This paper concentrates on the general birth-death processes with two different types of catastrophes. The Laplace transform of transition probability function for birth-death processes with two-type catastrophes are is successfully expressed with the Laplace transform of transition probability function of the birth-death processes without catastrophe. The first effective catastrophe occurrence time is considered. The Laplace transform of its probability density function, expectation and variance are obtained.

The regulation of cell death is a fundamental issue in cell biology and continues to be intensely investigated worldwide. The significance of research in this field persists because understanding the determinants of cell lifespan directly impacts the maintenance of multicellular organism homeostasis and, consequently, is crucial for addressing biomedical challenges associated with various diseases. It is recognized that the initiation of cell death can be prompted by both specific signals (such as cytokines or hormones) and nonspecific stimuli, including radiation, temperature increase, or oxidants. When these factors affect a cell, numerous signaling pathways are triggered in the cell, leading to neutralization of the effects of their negative effects or, in case of irreparable damage, to cell elimination. This removal of damaged cells occurs through apoptosis or programmed cell death, a highly regulated process. Numerous signaling molecules participate in orchestrating the apoptotic process, many of which also govern other essential functions within the organism. Physiological factors capable of triggering the apoptotic program in cells include nitric oxide (NO), which serves as one of the key signaling molecules regulating the functions of the cardiovascular, nervous, and immune systems of the organism. The unique chemical nature of NO, along with its numerous intracellular targets and physiologically active redox forms, raises questions about the specific mechanisms through which NO exerts its damaging effects on cells. Utilizing pharmacological preparations- such as sources (donors) of exogenous nitric oxide- represents an approach to investigating the initiation and execution of the apoptotic program in sensitive target cells. Furthermore, this approach holds promise as a direction for discovering new selective drugs.

The aim of this study was to investigate the physicochemical characterization and biological activities of chitosan (CH) based composite films with the incorporation of chestnut flower essential oil (CFEO). The composite films were prepared by casting method and characterized in terms of structural, morphological and mechanical properties via FT-IR, XRD, UV, SEM and TGA. The results proved the significantly increased water vapor permeability (WVP), heat resistance, antibacterial and antioxidant capabilities of CH-CFEO films. The incorporation of CH and CFEO enhanced the UV blocking, which made the film shield almost all UV light. Films with the tensile strength of 6.37 ± 0.41 MPa and elongation at break of 22.57 ± 0.35% were got with 6 mg mL-1 CFEO. Subsequently, the fruit preservation experiments also confirmed that the composite films could effectively extend the shelf life of bananas through their excellent water vapor and oxygen barrier. These desirable performances enable our newly developed composite films to be a remarkable packaging material to solve the fresh fruit preservation dilemma.

Arboviruses are infections caused by arboviruses that may be either symptomatic or asymptomatic, according to individuals' resistance and immune response, which dietary patterns can influence. Thus, this study aimed to investigate the possible association between the occurrence of clinical manifestations of arboviruses and the dietary pattern of the population studied. The study was conducted in a rural population in the metropolitan area of Belém, Pará State, Brazil. The sampling consisted of 95 individuals during a febrile outbreak. Two investigations were conducted: clinical-epidemiological-dietary and laboratory investigation based on blood samples taken for arbovirus analysis. Out of the 95 individuals studied, more than half (57.89%) showed clinical manifestations. Following the laboratory serology (HI and IgM ELISA) analyses, viral isolation in C6/36 cells, and viral genome detection (RT-qPCR), the final diagnosis of the cases was 47.37% Oropouche Fever, 2.11% Oropouche Fever and Chikungunya Fever, and 1.05% Mayaro Fever. Regarding dietary pattern, as for the comparison analyses, statistical significance was observed between dietary pattern and classification regarding the presence of symptoms (p<0.05); after the correspondence analysis, symptomatic cases were more associated with a bad dietary pattern, while asymptomatic cases were more associated with a good dietary pattern.

We revisit the argument that link the efficiency of a solar cell to its reverse operation as a LED, in the case where the material is organic. In organic cells, exciton transport is an intermediate process between sunlight absorption and the generation of electric current. We show that quenching exciton radiation can be beneficial to cell efficiency, without contradicting the general rule prevailing for semiconductor cells. Our treatment allows us to discuss both bulk heterojunction and planar junctions.

Intelligent fault diagnosis techniques have replaced the time-consuming and unreliable human analysis, increasing the efficiency of fault diagnosis. Deep learning model can improve the accuracy of intelligent fault diagnosis with the help of its multilayer nonlinear mapping ability. This paper has proposed a novel method named Deep Convolutional Neural Networks with Wide First-layer Kernels (WDCNN). The proposed method uses raw vibration signals as input (data augmentation is used to generate more inputs), and uses the wide kernels in first convolutional layer for extracting feature and suppressing high frequency noise. Small convolutional kernels in the preceding layers are used for multilayer nonlinear mapping. AdaBN is implemented to improve the domain adaptation ability of the model. The proposed model addresses the problem that currently, the accuracy of CNN applied to fault diagnosis is not very high. WDCNN can not only achieve 100% classification accuracy on normal signals, but also outperform state of the art DNN model which is based on frequency features under different working load and noisy environment.

Epidemic diseases that arise from infectious RNA viruses, particularly influenza viruses, pose a constant threat to the global economy and public health. Viral evolution has undermined the efficacy of acquired immunity from vaccines and the antiviral effects of FDA-approved drugs. As such, there is an urgent need to develop new antiviral lead agents. Natural compounds, owing to their historical validation of application and safety, have become a promising solution. In this light, a novel marine bacterium, Pseudomonas sp. M20A4R8, has been found to exhibit significant antiviral activity [half maximal inhibitory concentration (IC50) = 1.3 µg/mL, selectivity index (SI) = 919.4] against influenza virus A/Puerto Rico/8/34, surpassing the activity of chloroquine. The antiviral response by M20A4R8 extract was induced during post-entry stages of the influenza virus, indicating suitability for post-application after the establishment of viral infection. Furthermore, post-treatment with M20A4R8 extract protected the host from virus-induced apoptosis, suggesting its potential use in acute respiratory disease complexes resulting from immune effectors' overstimulation and autophagy-mediated self-apoptosis. The extract demonstrated an outstanding therapeutic index against influenza virus A/Wisconsin/15/2009 (IC50 = 8.1 µg/mL, SI = 146.2) and B/Florida/78/2015 Victoria lineage (IC50 = 3.5 µg/mL, SI = 343.8), indicating a broad anti-influenza virus activity with guaranteed safety and effectiveness. This study provides a new perspective on mechanisms for preventing a broad spectrum of viral infections through antiviral agents from novel and natural origins. Future studies on a single or combined compound from the extract hold promise, encouraging its use in preclinical challenge tests with various influenza virus strains.

Location-and-scale transformation of a random variable underpins normal distribution, but it is however fundamentally incorrect for scale estimation such as relative dispersion. In this paper, a parametrized alternative to a normal distribution, called scaloc-normal distribution, is proposed that efficiently works and is fundamentally correct with absolute and relative dispersion estimators. The Monte Carlos simulation experiment was used to generate a total of 600,000 artificial datasets in 600 different simulation scenarios from loc-normal (normal) and scaloc-normal distributions. The absolute and relative dispersion were estimated and compared from the two distributions. The results show that scaloc-normal distribution is a good parametrized alternative to loc-normal distribution, fundamentally correct and efficient with both standard deviation and coefficient of variation. The key statistical advancement from loc-normal to scaloc-normal distribution is its fundamental correctness (i.e., scale-invariant property) with an efficient relative estimator of dispersion (i.e., coefficient of variation). Parametrically, the loc-normal and scaloc-normal distributions are very different, but both have linear transformations.

Neuronal cell death in the central nervous system has always been a challenging process to decipher. In physiological condition, neuronal cell death is restricted in the adult brain even as people ages. However, in pathological conditions of various neurodegenerative diseases, the cell death and shrinkage of a specific brain region represent a fundamental pathological feature across different neurodegenerative diseases. In this review, we will briefly go through the general pathways of cell death and describe the evidence of the cell deaths in the context of common neurodegenerative diseases individually, discussing our current understandings of cell death in connecting with the renowned pathogenic proteins, including tau, amyloid-beta, alpha-synuclein, huntingtin, and TDP-43.

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

Escalation of commitment explains the choice for investing in an option for which great investments have previously been made even though better choices became available. The last 25 years of producing innumerous versions of Alzheimer Disease animal models with virtually no predictive validity should have exposed the fact that using animals for studying AD is clearly a failing course of action and as such should have been abandoned long ago, giving room to other alternatives to flourish. In this assay, I explore the idea that the investment in new animal models for studying Alzheimer (AD) represents a classic case of escalation of commitment, and sunk cost dilemma, in the biomedical research.

A wide range of research has been developed in the empirical literature regarding income and price elasticities of health care expenditure (HCE). The results are mixed, as researchers employ different methodologies and data sources. The benefits of the panel data method, such as greater data variation, less collinearity, and more degrees of freedom, made it attractive among economists. However, the pooled mean group (PMG) method provides robust estimates compared to conventional methods, such as the mean group estimator and dynamic fixed-effects estimator. As such, this paper applies the PMG method to scrutinize the effect of income and price on U.S. health care consumption using a panel of 46 states. The income and price elasticities were found to be 0.85 and -0.48, respectively, which partially describes the recessionary decline in health care consumption following the Great Recession. In addition, the model reveals that the short-run income elasticity is smaller than the long-run. This confirms that U.S. health care consumption follows the permanent income hypothesis. Consequently, the short-run efficacy of public policies targeting HCE remains limited. The results of this paper suggest reconsidering and adjusting health care policies during a recession so as to avoid probable long-run adverse effects on HCE.

In some species of salmon, reproductive maturity triggers the development of massive pathology resulting from reproductive effort, leading to rapid post-reproductive death. Such reproductive death, which occurs in many semelparous organisms (with a single bout of reproduction), can be prevented by blocking reproductive maturation, and this can increase lifespan dramatically. Reproductive death is often viewed as distinct from senescence in iteroparous organisms (with multiple bouts of reproduction) such as humans. Here we review the evidence that reproductive death occurs in C. elegans and discuss what this means for its use as a model organism to study aging. Inhibiting insulin/IGF-1 signaling and germline removal suppresses reproductive death and greatly extends lifespan in C. elegans, but can also extend lifespan to a small extent in iteroparous organisms. We argue that mechanisms of senescence operative in reproductive death exist in a less catastrophic form in iteroparous organisms, particularly those involving costly resource reallocation, and exhibiting endocrine-regulated plasticity. Thus, mechanisms of senescence in semelparous organisms (including plants) and iteroparous ones form an etiological continuum. Therefore understanding mechanisms of reproductive death in C. elegans can teach us about some mechanisms of senescence that are operative in iteroparous organisms.

Curcumin, found in the rhizome of turmeric, has extensive therapeutic promises via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown curcumin to be an effective treatment for multiple cancers. These effects are drived by curcumin's ability to induce G2/M cell cycle arrest, induction of autophagy, activation of apoptotic pathways, disruption of molecular signaling, inhibition of invasion and metastasis, and by increasing the efficacy of existing chemotherapeutics. Here we focused on the hormetic behaviour of curcumin. Frequently, low doses of toxins and other stressors not only are harmless but also activate an adaptive stress whereas high dose activates acute responses like autophagy and cell death. This phenomenon is referred to as hormesis. Many molecules that cause cell death elicite an initial autophagic step that is a cytoprotective mechanism relying on elimination of dysfunctional structures intracellular, notably by mitophagy. This phenomenon is considered as a primarily protective mechanism against stressors. At higher doses, cells undergo mitochondrial outer membrane permeabilization due to calcium release from the endoplasmic reticulum and die. Herein, we address the complex crosstalk between the induced mitochondrial biogenesis, mitochondrial destabilization accompanied by mitophagy and cell death that can also be at play.

Fish and fish products are very appreciated in the human diet because of high quality proteins and other important nutrients, such as minerals and polyunsaturated fatty acids. Maintaining freshness, quality and safety is essential in the fish supply chain, starting from on board vessels where the product must be carefully checked and protected from any source of contamination. Safe fishing and handling of fish are very important to reduce the risk of foodborne diseases caused by pathogenic microorganisms such as Salmonella spp., Vibrio spp., Listeria monocytogenes, Clostridium botulinum type E, viruses, and parasites. The inspection of raw material, use of good quality ice and water, high standards of personnel hygiene and cleanliness of equipment and fa-cilities as well as proper storage temperature are the most effective measures to ensure safety of fish and fish products for consumers. This review describes the good hygiene practice to be ap-plied on ships to preserve both fish products and public health.

For decades SrTiO3 is in the focus of research with seemingly never-ending new insights regarding its ground state properties, its application potentials, its surface and interface properties, the superconducting state, the twin boundaries and domain functionalities, etc. Here, we focus on the already well-investigated lattice dynamics of STO and show that four different temperature regimes can be identified which dominate the elastic properties, the thermal conductivity and the birefringence. These regimes are the low-temperature quantum fluctuation dominated one, followed by an intermediate regime, the region of the structural phase transition at ~105 K and its vicinity, and at high temperatures a regime characterized by precursor and saturation effects. They can all be elucidated by lattice dynamical aspects. The relevant temperature dependences of the soft modes are discussed and their relationship to lattice polarizability is emphasized.

The statistical properties of a good estimator include robustness, unbiasedness, efficiency, and consistency. However, the commonly used estimators of dispersion have lack or are weak in one or more of these properties. In this paper, I proposed statistical mirroring as a good alternative estimator of dispersion around defined location estimates or points. In the main part of the paper, attention is restricted to Gaussian distribution and only estimators of dispersion around the mean that functionalize with all the observations of a dataset were considered at this time. The different estimators were compared with the proposed estimators in terms of alternativeness, scale and sample size robustness, outlier biasedness, and efficiency. Monte Carlo simulation was used to generate artificial datasets for application. The proposed estimators (of statistical meanic mirroring) turn out to be suitable alternative estimators of dispersion that is less biased (more resistant) to contaminations, robust to scale and sample size, and more efficient to a random distribution of variable than the standard deviation, variance, and coefficient of variation. However, statistical meanic mirroring is not suitable with a mean (of a normal distribution) close to zero, and on a scale below ratio level.

To maintain proteostasis, cells must integrate information and activities that supervise protein synthesis, protein folding, conformational stability, and also protein degradation. Extrinsic and intrinsic conditions can both impact on normal proteostasis, causing the appearance of proteotoxic stress. Initially, proteotoxic stress elicits adaptive responses aimed to restore proteostasis, allowing cells to survival the stress condition. However, if the proteostasis restoration fails, a permanent and sustained proteotoxic stress can be deleterious and cell death ensues. Many cancer cells convive with high levels of proteotoxic stress and this condition could be exploited in a therapeutic perspective. Understanding the cell death pathways engaged by proteotoxic stress is instrumental to better hijack the proliferative fate of cancer cells.

This paper reports the findings from a pilot study designed to explore the barriers, facilitators and similarities with the delivery and implementation of two distinct models of Advance Care Planning (ACP) documentation for older adults in their last year of life used by health care professionals in their clinical practice. PACe (Proactive Anticipatory Care Plan): a GP led model and PEACE (Proactive Elderly Persons’ Advisory CarE): a nurse led model with community geriatrician oversight were used by participants in their clinical practice. Telephone interviews were conducted with general practitioners (GPs) to explore their views of using the PACe tool. Hospital admission avoidance matrons took part in face to face interviews and care staff employed in private residential care homes took part in individual telephone interviews to explore their views of using the PEACE tool. GPs and admission avoidance matrons were employed by Clinical Commissioning Groups (CCGs) and all study participants were recruited from the South East of England where data collection took place in 2015. Nine telephone interviews and two face-to-face interviews (one joint and one individual) were conducted with twelve participants. The data was analysed thematically. Participants highlighted the similarity of both tools in providing focus to ACP discussions to inform individual end-of-life care preferences. The importance of relationships was a pivotal theme-established, trusting inter-professional relationships to enable multidisciplinary teamwork and a prior relationship with the older person (or their proxy in the case of cognitive impairment) to enable conversations of this nature. Using both tools enabled participants to think critically and reflect on their own practice was another theme identified. Notwithstanding participants’ views to improve the layout of both tools, using a paper-based approach to deliver streamlined ACP and end-of-life care was a theme to emerge as a barrier which focused on the problems with access to paper-based documentation, accuracy and care co-ordination in the context of multidisciplinary team working. The value of technology in overcoming this barrier and underpin ACP as a means to help simplify service provision, promote integrated professional practice and provide seamless care was put forward as the solution.

The growing concern about climate change and global warming has driven greater involvement of international organizations, countries, companies, and society in general in acting and ensur-ing the life of our planet and the sustainability of future generations. Sustainability and finance are two concepts that are intertwined through sustainable finance, serving as an instrument that guides financial resources towards achieving sustainable development. Sustainability allows companies to identify risks and opportunities, being responsible for measuring their social, envi-ronmental, and economic impact under a multi-stakeholder approach. One of the three main cri-teria of sustainability is corporate governance, and the main corporate governance body is the board of directors, where the composition of the board and its supervision and monitoring func-tions improve the ESG performance. A relevant aspect within the board of directors is the ade-quate balance of gender diversity on the board, becoming an aspect regulated by laws and cor-porate governance code. This article develops the main concepts related to sustainability, sus-tainable finance and corporate governance describing the current situation of these topics and their relationship, creating a conceptual framework that allows identifying topics necessary for further empirical research and the implication of regulation in the scope of ESG issues.

The rise of multi-sided digital platforms has transformed the global economy, enabling individuals and companies to create, deliver, and capture value through innovative connections and network effects. While scholars have studied the core strategy concepts and proposed platform architectures, less attention has been paid to the long-term sustainability of these platforms. This paper addresses this gap by examining the relationship between sustainability and platform architecture. Specifically, it asks what mechanisms characterize digital platforms for sustainability, and whether there are design choices that optimize the business model for sustainability. Using a mixed-methods approach that draws on platform literature, business models, and sustainable innovation, the paper develops an integrative framework to identify elements and design choices in platform businesses which support sustainability outcomes. The framework is then used to classify the business models of the identified platforms, revealing specific design choices for platform architecture that can optimize their business models for sustainability. This contribution to existing literature provides an artifact that allocates key decisions on value creation, delivery, and capture that are key to platforms and includes an additional layer to optimize them for long-term sustainability. As digital platforms continue to drive the economy, this research is relevant not only to platform practitioners, but also to policy makers and society at large.

The disruptive application of ChatGPT (GPT-3.5, GPT-4) to a variety of domains has become a topic of much discussion in the scientific community and society at large. Large Language Models (LLMs), e.g., BERT, Bard, Generative Pre-trained Transformers (GPTs), LLaMA, etc., have the ability to take instructions, or prompts, from users and generate answers and solutions based on very large volumes of text-based training data. This paper assesses the impact and potential impact of ChatGPT on the field of digital forensics, specifically looking at its latest pre-trained LLM, GPT-4. A series of experiments are conducted to assess its capability across several digital forensic use cases including artefact understanding, evidence searching, code generation, anomaly detection, incident response, and education. Across these topics, its strengths and risks are outlined and a number of general conclusions are drawn. Overall this paper concludes that while there are some potential low-risk applications of ChatGPT within digital forensics, many are either unsuitable at present, since the evidence would need to be uploaded to the service, or they require sufficient knowledge of the topic being asked of the tool to identify incorrect assumptions, inaccuracies, and mistakes. However, to an appropriately knowledgeable user, it could act as a useful supporting tool in some circumstances.

Secondary and tertiary prevention strategies targeting people with disabilities to improve their health and wellbeing is important. In Sweden, >95% of all children with cerebral palsy (CP) participate in a follow-up program, where one of the goals is the prevention of hip dislocations. We reviewed the incidence of hip dislocations from 2010 to 2019 and the number of children who underwent different types of hip surgeries. The number of hip dislocations was reduced from 8.8% before introduction of the program to 0.3-0.4% up to 2015, followed by a gradual increase to 0.8% in 2019. The proportion of children who underwent adductor-psoas lengthening as their primary preventive surgery decreased from 50% in 2017 to 37% in 2019 with a corresponding increase of children undergoing femoral osteotomy, indicating more children underwent surgery at a later stage. Reasons for the increased number of children with hip dislocation may be that more children have moved to Sweden in recent years without corresponding compensation in health care resources and increased waiting times for surgery due to, among other things, a shortage of nurses. The results highlight the importance of constantly monitoring follow-up programs.

Good Boussinesq equations will be considered in this work. First we apply three combined compact schemes to approximate spatial derivatives of good Boussinesq equations. Then three fully discrete schemes are developed based on symplectic scheme in time direction, which are sympletic-structure preserving.Meanwhile, the convergence and conservation of the fully discrete schemes are analyzed. Finally, we present numerical experiments to confirm our theoretical analysis. Both our analysis and numerical test indicate that the fully discrete schemes are efficient in solving the spatial derivative mixed equation.

Hippocrate, the father of medicine, already said:"Wine is a thing wonderfully appropriate to man if, in health as in disease, it is administered with appropriate and just measure according to the individual constitution." wine has always accompanied humanity, for religion or for health. Christians and Jews need wine for the liturgy. For Platon the wine was an indispensable element in society and took all its importance in the symposium. In this second part of the banquet, mixed with water, the wine gave the word. If the french paradox made a lot of ink flow; it was the wine that was originally responsible for it. Many researchers have tried to share the alcohol and polyphenols in order to solve the mystery. Beyond its cardiovascular effects, there are also effects on longevity, metabolism, cancer prevention and neuroprotection, and the list goes on. The purpose of this work is to make an analysis of current knowledge on the subject. Indeed, if the paradigm of the antioxidants is seductive, it is perhaps by their prooxidant effect that the polyphenols could act, by an epigenetic process mediated by nrf2. Wine is a preserve of antioxidants for the winter and it is by this property that the wine acts, in alcoholic solution. A wine without alcohol is pure heresy. By the way, we were not talking about elixir to design all this millennial pharmacopee that made the man was able to heal and prosper on the planet. From Alvise Cornaro to Serge Renaud, nutrition was the key to health and longevity, whether Cretan or Okinawa diet, it is the small dose of alcohol (wine or sake) that allows the bioavailability of polyphenols. Moderate drinking give a protection for diseases and a longevity potential. In conclusion, let’s drink fewer, but drink better to live older.

Aneuploidy describes the gain or loss of entire chromosomes or chromosome arms. Already more than 100 years ago, aneuploidy was described to be featured in cancer and it is known today to be present in 68-90 % of cancers, depending on tumour entity. Aneuploidy is implicated to affect cancer growth, therapy response and frequently affects prognosis. Chromosomal instability (CIN) is recognized as the main cause of aneuploidy and is characterised as the fluent process of gaining or losing chromosomes. Chromosomally instable cells need to be kept in check, or cleared, to prohibit the sampling of aneuploid karyotypes able to drive tumorigenesis. Of note, even aneuploid cancer cells often show CIN, a feature that promotes therapy related drug-resistance. Here, we review how CIN can be prevented or limited to spread by the induction of cell death and the relevance of different p53 responses triggered in response to mitotic perturbations to prohibit the formation of cancer driving aneuploidies.

Extracellular vesicles (EVs) have been identified as novel mediators of intercellular communication. They work via delivering the sequestered cargo to cells in close vicinity as well as distant sites in the body, regulating pathophysiological processes. Cell death and inflammation are biologically crucial processes in both normal physiology and pathology. These processes are indistinguishably linked with their effectors modulating the other process. For instance, during an unresolvable infection, the upregulation of specific immune mediators leads to inflammation causing cell death and tissue damage. EVs have gained considerable interest as mediators of both cell death and inflammation during conditions such as sepsis. This review summarizes the types of extracellular vesicles known to date and their roles in mediating immune responses leading to cell death and inflammation with specific focus on sepsis and lung inflammation.

The main features of the instrumental global mean surface temperature (GMST) are reasonably well described by a simple linear response model driven by anthropogenic, volcanic and solar forcing. This model acts as a linear long-memory filter of the forcing signal. The physical interpretation of this filtering is the delayed response due to the thermal inertia of the ocean. This description is considerably more accurate if El Ni\~{n}o Southern Oscillation (ENSO) and the Atlantic Multi-decadal Oscillation (AMO) are regarded as additional forcing of the global temperature and hence subject to the same filtering as the other forcing components. By considering these as predictors in a linear regression scheme, more than 92\% of the variance in the instrumental GMST over the period 1870-2017 is explained by this model, and in particular all features of the 1998 -- 2015 hiatus, including its death. While the more prominent pauses during 1870 -- 1915 and 1940 -- 1970 can be attributed to clustering in time of strong volcanic eruptions, the recent hiatus is an unremarkable phenomenon that is attributed to ENSO and a small contribution from solar activity.

Risk management strategies protect the company as a whole as well as employees from unforeseen financial impacts. As in the case of personal finance, preparing for certain scenarios helps to face any difficulties that the company may encounter and allows it to get out of this impasse.For any project to be successful, the way the project executing agency will deal with potential risks must be determined so that it can identify, mitigate or avoid problems when it needs to do so. Successful project managers realize that risk management is important, because the achievement of project objectives depends on planning, preparation, results and evaluation that contribute to the achievement of strategic goals, especially the sustainable development of societies.Risk management strategies work to protect the company as a whole as well as employees from unexpected financial effects, and as is the case in personal finance, preparing for certain scenarios helps to face any difficulties that the company may face and allows it to get out of this impasse.To ensure the success of your project, determine how you will handle potential risks so that you can identify, mitigate or avoid problems when you need to do so. Successful project managers understand that risk management is important, because the achievement of project objectives depends on planning, preparation, results, and evaluation that contribute to the achievement of strategic objectives.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known to cause 2019-coronavirus disease (COVID-19) pandemic is a zoonotic coronavirus and crosses species to infect human populations, where an efficient transmission of virus occurs human-to-human. Nationwide lockdown is being adopted to stop public transport, keep people at their homes and out of their work, and maintain social distancing. In turn, large geographic areas in the world (including China, Italy, Spain, and USA) has been almost halted. This temporary halt is significantly slashing down the air pollution (air pollutants and warming gases) in most cities across the world. This paper: (i) introduces both COVID-19 and air pollution; (ii) overviews the relation of air pollution with respiratory/lung diseases; (iii) compiles and highlights major data appeared in media and journals reporting lowering of air pollution in major cities those have been highly impacted by the COVID-19; and also (iv) lists the way forward in the present context. Because COVID-19 is an ongoing pandemic and currently far from over, strong conclusions could not be drawn with very limited data at present. The temporary slashed down global air pollution as a result of COVID-19 restrictions are expected to stimulate the researchers, policy makers and governments for the judicious use of resources; thereby minimise the global emissions, and maintain their economies once the pandemic eases. On the other, lifting of the nationwide lockdown and eventual normalisation of the temporarily halted sectors may also reverse the currently COVID-19 pandemic-led significantly slashed down global air pollution that could make the future respiratory health crisis grimmer.

In California, an average of 41,900 patients are diagnosed annually with Staphylococcus bacterial infection; out of these, 24,090 patients have methicillin-resistant Staphylococcus aureus (MRSA) infection and 17,810 patients have methicillin-sensitive Staphylococcus aureus (MSSA) infection. The aim of this paper is to find out whether there is a significant difference in strain dominancy and in what direction. The paper gathered and analyzed data for period of five years of infection rate due to Staphylococcus aureus. This study indicates that a significant difference in dominancy exists, the MRSA infection rate (an average of five years period) is 1.35 times higher than the MSSA infection rate (P-value < 0.05, CI: 95%), but the gap between the two infection rates is decreasing. The infection rate of both MRSA and MSSA is in a path of decline.

As the EU is moving towards a low carbon economy and seeks to further develop its renewable energy policy, this paper quantitatively investigates the impact of plausible energy market reforms from the perspective of bio-renewables. Employing a state-of-the-art biobased variant of a computable general equilibrium model, this study assesses the perceived medium-term benefits, risks and trade-offs which arise from an advanced biofuels plan, two exploratory scenarios of a more 'sustainable' conventional biofuels plan and a 'no-mandate' scenario. Consistent with more recent studies, none of the scenarios considered present significant challenges to EU food-security or agricultural land usage. An illustrative advanced biofuels plan simulation requires non-trivial public support to implement whilst a degree of competition for biomass with (high-value) advanced biomass material industries is observed. On the other hand, it significantly alleviates land use pressures, whilst lignocellulose biomass prices are not expected to increase to unsustainable levels. Clearly, these observations are subject to assumptions on technological change, sustainable biomass limits, expected trends in fossil fuel prices and EU access to third-country trade. With these same caveats in mind, the switch to increased bioethanol production does not result in significant market tensions in biomass markets.

Basildon and Thurrock University Hospital in the East of England region of the United Kingdom (U.K), witnessed rapidly increasing numbers of pregnant women with diabetes, causing overburdened specialist clinics, poorer patient experience and worsening clinical outcomes. This prompted the multidisciplinary team’s remodelling of care pathways, launching the General ownership of Diabetes (GooD) Pregnancy Network in 2014. Contrary to conventional limitation of care to specialist diabetes antenatal clinics, this novel initiative highlights contemporary necessity to equip and empower all maternity stakeholders to deliver basic care of gestational diabetes (GDM). It strategically connects a Midwife Tele-Clinic “hub” to Educating Gestational diabetics Group Sessions (EGGS) and standard antenatal clinics. Patients were key partners, regularly participating in feedback surveys and promoting public awareness by co-producing local newspaper articles that served up their stories as case studies. Furthermore, the EGGS “faculty” includes a former GDM patient whose video testimony has inspired almost 2000 patients and their families; aiming to foster long term healthy lifestyle changes. Final summative evaluation in November 2019 showed the new culture of wider consciousness has shortened ‘diagnosis to first consultation’ intervals and eliminated overbooked specialist clinics (none since January 2016), without further worsening of clinical outcomes. It also boosted research recruitment and avoided additional running costs to the tune of £66,384 a year.

This article explores the enduring mysteries of consciousness and the afterlife, two enigmatic topics that have fascinated humanity for ages. Despite extensive scientific efforts, the existence of an afterlife remains unproven, and understanding consciousness remains a significant challenge. The research introduces innovative hypotheses through simple thought experiments with empirical evidence and robust theoretical foundations. It delves into the complexities of consciousness, its relationship with the brain, and the need for interdisciplinary approaches encompassing physics, psychology, and philosophy. Boldly contemplating the probability of a continuous consciousness after death, the study argues that existing evidence strongly supports this idea. Beyond theoretical implications, it envisions practical outcomes, suggesting that insights into these mysteries could enhance human well-being and contribute to a more harmonious world. In summary, this article embarks on a quest to shed light on age-old questions about consciousness and the afterlife. Through fresh methodologies, it aims to provide new perspectives that could reshape our understanding of existence and inspire intellectuals to positive individual and societal advancements including psychological well-being and intelligence.

Super-Resolution Microscopy enables non-invasive, molecule-specific imaging of the internal structure and dynamics of cells with sub-diffraction limit spatial resolution. One of its major limitations is the requirement for high-intensity illumination, generating considerable cellular phototoxicity. This factor considerably limits the capacity for live-cell observations, particularly for extended periods of time. Here, we overview new developments in hardware, software and probe chemistry aiming to reduce phototoxicity. Additionally, we discuss how the choice of biological model and sample environment impacts the capacity for live-cell observations.

The Sustainable Development Goals (SDGs) represent a central framework to guide sustainable urban development (2030 Agenda). However, it is not clear how and where SDG 11 (Sustainable Cities and Communities) is being implemented, and how such implementation might be improved. We investigated this subject by analyzing United Nations (UN) SDG Good Practices data from 2018 to 2021. We applied five criteria to the 336 SDG 11 responses: (1) geography; (2) actors; (3) progress toward targets; (4) areas of implementation; and (5) scale of action. Overall, 86 of the 193 countries that adopted the 2030 Agenda submitted at least one SDG 11 good practice. 33 countries contributed 73.8% of the total, and most developing countries did not make submissions. A very small number of responses (between 2.6 and 9.1%) addressed equity-related targets. Good practices from developed countries were usually more technology-based and system-forming; developing countries typically focused on issues of day-to-day concern. Overall, this analysis points to the need for better and more systematic reporting on SDG 11 implementation, a more active public sector role in SDG implementation and reporting, more focus on dimensions related to social equity, and better formulation of urban sustainability targets and indicators in the future.

In December 2012, DOAJ’s parent company, IS4OA, announced they would introduce new criteria for inclusion in DOAJ [1] and that DOAJ would collect vastly more information from journals as part of the accreditation process – and that journals already included, would need to reapply in order to be kept in the registry. My hypothesis was that the journals removed from DOAJ on May 9th 2016 would chiefly be journals from small publishers (mostly single journal publishers) and that DOAJ journal metadata information would reveal that they were journals with a lower level of publishing competence than those that would remain in the DOAJ. Among indicators of publishing competence could be the use of APCs, permanent article identifiers, journal licenses, article level metadata deposited with DOAJ, archiving policy/solutions and/or having a policy in SHERPA/RoMEO. The analysis shows my concerns to be correct.

Violence is a complex and multifaceted problem requiring a holistic and individualized response. The Good Lives Model (GLM) suggests violence occurs when an individual experiences internal and external obstacles in the pursuit of universal human needs (termed primary goods). With a twin focus, GLM-consistent interventions aim to promote attainment of primary goods, whilst simultaneously reducing risk of reoffending. This is achieved by improving an individuals’ internal (i.e., skills and abilities) and external capacities (i.e., opportunities, environments, and resources). This paper proposes that collaborations between different agencies (e.g., psychological services, criminal justice systems, social services, education, community organizations and healthcare) can support the attainment of primary goods through the provision of specialized skills and resources. Recommendations for ensuring interagency collaborations are effective are outlined, including embedding a project lead, regular interagency meetings and training, establishing information sharing procedures, and defining the role each agency plays in client care.

The state of epidemic emergency in force in our country since March and the related requirement to implement various sanitary procedures constitute problems for the operation of all companies. However, the unique operation of underground mining companies increases their scale considerably. However, despite initial turbulent moments related to the occurrence of an unknown threat, it was possible to stabilise the situation in all such companies as a result of implementing various anti-threat actions. Following the initial introduction to basic properties of the SARS-CoV-2 coronavirus, the paper presents the results of the study (a case study) on actions taken in individual mining companies. There was an attempt to formulate the so-called good work practices recommended to be applied.

The XChem facility at Diamond Light Source offers fragment screening by X-ray crystallography as a general access user program. The main advantage of X-ray crystallography as a primary fragment screen is that it yields directly the location and pose of the fragment hits, whether within pockets of interest or merely on surface sites: this is the key information for structure-based design and for enabling synthesis of follow-up molecules. Extensive streamlining of the screening experiment at XChem has engendered a very active user programme that is generating large amounts of data: in 2017, 36 academic and industry groups generated 35,000 datasets of uniquely soaked crystals. It has also generated a large number of learnings concerning the main remaining bottleneck, namely obtaining a suitable crystal system that will support a successful fragment screen. Here we discuss the practicalities of generating screen-ready crystals that have useful electron density maps, and how to ensure they will be successfully reproduced and usable at a facility outside the home lab.

Host immunological pathways have been proposed including TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ immune reactions. Besides TH2 and TH9 immune responses which are against multicellular parasites, host immunological pathways against viruses, intracellular micro-organisms (bacteria, protozoa, and fungi), and extracellular micro-organisms can use programmed cell death pathways to trigger immune reactions or to execute effective strategies to eliminate these pathogens. These programmed cell deaths include apoptosis, autophagic death, pyroptosis, ferroptosis, necroptosis, and NETosis. Apoptosis is related to host anti-virus eradicable THαβ immunity. Autophagic death is related to host anti-virus tolerable TH3 immunity. Pyroptosis is related to host anti-intracellular micro-organism eradicable TH1 immunity. Ferroptosis is related to host anti-intracellular micro-organism tolerable TH1-like immunity. Necroptosis is related to host anti-extracellular micro-organism eradicable TH22 immunity. NETosis is related to host anti-extracellular micro-organism tolerable TH17 immunity.

High-grade gliomas are the most common and aggressive adult primary brain tumors with a median survival of only 12-15 months. Current standard therapy consists of maximal safe surgical resection followed by DNA-damaging agents, such as irradiation and chemotherapy that can delay but not prevent inevitable recurrence. Some have interpreted glioma recurrence as evidence of glioma stem cells which persist in a relatively quiescent state after irradiation and chemotherapy, before the ultimate cell cycle re-entry and glioma recurrence. Conversely, latent cancer cells with a therapy-induced senescent phenotype have been shown to escape senescence, giving rise to more aggressive stem-like tumor cells than those present in the original tumor. Therefore, approaches are needed to either eliminate or keep these glioma-initiating cells in a senescent state for a longer time to prolong survival. In our current study, we demonstrate that the radiation-induced cell cycle inhibitor P21 can provide a powerful route to induce cell death in short-term explants of PDXs derived from three molecularly diverse human gliomas. Additionally, cells not killed by P21 overexpression were maintained in a stable senescent state for longer than control cells. Collectively, these data suggest that P21 activation may provide an attractive therapeutic target to improve therapeutic outcomes.

Hox genes represent an important gene family that is involved in the segmentation pattern and identity of the segments during the formation of the body plan in metazoans. For many years, several studies have sought to establish a correlation between the evolution of these genes and the evolution of large groups of metazoans. Here, we use publicly available sequences of Hox gene clusters to reconstruct the evolutionary history of anterior Hox genes. We show that information harbored by these genes, in part, reflects the evolution and diversification of most animal archetypes, but in many cases, there were conflicts between the evolutionary history of some genes and the history of large groups, these cases may have occurred due to specific and similar selective pressures in relatively distant groups, which may have led to evolutionary convergences. Our findings also reveal that the evolution of Hox genes (and clusters) as a multigene family is consistent to a birth-and-death model constrained by development, where there is a trade-off between a relatively fast gene turnover and their central developmental roles

Eukaryotic plasma membrane (PM) transporters face critical challenges that are not widely present in prokaryotes. The two most important issues are proper subcellular traffic and targeting to the PM, and regulated endocytosis in response to physiological, developmental or stress signals. Sorting of transporters from their site of synthesis, the Endoplasmic Reticulum (ER), to the PM has been long thought, but not formally shown, to occur via the conventional Golgi-dependent vesicular secretory pathway. Endocytosis of specific eukaryotic transporters has been studied more systematically and shown to involve ubiquitination, internalization, and sorting to early endosomes, followed by turnover in the MVB/lysosomes/vacuole system. In specific cases internalized transporters have been shown to recycle back to the PM. However, the mechanisms of transporter forward trafficking and turnover have been overturned recently through systematic work in the model fungus Aspergillus nidulans. In this review we present evidence that shows that transporter traffic to the PM takes place through Golgi-bypass and transporter endocytosis operates via a mechanism that is distinct from that of recycling membrane cargoes essential for fungal growth. We discuss these findings in relation to adaptation to challenges imposed by cell polarity in fungi as well as in other eukaryotes and provide a rationale why transporters and possibly other housekeeping membrane proteins ‘avoid’ routes of polar trafficking.

Carbohydrates such as fructooligosaccharides (FOS) are associated with improved gastrointestinal health and prevention of excess body fat. We evaluated the long-term effects of high amounts of FOS on metabolic parameters, non-alcoholic fatty liver disease (NAFLD) and short-chain fatty acids (SCFA). Sixty C57BL/6 mice received diets for four months: control (C), normolipid rich in fiber (F), normolipid supplemented with FOS (FOS), high fat (HL), high fat with high fiber (HLF) and high fat with FOS (HLFOS). We analyzed: animal weight; body composition; food intake; fasting blood glucose; serum and liver lipid profile; liver and intestinal histologies; malondialdehyde (MDA), hepatic retinol and α-tocopherol; SCFA in the feces. Supplementation with FOS in a high-fat diet promoted less body weight gain and reduced liver and retroperitoneal adipose tissue weights compared to HL and HF. FOS prevented NASH and decreased alanine aminotransferase and serum cholesterol levels in experimental animal models of obesity and metabolic syndrome (MS). There was found statistical differences in the dosages of the three main SCFAs in feces (acetic, isobutyric and isovaleric acids). Long-term supplementation with high doses of FOS was effective in reducing weight, adiposity, NAFLD and serum cholesterol in C57BL mice with obesity and MS induced by a high-fat diet.

Pompeii was connected to the great Serino aqueduct under the principate of Augustus. From that moment on, water became not only a precious resource for the inhabitants but also their true social indicator. It is no coincidence, in fact, that the concentration of sumptuous dwellings is in Regio VI, the district closest to the aqueduct reservoir (castellum aquae in Latin) and the one most equipped with piezometric towers, the first of the network, the ones that would never leave the decorative fountains of the peristyles dry. From this observation follows the original possibility of considering the water network a factor that contributed to designating the morphology of urban neighbourhoods and blocks.

Statistical mechanics investigates how emergent properties of macroscopic systems (such as temperature and pressure) relate to microscopic state fluctuations. The underlying idea is that global statistical descriptors of order and variability can monitor the relevant dynamics of the whole system at hand. Here we test the possibility of extending such an approach to psychotherapy research investigating the possibility of predicting the outcome of psychotherapy on the sole basis of coarse-grained empirical macro-parameters. Four good-outcome and four poor-outcome brief psychotherapies were recorded, and their transcripts coded in terms of standard psychological categories (abstract, positive emotional and negative emotional language pertaining to patient and therapist). Each patient-therapist interaction is considered as a discrete multivariate time series made of subsequent word-blocks of 150-word length, defined in terms of the above categories. Static analysis (Principal Component Analysis) highlighted a substantial difference between good-outcome and poor-outcome cases in terms of mutual correlations among those descriptors. In the former, the patient’s use of abstract language correlated with therapist’s emotional negative language, while in the latter it co-varied with therapist’s emotional positive language, thus showing the different judgment of the therapists regarding the same variable (abstract language) in poor and good outcome cases. On the other hand, the dynamic analysis, based on five coarse-grained descriptors related to variability, degree of order and complexity of the series, demonstrated a relevant case-specific effect, pointing to the possibility of deriving a consistent picture of any single psychotherapeutic process. Overall, the results showed that the systemic approach to psychotherapy (an old tenet of psychology) is mature to shift from a metaphorical to a fully quantitative status.

The fate of a viral infection in the host begins with various types of cellular responses, such as abortive, productive, latent, and destructive infections. Apoptosis, necroptosis, and pyroptosis are the three major types of regulated cell death mechanisms that play critical roles in viral infection response. Cell shrinkage, nuclear condensation, bleb formation, and retained membrane integrity are all signs of osmotic imbalance-driven cytoplasmic swelling and early membrane damage in necroptosis and pyroptosis. Caspase-driven apoptotic cell demise is considered in many circum-stances as an anti-inflammatory, and some pathogens hijack the cell death signaling routes to initiate a targeted attack against the host. In this review, we selected mechanisms by which viruses interfere with cell death are discussed in-depth and are used to illustrate the general principles and cellular signaling mechanisms of virus-host specific molecule interactions.

Background: New controversies have raised on brain death (BD) diagnosis when lesions are localized in the posterior fossa. Objective: To discuss the particularities of diagnosis BD in patients with posterior fossa lesions. Material and Methods. The author made a systematic review of literature on this topic. Results and Conclusions: A supratentorial brain lesion usually produces a rostrocaudal transtentorial brain herniation, resulting in forebrain and brainstem loss of function. In secondary brain lesions [i.e., cerebral hypoxia], the brainstem is also affected like the forebrain. Nevertheless, some cases complaining posterior fossa lesions [i.e., basilar artery thrombotic infarcts, or hemorrhages of the brainstem and/or cerebellum] may retain intracranial blood flow and EEG activity. In this article I discuss that if a posterior fossa lesion does not produce an enormous increment of intracranial pressure, a complete intracranial circulatory arrest does not occur, explaining the preservation of EEG activity, evoked potentials, and autonomic function. I also address Jahi McMath, who was declared braindead, but ancillary tests, performed 9 months after initial brain insult, showed conservation of intracranial structures, EEG activity, and autonomic reactivity to “Mother Talks” stimulus, rejecting the diagnosis of BD. Jahi McMath’s MRI study demonstrated a huge lesion in the pons. Some authors have argued that in patients with primary brainstem lesions it might be possible to find a in some cases partial recover of consciousness, even fulfilling clinical BD criteria. This was the case in Jahi McMath.

In relation to organizational performance measurement, there is a growing concern about the creation of value for people, society and the environment. The traditional corporate reporting does not adequately satisfy the information needs of stakeholders for assessing an organization’s past and future potential performance. Practitioners and scholars have developed new non-financial reporting frameworks from a social and environmental perspective, giving birth to the field of Integrated Reporting (IR). The Economy for the Common Good (ECG) model and its tools to facilitate sustainability management and reporting can provide a framework to do it. The present study is the first one that empirically validates such metrics on a sample of 206 European firms. Consequently, it allows knowledge to advance as it checks their statistical validity and reliability.

Forest canopy gaps are important for the ecosystem dynamics. Depending on tree species, small canopy openings might be also associated to intra-crown porosity and to space between crowns. Yet, little is known on the relationships between the fine-scaled pattern of canopy openings and biodiversity features. This research explored the possibility of i)- mapping forest canopy gaps from a very high resolution orthomosaic (10 cm), processed from a versatile imaging platform such as unmanned aerial vehicles (UAV), ii)- to derive patch metrics that can be tested as covariates of variables of interest for forest biodiversity monitoring. This is attempted in a test area of 240 ha covered by temperate deciduous forest types in Central Italy and containing 50 forest inventory plots of about 530 m². Correlation and linear regression techniques were used to explore relationships between patch metrics and understorey (density, development and species diversity) or forest habitat biodiversity variables (density of micro-habitat bearing trees, vertical species profile, tree species diversity). The results revealed that small openings in the canopy cover (75% smaller than 7 m²) can be faithfully extracted from UAV RGB imagery, using the red band and contrast split segmentation. Highest correlations were observed in the mixed forest (beech and turkey oak), while beech forest had the poorest ones and turkey oak forest displayed intermediate results. Moderate to strong linear relationships were found between gap metrics and understorey variables in mixed forest type, with adjusted R² from linear regression ranging from 0.52 to 0.87. Equally good results, in the same forest types, were observed for forest habitat biodiversity variables (0.52<adjusted R²<0.79) with highest values found for density of trees with microhabitats and vertical species profile. In conclusion, this research highlights that UAV remote sensing can potentially provide covariate surfaces of variables of interest for forest biodiversity monitoring, conventionally collected in forest inventory plots. By integrating the two sources of data, these variables can be mapped over small forest areas with satisfactory levels of accuracy, at a much higher spatial resolution than would be possible by field-based forest inventory solely.

The majority of cellular responses to external stimuli are mediated by receptors such as G protein-coupled receptors (GPCRs) and systems including endoplasmic reticulum stress (ER stress). Since GPCR signalling is pivotal in numerous malignancies, they are widely targeted by a number of clinical drugs. Cancer cells often negatively modulate GPCRs in order to survive, proliferate and to disseminate. Similarly, numerous branches of the unfolded protein response (UPR) act as pro-survival mediators and are involved in promoting cancer progression via mechanisms such as epithelial to mesenchymal transition (EMT). However, there are a few proteins among these groups which impede deleterious effects by orchestrating the pro-apoptotic phenomenon and paving a therapeutic pathway. The present review exposes and discusses such critical mechanisms and some of the key processes involved in carcinogenesis.

Receptor-interacting protein kinase 1 (RIPK1) plays a crucial role in controlling inflammation and cell death. Its function is tightly controlled through post-translational modifications, enabling its dynamic switch between promoting cell survival and triggering cell death. Phosphorylation of RIPK1 at various sites serves as a critical mechanism for regulating its activity, exerting either activating or inhibitory effects. Perturbations in RIPK1 phosphorylation status have profound implications for the development of severe inflammatory diseases in humans. This review explores the intricate regulation of RIPK1 phosphorylation and dephosphorylation and highlights the potential of targeting RIPK1 phosphorylation as a promising therapeutic strategy for mitigating human diseases.

The currently available anti-cancer therapies, such as gamma-radiation and chemotherapeutic agents, induce cell death and cellular senescence not only in cancer cells but also in the adjacent normal tissue. New anti-tumor approaches focus on limiting the side effects on normal cells. In this frame, the potential anti-tumor properties of Pulsed Electromagnetic Fields (PEMFs) through irradiation of breast cancer epithelial cells (MCF-7 and MDA-MB-231) and normal fibroblasts (FF95) were investigated. PEMFs had a frequency of 8 Hz, full-square wave type, magnetic flux density of 0.011 T and applied twice daily for 5 days. Data collected showcases that PEMF application decreases the proliferation rate and viability of breast cancer cells while having the opposite effect on normal fibroblasts. Moreover, PEMF irradiation induced cell death and cellular senescence only in breast cancer cells without any effect in the non-cancerous cells. These findings suggest PEMF irradiation as a novel, non-invasive anti-cancer strategy in combination with senolytic drugs, to eliminate both cancer and the remaining senescent cells while simultaneously avoiding the side effects of the current treatments.

According to Swiss-American Doctor of Sciences and Agricultural Engineer Jean-Pierre Jost, "plants communicate with each other by the quality of light emitted by their leaves or by means of stress hormones and other volatile chemicals. They also make use of cocktails of chemicals, pheromones, shape and colors to attract pollinators whereas other signals repel unwanted organisms. Insects are able to decode such messages and respond accordingly. Plants are apparently also communicating by sounds and electric signals." (1) How do plants do these things? Of course, it's easy to imagine it's all purely mechanical. But at the risk of sounding like a mysticism fanatic, I wonder if plants' activities are part of a spectrum of consciousness that pervades the entire universe. This spectrum would result from everything in the universe having the BITS or BInary digiTS of electronics as their ultimate composition. As explained in this hypothesis, something I call vector-tensor-scalar geometry is essential to my hypothesis. VTS geometry produces the particles of chemicals and pheromones, and refers to communication via electric signals when it speaks of electromagnetic-gravitational interaction. There's another consequence if everything in the universe is ultimately composed of electronic BITS and the cosmos is a spectrum of consciousness/artificial intelligence. It's impossible for an absence of consciousness to exist, either after death or before conception.

Objective: We aim to assess the reporting discrepancy and the difference between confirmed and unreported COVID-19-like death counts.Study Design: The study is based on time-series data.Methods: We used publicly available data to explore the differences between confirmed death counts and deaths with Codiv-19 symptoms between March 8, 2020, and July 11, 2020, in Bangladesh.Results: During the week ending May 9, 2020, the unreported COVID-19-like death count was higher than the confirmed COVID-19 death count; however, it was lower in the following weeks. On average, unreported COVID-19-like death counts were similar to the confirmed COVID-19 death counts during the same period. However, the reporting authority neither considers these deaths nor adjusts for potential seasonal influenza or other related deaths, which might produce incomplete COVID-19 data and respective mortality rates. Conclusions: Documenting unreported deaths with COVID-19 symptoms needs to be included in provisional death counts because it is essential to estimate a robust COVID-19 mortality rate and to offer data-driven pandemic response strategies. An urgent initiative is needed to prepare an acceptable guideline for COVID-19 death reporting.

The severe acquired respiratory coronavirus–2 (SARS–CoV-2) infection has initiated both acute and chronic COVID–19 disease between 2020 and 2022, currently evolving with other homologous prior coronavirus strains of the Nidoviridae order, which encompasses other prevalent alpha/ beta coronaviruses, but also the Middle East Respiratory Syndrome (MERS-CoV) and SARS-CoV-1, with recent SARS–CoV–2 variants, increasing demands for effective immunogens and therapeutic approaches that will reduce global disease burden and further infection from SARS–CoV-2 affected individuals that may experience post acute sequelae (PASC) or “Long COVID”. Following a worldwide programme of prophylactic vaccination, there is still a dilemma in the efforts to find prophylactic and early therapeutic approaches that would treat novel SARS-CoV-2 variants and prevent future epidemics or pandemics within host human and animal populations, where zoonotic or cross species transfer naturally occurs. Concerns about viral immune escape intersect at a specific point; a gained evolutionary ability of several viruses to co–infect and compete against previous scientific advances since 1796 that remain undetected or asymptomatic during the early stages of infection progressing to symptomatic and severe disease through capping of the 5' end of DNA and RNA genomes respectively, which is performed by the activated viral 2’ - O - Methyltransferase (MTase) enzyme, which is a complex of two viral non-structural proteins (NSPs) joined together through an activation process (NSP10/16). Moreover, it was discovered that certain polymorphic viruses translate NSP1, which prevents the activation of various Pattern Recognition Receptors (PRRs), directly silences important interferon-stimulated genes (ISGs), is signalled in a paracrine manner to neighbouring cells, and that induces the apoptosis of host cells, inducing an effect of “trace erase” effect and making the viral infection as immunologically “invisible” as possible during the initial, key stages of viral replication and distribution, all such mechanisms occurring independently of the viruses in cause. Other viral NSPs share a role with NSP1 in directly suppressing the activation of PRRs and ISGs, and all such viral proteins help the virus in its process of self-camouflaging against first- and second-line immunity, thereby often severely impacting the quality of the produced adaptive immune responses. The outcome of all such phenomena is the sharp decrease in the host Type I and Type III interferons' (IFNs) rate of synthesis by the host cells, that would usually occur and affect homeostatic cellular pathways, resulting in further viral replication and induced apoptosis. Nonetheless, effects of microbial immune evasion during the development of other viral or carcinogenic pathologies are not widely known. In short, polymorphic viruses developed a proportionate evolutionary response against developed adaptive immune responses, by currently relying on gaps mostly situated in the natural immune system in their process of molecular self-camouflaging. Scientists developed numerous approaches of early treatment that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration whilst filtering for the most appropriate solutions. For example, the administration of recombinant human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can simulate intracellular infection and stimulate cellular activity in a timely manner, training the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Another example could involve the treatment of natural and adaptive lymphocytes with a low dose of IFNs I and possibly III, prior to their insertion into the host lymphatic system, possibly alongside additional recruitment of plasmacytoid dendritic cells (pDCs) as further interferon “factories”, all with the purpose of early infection management. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. It is until the scientific community realises this potentially crucial aspect that large proportions of the world population will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently, monkeypox and possibly avian flu. Of note, it has been indicated that IFN I and / or III display significant immunising, early therapeutic and clinical disease onset-attenuating effects for many other microbial evoked diseases, as well as for a number of oncological diseases.

Introduction: Body size is correlated with many aspects of an animal species' natural history, such as life span, abundance, dispersal capacity and diet breadth. However, contrasting trends have been reported for the relationship between body size and these ecological traits. Methods: Butterfly species from fruit-feeding guilds were used to investigate whether body size correlates with species abundances, dispersal, permanence, and diet breadth in a Neotropical savanna in Brazil (Cerrado). We used Blomberg’s K and Phylogenetic Generalized Least Squares models (PGLS) to measure phylogenetic signal strength in species traits, and to estimate size-dispersal-diet breadth associations while taking shared ancestry into account. Results: 539 individuals from 27 species were captured, and 190 individuals were recaptured, representing a 35% recapture rate. We found that body size negatively influenced butterfly abundance. In contrast, body size was positively associated with dispersal levels, distance traveled, number of traps visited, individual permanence, and diet breadth. These results indicate that larger butterflies have a greater proportion of dispersing individuals over longer distances, as they permanence were detected over longer periods than their smaller relatives. Moreover, larger butterflies are more generalized, based on the number of host plant families and genera they consume. Smaller butterflies demand fewer resources, which is reflected in their higher survival in small patches, and may explain their lower dispersal ability, and higher diet specialization. Nevertheless, lower dispersal ability, if not compensated by large population sizes, may threaten small-bodied species inhabiting environments with intense deforestation rates, such as the Cerrado. Conclusions: Body size positively influences dispersal and diet breadth in the fruit-feeding butterflies collected in this study.

Silicified ostracods from the Lower Carboniferous (Lower Tin Mountain Limestone; Kinderhookian-early Osagean; 350-358.9 Ma) of Lost Burro Gap, Death Valley region, Inyo County, California, USA augment the diversity of Paleozoic ostracods of western North America. Acid maceration of pelmatozoan, micritic and silicate clay-rich micritic marine limestones yielded the following palaeocopid and podocopid ostracods: Acratia spp., Bairdia quasilecta Bushmina, 1975, Bairdia sp. cf. B. orientalis, Ceratobairdia sp., Kirkbya panamintensis sp. nov., Rectobairdia sp. cf. R. legumen, and Silenites sp. This is the first report of Ceratobairdia and Silenites from the Tin Mountain Limestone. These ostracods occupied a Panthalassan carbonate ramp environment, and represent part of a fauna that was widespread in shallow marine waters of Panthalassa.

COVID-19 is a potentially fatal viral infection. This study investigates geography, demography, socioeconomics, health conditions, hospital characteristics, and politics as potential explanatory variables for death rates at the state and county levels. Data from the Centers for Disease Control and Prevention, the Census Bureau, Centers for Medicare and Medicaid, Definitive Healthcare, and USAfacts.org were used to evaluate regression models. Yearly pneumonia and flu death rates (state level, 2014-2018) were evaluated as a function of the governors’ political party using repeated measures analysis. At the state and county level, spatial regression models were evaluated. At the county level, we discovered a statistically significant model that included geography, population density, racial and ethnic status, three health status variables along with a political factor. State level analysis identified health status, minority status, and the interaction between governors’ parties and health status as important variables. The political factor, however, did not appear in a subsequent analysis of 2014-2018 pneumonia and flu death rates. The pathogenesis of COVID-19 has greater and disproportionate effect within racial and ethnic minority groups, and the political influence on the reporting of COVID-19 mortality was statistically relevant at the county level and as an interaction term only at the state level.

Lewis et al. published an important and timely necessary article about the determination of death by neurological criteria, revising the Uniform Determination of Death.The acceptance of brain death (BD) has been progressively accepted beginning at the late 1950s. Nonetheless, contentious brain-death cases have recently raised new controversies about the diagnosis of BD, such as the Jahi McMath case, extensively covered by the US and international press. Jahi McMath meant a terrible tragedy for her and her family. But further than this gloomy story, the case has also raised confusion and challenging qualms about a fundamental query: how we confirm whether a person is dead or alive? Since 1981, the Uniform Determination of Death Act (UDDA) has served as the legal foundation for the medical practice of determining death. But, although death by neurologic criteria is considered legal death throughout the United States, several recent lawsuits have quizzed the rightfulness the authority of the UDDA to declare death by neurological criteria. This issue explains the importance of Lewis’s et al. paper. In this article I want to present the historical procedure for issuing a law in Cuba for the determination and certification of death. Of course, it is impossible to compare our country with USA. Cuba is a small and developing country, in which a law encompasses a national scenery, in contrast with USA, a multistate nation.

We seek to elucidate an aspirational vision for the food system and explore whether the characteristics of such a system inadvertently set unattainable standards for rural, low wealth communities. We apply discourse analysis to the following qualitative datasets: (1) interviews with food experts and advocates, (2) scholarly and grey literature, (3) industry websites, and (4) email exchanges between food advocates. The analysis revealed eight aspirational food system discourses: Production, Distribution, and Infrastructure; Healthy, Organic, Local Food; Behavioral Health and Education; Sustainability; Finance and Investment; Huger Relief; Demand Side Preferences; Romanticized, Community Led Transformations. Study findings reveal that of eight discourses only three encompass the experiences of rural, low wealth residents. This aspirational food system may result in the disempowerment of the needs of rural, low wealth groups; a perpetuation of the failure of groups who will be unable to reach the aspirational food vision; silencing of discourses that might question those that play a role in the inequitable distribution of income while sanctioning discourses that focus on personal or community solutions; and the absence of other policy-based solutions that address issues located within the food system. Further research is needed to inform policies and programs to mitigate food insecurity in rural, low wealth populations.

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

Jamoytius kerwoodi, is a primitive, eel-like jawless vertebrate found uniquely in an Early Silurian (Llandovery epoch; 444-433 Ma) horizon near Lesmahagow, Scotland. This species is a rare component of a low-diversity dominantly nektonic detritus and herbivorous fauna living over an anoxic bottom and is found at the transition from a marine-influenced, probably brackish-water, deep-water basin to a shallower-water, less saline and likely freshwater basin. In the absence of true teeth, Jamoytius was probably a detritivore or herbivore feeding on Ceratiocaris. Jamoytius may be a direct ancestor of living lampreys, especially as their ectoparasitic mode of life might have evolved from ancestral microphagous filterers or herbivores.

Apoptosis, necroptosis, and autophagy are cellular mechanisms by which cells are programmed to die under a wide range of physiological and developmental stimuli. A multitude of protein mediators of programmed cell death have been identified and apoptosis, necroptosis, and autophagy signals have been found to utilize common pathways elucidating the proteins involved. This narrative review focuses on caspase-dependent and caspase-independent programmed cell death systems. Included studies of caspase-dependent programmed cell death include extrinsic pathway apoptotic mechanisms including phosphatidylserine (PS), FAS (APO-1/CD95), Tumor Necrosis Factor (TNF) Receptor type 1 (TNF-R1) and TNF-Related Apoptosis-Inducing Ligand (TRAIL) and intrinsic or mitochondrial pathway such as Cytochrome C, the Bcl-2 family of proteins and Smac/Diablo. The Bcl-2 family has apoptotic mediators Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak), Bcl-2-Interacting Protein BIM (Bim), Bcl-2 agonist of cell death (Bad), Bid, Bcl-2 adenovirus E1B 19kDa-interacting protein 1 NIP3 (Bnip3), BMF, HRK, Noxa and PUMA and anti-apoptotic proteins such as Bcl-2 itself, Mcl-1, Bcl-w, A1, and Bcl-XL. Moreover, caspase-independent programmed cell death pathways include the mitochondrial pathway with the protein mediators Apoptosis Inducing Factor (AIF), and Endonuclease G, the pathways Necroptosis, and Autophagy. Understanding programmed cell death from those reported in this review could shed substantial light on the processes of biological homeostasis. In addition, identifying specific proteins involved in these processes is mandatory to identify molecular biomarkers as well as therapeutic targets. This knowledge could provide the ability to modulate the programmed cell death response and could lead to new therapeutic interventions in a wide range of diseases.

Prostate cancer (PCa) is a complex disease and the cause of one of the highest cancer-related mortalities in men worldwide. Annually, more than 1.2 million new cases are diagnosed globally, accounting for 7% of newly diagnosed cancers in men. Programmed cell death (PCD) plays an essential role in removing infected, functionally dispensable or potentially neoplastic cells. Apoptosis is the canonical form of PCD with no inflammatory responses elicited, and the close relationship between apoptosis and PCa has been well studied. Necroptosis and pyroptosis are two lytic forms of PCD resulting in the release of intracellular contents, which induces inflammatory responses. An increasing number of studies have confirmed that necroptosis and pyroptosis are also closely related to the occurrence and progression of PCa. Recently, a novel form of PCD named PANoptosis, which is a combination of apoptosis, necroptosis, and pyroptosis, revealed the attached connection among them and may be a promising target for PCa. Apoptosis, necroptosis, pyroptosis and PANoptosis are good examples to better understand the mechanism underlying PCD in PCa. This review aims to summarize the emerging roles and therapeutic potential of apoptosis, necroptosis, pyroptosis and PANoptosis in PCa.

ABSTRACT Two years after first patients approached the emergency rooms of hospitals in Wuhan becouse of respiratory distress,thousend of SARS-CoV-2 infected persons continue to die every day worldwide.SARS-CoV-2-infected patients undergo a process of dehydration and malnutrition before they develop respiratory problems and approach the emergency room of a hospital.This is,in many cases, the consequence of high fever which causes massive loss of fluids. In addition loss of appetite, is responsible for the deficit of protein intake.Most of the virus-infected patients admitted to the emergency room are therefore hypovolemic and hypoproteinemic and suffer of respiratory distress accompanied by ground grass opacities at CT-scan of the lungs.Critically ill patients are treated following the guidelines for treatment of septic shock but with „conservative“ fluid replacement and administration of diuretics to assure sufficient hourly urine production. The combination of conservative fluid administration with reduced protein content in the enterally administered diet, together with administration of diuretics, has severe hemodynamic consequenses in mostly aged,dehydrated,critically ill patients. Many of them will develop acute kidney injury in the next 24 hours.In most of the cases, patients continue to loose weight by loosing skeletal muscle mass. Ischemic damage in the lung capillaries is responsible for the acute respiratory distreass syndrome (ARDS) and for the hallmark of autoptic findings,diffuse alveolar damage (DAD) characterized by hyaline membrane formation,fluid invasion of the alveoli recruitment of some inflammatory cells and progressive arrest of blood flow in the pulmonary vessels.The consequence is progressive congestion , increase of lung weight and progressive hypoxia (progressive severity of ARDS).Sequestration of blood in the lungs worsen hypovolemia and ischemia in different organs.This is most probably responsible for recruitment of inflammatory cells and for persistance of elevated serum levels of positive acute-phase markers and of hypoalbuminemia. Autoptic studies have been performed mostly in patients who died in the ICU after SARS-CoV-2-infection because of progessive ARDS.In those patients, tubulus epithelium necrosis in the kidney is a frequent finding as it has been the case in the first SARS-CoV-1 pandemic.In the death certification charts, many times weeks after first symptoms have started ,cardiac arrest is the cause of death after respitatory insufficiency.Replacement therapy with sufficient amount of fluid and albumin should be part of the early individualized life-saving supportive measures avoiding mechanical ventilation.

Abstract. The COVID-19 has turned in to a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in R&D by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are ‘rate-limiting’ and ‘time-consuming’, many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human ‘challenge experiments’ to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying ‘Quick fix’ and ‘short cuts’ can lead to errors with disastrous consequences.

The Anthropocene has emerged as the dominant conceptualization of the current geological epoch and, more significantly, of Humanity’s relation to nature. By its proponents the Anthropocene is espoused as a “solution formulation,” an analytical tool which clarifies Humanity’s multifarious impacts on nature and nature’s subsequent crises; and further as a conceptual apparatus from which to launch mitigation and adaption strategies, promising deliverance from or at least engagement with ecological crises. However, the Anthropocene is not a neutral concept, merely illuminating transition within ecological conditions and connections between human activities and nature; rather, it is a particular prism from which to understand humanity’s relation to nature. And, as the Anthropocene becomes ascendant both analytically and politically, it becomes vital to question its imaginary, how it constructs nature and Humanity, how it influences and constrains responses to ecological crises, and what the long-term implications of operating within this imaginary are. I argue that the Anthropocene as a political/analytical prism rests upon flawed conceptions of nature, history, and humanity, rending it an impotent construct from which to respond to ecological crises; offering only partial and presumptive “solutions” in the form of intensified governmental regulation and the application of manifold technological “fixes” through the geoengineering of Earth’s systems, in an attempt to address isolated aspects of ecological destruction.

Abstract. The remarks by the Supreme Leader of the Islamic Revolution on the toll of the famines that afflicted occupied Iran in World War I and World War II indicate a desire to incorporate these calamities in Iran’s national narrative and collective memory. His criticism of famine historiography and stated toll numbers, and the unfolding catastrophic famine in Gaza, justify and necessitate a fresh look at each famine’s historiography and toll. This article re-estimates the toll of each famine by including many overlooked and neglected primary sources and in ways not previously done. It builds a trajectory of Iran’s demographic development from 1810 to 1944, and derives the toll of each famine. The World War II famine and typhus epidemics had claimed 5.5 million. World War I famine was also more deadly, though the 1869-73 famine was not far behind. At least 15.5 million Iranians died in the two world wars, a fact nowhere reflected in the history of the conflicts. Iran’s 1944 population of 12 million was unchanged from that of 1850 and a century of population growth obliterated

Excessive activation of frog eggs, so called overactivation, can be initiated by strong oxidative stress, leading to expedited calcium-dependent non-apoptotic cell death. Overactivation also occurs spontaneously, albeit with a low frequency, in natural populations of spawned frog eggs. Currently, cytological and biochemical events of the spontaneous process are not characterized. In the present study, we demonstrate that spontaneous overactivation of Xenopus frog eggs, similarly to oxidative stress- and mechanical stress-induced overactivation, is characterized by the fast and irreversible contraction of the egg’s cortical layer, increase in the egg size, depletion of intracellular ATP, drastic increase in the intracellular ADP/ATP ratio, and degradation of M phase-specific cyclin B2. These events manifest in eggs in the absence of caspase activation within just one hour of triggering overactivation. Importantly, large amounts of ATP and ADP leak from the overactivated eggs, indicating that plasma membrane integrity is compromised in these cells. The rapture of the plasma membrane and acute depletion of intracellular ATP define explicitly necrotic cell death. Finally, we report that egg overactivation can occur in the frog’s genital tract. Our data argue that mechanical stress may be a key factor promoting egg overactivation during natural spawning in frogs.

Background: Pulmonary emboli (PE) is a life threatening condition that is discovered in many patients only "post mortem". Adequate and timely detection of PE is crucial, because of the high mortality and morbidity and the sudden unexpected hemodynamic collapse that may occur in patients with PE. Objectives: To assess the ability to predict clinical outcome of patients with acute PE, using a non-gated computed tomography pulmonary angiography (CTPA), based on the dimensions of the right ventricle. Methods: A retrospective study that analyzed CTPA images of patients admitted with acute PE during the years 2012-2017 in Baruch Padeh Medical Center. The cohort study included 300 patients with documented acute PE, among them 255 were hospitalized in medical (non-intensive care unit) wards, and 45 were patients were hospitalized in an intensive care unit (ICU). Results: Among the 45 patients admitted to the ICU, 8% died. Larger RV diameters predicted mortality (OR=10.14, 95% CI [1.09-93.86]) as well as lower systolic and diastolic blood pressure measurements (p=0.001 and 0.01). Among the 255 patients that were admitted in the Internal Medicine Ward 7% died. Older age (p=0.028), sepsis and cancer (both p<0.001), high WBCs count (p<0.001), and renal failure (p<0.001) predicted death. Overall, of all 300 patients that were admitted, lower blood pressure (systolic and diastolic) (p<0.001, 0.008), older age (p<0.007), sepsis (p<0.001), cancer (p=0.006), higher WBCs count (p<0.001), and impaired renal function (p<0.001) predicted death among patients admitted with confirmed acute PE. Conclusions: Clinical parameters and hematological parameters could predict the outcome of patients admitted with acute PE. RV diameter, measured by the non-ECG gated CTPA had an additive predictive value for patients who were hemodynamically unstable on admission and were hospitalized in the ICU.

Fire-related deaths are issues for forensic pathologists particularly in ascertaining if death occurred before or during fire. The authors highlight a unique bronchiolar epithelial cytological clue (nuclear heat-induced elongation) determined by active inhalation of hot gases and fumes, not yet described in the literature at distal small airways level.

Dysfunction and selective loss of retinal ganglion cells (RGCs) is a known cause of vision loss in glaucoma and other neuropathies where ocular hypertension (OHT) is the major risk factor. We investigated the impact of transient non-ischemic OHT spikes (spOHT) on RGC function and viability in vivo to identify cellular pathways linking low-grade repetitive mechanical stress to RGC pathology. We found that repetitive spOHT had an unexpectedly high impact on intraocular homeostasis and RGC viability, while exposure to steady OHT (stOHT) of similar intensity and duration failed to induce pathology. The repetitive spOHT induced a rapid activation of the inflammasome, marked by the upregulation of NLRP1, NLRP3, AIM2, caspases -1, -3/7, -8, gasdermin D (GsdmD) and the release of interleukin-1β (IL-1β) and other cytokines into the vitreous. Similar effects were also detected after 5 weeks of exposure to chronic OHT in an induced glaucoma model. The onset of these immune responses in both spOHT and glaucoma models preceded a 50% deficit in pattern electroretinograms (PERG) amplitude, and significant loss of RGCs at 7 days post-injury. Inactivation of inflammasome complexes in NLRP1-/- , Casp1-/- and GsdmD-/- knockout animals, significantly suppressed the spOHT induced inflammatory response and protected RGCs. Our results demonstrate that mechanical stress produced by acute repetitive spOHT or chronic OHT is mechanistically linked to inflammasome activation, which leads to RGC dysfunction and death.

Acute chemical ablation of lateral line hair cells is an important tool to understand lateral line-mediated behaviors in free-swimming fish larvae and adults. However, lateral line-mediated behaviors have not been described in fish larvae prior to swim bladder inflation, possibly because single doses of ototoxin do not effectively silence lateral line function at early developmental stages. To determine if ototoxins can effectively silence the lateral line during early development, we repeatedly expose zebrafish larvae to the ototoxin neomycin during a 36-hour period from 3-4 days post-fertilization (dpf). We use simultaneous transgenic and vital dye labeling of hair cells to compare 6- hour and 12-hour repeated treatment timelines and neomycin concentrations between 0–400 µM in terms of larval survival, hair cell death, regeneration, and functional recovery. Following exposure to neomycin, we find that the emergence of newly functional hair cells outpaces cellular regeneration, likely due to the maturation of ototoxin-resistant hair cells that survive treatment. Furthermore, hair cells of 4 dpf larvae exhibit faster recovery compared to 3 dpf larvae. Our data suggest that the rapid functional maturation of ototoxin-resistant hair cells limits the effectiveness of chemical-based methods to disrupt lateral line function. Furthermore, we show that repeated neomycin treatments can continually ablate lateral line hair cells between 3–4 dpf in larval zebrafish.

Background Recent studies indicate that donor innate immune responses participate in initiating and accelerating innate responses and allorecognition in the recipient. These immune responses negatively affect recipient outcomes and predispose recipients to allograft coronary artery vasculopathy (CAV). We hypothesized that donor cause of death (COD) associated with higher levels of innate immune response would predispose recipients to more adverse outcomes post-transplant, including CAV. Methods We performed a single-institution retrospective analysis comparing donor characteristics and COD to recipient adverse cardiovascular outcomes. We analyzed the medical records of local adult donors (age 18-64) in a database of donors where adequate data was available. We linked donor characteristics and COD to recipient adverse cardiac outcomes after transplant, including cardiovascular (CV) death and incidence of significant antibody-mediated rejection (pAMR) after transplant (>2 episodes of pAMR within 90 days post-transplant). The data were analyzed using logistic regression, log-rank test of differences, and Tukey Contrast. Results Donor advanced age, female sex, and CODs of motor vehicle accident and intracranial hemorrhage were significantly associated with a higher incidence of recipient CV death and early pAMR compared to other donor characteristics and CODs. Conclusions In this single institution study, we found that recipients with hearts from donors over 40 years, donors who were female, or donors who died with a COD of motor vehicle accidents or intracranial hemorrhage had a higher frequency of CV related deaths and early pAMR. Donor monitoring and potential treatment of innate immune activation may decrease subsequent recipient innate responses and allorecognition stimulated by donor derived inflammatory signaling which lead to adverse outcomes.

Objective: The Asia-Pacific region (APAC) represents a unique environment for the publication of biomedical research, particularly industry-funded research. Awareness and adoption of international guidelines on ethical publication practices continues to increase across APAC, but the reframing and expansion of many of the recommendations in the Good Publication Practice (GPP) 2022 guidelines versus GPP3 published in 2015 have important implications for publishing industry-funded biomedical research in the region. Methods: This manuscript provides practical guidance for stakeholders in APAC on interpreting and applying the recommendations made in the GPP 2022 guidelines. Results: Key focus areas include navigating new opportunities for communicating industry-funded research, such as plain language summaries, social media, and preprints; implementing formal processes to improve the integrity of published research in APAC; and methods of promoting transparency and inclusion when publishing industry-funded research. Key APAC-specific issues, including encore presentations, leadership on publication ethics in the region, access to professional resources, and support for educating regional stakeholders are also discussed. Conclusions: Overall, this review offers a pragmatic guide for stakeholders in industry-sponsored research on applying GPP 2022 in practice with a focus on effectively integrating these guidelines in an APAC context.

The parameters of logistic regression models are usually obtained by the method of maximum likelihood (ML). However, in analyses of small data sets or data sets with unbalanced outcomes or exposures, ML parameter estimates may not exist. This situation has been termed “separation” as the two outcome groups are separated by the values of a covariate or a linear combination of covariates. To overcome the problem of non-existing ML parameter estimates, applying Firth’s correction (FC) was proposed. In practice, however, a principal investigator might be advised to “bring more data” in order to solve a separation issue. We illustrate the problem by means of an examples from colorectal cancer screening and ornithology. It is unclear if such an increasing sample size (ISS) strategy that keeps sampling new observations until separation is removed improves estimation compared to applying FC to the original data set. We performed an extensive simulation study where the main focus was to estimate the cost-adjusted relative efficiency of ML combined with ISS compared to FC. FC yielded reasonably small root mean squared errors and proved to be the more efficient estimator. Given our findings, we propose not to adapt the sample size when separation is encountered but to use FC as the default method of analysis whenever the number of observations or outcome events is critically low.

Toxoplasmosis is a zoonotic disease caused by the apicomplexa protozoan parasite Toxoplasma gondii. This disease is a health burden, mainly in pregnant women and immunocompromised individuals. Dehydroepiandrosterone (DHEA) has proved to be an important molecule that could drive resistance against a variety of infections, including intracellular parasites such as Plasmodium falciparum and Trypanozoma cruzi, among others. However, to date it has not been explored the role of DHEA on T. gondii. In here, we demonstrated for the first time the toxoplasmicidal effect of DHEA on extracellular tachyzoites. Ultrastructural analysis of treated parasites showed that DHEA alters the cytoskeleton structures, leading to the loss of the organelle structure and organization, as well as the loss of the cellular shape. In vitro treatment with DHEA reduces the viability of extracellular tachyzoites and passive invasion process. 2D SDS-PAGE analysis revealed that in the presence of the hormone a progesterone receptor membrane component (PGRMC) with a cytochrome b5 family heme/steroid binding domain-containing protein was expressed, while the expression of proteins that are essential for motility and virulence was highly reduced. Finally, in vivo DHEA treatment induced a reduction of parasitic load in male, but not in female mice.

In the Brazilian Amazon, rural settlements are increasingly isolated by large-scale production farms, jeopardizing their sustainability and the good living of family farmers. Works were carried out in settlements to measure sustainability. However, the majority does not consider the participation and the collectively of those involved. In this way, we propose to evaluate, in a collective and participatory way, the sustainability and good living of the SDP São Paulo Rural Settlement, of the northern Amazon of Mato Grosso. We used the didactic-pedagogical method Circle of Sustainability, developed from five points: 1st - circle of investigation of generating themes; 2nd - circle of the history of the subject world; 3rd - circle of diagnosis of rural settlements; 4th - circle of exchange of knowledge; and 5th - circle of sustainable perceptions and narratives. The historical, socioeconomic and cultural characterization of the settlement allowed us to understand how sustainability and good living are being built in the settlement history process. Sustainability and good living are dialectical processes, are under construction, in movement.

The coronavirus disease pandemic 2019 (COVID-19) has emerged in Wuhan province, China in December 2019 and has spread over all countries. The current study was carried out to predict active, death and cured rate of COVID 19 in Algeria for a future period of 35 days using FB prophet model. Results shoed that the active rate and the death rate decrease for the next days while the cured rate increase. The active, cured and death rates are estimated at 19.7% 78.85% and 2.55% respectively. These results highlight the importance of FB prophet model in COVID-19 prediction which could help national authorities in adopting the best preventive measures.

Standard evolutionary theory, supported by mathematical modelling of outbred, dispersed populations predicts that ageing is not an adaptation. We recently argued that in clonal, viscous populations, programmed organismal death could promote fitness through social benefits and has, in some organisms (e.g. Caenorhabditis elegans), evolved to shorten lifespan. Here we review previous adaptive death theory, including consumer sacrifice, biomass sacrifice, and defensive sacrifice types of altruistic adaptive death. In addition we discuss possible adaptive death in semelparous fish, coevolution of reproductive and adaptive death, and adaptive reproductive senescence in C. elegans. We also describe findings from recent tests for the existence of adaptive death in C. elegans using computer modelling. Such models have provided new insights into how trade-offs between fitness at the individual and colony levels mean that senescent changes can be selected traits. Exploring further the relationship between adaptive death and social interactions, we consider examples where adaptive death results more from action of kin than from self-destructive mechanisms and, to describe this, introduce the term adaptive killing of kin.

Autonomous systems and intelligent machines are involved in almost all areas of human activity and they are now more and more present in our everyday life. The reason for this extensive use certainly resides in all the benefits these machines offer to the users. In experimental settings, numerous studies have demonstrated the positive effects that the introduction of autonomous systems have on human decision-making and performance. However, studies have shown in addition that the introduction of these systems can have important negative effects as well. Considering that autonomous systems are now introduced in sensitive domains like the military or medicine, we need more than ever a comprehensive understanding of the effects they cause on human performance and decision-making, and particularly in tasks and contexts with a social or moral dimension. The aim of this narrative review is threefold. First, we will provide an overview of the main effects on a human agent’s decision-making and performance produced by the introduction of autonomous systems. Second, we will review the conditions identified as underlying factors of these effects, and see how current models of human – autonomous systems interaction integrate those conditions. Third, we will conclude this review by highlighting new directions for future investigations.

Our report presents the findings from a treatment program that involved plant-based diets (PBDs) and supplements for 1,750 elderly cardiology patients diagnosed with COVID-19 between April 2020 and June 2023. At the start of the program, there was no published data supporting the use of PBDs for COVID-19 patients. However, after 18 months, studies were released that indicated the effectiveness of PBDs in decreasing the incidence and severity of COVID-19. Our treatment protocol differed from these studies in several ways. We carefully controlled the quality, quantity, and processing method of the foods we provided, opting for raw instead of cooked vegetables. Additionally, we incorporated supplementation that complemented the nutrients lacking in a PBD and enhanced the anti-viral, anti-inflammatory, antioxidant, antithrombotic, and immunomodulatory properties of a PBD. Our patients recovered faster (12±1.4 days vs. 20.9±4.3 days), with lower severity (2% vs. 10-20%), hospitalizations (0 vs. 5-10%), and deaths (0 vs. 15-17%) compared to the general population. These favorable outcomes are particularly noteworthy given Indonesia's high COVID-19 morbidity and mortality rates, among the highest in Asia. The findings of this report provide valuable insights for practitioners in managing high-risk elderly COVID-19 patients, particularly in avoiding severity and mortality.

Is HSP-27 an emerging marker of good prognosis in septic shock patients – a pilot study Objective To estimate the value of serum changes of C-reactive protein, procalcitonin, presepsin, heat shock protein 27 (HSP27) and neutrophil to lymphocyte ratio in assessing the prognosis in patients with septic shock (SS) treated in intensive care unit. Methods The SS was diagnosed and treated in accordance with the guidelines of the Surviving Sepsis Campaign. 37 selected adult patients with SS were included. Serum concentrations of biomarkers were measured at admission and daily for 4 consecutive days (time points T0,T1, T2, T3 and T4 respectively). The mortality rate was determined 28 days after admission. Patients were divided into survivor and non-survivor groups according to their mortality. The differences between the levels of biomarkers at the T0 and T4 time points were analyzed. Results The mean value of the SOFA score on admission was 11.7 ± 2.7, and the APACHE II scale 29.9 ± 6.85. Nine patients died. Univariate logistic analysis revealed that changes between T0 and T4 time points of presepsin, procalcytonin, and HSP27 were associated with prognosis. A multivariate Cox analysis showed that an increase in HSP27 on T4 was the only independent predictor of good prognosis in SS patients. The area under the receiver operating characteristics curve for HSP27 was 0.785. Kaplan–Meier analysis showed that the mortality was lower (p=0.014) in patients who had an increase in HSP27 on T4 compared to those whose serum HSP27 did not increase on T4. Conclusions The increase of HSP27 level on the 4th day predicts favorable outcome in SS patients.

Artificial Intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use ChatGPT holds a prom-inent position using an innovative language model developed by OpenAI. Thanks to the use of deep learning techniques, ChatGPT stands out as an exceptionally viable tool, renowned for gen-erating human-like responses to queries. Various medical specialties, including rheumatology, oncology, psychiatry, internal medicine, and ophthalmology, have been explored for ChatGPT in-tegration, with pilot studies and trials revealing each field's potential benefits and challenges. However, the field of genetics and genetic counseling, as well as that of rare disorders, represents an area suitable for exploration, with its complex data sets and the need for personalized patient care. In this review, we synthesize the wide range of potential applications for ChatGPT in the medical field, highlighting its benefits and limitations. We pay special attention to rare and genetic disorders, aiming to shed light on the future roles of AI-driven chatbots in healthcare. Our goal is to pave the way for a healthcare system that is more knowledgeable, efficient, and centered around patient needs.

Risk stratification for malignant ventricular arrhythmias and sudden cardiac death is a daunting task for physicians in daily practice. Multiparametric mapping sequences obtained via cardio-vascular magnetic resonance imaging can improve the risk for malignant ventricular arrhythmias by unveiling the presence of pathophysiological pro-arrhythmogenic processes. However, their employment in clinical practice is still restricted. The present review explores the current evidence supporting the association between mapping abnormalities and the risk of ventricular arrhyth-mias in several cardiovascular diseases. The key message is that further clinical studies are needed to test the additional value of mapping techniques beyond conventional cardiovascular magnetic resonance imaging for selecting patients eligible for an implantable cardioverter defibrillator.

In order to meet the needs of an increasingly complex research landscape, researchers engage in “collaborative prosumption” through open data sharing and reuse. Although significant gains have been achieved in this regards because of growing requirements from funding agencies, governments and journals, the question of how reuse of openly available data for new research contribute to sustainability is yet to be appropriately addressed in the literature. Therefore, relying on a three stage stratified clustered random sampling of the Journal of Applied Econometrics data archive (JAEDA), the present research provides a case study of the value of research data recycling for sustainable research and economic development. More specifically our analysis show that reformatting from wide to long format, openly shared equity price index data on eleven European countries’ extracted from JAEDA, and augmented with country level geospatial Meta data, provides a new basis for interesting descriptive analytics and spatio-temporal econometric modeling and inference. Given the ever-increasing volume of openly available research data, our study provides a first-hand insight on open data reuse, which should benefit all stakeholders in the research community, as they seek sustainable solutions for scientific productivity and progress.

This paper presents a comprehensive analysis of the SEIRS COVID-19 pandemic model with saturated incidence rate. By modifying the existing model and proposing a new simplified version, we investigate the dynamics of disease transmission, including the impact of saturation terms on disease spread. Through stability analysis at disease-free and endemic equilibria, we aim to enhance understanding of the spread of COVID-19 and inform effective control strategies. Drawing on mathematical models and epidemiological insights, this study contributes to the ongoing efforts to combat the global pandemic.

Ferroptosis is an iron-dependent cell death pathway that involves depletion of intracellular glutathione (GSH) levels and iron-mediated lipid peroxidation. Ferroptosis is experimentally caused by inhibition of the cystine/glutamate antiporter xCT, which depletes cells of GSH, or by inhibition of Glutathione peroxidase 4 (GPx4), a key regulator of lipid peroxidation. The events that occur between GPx4 inhibition and the execution of ferroptotic cell death are currently a matter of active research. Previous work has shown that calcium release from the endoplasmic reticulum (ER) mediated by ryanodine receptor (RyR) channels contributes to ferroptosis-induced cell death in primary hippocampal neurons. Here, we used SH-SY5Y neuroblastoma cells, which do not express RyR channels, to test if calcium release mediated by the inositol 1,4,5-trisphosphate receptor (IP3R) channel plays a role in this process. We show that inhibition of GPx4 by RAS Selective Lethal Compound 3 (RSL3) generated an increase in reactive oxygen species (ROS), increased cytoplasmic and mitochondrial calcium levels, increased lipid peroxidation and caused cell death. The RSL3-induced calcium signals were inhibited by Xestospongin B, an inhibitor of the ER-resident IP3R calcium channel, by decreasing IP3R levels with carbachol and by IP3R1 knock-down. The intracellular calcium chelator BAPTA-AM inhibited RSL3-induced calcium signals, which were not affected by extracellular calcium depletion. We propose that GPx4 inhibition activates IP3R-mediated calcium release in SH-SY5Y cells, leading to increased cytoplasmic and mitochondrial calcium levels, which in turn stimulate the production of ROS and induce lipid peroxidation and ferroptotic cell death in a noxious positive feedback cycle.

Ceramide is a lipid that regulates cell death including apoptosis and necroptosis and acts as a powerful tumor suppressor. These characteristics have supported the development of ceramide-based cancer therapeutics. In the present study, ceramide mimetics (RT-25, RT-71 and YM-07) were designed and chemically synthesized, and their potential as necroptosis-inducing chemotherapeutic reagents was examined. RT-71 and YM-07, but not RT-25, potently decreased cell viability in multiple cancer cell lines. The ranges of IC50 values for RT-71 and YM-07 were 8.4–40.8 µM and 4.4–23.7 µM, respectively. Cleavage of PARP, an apoptosis marker, was not observed in MCF-7 cells treated with the mimetics. To determine the effects on necroptotic cell death, we used siRNAs specific to mixed lineage kinase domain-like protein (MLKL). MLKL knockdown significantly suppressed the cell death induced by YM-07 but not RT-71. These results suggest that YM-07 exhibits pro-necroptotic activity. Taken together, these findings indicate ceramide mimetic YM-07 as a lead compound for developing MLKL-activating necroptotic reagents. Our results help establish a foundation for pro-necroptotic therapy for cancer.

Sudden unexpected death (SUD) is a fatal event that occurs in an apparently healthy subject so that such an abrupt outcome could have not been predicted. SUD - including sudden intrauterine unexplained death (SIUD), sudden neonatal unexpected death (SNUD), sudden infant death syndrome (SIDS), sudden unexpected death of the young (SUDY), sudden unexpected death in the adult (SUDA) - occurs as the first manifestation of an unknown underlying disease or within a few hours of presentation of a disease. SUD is a major unsolved, shocking form of death that occurs frequently and can happen at any time without warning. For each case of SUD, a review of clinical history data and performance of a complete autopsy, particularly focused on the study of the cardiac conduction system were carried out according to the necropsy protocol devised by the Lino Rossi Research Center, Università degli Studi di Milano, Italy. Research cases are represented by 75 SUD victims, subdivided into 15 SIUD, 15 SNUD, 15 SUDY, and 15 SUDA victims, collected and selected for this study. After the routine autopsy and clinical history analysis, the death remained unexplained and hence a diagnosis of SUD was assigned to the 75. subjects, which included45 females (60%) and 30 (40%) males, ranging in age from 27 gestational weeks to 76 years. Serial sections of the cardiac conduction system disclosed frequent congenital alterations, of the cardiac conduction system in fetuses and infants. An age-related significant difference in distribution among the 5 age-related groups was detected for the following anomalies of the conduction system: central fibrous body (CFB) islands of conduction tissue, fetal dispersion, resorptive degeneration, Mahaim fiber, CFB cartilaginous meta-hyperplasia, His bundle septation, sino-atrial node (SAN) artery fibromuscular thickening, atrio-ventricular junction hypoplasia, intramural right bundle branch, and SAN hypoplasia. The results data are useful to understand the cause of death for all SUD cases that were unexpected and would have otherwise remained unexplained, so to motivate medical examiners and pathologists to perform more in-depth studies.

Background: Due to the importance of brain death (BD) diagnostic do not mistake, reliable confirmatory exams should be performed to enhance its security. This study aims to evaluate the intracranial pressure (ICP) pulse morphology behavior in brain-dead patients through a noninvasive monitoring system. Methods: A pilot case-control study was conducted in adults that met the BD national protocol criteria. Quantitative data from the ICP waveforms were extracted and analyzed comparing BD patients and health subjects. Results: Fifteen patients were included. ICP waveforms presented substantial differences amidst BD patients when compared to the control group. Moreover, pulse amplitude and time to peak variables values in the case group were also statistically significant. Conclusions: In this exploratory study, noninvasive ICP waveforms have shown potential as a screening method in patients with suspected brain death. Future studies should be carried out in a larger population.

Text fields in electronic medical records (EMR) contain information on important factors that influence health outcomes, however, they are underutilized in clinical decision making due to their unstructured nature. We analyzed 6,497 inpatient surgical cases with 719,308 free text notes from Le Bonheur Children’s Hospital EMR. We used a text mining approach on preoperative notes to obtain the text-based risk score algorithm as predictive of death within 30 days of surgery. We studied the additional performance obtained by including text-based risk score as a predictor of death along with other structured data based clinical risk factors. The C-statistic of a logistic regression model with 5-fold cross-validation significantly improved from 0.76 to 0.92 when text-based risk scores were included in addition to structured data. We conclude that preoperative free text notes in EMR include significant information that can predict adverse surgery outcomes.

Cosmetic surgery is the subfield of plastic surgery that enhances appearance mainly for aesthetic reasons. Currently, cosmetic surgery interventions are highly considered appealing and popular all around the world. Several factors have contributed in this rapidly evolving field such as scientific and economic development, breaking down barriers and cultural norms, globalization, social media and mental disorders. Nowadays, the morality of cosmetic surgery is facing many dilemmas due to its benefits and drawbacks. It is proven that the advantages of cosmetic surgery include improved body confidence, mental health, and function. Additionally, aesthetic corrections can upscale the quality of life and create career opportunities for special targeted groups. Also, cosmetic surgery has a major impact in gender affirmation procedures. Although, herein we also describe the disadvantages of this widely developing field such as minor and major medical complications, potential postoperative risks and addiction in plastic surgeries associated with damaging economic issues. Lack in self-confidence, altered mental health status and ethical crisis consist another negative aspects of aesthetic surgery’s impact.

Oral cancer ranks sixth among Taiwan's top 10 cancers, and most patients with poor prognosis acquire metastases. The essential fatty acid alpha-linolenic acid (ALA) has been found to diminish many cancer properties. However, the anti-cancer activity of ALA in oral cancer has yet to be determined. Migration and invasion assays confirmed OSCC cells' EMT capabilities, whereas flow cytometry and Western blotting identified the molecular pathways. ALA dramatically reduced cell growth in a concentration dependent manner, according to the findings. Low concentrations of ALA (100 or 200 μM) inhibit colony formation, expression of Twist and EMT-related proteins, expression of MMP2/-9 proteins and enzyme activity, as well as cell migration and invasion. Treatment with high concentrations of ALA (200 or 400 μM) greatly increases JNK phosphorylation and c-jun nuclear accumulation, then upregulates the FasL/caspase8/caspase3 and Bid/cytochrome c/caspase9/caspase3 pathways, leading to cell death. Low concentrations of ALA inhibit SAS and GNM cell migration and invasion by suppressing Twist and downregulating EMT-related proteins, or by decreasing the protein expression and enzyme activity of MMP-2/-9, whereas high concentrations of ALA promote apoptosis by activating the JNK/FasL/caspase 8/caspase 3-extrinsic pathway and the Bid/cytochrome c/caspase 9 pathway. ALA demonstrates potential as a treatment for OSCC patients.

Production of biofuel from lignocellulosic biomass is relatively low due to the limited knowledge about natural cell wall loosening and cellulolytic processes in plants. Industrial separation of cellulose fiber mass from lignin, its saccharification and alcoholic fermentation is still cost-ineffective and environmental unfriendly. Assuming that the green transformation is inevitable and that the new sources of raw materials for biofuels are needed, we decided to study cell death - a natural process occurring in plants in a context of reducing the recalcitrance of lignocellulose for production of second generation bioethanol. “members of the enzyme families responsible for lysigenous aerenchyma formation were identified during the root hypoxia stress in Arabidopsis thaliana cell death mutants. The cell death regulatory genes, LESION SIMULATING DISEASE 1 (LSD1), PHYTOALEXIN DEFICIENT 4 (PAD4) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) conditionally regulate the cell wall when suppressed in transgenic aspen. During four years of growth in the field the following effects were observed: lignin content was reduced, the cellulose fiber polymerization degree increased and the growth itself was unaffected. The wood of transgenic trees was more efficient as a substrate for saccharification, alcoholic fermentation and bioethanol production. The presented results may trigger the development of novel biotechnologies in the biofuel industry.

Phototherapy is an efficient strategy to respond to oxidative stress and has been in the spotlight in various therapeutic fields through its biological effect, but the exact molecular mechanism has not yet been established. As a result of irradiating RAW264.7 cells with a 630 nm or 850 nm LED with an energy intensity of 0.01J/cm2, cell viability was increased depend on the irradiation time. After H2O2 was added, 630 nm or 850 nm LEDs were irradiated for 10 min or 40 min to increase cell viability by about 1.7- or 1.6-fold, respectively. In addition, 630nm or 850nm LED irradiation showed a significant ROS scavenging effect and significantly reduced TUNEL-positive cells by 45.7% and 37.8%, respectively, compared to cells treated only with H2O2. In the result of flow cytometry, the number of cells in the late apoptosis stage was about 2.3- and 1.8-fold lower than that of the cells treated with H2O2 only, but there was no significance. The Bax/Bcl-2 ratio of cells irradiated with 630 nm or 850 nm LED was significantly lower than that of cells treated with H2O2 only, and the expression of procaspase-3 and cleaved PARP was also significantly expressed in the direction of suppressing cell death. In conclusion, the ROS scavenging activity by 630 nm or 850 nm LED irradiation, leading the expression of cell death pathway proteins in the direction of inhibiting cell death.

Gossypol is a complex plant polyphenol reported to be cytotoxic and anti-inflammatory, but little was known about its effect on gene expression in macrophages. The objective was to explore gossypol’s toxicity and its effect on gene expression involved in inflammatory responses, glucose transport and insulin signaling pathway in mouse macrophages. Mouse RAW264.7 macrophages were treated with multiple concentrations of gossypol for 2-24 h. Gossypol toxicity was estimated by MTT assay and soluble protein content. qPCR analyzed the expression of anti-inflammatory tristetraprolin family (TTP/ZFP36), proinflammatory cytokine, glucose transporter (GLUT) and insulin signaling genes. Cell viability was greatly reduced by gossypol, accompanied with dra-matic reduction of soluble protein content in the cells. Gossypol treatment resulted in an increase of TTP mRNA level 6-20 fold and increased ZFP36L1, ZFP36L2 and ZFP36L3 mRNA levels by 26-69 fold. Gossypol increased proinflammatory cytokine TNF, COX2, GM-CSF, INFγ and IL12b mRNA levels up to 39-458 fold. Gossypol treatment upregulated mRNA levels of GLUT1, GLUT3 and GLUT4 genes as well as INSR, AKT1, PIK3R1 and LEPR but not APP genes. This study demonstrated that gossypol induced macrophage death and reduced soluble protein content that was accom-panied with massive stimulation of anti-inflammatory TTP family and proinflammatory cytokine gene expression as well as elevation of gene expression involved in glucose transport and insulin signaling pathway in mouse macrophages.

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