Ageing wine is a commonly practice used in winemaking since the quality and sensory profile increase due to the extractable compounds coming from wood by means of barrels or chips. The quantitative and qualitative compounds from wood depend on the species, its origins and the treatments applied in cooperages. Traditionally, oak wood species are most often used in cooperage, specifically Quercus alba, Known as American oak and Q. robur and Q. petraea both known as French oak. However, although this stage is very common for red wines, its use is still restricted in the case of white wines. However, this topic is particularly interesting, since due to the sensorial benefits of wood contact, the option for ageing white wines in barrels or chips is increasingly and widely chosen by winemakers. This review compiles the novel strategies applied to white wines by means of wood contact in the last years with the aim to increase wine quality and sensorial features.

Researchers have reported various impacts of the COVID-19 outbreak on small-scale fishers, such as stagnating market demands, reduction of market price and income, etc. While literature have heeded to these impacts in a relatively short time frame, scant evidence exists on the changing impacts over time and on the detailed processes of how fishers have been coping with the challenges in a longer time period. Furthermore, few studies have comprehensively analysed the impacts and strategies from multiple perspectives. This study aims to explore the perceived impacts of the COVID-19 outbreak on small-scale fishing communities and to highlight the coping strategies adopted by fishers over a year since the initial outbreak, through a case study in Trang Province, Thailand. Analysis of both qualitative and quantitative data obtained through semi-structured interviews indicated that fishers wisely utilised natural, financial and social capitals at the early stages of the outbreak, while human capitals were essential for recovering from the impacts in the later stages. Our findings suggest that the adaptive capacity to flexibly change livelihood strategies are crucial, while alternative income source may not necessarily help small-scale fishers under stagnating global economy.

Climacteric fruits are characterized by a dramatic increase in autocatalytic ethylene production, which is accompanied by a spike in respiration, at the onset of ripening. The change in the mode of ethylene production from autoinhibitory to auto-stimulatory is known as the system 1 (S1) to system 2 (S2) transition. Existing physiological models explain the basic and overarching genetic, hormonal, and transcriptional regulatory mechanisms governing the S1 to S2 transition of climacteric fruit. However, the links between ethylene and respiration, the two main factors that characterize the respiratory climacteric, have been largely understudied at the molecular level. Results of recent studies indicate that the AOX respiratory pathway may play an important role in mediating cross talk between ethylene response, carbon metabolism, ATP production, and ROS signaling during climacteric ripening. New genomic, metabolic, and epigenetic information sheds light on the interconnectedness of ripening-associated metabolic pathways, necessitating expanding the current, ethylene-centric physiological models. Understanding points at which ripening responses can be manipulated may reveal key, speciesand cultivar-specific targets for regulation of ripening enabling superior strategies for reducing postharvest wastage.

Mitochondrial alternative oxidase 1a (AOX1a) plays an extremely important role in critical node of seed viability. However, the regulatory mechanism is still poorly understood. The study aims to identify regulatory mechanisms by comparing between OsAOX1a-RNAi and wild type (WT) rice seed during artificial aging treatment. Gain weight and P50 significantly decreased in OsAOX1a-RNAi rice seed, indicating that there might be impaired in seed development and storability. Compared to WT seeds in the 100%, 90%, 80%, and 70% germination, respectively, NADH and succinate-dependent O2 consumption, the activity mitochondrial malate dehydro-genase and ATP contents were decreased in OsAOX1a-RNAi seeds in the 100%, 90%, 80%, and 70% germination, respectively, indicating that mitochondrial status in the OsAOX1a-RNAi seeds after imbibition was weaken than the WT. In addition to, the reduced abundance of complex I N and P module subunits might showed that the capacity of mitochondrial electron transfer chain was significantly inhibited in the OsAOX1a-RNAi seed at critical node of seed viability. Above results might indicated that the ATP production was impaired in OsAOX1a-RNAi seeds during ageing. Therefore, we conclude that the activities of mitochondrial metabolism and alternative pathways were severely inhibited in OsAOX1a-RNAi seeds at critical node of viability, which was leading to accelerate the collapse of seed viability. The precise regulatory mechanism of the alternative pathway at the critical node of viability still needs to be further analyzed.

Salmonella enterica serovar Newport bacteriophage 7-11 shares 41 homologous ORFs with Escherichia coli phage phiEco32 and both phages encode a protein similar to bacterial RNA polymerase promoter specificity  subunit. Here, we investigated the temporal pattern of 7-11 gene expression during the infection and compared it to the previously determined transcription strategy of phiEco32. Using primer extension and in vitro transcription assays we identified eight promoters recognized by host RNA polymerase holoenzyme containing 7-11  subunit SaPh711_gp47. These promoters are characterized by a bipartite consensus GTAAtg-(16)-aCTA and are located upstream of late phage genes. While dissimilar from single-element middle and late promoters of phiEco32 recognized by holoenzyme formed by the phi32_gp36  factor, the 7-11 late promoters are located at genome positions similar to those of phiEco32 middle and late promoters. Two early 7-11 promoters are recognized by RNA polymerase holoenzyme containing host primary σ70 factor. Unlike the case of phiEco32, no shut off of σ70-dependent transcription is observed during 7-11 infection and there are no middle promoters. These differences can be explained by the fact that phage 7-11 does not encode a homologue of phi32_gp79, an inhibitor of host and early phage transcription and an activator of transcription by the phi32_gp36-holoenzyme.

Pronematus ubiquitus (McGregor) is a small iolinid mite that is capable of establishing on tomato plants. Once established, this mite has been shown to control both tomato russet mite, Aculops lycopersici (Tryon) (Acari: Eriophyidae) and tomato powdery mildew (Oidium neolycopersici L. Kiss). In the present study, we explored the nutritional value of various food sources in the laboratory. First, we assessed the reproduction of two food sources that P. ubiquitus can encounter on a tomato crop: tomato pollen and powdery mildew. In a second laboratory experiment, we evaluated the nutritional value of two types of prey mites: the astigmatid Carpoglyphus lactis L. (Acari: Carpoglyphidae) and the tarsonemid Tarsonemus fusarii (Acari: Tarsonemidae). Powdery mildew and C. lactis did not contribute to the reproduction, whereas tomato pollen and T. fusarii did allow egg-laying. However, Typha angustifolia pollen was a superior food source in both experiments. In a greenhouse trial on individual caged tomato plants, we evaluated the impact of pollen supplementation frequency on establishment of P. ubiquitus. Here, a pollen addition frequency of every other week was required to allow populations of P. ubiquitus to establish.

Background: Menopause symptoms and hormone replacement therapy (HRT) are among the most common reasons patients seek gynecological advice. Although at least half of all women in developed countries will take HRT during their lifetime, the treatment is not without risk and guidance on HRT is mixed. Greater awareness of negative HRT health effects from extended use has piqued interest in ‘safer options’. Menopause reversal with autologous ovarian platelet-rich plasma (OPRP) has brought this restorative approach forward for consideration, but appropriateness and cost-effectiveness require examination. Methods: HRT and OPRP data from USA were projected to compare cumulative 1yr patient costs using stochastic Monte Carlo modeling. Results: Mean±SD cost-to-patient for HRT including initial consult plus pharmacy refills was estimated at about USD 576±246/yr. While OPRP included no pharmacy component, an estimated 4 visits over 1yr for OPRP maintenance entailed ultrasound, phlebotomy/sample processing, surgery equipment, and incubation/laboratory expense, yielding mean±SD cost for OPRP at USD 8,710±4,911/yr (p<0.0001 vs. HRT, by t-test). Upper-bound estimates for annual HRT and OPRP costs were USD 1,341 and USD 22,232, respectively. Conclusions: While HRT and OPRP may have similar efficacy and safety for menopause therapy, they diverge sharply in cost-effectiveness. Most patients would likely find OPRP too complex, invasive, and expensive to be competitive vs. HRT. Although OPRP is an interesting and cautiously useful technique for selected menopause patients reluctant to use HRT, repurposing this infertility treatment for wider use appears inefficient compared to standard HRT currently available.

MicroRNA (miRNA) is a typical class of small RNAs that could modulate gene expression in trans at the post-transcriptional level. miRNAs bind to the miRNA binding sites (MBSs) in target mRNAs by sequence complementarity. Alternative splicing (AS) is another commonly occurred process in pre-mRNAs that changes the isoforms of a gene. It is hypothesized that there should be an interaction for gene regulation that involves both AS and miRNA targeting. Studies have verified this hypothesis in the model organism Arabidopsis thaliana. High-throughput sequencing data suggested that in Arabidopsis a considerably large fraction of MBSs are affected by AS events. The overlapping between MBS and AS exceeds the randomly simulated number. Functional experiments have indicated that the AS events are required for the gene expression changes of miRNA targets. Therefore, AS and MBS are mutually favored. The observed expression changes caused by miRNAs could also be contributed by AS events. In the present perspective article, we propose that the AS analysis should be incorporated in the differential-expression analysis of miRNA studies. When defining a differentially-expressed gene, it should be clarified whether the change in gene expression is caused by AS events or solely by miRNA targeting.

Cryptococcus neoformans is a human multidrug-resistant yeast with high mortality rates in immunocompromised patients. Recently, the synthetic peptide Mo-CBP3-PepII emerged as a potent anticryptococcal molecule with an MIC50 at low concentration. Here, the mechanisms of action of Mo-CBP3-PepII were deeply analyzed to provide new information about how it led C. neoformans cells to death. Light and fluorescence microscopies, analysis of enzymatic activities, and proteomic analysis were employed to understand the effect of Mo-CBP3-PepII on C. neoformans cells. Light and fluorescence microscopies revealed Mo-CBP3-PepII induced the accumulation of anion superoxide and hydrogen peroxide in C. neoformans cells. In addition to a reduction in the activity of superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT) in the cells treated with Mo-CBP3-PepII. In the presence of Ascorbic acid (AsA), no ROS were detected and Mo-CBP3-PepII lost the inhibitory activity against C. neoformans. Yet, Mo-CBP3-PepII inhibited the activity of lactate dehydrogenase (LDH), ergosterol biosynthesis, and induced the decoupling of cytochrome c from the mitochondrial membrane. Proteomic analysis revealed a reduction in the abundance of proteins related to energetic metabolism, DNA and RNA metabolism, pathogenicity, protein metabolism, cytoskeleton, and cell wall organization and division. Our findings indicated that Mo-CBP3-PepII might have multiple mechanisms of action against C. neoformans cells, mitigating the development of resistance and thus being a potent molecule to be employed in the production of new drugs against C. neoformans infections.

The current manuscript presents a review on existing kiln burner technologies for the cement production process, in the context of the current climate of energy transition and environmental remediation. Environmental legislation has become ever stricter in response to global climate change, and cement plants need to adapt to this new reality in order to remain competitive in the market and ensure their longevity. The cement production process is a well-established technology with more than a century of existence. There are several plants in operation whose process is outdated by modern standards, particularly considering the current industry decarbonization needs. The cement process requires tremendous amounts of energy, mainly recovered from the combustion of solid, liquid or gaseous fuels, which yields massive emissions of greenhouse gases. Thus, an important onus is placed upon the minimization of pollutant emission in the combustion system, as well as a substitution of fossil fuels with more sustainable alternatives. One of the sus-tainable alternative fuels comes in the form of refuse derived fuels (RDF). These high caloric frac-tions of municipal solid waste present a double advantage by reducing the amount of fossil fuels used and reducing the landfilling fraction of waste. However, their use in rotary kiln burners comes with important limitations for burner operation, namely that a high degree of control over primary air supply is needed to ensure complete combustion with minimal pollutant emission.

In this paper, we investigate the question of whether the generally accepted interpretation of the supermassive object in M87, investigated by EHT collaboration, is the only possible one. There are grounds for this, in particular, due to the detection of a magnetic field in its vicinity. For this purpose, the stability of self-gravitating objects is investigated based on the correct definition of the energy of gravitation in the framework of the bi-metric approach to the theory.

An increasing number of persons with cancer decide to choose complementary and alternative medicine. The purpose of the paper was to check the status of the use of complementary and alternative medicine methods in oncological patients and to compare health behaviours of patients using Complementary and Alternative Medicine (CAM) with those using neither of these methods. The studies were conducted from August till January 2020 in the Oncology Center in the south-eastern Poland. A cross-sectional study was conducted in a group of 208 oncological patients. The authors' own questionnaire and the standardized Health Behaviour Inventory were used. Most of the patients (85,09%) declared that they used complementary and alternative medicine methods. The most common methods chosen by the respondents included vitamin C, green tea and prayer. The vast majority of the respondents did not inform their oncologist about the use of CAM. 45,19% of the respondents had a high rate of health behaviours. It was observed that there was no communication related to the use of CAM among the patients and healthcare staff. Patients using CAM demonstrated more positive health behaviours than those who were not using these methods.

In Australia, orthodox soil scientists and alternative practitioners who promote ‘regenerative agriculture’ have not been communicating and engaging effectively with each other. Over many years scientists in CSIRO, state departments and universities have made significant achievements in mapping soil distribution, describing soil behaviour and identifying key soil properties and processes that are fundamental to healthy soil function. However, many alternative practitioners are dismissive of these achievements and highly critical of orthodox soil science. Yet many of the tools of soil science are essential to conduct evidence-based research towards elucidating how and why the exceptional results claimed by some alternative practitioners are achieved. We stress the importance of effective engagement and communication among all parties to resolve this ‘clash of cultures’.

In recent years, increasing attention has been paid to individuals organizing themselves and managing food systems in an ‘alternative’ and more sustainable way. Such emerging food initiatives are most commonly known as ‘Alternative Food Networks’ (AFNs). However, there is an ongoing debate concerning the extent to which AFNs facilitate social, economic and environmental change. There are criticisms of the overall sustainability promise of AFNs related to sufficiency of impact, possible counter effects and relevance of impacts. Because often empirical studies only focus on specific sustainability issues or AFNs, it has been difficult to develop more robust theories about the relations between diverse AFNs arrangements and sustainability. Thus, the aim of this paper is to contribute towards reducing this knowledge gap through a systematic literature review on AFNs in relation to sustainability. We summarize main methodological approaches, types of AFNs studied and sustainability dimensions addressed in literature to date. Findings serve as reference to propose opportunities for future research regarding sustainability in AFNs.

Alternaria brown spot (ABS) is a disease caused by the fungus Alternaria alternata f. sp. citri, which results in lesions on fruits, leaves, and branches of several mandarin varieties and their hybrids. Due to the high cost of fungicide application, alternative methods for controlling ABS need to be studied. Therefore, this study aimed to evaluate the use of essential oils (EOs) from different mandarin varieties to mitigate the effects of ABS. The inhibitory effect of different concentrations (1, 2, 4, 8, and 16 μL mL-1) of Fremont IAC 543 mandarin, IAC 2019Maria mandarin, Murcott IAC 221 tangor, and Late IAC 855 willowleaf. EOs on the in vitro mycelial growth of the fungus A. alternata was evaluated. Additionally, the curative and preventive effects of these EOs on ABS symptoms on detached leaves of Murcott IAC 221 tangor were also assessed. The EO of IAC 2019Maria mandarin induced less mycelial growth, and consequently, greater inhibition of the growth of the fungus A. alternata at a concentration of 16 μL mL-1. This EO was more effective in control than the other oils tested. In the detached leaf experiment, both the curative and preventive treatments at a concentration of 16 μL mL-1 showed lower values of disease severity.

The oral cavity is thought to be one of the portals for SARS-CoV-2 entry. Because there is limited evidence of active oral infection by SARS-CoV-2 viruses, we assessed the capacity of SARS-CoV-2 to infect and replicate in oral epithelial cells. Oral gingival epithelial cells (hTERT TIGKs), salivary gland epithelial cells (A-253), and oral buccal epithelial cells (TR146), which occupy different regions of the oral cavity, were challenged with replication competent SARS-CoV-2 viruses and with pseudo-typed viruses expressing SARS-CoV-2 spike proteins. All oral epithelial cells expressing undetectable or low levels of human angiotensin-converting enzyme 2 (hACE2) but high levels of the alternative receptor CD147 were susceptible to SARS-CoV-2 infection. Viral dynamics in hTERT TIGKs were different from those in A-253 and TR146 cells. For example, levels of viral transcripts were sustained in hTERT TIGKs but were significantly decreased in A-253 and TR146 cells at day 3 after infection. Analysis of oral epithelial cells infected by replication competent SARS-CoV-2 viruses expressing GFP showed that the signals of GFP and SARS-CoV-2 mRNAs were not evenly distributed. Taken together, our results demonstrated oral epithelial cells were susceptible to SARS-CoV-2 viruses despite of low or undetectable levels of hACE2, suggesting that alternative receptors contribute to SARS-CoV-2 infection and may be considered for development of future vaccines and therapeutics.

Colorectal cancer prognosis get worse with advancement of disease into metastatic stage. There is a pertinent need to develop prognostic biomarkers that can be used for personalized and precision medicine. Alternative splicing provides an insight into understanding of changes at isoform expression level which may not be evident at gene level. In this direction, we utilized our prior knowledge about significant alternatively spliced genes and chose ADAM12 and MUC4 for further characterization in a metastatic cell line model. These genes were found to be good prognostic indicators in The Cancer Genome Atlas database. We studied the gene organization and designed primers to specifically amplify a group of isoforms. Differential expression of these group of isoforms was observed in normal, primary and metastatic colorectal cancer cell lines. We further validated the results using sanger sequencing. Isoform expression was found to respond to the 5-fluorouracil treatment. RNAseq analysis of the cell lines further validated the differential expression of gene isoforms. Successful detection of ADAM12 and MUC4 in cell lysates varied according to the antibody used which may reflect differential expression of isoforms. This comprehensive study underscores the importance of studying alternatively spliced isoforms and their probable used as prognostic or predictive biomarkers.

In this work, we study the existence of strange star in the background of f(T,T) gravity in the Einstein spacetime geometry, where T is the torsion tensor and T is the trace of the energy-momentum tensor. The equations of motion are derived for anisotropic pressure within the spherically symmetric strange star. We explore the physical features like energy conditions, mass-radius relations, modified TOV equations, principal of causality, adiabatic index, redshift and stability analysis of our model. These features are realistic and appealing to further investigation of properties of compact objects in f(T,T) gravity as well as their observational signatures.

Conyza canadensis is a species invading large agricultural areas throughout the world, mainly to its ability to evolve herbicide resistance. Specifically, in Hungary, extensive areas have been infested by this species due to the difficulty in controlling it with glyphosate. To corroborate this fact as resistance and not as an incorrect herbicide application, eight suspicious glyphosate-resistant C. canadensis populations from different Hungarian regions were studied. In dose-response assays with glyphosate, the LD50 and GR50 values indicated that populations 1 to 5 were resistant to this herbicide (H-5 population the most resistant). Besides, the shikimic acid accumulation tests corroborated the results observed in the dose-response assays. 11 alternative herbicides from 6 different mode of action (MOA) were applied at field doses as control alternatives on populations H-5 and H-6 (both in the same regions). The H-5 population showed an unexpected resistance to flazasulfuron (ALS-inhibitor). The ALS enzyme activity studies indicated that the I50 for H-5 was 63.3 fold higher compared to its correspondent susceptible population (H-6). Therefore, the H-5 population exhibited multiple-resistance to flazasulfuron and glyphosate, being the first case reported in Europe for this two MOA. For that reason, the other herbicides with different MOA have to be tested here.

Hexane is a solvent used extensively in the food industry for the extraction of various products such as vegetable oils, fats, flavours, fragrances, colour additives or other bioactive ingredients. As it is classified as a "processing aid", it does not have to be declared on the label under current legislation. Therefore, although traces of hexane may be found in final products, especially in processed products, its presence is not known to consumers. However, hexane, and in particular the n-hexane isomer, has been shown to be neurotoxic to humans and has even been listed as a cause of occupational diseases in several European countries since the 1970s. In order to support the European strategy for a toxic-free environment (and toxic-free food), it seemed important to collect scientific information on this substance by reviewing the available literature. This review contains valuable information on the nature and origin of the solvent hexane, its applications in the food industry, its toxicological evaluation and possible alternatives for the extraction of natural products. Numerous publications have investigated the toxicity of hexane, and several studies have demonstrated the presence of its toxic metabolite 2,5-hexanedione (2,5-HD) in the urine of the general, non-occupationally exposed population. Surprisingly, a tolerable daily intake (TDI) has apparently never been established by any food safety authority. Since hexane residues are undoubtedly found in various foods, it seems more than necessary to clearly assess the risks associated with this hidden exposure. A clear indication on food packaging and better information on the toxicity of hexane could encourage industry to switch towards one of the numerous other alternative extraction methods already developed.

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Since the 70s, many countries have adopted different CRC screening programs which has resulted in a decrease in mortality. However, current screening test options still present downsides. The commercialized stool-based tests present high false-positive rates and low sensitivity, which negatively affects the detection of early stage carcinogenesis. The gold standard colonoscopy has low uptake due to its invasiveness and the perception of discomfort and embarrassment that the procedure may bring.In this review, we collected and described the latest data about alternative CRC screening techniques that can overcome these disadvantages. Web of Science and PubMed were employed as search engines for studies reporting on CRC screening tests and future perspectives. The searches generated 555 articles, of which 93 titles were selected. Finally, a total of 50 studies, describing 14 different CRC alternative tests, were included. Among the investigated techniques the main feature that could have an impact on CRC screening perception and uptake was the ease of sample collection. Urine, exhaled breath and blood-based tests promise to achieve good diagnostic performance (sensitivity of 63-100%, 90-95%, 47-97%, respectively) while minimizing stress and discomfort for the patient.

Background: DSCAM-AS1 is a cancer-related long noncoding RNA with higher expression levels in Luminal A, B and HER2-positive Breast Cancer (BC), where its expression is strongly dependent on Estrogen Receptor Alpha (ERα). Methods: To decipher its function, DSCAM-AS1 expression was measured by qRT-PCR in tissue samples from 93 BC patients in addition to a meta-analysis of 30 gene expression datasets, together with the evaluation of its association with clinical data. By computational analyses of our RNA-Seq in MCF-7 cells, we investigated the DSCAM-AS1 knock-down effects at both gene and isoform levels. Results: We confirmed DSCAM-AS1 overexpression in high grade Luminal A, B and HER2+ BCs and found a significant correlation with disease relapse. 908 genes were regulated by DSCAM-AS1-silencing, primarily involved in cell cycle and inflammatory response. Noteworthy, the analysis of alternative splicing and isoform regulation revealed 2,085 splicing events regulated by DSCAM-AS1, enriched in differential polyadenylation sites and 3’UTR shortening events. Finally, the DSCAM-AS1-interacting splicing factor hnRNPL was predicted as the most enriched RBP for exon skipping and 3’UTR events. Conclusion: The relevance of DSCAM-AS1 overexpression in BC is confirmed by clinical data and further enhanced by its possible involvement in the regulation of RNA processing, which is emerging as one of the most important dysfunctions in cancer.

Understanding the role of invasive species in ecosystem functioning represents one of the main challenges in ecology. Pteridium aquilinum is a successful cosmopolitan invasive species with negative effects on the ecological mechanisms that allow secondary succession. In this study we evaluated whether P. aquilinum favours the establishment of alternative states, as well as the effect of recovery strategies on the secondary succession. A random stratified sampling was established with three treatments, each one with at least 50 year of fern invasion and with variations on the periodicity of fires and cuttings (chapeos) vs one control without fern bracken We determined the species richness and composition, as well as the relative importance value (IVI) in each treatment. We found that P. aquilinum decreases the action of the mechanisms that allow secondary succession, particularly facilitation. The recovery strategies consist in monthly cuttings and control fires allow to recover the secondary succession and eventually, the regeneration of areas invaded by P. aquilinum. Our study has relevant implications on the ecology of alternative state, and in practical strategies to maintain tropical forests, as well as for the maintenance of environmental services and sustainability.

Coronavirus disease 2019 (COVID-19) is a potentially serious acute respiratory infection caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Since the World Health Organization (WHO) declared COVID-19 a global pandemic, the virus has spread to more than 200 countries with more than 500 million cases and more than 6 million deaths reported globally. It has long been known that viral respiratory tract infections predispose patients to bacterial infections and that these co-infections often have an unfavourable clinical outcome. Moreover, nosocomial infections, also known as health care-associated infections (HAIs), are those infections that are absent at the time of admission and acquired after hospitalization. However, the impact of coinfections or secondary infections on the progression of COVID-19 disease and its lethal outcome is still debated. The aim of this review was to assess the literature on the incidence of bacterial co-infections and superinfections in patients with COVID-19. The review also highlights the importance of the rational use of antibiotics in patients with COVID-19 and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, alternative antimicrobial agents to counter the emergence of multidrug-resistant bacteria causing healthcare-associated infections in COVID-19 patients will also be discussed.

Advancements in genomics, bioinformatics and genome editing have uncovered new dimensions in gene regulation. Post-transcriptional modifications by the alternative splicing of mRNA transcripts are critical regulatory mechanisms of mammalian gene expression. In the heart, there is an expanding interest in elucidating the role of alternative splicing in transcriptome regulation. Substantial efforts have been directed towards investigating this process in heart development and failure. However, few studies have shed light on alternative splicing products and their dysregulation in congenital heart defects (CHDs). While elegant reports have shown the crucial roles of RNA binding proteins (RBPs) in orchestrating splicing transitions during heart development and failure, the impact of RBPs dysregulation or genetic variation on CHDs has not been fully addressed. Herein, we review the current understanding of alternative splicing and RBPs’ roles in heart development and CHDs and discuss the impacts of perinatal splicing transition and its dysregulation in CHDs. We further summarize discoveries made of causal splicing variants in key transcription factors that have been implicated in CHDs. Improved understanding of the roles of alternative splicing in heart development and CHDs may potentially inform novel preventive and therapeutic advancements for newborn infants with CHDs.

The incidence of lung cancer has increased in recent years and causes major mortalities across the globe. Besides, the availability of the several chemotherapeutics modalities in the management, there is still a challenge to find out an efficient remedy with lesser or no toxic effects. Hence, there is a necessity to employ complementary research to establish effective management for lung cancer. In this study, we have implemented a novel herbal informatics model to find out the alternative remedy in the treatment of lung cancer. This model utilizes five major steps of the bioprospection process based on the classical surge followed by the binary index and rationale-based selection of herbal products targeting the cancer-causing factors which are explained in detail in the methodology section of this model. This study revealed 07 herbals such as Withania somnifera (Ws), Berberis vulgaris(Bv), Glycyrrhiza glabra(Gg), Andrographis paniculate(Ap), Azadirachta indica(Ai), Cinnamomum Verum(Cv), Piper longum(Pl) based on the fuzzy set optimization scoring(0.6-1) that could be further studied in vitro and in vivo level for utilization in the management of lung cancer.

A growing number of health conscious consumers are looking for animal protein alternatives with similar texture, appearance, and flavor. There has been a lot of interest in meat analogs as potential meat substitutes. However, research and development still needs to find any alternative non-meat materials. The objective of the current research was to develop fungi minced meat alternative (FMMA) from edible mushrooms. Pleurotus Sajor-caju (SC) was used as the starting material. SC mushroom was selected for starting materials based on high protein content (41.99%.) and sensory attributes. Chickpea flour was used to improve the textural properties by mixing with SC mushroom at a ratio of 0:50, 12.5:37.5, 25:25, 37.5:12.5, and 50:0 (w/w). Textural and sensory attributes suggest that SC mushroom to chickpea at a ratio of 37.5:12.5, shows higher acceptability of FMMA with the protein content up to 47%. Beetroot extract 0.2% (w/w), and 5% (w/w) canola oil showed the most acceptable color parameters and consumer acceptability. This research suggested that SC mushroom with 12.5% chickpea flour, 0.2% beetroot extract and 5% canola oil could be suitable ingredients for the mushroom-based FMMA.

Antibiotics are in excessive use that has extensively increased antimicrobial resistance worldwide which has become the major public concern among the countries. To control this threat proper monitoring of the antimicrobial usage along with the increasing rate of antimicrobial resistance (AMR) is required. Further, surveillance of both the parameters is highly recommended for comparing the differences in distinct countries. Moreover, alternatives for antibiotics are also surveyed and are being researched for quick use in the near future. AMR is an issue that needs immense attention from various sectors. Thus, intervention of multisector is highly encouraged for better outcomes. One Health is one of the approaches that play a vital role in resolving this issue. In this research paper, six different European countries are discussed in terms of antimicrobial usage and AMR in the human and livestock sectors with the help of literature study and various reports published by different organizations. Data study has been conducted to collect the data for comparison study. Data sources of AMR and antimicrobial usage are analyzed and a thorough comparison of both antimicrobial use and AMR are conducted. Also, the application of One Health is studied for a balanced system. This article provides about various surveillance systems that are formed only to keep a track on the upcoming situation of AMR and the consumption of antimicrobials by the humans as well as animals. The article does not provide about all the details required to monitor the AMR issue but firmly allow the readers to get acknowledged with the broad information about the antimicrobial resistance across the six countries of Europe. The regular data collected by the different organizations play a vital role in monitoring the status of AMR and antimicrobial usage by humans and in live stocks. These annual reports have highly helped the government to decide for alternatives and have focused in many training activities to combat the AMR situation globally. AMR prevention is linked to the One Health concept. As antibiotic resistance genes persist on an interface between environment and animal and animal health, an approach is required in all three areas that stress the concept of 'One Approach to Health.'

In this paper any superalgebra is generalized to a new form, namely ultra algebra. We study some algebraic structure results for ultra algebras and we have defined some maps on ultra algebras to know ultra derivation and Jordan ultra derivation. Moreover on certain assumptions we have proved that Jordan ultra derivation is an ultra derivation.

Mental stress represents a pivotal factor in cardiovascular diseases. The mechanism by which stress produces its deleterious effects is still under study but one of the most explored pathway is cell senescence. In this scenario, circulating microRNAs appear to be mobile regulatory elements of the telomerase activity and alternative splicing within the ”senectome” network. Anti-stress techniques seem to be able to slow-down aging process. As we have recently verified how the practice of Relaxation Response (RR), counteracting psychological stress, determines favorable changes of some inflammatory genes expression, of some neurotransmitters, hormones, cytokines and inflammatory circulating microRNAs, we aimed to verify a possible change even in serum levels of 4 senectome micro-RNAs (SE-miRNAs -20, -30, -410, -515), testing the activity of telomerase in peripheral blood mononuclear cells-PBMCs. We analyzed also alternative splicing microRNAs 134 and 183. According to our data, miRNA-20 and -30 levels and PBMCs-telomerase activity increase during the RR while -410 and -515 levels decrease. Moreover, during the RR sessions both miRNA-134 and -183 decrease. The mediators considered in this work seem to vary rapidly according to a (stress)-relaxation condition showing that psychic activity should be part of the study of aging factors.

We tested the use of mosquito traps as an alternative to insecticide spraying in Camargue (France) following the significant impacts observed on the non-target fauna through Bti persistence and trophic perturbations. In a village of 600 inhabitants, 16 Techno-Bam traps emitting CO₂ and using octenol lures were set from April to November 2016. Trap performance was estimated at 70% overall based on mosquito landing on human baits in areas with and without traps. Reduction of Ochlerotatus caspius and Oc. detritus, the two species targeted by Bti spraying, was respectively 74 and 98%. Traps were less efficient against Anopheles hyrcanus (46%), which was more attracted by lactic-acid than octenol lures based on previous tests. Nearly 300 000 mosquitoes from nine species were captured, with large variations among traps, emphasizing that trap performance is also influenced by surrounding factors. Environmental impact, based on the proportion of non-target insects captured, was mostly limited to small chironomids attracted by street lights. Breeding success of a house martin colony was not significantly affected by trap use, in contrast to Bti spraying. Our experiment confirms that deployment of mosquito traps can offer a cost-effective alternative to Bti spraying for protecting local populations from mosquito nuisance in sensitive natural areas.

Beef has one of the highest climate footprints of all foods, and therefore the hamburger has been targeted for substitution by numerous plant-based alternatives. However, many consumers find the taste of these alternatives lacking, and thus we proposed a hybrid meat and plant-based burger as a lower threshold alternative for these consumers. The burger was made from 50% meat (beef and pork, 4:1) and 50% plant-based ingredients, including texturised legume protein and had a climate footprint less than half that of a beef burger. Texture and sensory properties were evaluated instrumentally and through a consumer survey (n = 381) using the check-all-that-apply (CATA) method. Moisture properties indicated a significantly juicier eating experience for the hybrid compared to a beef burger, which was supported by the CATA survey. From texture profile analysis the hybrid burger was significantly softer and less cohesive than a beef burger. Despite having different CATA term profiles overall liking of the hybrid and a beef burger were not significantly different. Penalty analysis indicated that “meat flavour”, “juiciness”, “spiciness”, and “saltiness” are the most important attributes for a burger. In conclusion, consumers may be open to reducing their meat consumption by way of hybrid meat and plant-based products.

The holographic principle states that the information about the volume of space is stored on its boundary. Assuming this holds, we can explain the aspects of gravity. It strongly seems that ”information” is a more fundamental entity than the structure of spacetime as used as basis in almost every gravity theory. In this paper, we present this connection between gravity and information. This naturally explains the four classical tests of gravity namely the gravitational redshift, the perihelion precession, the bending of light and the gravitational time delay. The spacetime need to be extended to 5D to explain gravity in this context.

The present is a study of the CFD simulations intended to simulate the emissions of pollutants that are generated after the combustion of proposed alternative aircraft fuels (Hydrogen, Ethanol and Methane) to compare with the emissions generated after the combustion of Kerosene and Benzene in a 2D cylindrical combustion chamber. Given that air traffic is a main contributor to not only 3% of man-made greenhouse effects but also of the generation of smog over heavy air traffic urban areas generating an impact on the air quality and the population of those areas.

Gene expression data is key for the functional annotation of single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS). Expression and splicing quantitative trait loci (e/sQTLs) in normal colon tissue, such as those from the University of Barcelona and University of Virginia RNA sequencing project (BarcUVa-Seq) and the Genotype-Tissue Expression project (GTEx), are required to gain biological insight of colon-related diseases risk loci. Moreover, transcriptome-wide association studies (TWAS) rely on reference gene expression imputation panels in the tissue of interest to nominate susceptibility genes. Also, it is of high interest to study the relationships between genes in a network framework. For facilitating these analyses, we have updated and expanded the scope of the Colon Transcriptome Explorer (CoTrEx) to the version 2.0. This web-based resource provides exhaustive visualization and analysis of transcriptome-wide gene expression profiles of normal colon tissue from BarcUVa-Seq and GTEx. In addition to the integration of new datasets, CoTrEx 2.0 provides additional e/sQTLs sets, as well as gene expression prediction models and regulatory and co-expression networks. It is freely available at https://barcuvaseq.org/cotrex/. Overall, it is of high interest for researchers aiming to investigate the genetic susceptibility to colon-related complex traits and diseases.

Conventionally, eukaryotic mRNAs were thought to be monocistronic, leading to the translation of a single protein. However, large-scale proteomics has led to a massive identification of proteins translated from mRNAs of alternative ORF (AltORFs), in addition to the predicted proteins issued from the reference ORF or from ncRNAs. These alternative proteins (AltProts) are not represented in the conventional protein databases and this “Ghost proteome” was not considered until recently. Some of these proteins are functional and there is growing evidence that they are involved in central functions in physiological and physiopathological context. Based on our experience with AltProts we have got interested in finding out their involvement in development of the SARS-CoV-2 virus, responsible for the 2020 Covid-19 outbreak. Thus, we have scrutinized the recently published data by Krogan and coworkers (2020) on the SARS-CoV-2 interactome with host cells by co-IP in the perspective of drug repurposing. The initial work has revealed the interaction between 332 human cellular RefProts with the 27 viral proteins. Re-interrogation of this data using 23 viral targets and including AltProts, followed by enrichment of the interaction networks, leads to identify 218 RefProts (in common to initial study) plus 56 AltProts involved in 93 interactions. This demonstrates the necessity to take into account the Ghost proteome for discovering new therapeutic targets and establish new therapeutic strategies. Missing the ghost proteome in the drug metabolism and pharmacokinetic (DMPK) drug development pipeline will certainly be a major limitation to the establishment of efficient therapies.

As a holistic medical school, Iranian traditional medicine (ITM) considers the human body as a dynamic and intricate network of interconnecting processes. Currently, systems biology and more precisely systems medicine and pharmacology can be an aid in providing rationalizations for many traditional medications and treatments and elucidating a great deal of knowledge they can offer to guide future research in medicine. Therefore, re-organization and standardization of traditional medicine data are requested more than ever before. To address this issue, we have constructed UNaProd, a Universal Natural Product database for materia medica of ITM. Primarily based on Makhzan al-Advieh, which is the most recent encyclopedia of materia medica in ITM with the largest number of monographs, this database was created using both text mining methods and manual editing. UNaProd is currently hosting to 2696 monographs from herbal to animal to mineral compounds in 16 diverse attributes such as origin and scientific name. In the current version, UNaProd is hyperlinked to IrGO and CMAUP databases for Mizaj and molecular features respectively and it is freely available at http://jafarilab.com/unaprod/.

This study assesses the pursued impacts of Tulsi value chain development intervention on the livelihoods of rural poor in Uttarakhand state of India. Tulsi as an alternative livelihood, particularly for the rural poor, is less explored. With increased crop depredation of major cereal crops grown in the district by wild animals and pests, and decreasing availability of water agriculture, attempts were made to improve earnings from Tulsi as an alternative livelihood. Findings suggest that the average households’ gross profit from Tulsi farming increases by more than double within a span of two years. Total crop income of beneficiary farmers’ increases by 0.8 percent for every 1 percent increase in Tulsi income. Intervention helped enhance productivity of Tulsi, thereby enhancing earnings from Tulsi farming. Most importantly, intervention has shown a tremendous adoption rate. Towards the end of the intervention, the value chain work was out-scaled to another 19 villages in Chamoli district, thereby reaching out to more than 400 households.

It is known that the class of p-normed spaces (0 < p ≤ 1) is an important generalization of usual normed spaces with rich topological and geometrical structure, but the most of tools and general principles in nature with nonlinearity have not been developed yet, thus the main goal of this paper is to develop tools for nonlinear analysis under the framework of p-vector spaces. In particular, we first develop the general fixed point theorems which provide solutions to answer Schauder conjecture since 1930’s in the affirmative for p-vector spaces when p = 1 (which is just general topological vector spaces); then the one best approximation result for upper semi-continuous mappings is given, which is used as a powerful tool to establish fixed points for non-self set-valued mappings with either inward or outward set conditions; and finally we establish comprehensive existence results of solutions for Birkhoff-Kellogg Problems, and the general principle of nonlinear alternative by including Leray-Schauder alternative and related results. The results given in this paper not only include the corresponding results in the existing literature as special cases, but also expected to be useful tools for the study of nonlinear problems arising from theory to practice.

Facebook (FB) is the most popular online networking platform. There are several FB pages dedicated to spreading awareness about the Celiac disease (CD). To get the latest information, a huge number of CD patients follow Celiac disease Facebook (CD-FB) pages. Such pages frequently post beneficial information. However, very less is known if they provide appropriate information to CD patients. We conducted this study to know if CD-FB pages spread misleading information to CD patients. CD-FB pages from three celiac-influenced countries were explored using the FB platform and Google search engine. From October 2021 to April 2022, a total of 147 CD-FB, Italy (n=63), the USA (n=46), and India (n=38), were found eligible. Of them, 13% of pages (followers Mean±SD; Italy 2478±2011; USA 12635±12486; India 667±313) shared misleading information, particularly about gluten-free ingredients, and treatment of CD. In total,16% of CD-FB pages discussed alternative treatments option. Surprisingly, 7% of pages (followers Mean±SD; USA 23800±10465; India 628±333) supported alternative treatments for CD. CD-FB pages are useful for disseminating celiac-related information. While most of such pages provide useful information, a few pages sometimes contain misleading information. CD patients must consult their treating unit before following any uncertain information posted on CD-FB pages.

Locally finiteness of some varieties of nonassociative coalgebras is studied and the Gelfand-Dorfman construction for Novikov coalgebras and the Kantor construction for Jordan super-coalgebras are given. We give examples of a non-locally finite differential coalgebra, Novikov coalgebra, Lie coalgebra, Jordan super-coalgebra, and right-alternative coalgebra. The dual algebra of each of these examples satisfies very strong additional identities. We also constructed examples of an infinite dimensional simple differential coalgebra, Novikov coalgebra, Lie coalgebra, and Jordan super-coalgebra over a field of characteristic zero.

The peptidyl-prolyl isomerases of the cyclophilin type are distributed throughout human cells, including eight found solely in the nucleus. Nuclear cyclophilins are involved in complexes that regulate chromatin modification, transcription, and pre-mRNA splicing. This review collects what is known about the eight human nuclear cyclophilins: PPIH, PPIE, PPIL1, PPIL2, PPIL3, PPIG, CWC27, and PPWD1. Each “spliceophilin” is evaluated in relation to the spliceosomal complex in which it has been studied, and current work studying the biological roles of these cyclophilins in the nucleus are discussed. All eight of the human splicing complexes available in the PDB are analyzed from the viewpoint of the human spliceophilins. Future directions in structural and cellular biology, and the importance of developing spliceophilin-specific inhibitors, are considered.

The urinary tract infection (UTI) is the most common bacterial infection, especially in women. The increased incidence of UTIs, at the last decades have paralleled with the growing emergence of antibiotic resistance. The aim is to evaluate aqueous garlic extract (AGE) susceptibility against multidrug-resistant (MDR) bacteria isolated in urine of women. The investigation of antibacterial propriety and time kill effect of AGE was performed by the well method, microdilution method and spectrophotometer assay. Antibiotics susceptibility assay revealed that the nine MDR bacteria had high resistance against Amoxicillin/ clavulanic acid (100%) and Erythromycin (100%), Cefotaxime (83.33%) and Ceftazidime (83.33%). AGE exhibited potent antibacterial activity against the nine MDR bacteria tested. In Gram-negative bacteria, the inhibition diameters ranged from 20 ± 3 to 32 ± 4 mm, with Minimum Inhibitory Concentrations (MICs) ranging from 10% to 12.5% (w/v) and Minimum Bactericidal Concentration (MBCs) was 12.5 % (w/v). Gram-positive bacteria exhibited diameters ranging from 38 ± 2 to 45 ± 1 mm; MIC and MBC values ranged from 05 to 10 % (w/v) and were found more susceptible than Gram-negative bacteria. To conclude, this investigation shown that AGE have high potential antibacterial to use as an alternative to treat women UTIs.

Phage, which is often used therapeutically, has begun to receive interest as an alternative to antibiotic growth promoters (AGPs) to enhance chicken growth. Another option that has been extensively studied as a growth promoter in chicken is probiotics. However, there are no studies using phages and probiotics as prospective feed additives for broiler chickens. Therefore, this study demonstrated the effects of phage cocktail, probiotics and their combinations on growth performance and gut microbiota of broiler chickens. A total of 288 one-day-old male Cobb 500 broilers were randomly allotted to 1 of 6 treatments in a completely randomised design. The treatments were: (i) C (basal diet (BD) only), (ii) 1ɸ (BD + 0.1% phage cocktail), (iii) 2ɸ (BD + 0.2% phage cocktail), (iv) P (BD + 0.1% probiotic), (v) 1ɸP (BD + 0.1% phage cocktail + 0.1% probiotic), (vi) 2ɸP (BD + 0.2% phage cocktail + 0.1% probiotic). The 1ɸP treatment had significantly (P < 0.05) better BW (35 d), BWG (22 – 35 d, 1 – 35d), and FCR (1-21 d. 22-35 d, 1-35 d) compared to C. Unique gut microbiota diversity was also found between the ɸP (1ɸP and 2ɸP) and non-ɸP groups (C, 1ɸ, 2ɸ and P) in ilea, particularly in the 35 d chickens. Microorganisms associated with short-chain fatty acid (SCFA) producers were significantly (P <0.05) present in the ɸP group than in the non- ɸP group. The carbohydrate and amino acid metabolism predicted genes were significantly upregulated in ɸP groups compared to non- ɸP groups. These genes were involved in the digestion and absorption of nutrients as well as the production of energy. Our findings showed that 1ɸP treatment could be a potential alternative to AGPs for poultry where growth performance was enhanced, and gut microbiota was positively modulated.

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.

The members of the IgLON superfamily of cell adhesion molecules facilitate fundamental cellular communication during brain development, maintain functional brain circuitry, and are associated with several neuropsychiatric disorders. Usage of alternative promoter-specific 1a and 1b mRNA isoforms in Lsamp, Opcml, Ntm and the single promoter of Negr1 in the mouse and human brain has been previously described. To determine the precise spatiotemporal expression dynamics of Lsamp, Opcml, Ntm isoforms and Negr1, in the developing brain, we generated isoform-specific RNA probes and carried out in situ hybridization in the developing (embryonic, E10.5, 13.5, 17; post natal, P0) and adult mouse brains. We show that promoter-specific expression of IgLONs is established early during pallial development (at E10.5), where it remains throughout its differentiation through adulthood. In the diencephalon, midbrain and hindbrain, strong expression patterns are initiated a few days later and begin fading after birth, being only faintly expressed during adulthood. Thus, the expression of specific IgLONs in the developing brain may provide the means for regionally specific functionality as well as for specific regional vulnerabilities. The current study will therefore improve the understanding of how IgLON genes are implicated in the development of neuropsychiatric disorders.

Background and objectives: The inadequate knowledge of complementary and alternative medicine (CAM) among health professionals may put their clients in risky situation because they then would find information about CAM from unreliable sources. Clinical psychologists (CPs), as health professionals, have also the opportunity to provide psychoeducation on the latest CAM scientific research to their clients. The current study aimed to explore knowledge and educational needs of CAM among CPs in Indonesia because previous studies on exploring CAM knowledge and educational needs of CAM were primarily conducted in Western countries. Materials and Methods: Data were collected through semi-structured face-to-face interviews with 43 CPs in public health centers (PHCs) in Indonesia. Most interviews were held at the PHCs where participants worked and interviews lasted for 55 minutes, on average. The interview recordings were transcribed and were analyzed using deductive thematic analysis. Results: Five main themes emerged within participants’ responses regarding CAM knowledge and educational needs. First (CAM understanding), participants’ responses ranged from those with little or no prior knowledge of CAM treatments and uses, to those with much greater familiarity. Second (source of knowledge), participants’ access ranged widely in terms of references, from popular to scientific literature. Third (why is it important?), participants identified CAM essentially as part of Indonesian culture and it was therefore crucial to have this cultural knowledge. Fourth (the challenges and what is needed?), the challenges for improving participants’ knowledge came from personal and institutional levels. Fifth (what and how to learn?), participants advised that only CAM treatments that fit in brief psychotherapy sessions should be introduced in professional training. Conclusions: This qualitative study discovered that CAM was neither well-known nor understood widely. Participants advised that professional associations and health institutions should work together in enhancing knowledge of CAM and incorporating CAM education into psychology education.

Precast concrete sandwich panels (PCSP) are energy efficient building system that is achieved through an insulation layer created between the concrete wythes. The insulation layer is usually of low bearing strength material making it more applicable for non-structural building systems. Hence, shear connectors are introduced to improve its structural capacity, which subsequently degrades it thermal performance by serving as thermal bridges across the panel. This article review researches of alternative materials and methods used to improve the thermal efficiency as well as reduced the strength loss due to insulation in PCSP. The alternative materials are basalt fibre reinforced polymer (BFRP), carbon fibre reinforced polymer (CFRP), glass fibre reinforced polymer (GFRP), and foam concrete which are selected due to their low thermal conductivity for use in shear connection. While thermal path method has been used to prevent the effect of thermal bridges. Although, some of these materials have successfully achieved the desirable behaviours, however, several undesirable properties such as brittleness, bond slip, the sudden crushing of the panel system, and FRP failure below its ultimate strength were observed. Hence, the practicality of the alternative materials is still questionable despite its higher cost compared to the conventional steel and concrete used in the PCSP system.

Alternative fuel vehicles, such as battery electric vehicles and hydrogen fuel cell vehicles, support the imperative to decarbonise the transport sector, but are not yet at a stage in their development where they can successfully compete with conventional fuel vehicles. This paper examines the influence of knowledge and persuasion on the decision to adopt or reject alternative fuel vehicles, underpinned by Rogers’ Diffusion of Innovations theory. A household questionnaire survey was undertaken with respondents in the Sutton Coldfield suburb of the United Kingdom city of Birmingham. This suburb was previously identified as having a strong spatial cluster of potential early adopters of alternative fuel vehicles. The results confirm that among respondents the knowledge of alternative fuel vehicles was limited and perceptions have led to the development of negative attitudes towards them. The reasons largely relate to three problems: purchase price, limited range, and poor infrastructure availability. The majority of respondents have passively rejected alternative fuel vehicles, such that they have never given consideration to adoption. This confirms that a concerted effort is required to inform the general public about alternative fuel vehicles.

Biocultural heritage-based products, including regional specialty foods, are increasingly part of sustainable rural development strategies. While export-oriented biocultural products are often the most visible, we examine the role of campesino gastronomic heritage in the Central Valley of Tarija, Bolivia, as a case study of a local market-centered biocultural resource-based development strategy reflected in an alternative agri-food network. We develop a biocultural sustainability framework to examine this network from ecological, economic and sociocultural perspectives. Data are drawn from interviews (n=77), surveys (n=89) and participant observation, with primary and secondary producers of traditional and new products, as well as restaurant owners, market vendors and local consumers. We find that campesino biocultural heritage and the alternative agri-food network surrounding it represent an influential territorial project that underpins many household economies, particularly for women. We conclude that the relatively small investments by local governments to promote campesino gastronomic heritage are having positive ripple effects on small-scale producer livelihoods and on biocultural sustainability. We suggest that further support to increase market access and reduce other barriers to participation in alternative food networks will likely increase the options and benefits available to small-scale producers mobilising campesino gastronomic heritage within the local economy.

Renewable active sludge is a smart material for wastewater treatment and the protection of surface water bodies. The generated pellets (dried and pelletised dehydrated anaerobically stabilised excess sludge) are produced in a quantity of 31.4 g ± 5.6 g dry matter (DM) per one Population equivalent (PE) calculated to COD (PE_COD) in one day. As pellets are combustible material, their energy utilisation must reach sustainable development goals (SDGs) - a bridge must be created between »treated sewage sludge as the tool to remove pollutants and nutrients from wastewater« and »preparation of the valuable material as a solid recovered fuel (SRF) that meets customer-specific requirements«. Technical Report CEN/TR 15508 and Technical Standard EN ISO 21640 set up methods for specifying and classifying pellets as an SRF. In the last eleven years (2010 – 2021), pellets' net calorific value (NCV) is 13.0 ± 0.7 MJ kg^-1 as received (ar). In 2021, the 80^th percentile of the Hg/NCV ratio was 0.079 mg Hg MJ^-1. In 2010 – 2021, the annual amount of Hg transferred to stakeholders reduced by 64.3 % m/m - from 10.1 kg to 3.67 kg. The halogen contents of the pellets do not threaten corrosion to the incineration facility. Stable pellets' energy potential and perspective ash composition for critical raw materials recovery qualify pellets as a specific waste stream and a renewable material for SRF production.

Background: Although rarely indicated, antibiotics are commonly used for acute diarrhoea in China. We conducted a randomized, double blind exploratory clinical trial of loperamide, berberine and turmeric for treatment of acute diarrhoea. Methods: Adults with acute uncomplicated diarrhoea were randomized to 4 groups: (A) loperamide; (B) loperamide and berberine; (C) loperamide and turmeric; (D) loperamide, berberine and turmeric. All participants were given rescue ciprofloxacin for use after 48 hours if symptoms worsened or were unimproved. Primary endpoints were feasibility and ciprofloxacin use during the 2 week follow-up period. Semi-structured interviews were conducted following recruitment. Results: Only 21.5% (278/1295) of patients screened were deemed eligible, and 49% (136/278) of these consented and entered into the final analysis. Most participants had mild symptoms, because most patients with moderate or severe symptoms wanted to be given antibiotics. Follow-up was good (94% at 2 weeks). Only two participants used rescue antibiotics compared to 65% of acute diarrhoea patients in the hospital during the recruitment period. The median symptom duration was: 14 hours in group B (IQR 10-22), 16 hours in group D (IQR 10-22), 18 hours in group A (IQR 10-33), 20 hours in group C (IQR 16-54). Re-consultation rates were low. There were no serious treatment-related adverse events. Most interviewed participants said the treatment was effective. Conclusion: Although recruitment was challenging because of widespread expectations for antibiotics, patients with mild diarrhoea accepted to try an alternative. This therapy requires further evaluation in a fully powered, randomised controlled trial among a broader sample.

Wall–stabilized arcs dominated by nozzle–ablation are key elements of self–blast circuit breakers. In the present study, high–current arcs were investigated using a model circuit breaker (MCB) in CO2 as gas alternative to SF6 and in addition a long polytetrafluoroethylene nozzle under ambient conditions for stronger ablation. The assets of different methods for optical investigation were demonstrated, e.g. high-speed imaging with channel filters and optical emission spectroscopy. Particularly the phase near current zero (CZ) crossing was studied in two steps. In the first step using high-speed cameras, radial temperature profiles have been determined until 0.4 ms before CZ in the nozzle. Broad temperature profiles with a maximum of 9400 K have been obtained from analysis of fluorine lines. In the second step, the spectroscopic sensitivity was increased using an intensified CCD camera, allowing single-shot measurements until few microseconds before CZ in the MCB. Ionic carbon and atomic oxygen emission were analyzed using absolute intensities and normal maximum. The arc was constricted and the maximum temperature decreased from &gt;18000 K at 0.3 ms to about 11000 K at 0.010 ms before CZ. The arc plasma needs about 0.5-1.0 ms after both the ignition phase and the current zero crossing to be completely dominated by the ablated wall material.

In most countries, the incidence of nasopharyngeal carcinoma (NPC) is no more than 1 per 100,000 for both men and women; however, it is much higher for men and women in Taiwan. The use of traditional Chinese medicine (TCM) as complementary and alternative medicine for the treatment of NPC and its treatment-related side effects has been increasing. The National Health Insurance (NHI) covers 99.6% of Taiwan’s residents. In the present population-based cohort study, we aimed to investigate the pattern of utilization of Chinese herbal products (CHPs) for NPC from 2001 through 2011 in Taiwan. We identified a total of 30294 patients with newly diagnosed NPC from the Registry for Catastrophic Illnesses Patient Database (RCIPD). Descriptive statistics and multiple logistic regression analysis were employed to estimate the adjusted odds ratios (aORs) for CHP utilization. From 2001 through 2011, 17816 patients aged ≥20 years were newly diagnosed with NPC. Of these, 4749 patients used TCM outpatient services for NPC treatment. TCM users were more likely to be women, young, residents of Central Taiwan, and white-collar workers. The most commonly prescribed formula CHP was Gan-Lu-Yin, followed by Xin-Yi-Qing Fei-Tang and Shan-Shen-Mai-Men-Dong-Tang. The most commonly prescribed single CHP was Hedyotis diffusa, followed by Radix Scrophulariae and Radix Ophiopogonis. These findings provide information regarding personalized therapies for NPC and can promote further clinical experiments and pharmacological research on CHPs for NPC treatment in Taiwan. Further well-designed randomized controlled studies and basic mechanistic studies should assess the safety and effectiveness of CHPs for NPC treatment.

In the paper, the authors discover several series identities involving the Catalan numbers, the Catalan function, the Riemanian zeta function, and the alternative Hurwitz zeta function.

Currently, some non-conventional therapies (NCT), such as acupuncture, homeopathy, osteopathy, naturopathy, herbology, and Traditional Chinese Medicine are structured and well-regulated for a market of teaching and clinical practice in Portugal, among which acupuncture has become one of the most appealing and functional branches. Through investigation of acupuncture laws, field surveys, teaching work and interviews with people from NCT field in Portugal, we showed the current acupuncture education in Portugal and found that according to the academic norms and rules of education in Portugal, there is a gradual difficulty in the progression and maintenance of the degree training dynamics, due to the lack of more tolerant transitional measures and also, a timid commitment on the part of the institutions that embark on these complementary programs. Therefore, it will be necessary to promote additional programs and measures that avoid a total emptiness of the teaching of acupuncture and at the same time losses of clinicians, competencies and quality of information that are difficult to recover. It could be very meaningful and thought-provoking to the future development and improvement of acupuncture in Portugal and in other countries that welcome acupuncture and intend to have a better legislation and application.

Different external stimuli are perceived by multiple sensor histidine kinases and transmitted by phosphorylation via the phosphotransfer protein Ypd1p in the multistep phosphorelay system of the high osmolarity glycerol signaling pathway of filamentous fungi. How the signal propagation takes place is still not known in detail, since multiple sensor histidine kinase genes in most filamentous fungi are coded in the genome, whereas only one gene for Ypd1 exists. That raises the hypothesis that various Ypd1 isoforms are produced from a single gene sequence, perhaps by alternative splicing, facilitating a higher variability in signal transduction. We found that the mRNA of MoYPD1 in the rice blast fungus Magnaporthe oryzae is subjected to an increased structural variation and amplified putative isoforms on a cDNA level. We then generated mutant strains overexpressing these isoforms, purified the products and present here one previously unknown MoYpd1 isoform on a proteome level. Alternative splicing was found to be a valid molecular mechanism to increase the signal diversity in eukaryotic multistep phosphorelay systems.

Multiple mRNA isoforms of the same gene are produced via alternative splicing, a biological mechanism that regulates protein diversity while maintaining genome size. Alternatively spliced mRNA isoforms of the same gene may sometimes have very similar sequence, but they can have significantly diverse effects on cellular function and regulation. The products of alternative splicing have important and diverse functional roles, such as response to environmental stress, regulation of gene expression, human heritable and plant diseases. The mRNA isoforms of the same gene, such as the apoptosis associated CASP3 gene, can have dramatically different functions. The shorter mRNA isoform product CASP3-S inhibits apoptosis, while the longer CASP3-L mRNA isoform promotes apoptosis. Despite the functional importance of mRNA isoforms, very little has been done to annotate their functions. The recent years have however seen the development of several computational methods aimed at predicting mRNA isoform level biological functions. These methods use a wide array of proteo-genomic data to develop machine learning-based mRNA isoform function prediction tools. In this review, we discuss the computational methods developed for predicting the biological function at the individual mRNA isoform level.

Biochemical signaling is the key mechanism to coordinate a living organism in all aspects of its life. It is still enigmatic how exactly cells and organisms deal with environmental signals and irritations precisely because of the limited number of signaling proteins and a multitude of transitions inside and outside the cell. Many components of signaling pathways are functionally pleiotropic, which means they have several functions. A single stimulus often activates multiple effectors, a distinct effector can be activated by numerous stimuli and signals triggered by different stimuli are often transduced via shared network components. This very compact and concise review sheds light on the most important molecular mechanisms of cellular signaling in fungi.

High-tech augmentative and alternative communication (AAC) methods are on a constant rise; however, the interaction between the user and the assistive technology is still challenged for an optimal user experience centered around the desired activity. This review presents a range of signal sensing and acquisition methods utilized in conjunction with the existing high-tech AAC platforms for speech disabled individuals, including imaging methods, touch-enabled systems, mechanical and electro-mechanical access, breath-activated methods, and brain computer interfaces (BCI). The listed AAC sensing modalities are compared in terms of ease of access, affordability, complexity, portability, and typical conversational speeds. A revelation of the associated AAC signal processing, encoding, and retrieval highlights the roles of machine learning (ML) and deep learning (DL) in the development of intelligent AAC solutions. The demands and the affordability of most systems were found to hinder the scale of usage of high-tech AAC. Further research is indeed needed for the development of intelligent AAC applications reducing the associated costs and enhancing the portability of the solutions for a real user’s environment. The consolidation of natural language processing with current solutions also needs to be further explored for the amelioration of the conversational speeds. The recommendations for prospective advances in coming high-tech AAC are addressed in terms of developments to support mobile health communicative applications.

Numerous dynamic and complicated processes characterize development from the oocyte to the embryo. However, given the importance of functional transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms, and alternative splicing during embryonic development, the effect that these features have on the blastomeres of 2-, 4-, 8-, 16-cell, and morula stages of development have not been studied. Here, we conducted a scRNA-seq survey of cells from sheep from the oocyte to the blastocyst developmental stages. We then carried out experiments to identify and functionally analyze the transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms (SNPs), and alternative splicing (AS). We founded that between the oocyte and zygote groups significantly down-regulated genes and the second-largest change in gene expression occurred between the 8- and 16-cell stages. We used various methods to construct a profile to characterize cellular and molecular features and systematically analyze the related GO and KEGG profile of cells of all stages from the oocyte to the blastocyst. This large-scale, single-cell atlas provides key cellular information and will likely assist clinical studies in improving preimplantation genetic diagnosis.

The spillover of a virus from an animal reservoir to humans requires both molecular and ecological risk factors to align. While extensive research both before and after the emergence of SARS-CoV-2 in 2019 implicates horseshoe bats as the significant animal reservoir for the new human coronavirus, it remains unclear why it emerged at this time. One massive disruption to animal-human contacts in 2019 is linked to the on-going African swine fever virus (ASFV) pandemic. Pork is the major meat source in the Chinese diet. We hypothesize that the dramatic shortage of pork following large-scale culling and restrictions of pig movement (resulting in marked price increases) led to alternative sources of meat and unusual animal and meat movements nationwide, e.g., involving wildlife, and thus greatly increased opportunities for human-sarbecovirus contacts. Pork prices were particularly high in southern provinces (Guangdong, Guangxi, Fujian, Jiangxi, Hunan, and Hubei), where wildlife is farmed and more frequently consumed. Major wildlife farming provinces are spread from Northern to Southern China, which overlaps with horseshoe bat host ranges, potential hosts of the proximal SARS-CoV-2 ancestor, and wildlife sourcing provinces of Wuhan Huanan market and possibly other markets. Trading of SARS-CoV-2 susceptible wildlife in these markets, such as minks, raccoon dogs, foxes and palm civets in Wuhan markets, could have increased the risk of SARS-CoV-2 from an intermediary host. Moreover, large quantities of animals raised for fur could have entered the human food chain undetected and significantly increased risks of animal-human contact. Performing retrospective testing of stored susceptible animals and their meat sold before December 2019 may be helpful in the next stage of tracing the animal origin of SARS-CoV-2 as spillover events are more likely to have taken place in 2019 when China was experiencing the worst effects of the ASFV pandemic.

Alternative fuels containing biocomponents produced in various technologies are introduced in aviation to reduce its carbon footprint but there is little data describing their impact on the performance and emissions of engines. The purpose of the work is to compare the performance and gas emissions produced from two different jet engines: the GTM-140 microturbine and the full-size DGEN380 turbofan, powered by blends of Jet A-1 and one of two biocomponents: 1) ATJ and 2) HEFA produced from used cooking oil (UCO) in various concentrations. The acquired data will be used to develop an engine emissivity model to predict gas emissions. Blends of the mineral fuel with synthetic components were prepared in various concentrations, and their physicochemical parameters were examined in the laboratory. Measurements of emissions from both engines were carried out in selected operating points using the Semtech DS gaseous analyzer and the EEPS spectrometer. The impact of tested blends on engine operating parameters is limited, and their use does not carry the risk of a significant decrease in aircraft performance or increase in fuel consumption. Increasing the content of biocomponents causes a noticeable rise in the emission of CO and slight increase for some other gasses (HC and NOx), which should not, however, worsen the working conditions of the ground personnel. This implies that there are no contraindications against using tested blends for fuelling gas-turbine engines.

Complementary and alternative treatment approaches are becoming more common among children with chronic conditions. The pravelance of CAM use among US adults was estimated to be around 42% in 2015, and around 44% to 50% among adults with neurologic disorders. Studies report children with chronic illnesses such as cancer, asthma, attention-deficit/hyperactivity disorder (ADHD), genetic disorders, and other neurodevelopmental disorders are treated with complementary and alternative treatments at higher rates. Dietary therapies are gaining increasing popularity in the mainstream population, due to the heavy media involvement. Although, majority of “fad” diets do not have enough supporting evidence, some dietary therapies have been utilized for decades and have numerous published studies. The objective of this review is to describe the dietary interventions used in children with the specific chronic conditions, to evaluate their efficacy based on published data, and to encourage pharmacist involvement in the management and care of such patients.

Molecule radiation can be used as a tool to study colder regions in switching arc plasmas like arc fringes in contact to walls and ranges around current zero (CZ). This is demonstrated in the present study for the first time for the case of ablation-dominated high–current arcs as key elements of self–blast circuit breakers. The arc in a model circuit breaker (MCB) in CO2 with and an arc in a long nozzle under ambient conditions with peak currents between 5 and 10 kA were studied by emission and absorption spectroscopy in the visible spectral range. The nozzle material was polytetrafluoroethylene (PTFE) in both cases. Imaging spectroscopy was carried out either with high-speed cameras or with intensified CCD cameras. A pulsed high-intensity Xe lamp was applied as background radiator for the broad-band absorption spectroscopy. Emission of Swan bands from carbon dimers was observed at the edge of nozzles only or across the whole nozzle radius with highest intensity in the arc center, depending on current and nozzle geometry. Furthermore, absorption of C2 Swan bands and CuF bands were found with the arc plasma serving as background radiator. After CZ, only CuF was detected in absorption experiments.

Inhalation is the main route of exposure to airborne pollutants. To evaluate the safety and assess the risks of occupational hazards different testing approaches are used. 3D airway epithelial tissues allow to mimic exposure conditions in vitro, generates human-relevant toxicology data, allows to elucidate mode of action of pollutants. Gilian 3500 pumps equipped with Standard Midget Impingers were used to collect the airborne particulate from woodworking and metalworking environments. EpiAirway™ tissues were used to model half working day (4 h), full working day (8 h), and 3 working day exposures to occupational pollutants. Tissue viability was assessed using MTT assay. RT-qPCR analyses performed to analyze the expression of gelsolin, caspase-3, and IL-6. Tissue morphology was assessed by hematoxylin/eosin staining. Acute exposure to workspace pollutants slightly affected tissue viability and did not change the morphology. Both types of particles suppressed expression of gelsolin, with metalworking samples showing the most pronounced effect. A slight reduction in caspase-3 expression was observed. Particles from metalworking suppressed IL-6 expression. 3D Epithelial tissues can be used to model exposures to airborne pollutants. Exposure to particles from woodworking and metalworking had a minor effect on tissue viability but affected the expression of inflammation and apoptosis-related genes.

Synthetic fuels play an important role in the defossilization of future aviation transport. To reduce the ecological impact of remote airports due to long range transportation of kerosene, a decentralized on-site-production of synthetic paraffinic kerosene is applicable, preferably as near-drop-in fuel or alternatively as blend. One possible solution for such a production of synthetic kerosene is the Power-to-Liquid process. The basic development of a simplified plant layout addressing the specific challenges of a decentralized kerosene production which differ from most current approaches for infrastructural well-connected regions is described. The decisive influence of the Fischer-Tropsch synthesis on the PtL process is shown by means of a steady-state reactor model which was developed in Python and serves as basis for further development of a modular environment able to represent entire process chains. The reactor model is based on reaction kinetics according current literature. The effects of adjustments of the main operation parameters on the reactor behavior are evaluated and the impacts on up- and downstream processes are described. The results prove the governing influence of the Fischer-Tropsch reactor on the PtL process and show its flexibility regarding the desired product fraction output, which makes it an appropriate solution for a decentralized kerosene production.

Background: Recent developments in our understanding of the interactions between long non-coding RNA (lncRNA) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks. Results: Analysis of alternative splicing events across 39 lncRNA wildtype and knockout RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 4432 skipped exon events and 2474 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockout were specific to the cell type, in agreement with the finding that genes affected by alternative splicing also displayed enriched functions in a cell type specific manner. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions. Conclusions: Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs due to altered titration of the RBPs from their target loci. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner.

Currently, there is increasing industrial demand for rare earth elements (REE) as these elements are now integral to the manufacture of many carbon-neutral technologies. The depleting REE ores and increasing mining costs are prompting to look for alternative sources for these valuable metals, particularly from waste streams. Although REE concentrations in most of the alternate resources are lower than current REE ores, some sources such as marine sediments, coal ash, and industrial wastes like red mud are looking promising with significant concentrations of REE in them. This review focuses on the alternative resources for REE such as ocean bottom sediments, continental shelf sediments, river sediments, stream sediments, lake sediments, phosphorites deposits, industrial waste products like red mud, and phosphogypsum, coal, coal fly ash, and related materials, waste rock sources from old and closed mines, acid mine drainage, and recycling of e-waste. Possible future Moon exploration and mining for REE and other valuable minerals are also discussed. It is evident that REE extractions from both primary and secondary ores alone are not adequate to meet the current demand, and sustainable REE recovery from the alternative resources described here is also necessary to meet the growing REE demand. An attempt is made to identify the potential of these alternative resources and sustainability challenges, benefits, and possible environmental hazards to meet the growing challenges in meeting the future REE requirements.

Pieron's and Chocholle’s seminal psychophysical work predicts that human response time to information relative to visual contrast and/or sound frequency decreases when contrast intensity or sound frequency increases. The goal of this study is to bring to the fore the ability of individuals to use visual contrast intensity and sound frequency in combination for faster perceptual decisions of relative depth (“nearer”) in planar (2D) object configurations on the basis of physical variations in luminance contrast. Computer controlled images with two abstract patterns of varying contrast intensity, one on the left and one on the right, preceded or not by a pure tone of varying frequency, were shown to healthy young humans in controlled experimental sequences. Their task (two-alternative forced-choice) was to decide as quickly as possible which of two patterns, the left or the right one, in a given image appeared to “stand out as if it were nearer” in terms of apparent (subjective) visual depth. The results show that the combinations of varying relative visual contrast with sounds of varying frequency exploited here produced an additive effect on choice response times in terms of facilitation, where a stronger visual contrast combined with a higher sound frequency produced shorter forced-choice response times. This new effect is predicted by cross-modal audio-visual probability summation.

In the event of an abrupt sunlight reduction scenario there is a time window that occurs between when food stores would likely run out for many countries (~6 months or less) and ~1 year when resilient foods are scaled up. A promising temporary resilient food is leaf protein concentrate (LPC). Although it is possible to extract LPC from tree biomass (e.g. leaves and needles), neither the yields nor the toxicity of the protein concentrates for humans from the most common tree species has been widely investigated. To help fill this knowledge gap, this study uses high-resolution mass spectrometry and an open source toolchain for non-targeted screening of toxins on five common North American coniferous species: Western Cedar, Douglas Fir, Ponderosa Pine, Western Hemlock, and Lodgepole Pine. The yields for LPC extraction from the conifers ranged from 1% to 7.5%. The toxicity screenings confirm that these trees may contain toxins that can be consumed in small amounts and additional studies including measuring the quantity of each toxin are needed. The results indicate that LPC is a promising candidate to be used as resilient food, but future work is needed before LPCs from conifers can be used as a wide-scale human food.

Pathogenicity is unknown for the majority of human gene variants. For prioritization of sequenced somatic and germline mutation variants, in silico approaches can be utilized. In this study, 84 million non-synonymous Single Nucleotide Variants (SNVs) in the human coding genome were annotated using consensus Variant Effect Prediction (cVEP) method. An algorithm, implemented as a stacked ensemble of supervised learners, performed combination of the 39 functional, conservation mutation impact scores from dbNSFP4.0. Adding gene indispensability score, accounting for differences in the pathogenicities of the variants in the essential and the mutation-tolerant genes, improved the predictions. For each SNV the consensus combination gives either a continuous-value pathogenicity score, or a categorical score in five classes: pathogenic, likely pathogenic, uncertain significance, likely benign, benign. The provided class database is aimed for direct use in clinical practice. The trained prediction models were 5-fold cross-validated on the evidence-based categorical annotations from the ClinVar database. The rankings of the scores based on their ability to predict pathogenicity were obtained. A two-step strategy using the rankings, scores and class annotations is suggested for filtering and prioritization of the human exome mutations in clinical and biological applications of NGS technology.

As a complementary and alternative medicine in the western countries for decades, traditional Chinese medicine (TCM) has been used for more than 2000 years in China. Because of the characteristics of the philosophical style and the unknown mechanism of action, TCM sometimes has been biasedly described as "fraught with pseudoscience". From the scientific basis of the systems biology, here we promoted a novel medical model called the entropic systems medicine which could be applied to scientize TCM in future. In entropic systems medicine, TCM and Western modern biomedicine target the different variables of the entropic system. For instance, while Western modern biomedicine directly targets the phenotypes and its SOCs of macrostates, TCM differently targets the microstates, entropy and entropic force to generate SOTFs gradually causing the differentiated syndromes to be slowly rearranged. The prerequisites to modernize TCM are the entropic systems biology having been well established so that the variables could be precisely monitored and mathematically calculated.