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 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

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.

Foundational and state-of-the-art anomaly detection methods through power system state estimation are reviewed. The traditional components for bad data detection such as chi-square testing, residual-based methods, and hypothesis testing are discussed to explain the motivations for recent anomaly detection methods given the increasing complexity of power grids, energy management systems, and cyber-threats. In particular, state estimation anomaly detection based on data-driven quickest change detection and artificial intelligence are discussed and directions for research are suggested with particular emphasis on considerations of the future smart grid.

A Berry geometrical phase is identified in a strongly metastable system containing dynamically responsive clathrate hydrate structures within a crystal-fluid material. High energy degeneracy in the associated chemistry produces local stability and false vacuum conditions that lead to non-extensive and non-additive contributions in the fundamental thermodynamic relation. The reciprocating action of a piston expander confirms a net energy gain despite the crystal-fluid material maintaining almost constant density. Application of Ginzburg-Landau theory and the scaling laws reveals a coherence length and a penetration depth for a macro-scale dual superconductor. The coherence length determines non-extensive volume changes whilst its inverse gives the Higgs mass. The penetration depth determines the extent of QCD vacuum suppression whilst its inverse gives the vector boson mass together with indirect manifestation as non-additive hyperbolic curvature. External pressure perturbations of the low-energy system initiate ‘rolling’ critical responses that see energy and momentum conserved across a synchronized U(2) symmetry group whilst a complex gauge field is also exposed. Simultaneous emergence of the Ginzburg-Landau superconducting phase transition is consistent with gauge-invariant coupling of this scalar field to the Yang-Mills action in QCD. The discovery of an energy gap in the gradient energy term of the system Lagrangian is associated with a critical correlation length revealed in the transition from a gapped to a gapless superconducting state. Together with the emergence and absorption of the Higgs-like scalar field, a mechanism for describing the QCD mass gap arises.

Nowadays, technological advancement has transformed traditional vehicles into Au-tonomous Vehicles (A.V.s). In addition, in our daily lives, A.V.s play an important role since they are considered an essential component of smart cities. A.V. is an intelligent vehicle capable of main-taining safe driving by avoiding crashes caused by drivers. Unlike traditional vehicles, which are fully controlled and operated by humans, A.V.s collect information about the outside environment using sensors to ensure safe navigation. Furthermore, A.V.s reduce environmental impact because they usually use electricity to operate instead of fossil fuel, thus decreasing the greenhouse gasses. However, A.V.s could be threatened by cyberattacks, posing risks to human life. For example, re-searchers reported that Wi-Fi technology could be vulnerable to cyberattacks through Tesla and BMW AVs. Therefore, more research is needed to detect cyberattacks targeting the components of A.V.s to mitigate their negative consequences. This research will contribute to the security of A.V.s by detecting cyberattacks at the early stages. First, we inject False Data Injection (FDI) attacks into an A.V. simulation-based system developed by MathWorks. Inc. Second, we collect the dataset generated from the simulation model after integrating the cyberattack. Third, we implement an intelligent symmetrical anomaly detection method to identify FDI attacks targeting the control system of the A.V. through a compromised sensor. We use long short-term memory (LSTM) deep networks to detect FDI attacks in the early stage to ensure the stability of the operation of A.V.s. Our method classifies the collected dataset into two classifications: normal and anomaly data. The ex-perimental result shows that our proposed model's accuracy is 99.95%. To this end, the proposed model outperforms other state-of-the-art models in the same study area.

The spread of the Coronavirus pandemic has been accompanied by an infodemic. The false information that is embedded in the infodemic affects people’s ability to have access to safety information and follow proper procedures to mitigate the risks. This research aims to target the falsehood part of the infodemic, which prominently proliferates in news articles and false medical publications. Here, we present NeoNet, a novel supervised machine learning text mining algorithm that analyzes the content of a document (news article, a medical publication) and assigns a label to it. The algorithm is trained by TFIDF bigram features which contribute a network training model. The algorithm is tested on two different real-world datasets from the CBC news network and Covid-19 publications. In five different fold comparisons, the algorithm predicted a label of an article with a precision of 97-99 %. When compared with prominent algorithms such as Neural Networks, SVM, and Random Forests NeoNet surpassed them. The analysis highlighted the promise of NeoNet in detecting disputed online contents which may contribute negatively to the COVID-19 pandemic.

Medical data flows in streams as the data related to clinical tests and administered drugs by the doctors flows continuously. The doctors must be immediately alerted if negative associations are found among the drugs they prescribe. Data streams are to be processed in single scans as it is not possible to re-scan the data for any iterative processing. To detect negative drug connections, regular and frequent drug patterns must be processed. Negative correlations between disease-curing medications might create adverse responses that kill patients. This paper proposes an algorithm that finds the negative associations among regular and frequent patterns mined from medical data streams. The negative associations mined are the most effective and reduce the negative associations, which are more critical by 50%.

The antimicrobial quantitative structure–activity relationship of plant flavonoids against Gram-positive bacteria was established in our previous works, and the cell membrane was confirmed as a major site of action. To investigate whether plant flavonoids have similar antibacterial effects and mechanisms against both Gram-negative and Gram-positive bacteria, here, the minimum inhibitory concentrations (MICs) of 37 plant flavonoids against Escherichia coli were determined using the microdilution broth method, and then the correlation between their lipophilic parameter ACD/LogP or LogD_7.40 value and their MIC was analyzed. Simultaneously, the correlation between the ACD/LogP or LogD_7.40 value and the MIC of 46 plant flavonoids reported in literature against E. coli was also analyzed. Both sets of results showed that there is a significant correlation between the LogP value and the MIC of plant flavonoids against Gram-negative bacteria. However, it is difficult to effectively predict the MIC of plant flavonoids against Gram-negative bacteria from their lipophilic parameters. By comparing two regression curves derived from plant flavonoids against Gram-negative and Gram-positive bacteria, it was further discovered that the antibacterial activities of most plant flavonoids against Gram-negative bacteria are stronger than those against Gram-positive bacteria when their LogP values are less than about 3.0, but the opposite is true when their LogP values are more than about 3.6. Moreover, this comparison also suggests that unlike mainly acting on the cell membrane of Gram-positive bacteria, plant flavonoids have multiple mechanisms against Gram-negative species, while the cell membrane is also an important action site among them. Combined with the correlation analyses between the enzyme inhibitory activity and the LogP value of the reported flavonoids, it was further suggested that DNA gyrase is another important target of plant flavonoids against Gram-negative bacteria.

The study aimed to investigate the effect of climate change exposure on affect and pro-environmental behavioural intentions in a randomised controlled trial. An online survey was completed by 100 adult participants and included measures of affect and pro-environmental behavioural intentions pre- and post-exposure. Participants were randomly allocated to a group that saw a climate change video (n=55) or a group that saw a non-climate change video (n=45). The findings showed were that participants in the climate change group showed a significant increase in negative affect and pro-environmental behavioural intention scores post-video exposure compared to the non-climate change video group. This suggests that climate change video exposure negatively influences affect but also potentially increases the intention to act pro-environmentally. These findings have the potential to support policies and societal change, however further investigation into the type of contents, actual behaviour change, and impacts on diverse populations (e.g., minority groups) is needed that influences pro-environmental behaviours is required. Furthermore, to achieve a greater impact, future research should be conducted measuring actual pro-environmental behaviour change, including with those from diverse populations.

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

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

In this work, a simple and environmentally friendly process combining low pressure (vacuum) and mechanical compression is proposed to convert recycled polypropylene (PP) foams (28 kg/m3) into low density foams (90-131 kg/m3) having negative tensile and compressive Poisson's ratios (NPR). The effect of processing conditions (vacuum time, temperature, and mechanical pressure) was studied. Based on the optimized conditions, the tensile Poisson’s ratio of the resulting auxetic foams reached −1.50, while the minimum compressive Poisson's ratios was −0.32 for the same sample. The foam structure was characterized via morphological analysis (SEM) to determine any changes related to the treatment applied. Finally, tensile and compressive properties (Young's modulus, strain energy, energy dissipation and damping capacity) are also presented and discussed. It was observed that the mechanical properties of the resulting auxetic foams were improved compared to the original PP foam (PP-O) for all tensile properties in terms of modulus (19.9 to 59.8 kPa), strength (0.298 to 1.43 kPa) elongation at break (28 to 77%), energy dissipation (14.4 to 56.3 mJ/cm3) and damping capacity (12 to 19%). Nevertheless, improvements were also observed under compression in terms of energy dissipation (1.6 to 3.6 mJ/cm3) and damping capacity (13 to 19%). These auxetic foams can find applications in sport and military protective equipment, as well as any energy mitigation system.

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

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

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

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

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

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

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

Background and Objectives: Acute compartment syndrome (ACS) is an emergency condition of the lower limb in which prophylactic fasciotomy is required to prevent complications. A negative pressure wound therapy (NPWT) used to the treatment of fasciotomy wounds provide beneficial clinical results. This study aimed to exchange the authors’ experience of using the NPWT installation system on the lower limb wounds after fasciotomy in ACS. Materials and Methods: This is a retrospective study enrolled consecutive patients with ACS, who underwent fasciotomy and was treated with the NPWT installation system at Department of Vascular Surgery, Provincial Hospital in Kielce from April 2016 to July 2017. Results: The study enrolled 15 patients with a diagnosis of ACS (87% men, mean age 65 years old). An open four-compartment fasciotomy (87%) or two-compartment fasciotomy (13%) was performed. The NPWT was applied on the first day after fasciotomy in 87% of patients. Therapy was initiated by the negative pressure of 125 mm Hg, which maintained at this level until the therapy was finalized. In 80% of patients, the vacuum-assisted wound closure (VAC) dressing changes were performed every 3 days. The first approximation of fasciotomy wounds margins occurred on the 4th day after surgery among 67% of individuals. The average time of using VAC on fasciotomy wounds was 9 days. The average time to definitive closure edges of fasciotomy wounds was 12 days. The average time of hospital stay was 17 days. Conclusions: Our experience indicates the legitimacy of using NPWT in wound treatment after fasciotomy in ACS. The NPWT enables faster primary closure of wounds, reduces edema, as well as decreases hospitalization time.

The technique of obtaining information or data about any feature or object from afar, called in technical parlance as remote sensing, has proven extremely useful in diverse fields. In the ecological sphere, especially, remote sensing has enabled collection of data or information about large swaths of areas or landscapes. Even then, in remote sensing the task of identifying and monitoring of different water reservoirs has proved a tough one. This is mainly because getting correct appraisals about the spread and boundaries of the area under study and the contours of any water surfaces lodged therein becomes a factor of utmost importance. Identification of water reservoirs is rendered even tougher because of presence of cloud in satellite images, which becomes the largest source of error in identification of water surfaces. To overcome this glitch, the method of the shape matching approach for analysis of cloudy images in reference to cloud-free images of water surfaces with the help of vector data processing, is recommended. It includes the database of water bodies in vector format, which is a complex polygon structure. This analysis highlights three steps: First, the creation of vector database for the analysis; second, simplification of multi-scale vector polygon features; and third, the matching of reference and target water bodies database within defined distance tolerance. This feature matching approach provides matching of one to many and many to many features. It also gives the corrected images that are free of clouds.

.Background: Negative outcomes associated with medications (NOM) and drug-related problems (DRP) significantly impact individuals with kidney replacement therapy (KRT) given the complexities of managing kidney disease and associated comorbidities. The present study aims to assess the frequency of NOMs/DRPs among KRT patients and identify contributing factors. Methods: A cross-sectional study was conducted at the Virgen de las Nieves University Hospital (Granada, Spain), involving 117 outpatient adults with KRT. Data were collected from February 2021 to July 2023 using electronic records, semi-structured interviews (Dáder Method), and discussions with nephrology specialists. NOMs/DRPs were identified following treatment guidelines. Binary logistic regression determined associated factors (p-value < 0.05). Results: Across 117 patients, 2,436 NOMs and 3,303 DRPs were identified, averaging 20.82 NOMs and 28.23 DRPs per patient. Prevalent NOMs included untreated conditions (58.95%), quantitative ineffectiveness (35.43%), and non-quantitative safety problems (5.13%). Dominant DRPs were undertreated conditions (37.63%), wrong dose/posology/length (33.00%), risk of adverse drug reactions (ADR) (16.14%), and non-adherence (6.87%). Patients with ADR, undertreated condi-tions, and anemia were associated with quantitative ineffectiveness. Risk of ADR and vitamin D deficiency/insufficiency correlated with non-quantitative safety problems. Conclusions: KRT pa-tients exhibited a substantial prevalence of NOMs/DRPs. Further research is needed to deepen our understanding of these complexities for improved patient care.

Diffusion-controlled cyclic voltammograms at fast scan rates show peak shifts as well as decreases in the peak currents from the predicted diffusion-controlled currents especially when currents are large in low concentration of supporting electrolyte. This has been conventionally recognized as an IR-drop effect by solution resistance on the peaks as well as heterogeneous kinetics. It is also brought about by negatively capacitive currents associated with charge transfer reactions. The reaction product generates dipoles with counterions to yield a capacitance, of which current flows oppositely to that of the double layer capacitance. The three effects are specified here in the oxidation of a ferrocenyl derivative by fast scan voltammetry. The expression for voltammograms complicated with IR-drop is derived analytically, and yields deformed voltammograms. The peak shift is approximately linear with the IR-term, but exhibits a convex variation. Dependence of some parameters on the peaks by the IR-drop is compared with those by the negative capacitance. The latter is more conspicuous than the former under conventional conditions. The two effects cannot be distinguished specifically except for variations of conductance of the solution.

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

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

The term dehumanisation refers to the ways in which a person is perceived to be less than human or treated as if they are less than human. It involves treating a person as if they are a child or infant, like an animal or non-living object, or as if they are dead, or any other way in which someone fails to be treated like a human being with an adult identity. Dehumanisation is widespread in dementia care; it is a major obstacle to person-centred care and has poor outcomes for people with dementia. This article proposes a new model of dehumanisation. The New Model presents a new way of describing dehumanisation that has been synthesised from current understanding about the phenomenon and reflects what is presently known about the subject. The model aims to summarise existing theories and models of dehumanisation and make dehumanisation theory accessible to students and trainees in healthcare. This article describes the new model, discusses existing models and theories in the literature, and explores the potential role of the new model in solutions for reducing dehumanisation in dementia care.

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.

Antibiotic resistance represents a significant threat to the modern healthcare provision. The ESKAPEE pathogens, in particular, have proven to be especially challenging to treat, due to their intrinsic and acquired ability to rapidly develop resistance mechanisms in response to environmental threats. The development of biofilm has been characterised as an essential contributing factor towards antimicrobial-resistance and tolerance. Several studies have implicated the involvement of efflux pumps in antibiotic resistance, both directly, via drug extrusion and indirectly, through the formation of biofilm. As a result, the underlying mechanism of these pumps has attracted considerable interest due to the potential of targeting these protein structures and developing novel adjunct therapies. Subsequent investigations have revealed the ability of efflux pump-inhibitors (EPIs) to block drug-extrusion and disrupt biofilm formation, thereby, potentiating antibiotics and reversing resistance of pathogen towards them. This review will discuss the potential of EPIs as a possible solution to antimicrobial resistance, examining different challenges to the design of these compounds, with an emphasis on Gram-negative ESKAPEE pathogens.

This study introduces a new discrete distribution which is a weighted version of Poisson-Lindley distribution. The weighted distribution is obtained using the negative binomial weight function and can be fitted to count data with over-dispersion. The p.m.f., p.g.f. and simulation procedure of the new weighted distribution, namely weighted negative binomial Poisson-Lindley (WNBPL), are provided. The maximum likelihood method for parameter estimation is also presented. The WNBPL distribution is fitted to several insurance datasets, and is compared to the Poisson and negative binomial distributions in terms of several statistical tests.

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

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

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

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

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

Background. 46,XX disorders of sex development are rare. Approximately, 90% of XX males are SRY-positive, while testicular development in the absence of SRY takes place in a minority. Methods: A boy with 46,XX karyotype (SRY-negative; absence of SOX9 duplications) was investigated by targeted Next Generation Sequencing (NGS), Multiplex ligation-dependent probe amplification (MLPA), and Comparative Genomic Hybridization array (CGH-array). Results: The boy had normal male phenotype and normal prepubertal values of testicular hormones. He presented a heterozygous duplication of 49.626 bp, encompassing exons 2 and 3 of DMRT1. The result was arr[GRCh37] 9p24.3(845893_895518)x3. Since both breakpoints are harbored in the intronic regions, the duplication does not stop or shift the coding frame. Additional known pathogenic or uncertain variants in pro-testis gene cascade were not identified. Conclusions: This study report a boy with 46,XX testicular disorder of sex differentiation, showing a de novo partial intragenic duplication of DMRT1. This intragenic duplication may result in a gain of function, acting as primary pro-testis gene (or anti-ovary gene) in a 46,XX human foetus and permitting normal pre-pubertal endocrine testis function.

1) Introduction: Negative pressure wound therapy (NPWT) is a frequently applied open abdomen (OA) treatment. There are only a few experimental data supporting this method and describing the optimal settings and pressure distribution in the abdominal cavity during this procedure. The aim of our study was to evaluate pressure values at different points of the abdominal cavity during NPWT in experimental abdominal compartment syndrome (ACS) animal model. 2) Methods: In this study (permission Nr. 13/2014/UDCAR) 27 Hungahib pigs (15.4- 20.2 kg) were operated. ACS was generated by implanting a plastic bag in the abdomen through mini-laparotomy and filled with 2100- 3300 ml saline solution (37 C°) to an intraabdominal pressure (IAP) of 30 mmHg. After 3 hours, NPWT (Vivano Med ® Abdominal Kit, Paul Hartmann AG, Germany) or Bogota bag was applied. NPWT group was divided into -50, -100 and 150 mmHg suction group. Pressure distribution to the abdominal cavity was monitored at 6 different points of the abdomen via a multichannel pressure monitoring system. 3) Results: The absolute pressure levels were significantly higher above than below the layer. The values of the pressure were similar in the midline than laterally. Amongst the bowels, the pressure values changed periodically between 0 and -12 mmHg which might be caused by the peristaltic movements. 4) Conclusions: The porcine model of the present study seems to be well applicable for investigating ACS and NPWT. It was possible to provide valuable for clinicians. The pressure was well distributed by the protective layer to the lateral parts of the abdomen and this phenomenon did not change considerably during the therapy.

This paper assesses whether there is intrinsic positive educational value in travelling animal presentations and exhibits, referred to here as Mobile Live Animal Programs (MLAPs). Given that educational claims serve as the basis for allowing MLAPs to operate in many jurisdictions throughout Canada and the United States, it is essential to examine whether these purported claims are valid. This study takes a twofold approach of examining first, what constitutes an MLAP and how such programs are situated within the larger context of animal observation and tourism, and second, what constitutes both positive and negative education, and how such learning can empirically be measured in these settings. This approach provokes the ethical question of whether or not MLAPs should be allowed to operate given the high price paid not only by the individual animals used, but also to our psychological, emotional, and intellectual relationship with other species when we use non-human animals for our own knowledge, pleasure or comfort. The paper concludes that we must consider that the pervasive problem of negative education, that using displaced captive wild animals as learning tools that highlights human control over them, their objectification and their exploitation, is not justified by the purported positive educational claims of MLAPs.

This paper identifies a criterion for choosing the largest set of rejected hypotheses in high-dimensional data analysis where Multiple Hypothesis testing is used in exploratory research to identify significant associations among many variables. The method neither requires predetermined thresholds for level of significance, nor uses presumed thresholds for false discovery rate. The upper limit for number of rejected hypotheses is determined by finding maximum difference between expected true hypotheses and false hypotheses among all possible sets of rejected hypotheses. Methods of choosing a reasonable number of rejected hypotheses and application to non-parametric analysis of ordinal survey data are presented.

Public restrooms are often a hub of microbial contamination, and the examination of bacterial contamination in these facilities can serve as an important indicator of the transmission of infectious diseases. This study was conducted to determine the prevalence of bacterial contamination in public restrooms based on the economic class of the building. Samples were collected from various spots in 32 restrooms found in 10 shopping malls, classifying them into two categories: upper-end restrooms and lower-end restrooms. The findings showed that the level of contamination was higher in the lower-end restrooms, with the seat being the most contaminated area. The most dominant Gram-positive bacteria were coagulase-negative staphylococci species, making up 86% of the identified Gram-positive isolates. The most dominant Gram-negative bacteria identified were Klebsiella pneumoniae and Pseudomonas aeruginosa. The antibiotic sensitivity test results revealed the presence of multi-drug resistant bacteria among the Gram-positive and negative isolates, including Staphylococcus haemolyticus, Staphylococcus kloosi, Acinetobacter baumanii, and Pseudomonas aeruginosa. In conclusion, the study underscores the significance of monitoring bacterial contamination in public restrooms and the need for measures to reduce the spread of infectious diseases. Further research is crucial to gain a complete understanding of the bacterial contamination in public restrooms and their resistance patterns, to ensure the safety and health of the public. The implementation of improved cleaning practices and hands-free designs in restrooms can help reduce the risk of cross-contamination and prevent the spread of diseases.

Count data analysis presents unique challenges due to its discrete nature, often exhibiting excessive zeros and overdispersion. To address these complexities, count models, such as Poisson regression and Negative Binomial regression, have been developed, enabling modeling and prediction of count-based phenomena. Additionally, it’s important to notice that zero inflation, a phenomenon commonly observed in count data, requires specialized techniques for robust analysis. This article provides an overview of count data and count models, explores zero inflation, introduces Likelihood Ratio Tests, and explains how the Vuong Test can be used as a model selection criteria. Furthermore, we created a Vuong Test implementation from scratch using the Python programming language. This implementation enhances the accessibility and applicability of the Vuong Test in real-world scenarios, providing a valuable contribution to the academic community, since Python didn’t have an implementation of this statistical test.

Background: Extracellular Vesicles are pivotal mediators in intercellular communication, facilitating the exchange of biological information among healthy, pathological and tumor cells. Between the diverse subtypes of extracellular vesicles, exosomes have unique properties, clinical and therapeutical applications, even towards cancer. Breast cancer ranks as one of the most prevalent malignancies across the globe. Both the tumor core and its surrounding microenvironment engage in a complex, orchestrated interaction that facilitates the cancer’s growth and spread. Methods: The most valuable and significant PubMed Literature about extracellular vesicles and adipose–derived stem cells exosomes was selected and analyzed in order to report their biological properties and potential applications, in particular on the Triple–Negative Breast Cancer. Results: Adipose–derived stem cells exosomes represent a potential tool to target the tumor core of the Triple–Negative Breast Cancer, its microenvironment and surrounding tissues including metastasis. The authors are developing a supportive Triple–Adipose–derived stem cells Exosomes [T.A.E.] Technology against breast cancer in order to perform a selective preconditioning of the cancer before or while the traditional oncological treatments are running. Conclusion: The possibility to exploit the impact of Adipose–derived stem cells exosomes within the T.A.E. Technology against the Triple–Negative breast cancer is real, highlighting a new era for supportive measures against breast cancer.Keywords: Extracellular vesicles; Exosomes; Adipose–derived stem cells, Tumor microenvironment, Triple–Negative Breast Cancer, T.A.E. Technology.

A significantly reduced stress concentration effect and a stable deformation behavior are exhibited by the arc-like S-shaped auxetic structure. Analytical works beyond the bar and hinge method to capture structural effects, such as bending, shearing, etc., in the S-structure are scarce in the literature. The deformation pattern of the S-structure is dominated by bending and shearing within the linear elastic region. In this work, Timoshenko beam theory is used to derive closed-form expressions for overall elastic modulus and Poisson’s ratio. This agrees well with the results of finite element simulations. An adjusted R-square value of over 0.99 and almost 0.82 is obtained for elastic modulus and Poisson’s ratio, respectively. From parametric studies, it’s established that under quasi-static transverse load, strut thickness and the angle `α’ are the most important parameters for controlling elastic modulus, specific energy absorption, negative Poisson’s ratio (NPR) effect, and relative density of the entire auxetic structure. Also, it’s found that energy absorption and elastic modulus increase together. Interestingly, the elastic modulus of the structure under transverse load lies in the range from 3 MPa to 250 MPa, which means this structure is compliant enough and can be used in cushioning, packaging, soft robotics applications, etc.

In this communication, we present an innovative approach leveraging advanced Machine Learning (ML) and Artificial Intelligence (AI) techniques, specifically the Non-Negative Matrix Factorization (NMF) method, to analyze downward and upward light spectra collected by Hyperspectral Ocean Color Radiometer (HyperOCR, HOCR) sensors in the water column. Our work focuses on the development of a robust and efficient tool for unraveling the structure and activities of natural microbial assemblages in the ocean. By applying the NMF method to HyperOCR data, we successfully extracted five spectral signatures, representing unique patterns in the data. These signatures were instrumental in predicting the abundances of various microbial components, including bacteria, heterotrophic nanoflagellates, and picoeukaryotes, showcasing the potential of ML and AI in advancing oceanographic studies. To validate the methods, the study area included a shallow coastal area under the influence of freshwater inflow and an open offshore area with a depth of 100 m. The study sites in coastal and offshore waters (Kaštela Bay and Stončica Vis, respectively) had significantly different hydrographic and microbiological characteristics. Kaštela Bay had lower temperatures and salinity than the site on Vis. We have proved by application of different AI and ML methods with specific HOCR sensors prediction of the structure of the microbial community.

To better understand farmers’ refusal and corresponding negative emotions to pay agricultural water fee under current policy in rural China, this paper applies mental accounting, a behavioral economics framework, to explore how the governmental policies of reform of rural taxes and fees, direct agricultural subsidy programs and agricultural water fee individually influence farmers’ decisions in paying agricultural water fee. Using fieldwork data from 577 farmers and 20 water managers in Sichuan, we explore farmers’ information processing regarding paying agricultural water fee via three sequential mental accounting processes, with the associated underlying principles and measures behind each process. We find that the information processing in three mental accounting scenarios related to the agricultural water fee elucidates farmers’ observed behaviors in rural China. Generally, in the three mental accounting scenarios, two conditional intuitive expectations and nine conditional intuitive preferences are formed, however, the conditions of those expectations or preferences cannot be matched with the facts due to the reform of rural taxes and fees, the direct agricultural subsidy programs and the internal attributes of agricultural water fee, which interpret those negative behaviors in rural China. Additionally, this paper offers a view into how previous policies create negative psychological externalities (such as farmers’ psychological dependence on the government) through mental accounting to negatively influence agents’ subsequent decision making; it highlights the significance of underlying mental factors and information processing of negative behaviors in policymaking for managing or conserving common pool resources.

An effective process monitoring strategy is a requirement for meeting the challenges posed by increasingly complex products and manufacturing processes. To address these needs, this study investigates a comprehensive scheme based on classical machine learning methods, deep learning algorithms, and feature extraction and selection techniques. In a first step, a novel deep learning architecture based on convolutional neural networks (CNN) and gated recurrent units (GRU) is introduced to predict the local weld quality based on mid-wave infrared (MWIR) and near-infrared (NIR) image data. The developed technology is used to discover critical welding defects including lack of fusion (false friends), sagging and lack of penetration, and geometric deviations of the weld seam. Additional work is conducted to investigate the significance of various geometrical, statistical, and spatio-temporal features extracted from the keyhole and weld pool regions. Furthermore, the performance of the proposed deep learning architecture is compared to that of classical supervised machine learning algorithms, such as multi-layer perceptron (MLP), logistic regression (LogReg), support vector machines (SVM), decision trees (DT), random forest (RF) and k-Nearest Neighbors (kNN). Optimal hyperparameters for each algorithm are determined by an extensive grid search. Ultimately, the three best classification models are combined into an ensemble classifier that yields the highest detection rates and achieves the most robust estimation of welding defects among all classifiers studied, which is validated on previously unknown welding trials.

Both SARS-CoV-2 and SARS-CoV initially appeared in China and spread to other parts of the world. SARS-CoV-2 has generated a COVID-19 pandemic causing more than 6 million human deaths worldwide while the SARS outbreak quickly ended in six months with a global total of 774 reported deaths. One of the factors contributing to this stunning difference in the outcome between these two outbreaks is the inaccuracy of the RT-qPCR tests for SARS-CoV-2, which generated a large number of false-negative and false-positive test results that have misled patient management and public health policy-makers. This article presented Sanger sequencing evidence to show that the RT-PCR diagnostic protocol established in 2003 for SARS-CoV can in fact detect SARS-CoV-2 accurately due to the well-known nonspecific PCR amplification of DNAs with similar sequences. Using nested RT-PCR followed by Sanger sequencing to retest 50 patient samples collected in January, 2022 and sold as RT-qPCR positive reference confirmed 21 (42%) were false-positive. Although the other 29 positive isolates were categorized as Omicron variant by partial sequencing of the N gene, and the RBD and the NTD of the S gene, 9 (31%) showed focal to complete sequencing failure in the S gene segments due to multi-allelic SNPs. During the course of the study, an Omicron variant isolate containing a BA.1 NTD and a BA.2 RBD in its S gene was also detected. Routine partial S gene sequencing of all PCR-positive samples can timely discover multi-allelic SNPs and viral recombination in the circulating variants for investigation of their impacts on vaccine efficacies, therapeutics and diagnostics.

Deep Neural Network (DNN) inference demands substantial computing power, resulting in significant energy consumption. A large number of negative output activations in convolution layers are rendered zero due to the invocation of the ReLU activation function. This results in a substantial number of unnecessary computations that consume significant amounts of energy. This paper presents ECHO: Energy-efficient Computation Harnessing Onilne Arithmetic - A MSDF-based accelerator for DNN inference, designed for computation pruning, utilizing an unconventional arithmetic paradigm known as online/ most-significant digit first (MSDF) arithmetic which performs computations in a digit-serial manner. The MSDF digital serial computation of online arithmetic enables overlapped computation of successive operations leading to substantial performance improvements. The online arithmetic, coupled with a negative output detection scheme, facilitates early and precise recognition of negative outputs. This, in turn, allows for the timely termination of unnecessary computations, resulting in a reduction of energy consumption. The implemented design has been realized on the Xilinx Virtex-7 VU3P FPGA and subjected to a comprehensive evaluation through a rigorous comparative analysis involving widely used performance metrics. Experimental results demonstrate promising power and throughput improvements compared to contemporary methods. In particular, the proposed design achieved an average improvement in power consumption of up to 81%, 82.9%, and 40.6% for VGG-16, ResNet-18, and ResNet-50 workloads compared to the conventional bit-serial design, respectively. Furthermore, significant average speedups of 2.39×, 2.6×, and 2.42 were observed when comparing the proposed design to conventional bit-serial designs for VGG-16, ResNet-18, and ResNet-50 models respectively.

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

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

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

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

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

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

In cosmology, the cosmic curvature $K$ and the cosmological constant $\Lambda$ are two most important parameters, whose values have strong influence on the behavior of the universe. By analyzing the energy-momentum tensor and equations of state of ideal gas, scalar, spinor and vector potential in detail, we find that the total mass density of all matter is always positive, and the initial total pressure is negative. Under these conditions, by qualitatively analyzing the global behavior of the dynamical equation of cosmological model, we get the following results: (i) $K= 1$, namely, the global spatial structure of the universe should be a 3-dimensional sphere $S^3$. (ii) $0\le\Lambda < 10 ^ {-24} {\rm ly} ^ {-2}$, the cosmological constant should be zero or an infinitesimal. (iii) $a(t)>0$, the initial singularity of the universe is unreachable, and the evolution of universe should be cyclic in time. This means that the initial Big Bang is impossible at all. Since the matter components considered are quite complete and the proof is very elementary and strict, these logical conclusions should be quite reliable. Obviously, these conclusions will be much helpful to correct some popular misconceptions and bring great convenience to further research other problems in cosmology such as property of dark matter and dark energy.

Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathway linked to their proliferation and invasiveness. In particular, ω−3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study 16-(4’-chloro-3’-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω−3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI<0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.

This paper reports a new control strategy to improve sharing of unbalanced currents in islanded LV microgrids. This technique provides fast and effective sharing of positive-, negative- and zero-sequence currents, and is the first example of zero-sequence current sharing in the literature. The controllers are designed in the stationary frame. The control structure consists of four loops; 1)~the current controller; 2)~the voltage controller; 3)~the droop controller and the 4)~negative and zero sequence current controllers. The output current is considered unknown for the controller and is added to the control system as a disturbance. The proposed controller features a high gain in fundamental and harmonic frequencies, hence a good voltage quality is obtained in the presence of unbalanced and nonlinear loads. To this aim, a proportional-resonant (PR) controller is adopted as the current controller. By using a multi-resonant controller as current controller, a unified control structure is obtained which is suitable for both grid-connected and islanded modes. The voltage controller is designed using a resonant controller so that the voltage can have low VUF and THD in the presence of unbalanced and nonlinear loads. Furthermore, in this paper droop method is applied to the control structure to share real and reactive powers. Simulation studies show that the conventional droop method cannot share the oscillatory part of the output power that is due to the presence of unbalanced loads in the microgrid. This paper relies on using zero and negative sequence virtual impedance controller to share the oscillatory part of output power. By using zero-sequence virtual impedance controller (ZSVIC) and negative-sequence virtual impedance controller (NSVIC), the zero and negative sequence currents in the microgrid are controlled and shared effectively. By compensating zero- and negative-sequence currents locally, the flow of these currents in the microgrid is minimized, and the overall power quality of the islanded LV microgrid is improved.

The primary screening of hybridoma cells is a time-critical and laborious step during the development of monoclonal antibodies. Often critical errors occur in this phase, which supports the notion that the generation of monoclonal antibodies with hybridoma technology is difficult to control and hence a risky venture. We think that it is crucial to improve the screening process to eliminate most of the immanent deficits of the conventional approach. With this new microarray-based procedure, several advances could be achieved: Selectivity for excellent binders, high throughput, reproducible signals, avoidance of misleading avidity (multivalency) effects, and simultaneous performance of competition experiments. The latter can directly be used to select clones of desired cross-reactivity properties. In this paper, a model system with two excellent clones against carbamazepine, two weak clones and blank supernatant has been designed to examine the effectiveness of the new system. The excellent clones could be detected largely independent of the IgG concentration, which is unknown during the clone screening since the determination and subsequent adjustment of the antibody concentration is not possible in most cases. Furthermore, in this approach, the enrichment, isolation, and purification of IgG for characterization is not necessary. Raw cell culture supernatant can be used directly, even when fetal calf serum (FCS) or other complex media had been used. In addition, an improved method for the oriented antibody-immobilization on epoxy-silanized slides is presented. Based on the results of this model system, we conclude that this approach should be preferable to most other protocols leading to many of false positives, causing expensive and lengthy confirmation steps to weed out the poor clones.

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumour distribution of ZST316, an arginine analogue with inhibitory activity towards dimethylarginine dimethylaminohydrolase 1 (DDAH1) and vasculogenic mimicry, and its active metabolite L-257 in a xenograft model of triple negative breast cancer (TNBC). The method proved to be reproducible, precise, and highly accurate for the measurement of both compounds in plasma and tumour tissue following acute and chronic (five days) intraperitoneal administration of ZST316 (30mg/Kg daily) in six-week-old SCID mice inoculated with MDA-MB-231 TNBC cells. ZST316 was detected in tumour tissue and plasma after 1 hour (6.47 and 9.01M, respectively) and 24 hours (0.13 and 0.16M, respectively) following acute administration, without accumulation during chronic treatment. Similarly, the metabolite L-257 was found in tumour tissue and plasma after 1 hour (15.06 and 8.72M, respectively) and 24 hours (0.17 and 0.17M, respectively) following acute administration of ZST316, without accumulation during chronic treatment. The half-live after acute and chronic treatment ranged between 4.4-7.1hrs (plasma) and 4.5-5.0hrs (tumour) for ZST316, and 4.2-5.3hrs (plasma) and 3.6-4.9hrs (tumour) for L-257. The results of our study demonstrate the a) capacity to accurately measure ZST316 and L-257 concentrations in plasma and tumour tissue in mice using the newly developed HPLC-MS/MS method, b) rapid conversion of ZST316 into L-257, c) good intra-tumour penetration of both compounds, and d) lack of accumulation of both ZST316 and L-257 in plasma and tumour tissue during chronic administration. The new HPLC-MS/MS method is useful to investigate the in vivo effects of ZST316 and L-257 on vasculogenic mimicry, tumour mass, and metastatic burden in xenograft models of TNBC.

Transportation authorities aim to boost road safety by identifying risky locations and applying suitable safety measures. The Highway Safety Manual (HSM) is a vital resource for US transportation professionals, aiding in the creation of Safety Performance Functions (SPFs), which are predictive models for crashes. These models rely on Negative Binomial distribution-based regression and misinterpreting them due to unmet statistical assumptions can lead to erroneous conclusions, including inaccurately assessing crash rates or missing high-risk sites. The Florida Department of Transportation (FDOT) has introduced context classifications to HSM SPFs, complicating assumption violation identification. This study, part of an FDOT-sponsored project, investigates established statistical diagnostic tests to identify model violations and proposes a novel approach to determine optimal spatial regions for Empirical Bayes adjustment. This adjustment aligns HSM-SPFs with regression assumptions. The study employs a case study involving Florida roads. Results indicate that a 20-mile radius offers an optimal spatial sample size for modeling crashes of all injury levels, ensuring accurate assumptions. For severe injury crashes, which are less frequent and harder to predict, a 60-mile radius is suggested to fulfill statistical modeling assumptions. This methodology guides FDOT practitioners in assessing the conformity of HSM-SPFs with intended assumptions and determining appropriate region sizes.

(1) Background: Retroareolar breast tumors are common, but they rarely progress to malignancy. This report presents a case of a 41-years-old woman with a superficial breast tumor, emphasizing the significance of considering a wide range of options when evaluating breast lumps. (2) Methods: The patient presented with a steadily growing, ulcerating superficial tumor in her left breast. To determine the nature of the tumor, a diagnostic assessment was conducted, which included a positron emission tomography (PET) scan and histological analysis. (3) Results: The diagnostic assessment confirmed the presence of a malignant Grade II superficial infiltrating ductal carcinoma. Following the diagnosis, the patient underwent a modified radical mastectomy under general anesthesia. Subsequently, she received four cycles of adjuvant chemotherapy, followed by taxol administrations. (5) Conclusions: This case report underscores the importance of conducting a thorough examination and maintaining a high index of suspicion for breast tumors. By documenting this case, the report contributes to the existing knowledge on various manifestations of breast cancer and highlights the necessity of early identification and aggressive treatment. This knowledge can be applied to identify and manage similar cases in the future, leading to improved patient outcomes.

Triple negative breast cancer (TNBC) has a higher mRNA expression of programmed cell death ligand 1 (PD-L1) which is a ligand to programmed cell death protein 1 (PD-1). The binding of the ligand leads to suppressed activity of T-cell-mediated immune response against cancer cells. The approval of anti-PD-L1 drugs including pembrolizumab and atezolizumab in subgroups of TNBC offer potential improvement to the current treatment regimens available for TNBC. We conducted a meta-analysis to review the efficacy of pembrolizumab and atezolizumab for the treatment of TNBC in both adjuvant and neo-adjuvant settings. A systematic strategy was used as per the PRISMA 2020 statement. All statistical analyses were conducted using Review Manager 5.4. Outcome measures included objective response rate, progression free survival, overall survival in adjuvant therapy groups, and pathological complete response rates in neoadjuvant groups. Six clinical trials were included. For adjuvant therapies, the ORR (OR=1.26, P = 0.04) of Atezolizumab/Pembrolizumab plus chemotherapy was higher in intention to treat (ITT) arms than the placebo groups in TNBC. A positive effect size was found for PFS in the ITT arms (Cohen’s d = 1.55, P<0.001). The Atezolizumab plus chemotherapy group had a positive effect size for OS compared to the control groups (Cohen’s d = 0.52, P<0.001). In the neo-adjuvant setting, patients in ITT arms had higher pCR rates as compared to the control groups (OR= 1.61, P = 0.001). Our findings collate evidence of pembrolizumab and atezolizumab as a viable treatment option among patients with TNBC with PDL1+ subgroups deriving benefits.

To implement renewable energy resources, microgrid systems have been adopted and developed into the technology of choice to assure mass electrification in the next decade. Microgrid systems have a number of advantages over the conventional utility grid systems, however, it faces severe instability issues due to continually increasing constant power loads. To improve the stability of the entire system, load side compensation technique is chosen because of its robustness and cost effectiveness. In this particular occasion, a sliding mode controller is developed for microgrid system in the presence of CPL to assure certain control objective of keeping the output voltage constant at 480V. After that, the robustness analysis of the sliding mode controller against parametric uncertainties is presented. The sliding mode controller robustness against parametric uncertainties, frequency variations, and additive white Gaussian noise (AWGN) are illustrated in this paper. Later, the performance of the PID and sliding Mode controller is compared in case of nonlinearity, parameter uncertainties, and noise rejection to justify the selection of Sliding Mode controller over PID controller. All the necessary calculations are reckoned mathematically and results are verified in the virtual platform such as MATLAB/Simulink with the appreciable outcome.

The present study aims to evaluate the antibacterial activity of five commercially available essential oils (EOs): Lavender (LEO), Clove (CEO), Oregano (OEO), Eucalyptus (EEO), and Peppermint (PEO) against the most-known MDR Gram-positive and Gram-negative bacteria - Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853) - alone and in various combinations. Gas Chromatography-Mass Spectrometry (GC-MS) analysis established their complex composition. Then, the antibacterial activity was investigated in vitro by diffusimetric antibiogram method, using sterile cellulose discs with Ø 6 mm impregnated with 10 µl of sample and sterile borosilicate glass cylinders loaded with 100 µl of sample; MIC (µg/mL) for each EO was calculated from IZD values (mm) measured after 24 hours. The following EO combinations were evaluated: OEO+CEO, CEO+EEO, CEO+PEO, LEO+EEO, and EEO+PEO. Then, the influence of each dual combination on 3 conventional antibacterial drugs – Neomycin (NEO), Tetracycline (TET), and Bacitracin (BAC) - activity was investigated. The most active EOs against S. aureus and E. coli were LEO and OEO (IZD = 40 mm). They were followed by the CEO and EEO (IZD = 20-27 mm); PEO exhibited the lowest antibacterial activity (IZD = 15-20 mm). EEO alone showed the highest inhibitory activity on P. aeruginosa (IZD = 25-35 mm). It was followed by the CEO, LEO, and EEO (IZD = 7-11 mm), while PEO proved no antibacterial action against it (IZD = 0 mm). Only one synergic action was recorded (OEO+CEO against P. aeruginosa); EEO+PEO revealed partial synergism against S. aureus and CEO+PEO additive behavior against E. coli. Two triple associations with TET showed partial synergism against E. coli, and the other 2 ones (with NEO and TET) evidenced the same behavior against S. aureus; all contained EEO+PEO or CEO+PEO. Most combinations reported indifference. However, numerous cases were of antagonism between constituents included in double and triple combinations, and EOs with the strongest antibacterial activities belong to the highest antagonistic combinations. A consistent statistical analysis supports our results, showing that EOs with moderate antibacterial activities could generate combinations with higher inhibitory effects based on synergistic or additive interactions.

We have now identified two thermodynamically distinct types (A and B) of energetic processes naturally occurring on Earth. Type A energy processes such as the classical heat engines, apparently well follow the second law of thermodynamics; Type B energy processes, such as the newly discovered thermotrophic function that isothermally utilizes environmental heat energy to do useful work in driving ATP synthesis, which follows the first law of thermodynamics (conservation of mass and energy) but does not have to be constrained by the second law, owing to their special asymmetric functions. Several Type-B energy processes such as asymmetric-function-gated isothermal electricity and epicatalysis have been created through human efforts. The innovative efforts on Type-B processes to enable isothermally utilizing endless environmental heat energy could help to liberate all peoples from their dependence on fossil fuel energy, thus helping to reduce greenhouse gas CO2 emissions and control climate change towards a sustainable future for the humanity on Earth.

Triple-negative breast cancer (TNBC) is an aggressive and highly metastatic type of tumor. TNBC is often enriched in tumor-infiltrating neutrophils (TINs), which support cancer growth in part by counteracting tumor-infiltrating lymphocytes (TILs). Prior studies identified the enhancer of zeste homolog 2 (EZH2) as a pro-tumor methyltransferase in primary and metastatic TNBC. We hypothesized that EZH2 inhibition in TNBC cells per se would exert anti-tumor activity by altering the tumor immune microenvironment. To test this hypothesis, we used CRISPR to generate EZH2-knockout (KO) and overexpressing lines from parent (wild-type -WT) 4T1 cells, an established murine TNBC model. In vitro, EZH2 KO and OE cells showed little change in replicative capacity and invasiveness, but marked changes in surface marker profile and cytokine/chemokine secretion compared to WT cells. On in vivo injection, EZH2 KO cells showed significantly reduced primary tumor growth and a 10-fold decrease in lung metastasis compared to WT cells, while EZH2 OE cells were unchanged. Compared to WT tumors, TIN:TIL ratios were greatly reduced in EZH2 KO tumors but unchanged in EZH2 OE tumors. Our findings show a tumor-intrinsic role of EZH2 in the 4T1 TNBC model in regulating TIN/TIL poise, primary tumor progression and lung metastasis in vivo.

In our study we used the data set on morphimetric traits in beetles species. It has been constantly replenishing for 20 years by the samples, received from different regions of Russia and abroad. In this case we have selected data on nine species for which the left and right sides had been measured and fluctuating asymmetry (FA) could be estimated. The samples were from 6 provinces of Russia and Belarus, which ranged in 3 degrees in latitude and 57 degrees in longitude and included more than 150 plots in different types of biotopes. FA was assessed according to the standard method in 5265 specimen in one dimensional trait and one - meristic. ANOVA showed that biotope, species and their interaction affected FA in both traits, that is different species reacted differently to biotope type. In uncommon biotopes (according to accepted in carabidology classification) FA was increased. In forest species the negative relationship between FA in dimensional and meristic traits in the range in biotopes was revealed. In those species only FA values were higher in males than in females. In generalist species FA varieв similarly in both sexes and in both traits being the highest in open biotopes. In eudomonant of arable lands biotopes – Poecilus cupreus – the highest values of FA were recorded in the meadows, being about equal in all types of crops.

G protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions as well as in the pathology of many diseases including cancer progression and metastasis. Only a few GPCR members have been exploited as targets for developing drugs with therapeutic benefit in cancer. Present review deals with the Prostaglandin E receptor EP4, a member of the EP family of GPCR, as a promising newer therapeutic target for treating breast cancer. We show that aberrant over-expression of cyclooxygenase (COX)-2, an inflammation-associated enzyme, occurring in 40-50% of breast cancer patients leads to tumor progression and metastasis due to multiple cellular events resulting from an increased prostaglandin (PG) E2 production in the tumor milieu. They include inactivation of host anti-tumor immune (NK and T) cells, increased immuno-suppressor function of tumor-associated macrophages, promotion of tumor cell migration, invasiveness and tumor-associated angiogenesis (due to upregulation of VEGF-A), lymphangiogenesis (due to upregulation of VEGF-C/D) and a stimulation of stem-like cell (SLC) phenotype in cancer cells. All these events were primarily mediated by activation of the PGE receptor EP4 on tumor or host cells. We show that selective EP4 antagonists (EP4A) could mitigate all these events tested with cells in vitro as well as in vivo in syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice bearing COX-2 over-expressing human breast cancer xenografts. We suggest that EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced oncogenic and SLC-stimulating microRNAs - miR526b and miR655, one of which (miR655) appears to be a potential blood biomarker in breast cancer patients, for monitoring SLC-ablative therapies such as with EP4A. We suggest that EP4A will likely produce the highest benefit in aggressive breast cancers such as COX-2 expressing triple-negative breast cancers, when combined with other newer agents such as PD-1 or PD-L1 inhibitors.

For esophageal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), restaging using F-18-fluorodeoxyglucose (18F-FDG) positron emission tomography computed tomography (PET-CT) following nCRT can detect interval metastases, including liver metastases, in almost 10% of patients. However, in clinical practice, focal FDG liver uptake, unrelated to liver metastases, is observed after chemoradiotherapy. This radiation-induced liver injury (RILI) can potentially lead to overstaging. Liver radiation damage is also a concern during distal esophageal cancer radiotherapy due to proximity to the left liver lobe, typically included in the radiation field. Post-CRT, if FDG activity appears in the left or caudate liver lobes, thorough investigation is needed to confirm or rule out distant metastases. The increased FDG uptake in liver lobes post-CRT often presents a diagnostic dilemma. Distinguishing between radiation-induced liver disease and metastasis is vital for appropriate patient management, necessitating a combination of imaging techniques and an understanding of the factors influencing radiation response. Diagnosis involves identifying new foci of hepatic FDG avidity on PET/CT scans. Geographic regions of hypoattenuation on CT and well-demarcated regions with specific enhancement patterns on contrast-enhanced CT scan and MRI are characteristic of radiation-induced liver disease (RILD). Lack of mass effect on all three modalities (CT, MRI, PET) indicates RILD. Resolution of abnormalities on subsequent examinations also helps in diagnosing RILD. Moreover, it can also help to rule out occult metastases, thereby excluding those patients from further surgery who will not benefit from esophagectomy with curative intent.

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

The author’s opinion is that the negative energy solutions of the Dirac equation mean that a particle can be of negative kinetic energy (NKE) besides positive kinetic energy (PKE). We think that NKE particles are dark ones and NKE matter is dark matter. In our previous works, the dark matter theory of the NKE version and the dark energy theory that matched dark matter theory were put forth. In this work, we investigate the topics related to the metamorphosis of objects between PKE and NKE. We first evaluate the collosions between a PKE and a NKE particles. A scenario of accelerating PKE particles is raised. We put forth the cosmic dark radiation background and gravity potential background. In the universe, negative energy is predominating. In the observable universe, substances constitute stable PKE systems. The total energy of every such system is negative. We propose a mechanism that NKE substances combine into stable PKE systems. Macroscopically, NKE objects can constitute stable PKE astrophysical systems by means of gravity between them. Microscopically, NKE particles can combine into stable PKE systems by means of attractive interactions between them, say, Coulomb attraction. Currently, people think that there are four ingrediants in the universe: photons \Omega_R0, matter \Omega_M0, dark matter \Omega_DM, and dark energy \Omega_\lambda0. We analyze the order of the appearance of the four ingredients and conclude that qualitatively, their proportions should be \Omega_\lambda0 > \Omega_DM > \Omega_M0 > \Omega_R0.

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

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

Zingiber cassumunar Roxb. is a powerful medicinal plant that has been used as traditional medicine to cure respiratory problems, pain, and inflammation in China, Indonesia, Thailand and other Asian countries by using the crude extracts. The objective of this research is to identify phytochemical composition of Z. cassumunar Roxb. and to analyze antibacterial activity of crude extract, purified compounds, and their microencapsulated products of Rhizome Z. cassumunar Roxb. Identification of phytochemical composition in crude extract of rhizome Z. cassumunar Roxb. was achieved by chromatography-mass spectrophotometer. The major phytochemical composition in crude extract of Z. cassumunar Roxb. is essential oils, including terpinen4-ol (37.7%), β-pinene (20.8%), and (E)-1-(3,4-dimethoxyphenyl)but-1-ene (13.3%). Crude extract of Z. cassumunar Roxb. was purified with silica gel flash column chromatography, resulting two purified compounds. The antibacterial activity of crude extract, purified compounds, and their microencapsulated products of Rhizome Z. cassumunar Roxb. were evaluated against agricultural and foodborne pathogens by using disc agar diffusion and broth microdilution techniques. All of the samples studied (crude extracts, purified compounds, and microencapsulated of Z. cassumunar Roxb.) were effective against all the bacteria. Based on the results of the disc-diffusion assay suggested that amongst the samples studied, purified compounds (compound 1 and 2) and microencapsulated purified compounds (compound 1 and 2) exhibited more effective against all the bacteria compared to the crude extracts. Antibacterial activity of the rhizome of Z. cassumunar Roxb. was contributed mainly by the essential oils components as the active compounds. Gram-negative bacteria (X. oryzae, X. translucens, Pseudomonas spp, E. coli, and S. typhimurium) appeared to the most resistant to the crude extracts, purified compounds, and microencapsulated of Z. cassumunar Roxb. compared to the gram-positive bacteria (S. aureus, B. cereus, and L. monocytogenes). Microencapsulated of the tested samples (crude extract, purified compound 1, and purified compound 2) of the rhizome Z. cassumunar Roxb. exhibited high antibacterial activity with no significantly different with the tested samples without microencapsulation. These results suggest potential antibacterial properties of Z. cassumunar Roxb., which useful for agricultural plant health, food preservation, natural therapies, and pharmaceuticals.

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

With the economic recession and the deterioration of the ecological environment becoming more and more prominent in the world, the sustainable operation of enterprises is facing the most difficult choice in history. For each responsible enterprise, it is crucial to choose the market power expansive strategy that can improve the realistic viability or the technological innovation strategy that can improve the future development potential. This is of great significance to reduce the negative external effects of the corporate social environment and ensure their sustainable development. In this paper, we select the data of 18 large listed petrochemical companies from 2003 to 2018 as samples and construct a linear regression model for empirical analysis. Meanwhile, we put forward more practical business management strategies for the sustainable development of petrochemical enterprises in developing countries in further research.

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

Most of the research in data mining concentrated on finding the positive associations that exist in frequent patterns. Frequent patterns have no bearing on the time duration and, therefore, lose interestingness. The Regularity of an itemset is related to the time at which the transaction occurred and the time distance between the transactions. Frequent Regular item sets can be generated considering the Frequency and the Regularity of the occurrence of the Item Sets. The frequent and regular Item sets will be so huge that they cannot be handled in real time. The count of Frequent and regular item sets gets reduced drastically when the properties “closed” and “Maximality” are applied. Finding negative associations among such patterns are important in the field of medicine. Many drugs administered to cure some diseases have counter reactions leading to many other diseases. Negative associations among the mined patterns are important as they reveal significant contradictions frequently among medical drugs administered by medical practitioners to cure some diseases. This paper proposes a method that mines medical databases to find regular, frequent patterns applied with closed and maximal properties and find negative associations among those patterns. The proposed algorithm is accurate to 98% and performs 9% more efficiently than the other algorithms presented in the literature.

Google Trends data can be informative for infectious disease incidences, including Lyme disease. However, the use of Google Trends for predictive purposes is underutilized. In this study, we tested the ability of Google Trends search data to predict monthly state-level Lyme disease case counts in the United States. We requested Lyme disease data for the years 2010-2021. We downloaded Google Trends search data on terms for Lyme disease, symptoms of Lyme disease, and diseases with similar symptoms as Lyme disease. We built mixed negative binomial models based on a training dataset (2010-2016) and tested the models on a test dataset (2017-2021). A model was built for each search term and monthly lags of search terms were included as predictors. The highest performing models had high predictive ability, indicated by low Root Mean Squared Errors (RMSEs) and close association between observed and predicted case counts. The highest performing model was for the search term “Summer Flu”, which indicates low specificity of some of the terms. We outline challenges of using Google Trends data, including data availability and a mismatch between geographic units. We discuss opportunities for Google Trends data, including prediction of additional zoonotic diseases and incorporating environmental and companion animal data.

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

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

Ongoing COVID-19 Pandemic has resulted into massive damage to various platforms of global economy which has caused disruption to human livelihood. Natural Language Processing has been extensively used in different organizations to categorize sentiments, perform recommendation, summarizing information and topic modelling. This research aims to understand the non-medical impact of COVID-19 on global economy by leveraging the natural language processing methodology. This methodology comprises of text classification which includes topic modelling on unstructured COVID-19 media articles dataset provided by Anacode. Like other Natural Language Processing algorithms, Latent Dirichlet allocation (LDA) and Non-negative matrix factorization (NMF) has been proposed to classify the media articles dataset in order to analyze COVID-19 pandemic impacts in the different sectors of global economy. Model Accuracy was examined based on the coherence and perplexity score which came out to be 0.51 and -10.90 using LDA algorithm. Both the LDA and NMF algorithm identified similar prevalent topics that was impacted by COVID-19 pandemic in multiple sectors of economy. Through intertopic distance map visualization produced by LDA algorithm, it can be reciprocated that general industries which includes children schooling, parental care, and family gatherings had the major impact followed by business sector and the financial industry.

The move to a low carbon economy is very important for enhancing international competitiveness. The eco-innovation is the critical factor of the green paradigm. This study is designed to investigate deeply the determinants of eco-innovation of manufacturing firms in Korea by suggesting anticipated regulations, self-regulations, and industry-specific characteristics as external factors and open information sources as internal factors. The data used in the analysis is 1946 sample firms from Korean Innovation Survey 2010 based on the Oslo Manual. Using the multi-variate probit analysis and the zero-inflated negative binomial (ZINB) regression analysis, we have found out that the anticipated regulations and self-regulations have significant influences both on eco-process innovation and eco-product innovation, while industrial characteristics have no effects. The empirical results also show that the breadth of information sources has a positive effect on businesses in implementing eco-innovations. Our findings show that the Korean government should provide a good platform where firms can better understand the future trends of environmental policies, particularly policies on anticipated and self-regulations. At the same time, Korean firms should establish a voluntary system to control environmental activities so that they can improve eco-innovations through integrating external information.

Crash prediction of the sharp horizontal curve segment (SHCS) of a freeway is an important tool in analyzing safety of SHCSs and in building a crash prediction model (CPM). The design and crash report data of 88 SHCSs from different institutions were surveyed and three negative binomial (NB) regression models and three generalized negative binomial (GNB) regression models were built to prove that the interactive influence of explanatory variables plays an important role in fitting goodness. The study demonstrates the effective use of the GNB model in analyzing the interactive influence of explanatory variables and in predicting freeway basic segments. Traffic volume, highway horizontal radius, and curve length have been formulated as explanatory variables. Subsequently, we performed statistical analysis to determine the model parameters and conducted sensitivity analysis. Among the six models, the result of model 6, which considered interactive influence, is much better than those of the other models by fitting rules. We also compared the actual results from crashes of 88 SHCSs with those predicted by models 1, 3, and 6. Results demonstrate that model 6 is much more reasonable than models 1 and 3.

Sepsis is a life-threatening complication of an infectious process that results from excessive and uncontrolled activation of the host's pro-inflammatory immune response to a pathogen. Lipopolysaccharide (LPS), also known as endotoxin, which is a major component of the Gram-negative bacteria outer membrane, plays a key role in the development of Gram-negative sepsis and septic shock in humans. To date, no specific and effective drug against sepsis has been developed. This review summarizes data on LPS-binding proteins from marine invertebrates (ILBPs), that inhibit LPS toxic effects, and are of interest as potential drugs for the sepsis treatment. The structure, physicochemical properties, antimicrobial and LPS-binding/neutralizing activity of these proteins and their synthetic analogues are considered in details. Problems that arise during clinical trials of potential anti-endotoxic drugs are discussed.

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

Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Here, we introduce an in vitro/in vivo model of organ-specific micrometastases of triple-negative breast cancer (TNBC) that is fully implemented in a cost-efficient chick embryo (CE) experimental platform. The model is built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellular-ized CE organ-specific scaffolds. TNBC cells colonized CE organ-specific scaffolds in 2-3 weeks, forming tissue-like structures. The feasibility of this methodology for basic cancer research, drug development and nanomedicine was demonstrated on a model of hepatic micrometastasis of TNBC. We revealed that MDA-MB-231 differentially colonize parenchymal and stromal com-partments of the liver-specific extracellular matrix (LS-ECM) and become more resistant to the treatment with molecular Doxorubicin (Dox) and Dox-loaded mesoporous silica nanoparticles than in monolayer cultures. When grafted on CE chorioallantoic membrane, LS-ECM-based TECs induced angiogenic switch. These findings may have important implications for the diag-nosis and treatment of TNBC. The methodology established here is scalable and adaptable for pharmacological testing and cancer biology research of various metastatic and primary tumors.

Patients diagnosed with unresectable locally advanced Triple Negative Breast Cancer (TNBC) usually have poor outcome for its aggressive clinical behaviour. Atezolizumab plus nanoparticle albumin-bound (nab)-Paclitaxel prolonged progression-free survival (PFS) and overall survival (OS) among patients with unresectable locally advanced TNBC but its use is hampered by the lack of reliable predictors of tumor response. Seventy-seven consecutive patients with unresectable locally advanced TNBC treated with Atezolizumab plus nab-Paclitaxel were studied by blood draws at baseline, 28 days and 56 days after initiation of treatment. Exosomal PD-L1 mRNA in plasma was determined using Bio-Rad QX100 digital droplet PCR system and exoRNeasy kit and objective responses were defined following the RECIST criteria v.1.1. The study evaluates whether PD-L1 mRNA copies per ml in plasma-derived exosomes may predict response to anti-PD-L1 antibodies early in the course of therapy. Our data showed patients with unresectable locally advanced TNBC and higher levels of PD-L1 mRNA expression in plasma-derived exosomes at baseline demonstrated greater response to atezolizumab plus nab-paclitaxel. Furthermore, the levels of mRNA decreased with successful treatment while the copy number increased in patients experiencing disease progression following atezolizumab plus nab-paclitaxel. For the first time, our data showed the usefulness of assessment of exosomal PD-L1 as non-invasive real-time biopsy in patients diagnosed with TNBC suggesting exosomal PD-L1 is significantly associated with outcome and response to Atezolizumab plus nab-Paclitaxel.

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

Tuberculosis cause of death worldwide and the leading cause from a single infectious agent, ranking above Human immunodeficiency virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). The aim of this study is to ascertain the trend of tuberculosis prevalence and the effect of HIV prevalence onl Tuberculosis case in some West African countries from 2000 to 2016 using count panel data regression models. The data used annual HIV and Tuberculosis cases spanning from 2000 to 2016 extracted from online publication of World health Organization (WHO). Panel Poisson regression model and Negative binomial regression model for fixed and random effects were used to analyzed the count data, the result revealed a positive trend in TB cases while increased in HIV cases leads to increase in TB cases in West African countries. Among the competing models used in this study, Panel Negative Binomial Regression Model with fixed effect emerged the best model with log likelihood value of -1336.554. This study recommended that Government and NGOs need more strategies to fight against HIV menace in West Africa as this will in turn reduced TB cases in West Africa.

In Sub-Saharan African Countries such as Nigeria with high prevalence rate, Child HIV/AIDs acquired through Mother-to-Child transmission (MTCT) can be largely prevented by using a well-established prevention programme and scheme. This study examined factors that can enhanced Prevention of Mother-to-Child transmission (PMTCT) in Nasarawa State. To achieve this, structured questionnaire were used to collect data from one hundred and sixteen (116) women attending two (2) primary facilities and two (2) secondary facilities in the State. This study utilized methods of Poisson Regression, Negative Binomial Regression and Logistic Regression Analyses. Results revealed that women with at least a secondary school education, women with husband in military and women with perceived confidentiality of their HIV status significantly enhanced PMTCT of HIV in Nasarawa State while significant proportion of the women attest to the fact that drugs are available in the facilities (p-value=0.0000<0.05) . Other factors include mother income level, willingness to continue with PMTCT programme and women in support group can also enhanced PMTCT though they are not significant. This study recommends that the factors identified should be explored by NGOs, Ministry of Health and, Support groups and other relevant agencies since they have the capacity to enhanced PMTCT of HIV in Nasarawa State, Nigeria.