studies and explored the emotional and neuro-hormonal systems involved in play. We considered ethological data possibly indicating the emotional states underlying play and we focused on the cooperative and competitive elements of play. We investigated the relationship between play and affiliative/aggressive behaviours, the communicative meaning of play signals (especially primate play faces), and the motor and possibly emotional contagion func-tion of rapid motor mimicry during play. Of all the literature on play, this review selects and com-bines the studies in an innovative way, to present the methods, tools, and evidence indicative of the emotional nature underlying play, which is much more complex than previously thought.

Background: A Morel–Lavallée lesion (MLL) is a traumatic, internal closed degloving injury that results from shearing of subcutaneous tissue away from underlying fascia, usually associated with high-velocity trauma. Case presentation: A 52-year-old man was transported to hospital for further follow-up of a superficial femoral artery injury. Examination on admission showed bruising seen around the left thigh. Contrast-enhanced computed tomography of the left thigh revealed hematoma with extravasation from a branch of the left superficial femoral artery, but no apparent aneurysms or femoral fractures. The patient was treated with compression bandages and discharged on hospital day 6. He left hospital able to walk unaided. He subsequently complained of left thigh pain with swelling and visited the hospital several times. He was treated at another outpatient clinic and was diagnosed with MLL. Single-use disposable portable negative pressure wound therapy (NPWT) was applied for about 2 months, achieving a stable wound site. Conclusion: We encountered a case of MLL successfully treated with single-use portable NPWT. This report presents the case of a patient with isolated MLL without fracture in the left thigh, in which the diagnosis was missed on initial admission. Finally, the patient received minor interventions including drainage along with tissue debridement and portable NPWT. We reviewed the relevant literature and summarize the pathogenesis, clinical manifestations, and treatment strategies for MLL. Emergency physicians require an increased understanding of MLL to avoid misdiagnosis and missed diagnosis.