Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track response to therapy, and parse causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD).

Gene regulation is vital for cellular function and homeostasis, involving diverse mechanisms controlling specific gene products and contributing to tissue-specific gene expression. Dysregulation leads to diseases, emphasizing the need for understanding these mechanisms. Non-coding regions, notably enhancers and super-enhancers (SEs), act as crucial gene regulators, orchestrating transcriptional activity via transcription factors (TFs). SEs, with high activity, are pivotal in cell identity and disease progression. Current computational approaches focus on individual regulators like TFs and miRNAs, neglecting SE interactions. We emphasize incorporating SEs into models to enhance understanding. Experimental studies have recently linked miRNAs and TFs to SEs. Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) provides valuable SE information. In this review, we categorize computational methods leveraging TF and miRNA data into three areas and explore challenges integrating enhancers/SEs. These include unraveling indirect regulatory networks, identifying network motifs, and enriching pathway identification by dissecting gene regulators, including SEs. We hypothesize that addressing these challenges will enhance our understanding of gene regulation, aiding in identifying therapeutic targets and disease biomarkers. We believe that understanding the role of ChIP-Seq data in predicting the effect of miRNA on gene regulation is crucial to construct statistical/computational model that would tackle these challenges.

The p53 tumor suppressor protein shows antiviral activity. The replication of viruses is also antagonized by interferons (IFNs) – cytokines, which control immunity genes by the STAT transcription factors. The best studied interferons belong to type I (e.g. IFNα) and type II (IFNγ) groups. IFNα and IFNγ both induce activating phosphorylation of STAT1 on Tyr701. Previously, we noticed that p53 activates SOCS1, which is a negative regulator of STAT1 phosphorylation. Thus, we hypothesized that p53 by activating SOCS1 expression reduces phosphorylation of STAT1 and attenuates activation of genes stimulated either by IFNα or IFNγ. To test this hypothesis, we exposed p53-proficient and p53-deficient cells to strong p53 activators, and either to IFNα or IFNγ. Subsequently, we estimated the phosphorylation status of STAT1 and the expression of genes regulated by either of these cytokines. Strong activation of p53 reduced the phosphorylation of STAT1 on Tyr701, however surprisingly it did not lead to reduced expression of most tested interferon-stimulated genes. On contrary, p53 and IFNγ synergized in the activation of CASP1, IFIT1 and IFIT3 genes. We conclude that the interactions between p53 and interferon-activated pathways are more complicated than initially expected, but the apparent cooperation between p53 and IFNγ deserves further studies.

From their discovery in 2002, BRAF mutations have been identified as clear drivers of oncogenesis in several cancer types. Currently, their incidence rate is nearly 7% of all solid tumors with BRAF V600E constituting approximately 90% of these diagnoses [1]. In melanoma, thyroid cancer, and histiocytic neoplasms, BRAF hotspot mutations are found at a rate of about 50%, while in lung and colorectal cancers they range from 3 to 10% of reported cases [2-5]. Though present in other malignancies such as breast and ovarian cancers, they constitute a small portion of diagnoses (<1%). Given their frequency along with advancements in screening technologies, various methods are used for the detection of BRAF-mutant cancers. Among these are targeted next-generation sequencing (NGS) on tumor tissue or circulating tumor DNA (ctDNA) and immunohistochemistry (IHC)-based assays. With advancements in detection technologies, several approaches have been taken for the treatment of BRAF mutant cancers. In this review we retrace the milestones that led to the clinical development of targeted therapies currently available for these tumors.

Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

Xinjiang, as a climate-sensitive region in northwest China, holds significant importance in studying extreme weather events for agricultural production and socioeconomic development. Based on data from 52 meteorological stations and 23 extreme climate indicators in Xinjiang from 1960 to 2021, the 5a moving average, linear trend estimation, climate tendency rate, and GIS spatial analysis methods are used to analyze the distribution and change characteristics of extreme climate. The results revealed that from 1960 to 2021, TXx, TNx, TXn, TNn, FD, ID, TN10p, TX10p, and WSDI showed a significant upward trend, while SU, TR, TN90p, TX90p, and CSDI showed a significant downward trend. What is more, the range of changes in the extreme temperature indexes from 1990 to 2021 is higher than that of 1960 to 1989. The high-value areas of extreme indexes are primarily concentrated in the northern part, while the high-value areas of cold event indexes are mainly distributed in the southern part. The upward/downward trends all accounting for over 80.00% of the entire region. The Rx1day, Rx5day, PRCPTOT, R95p, R99p, R10, R20, and R25 showed a significant growth trend from 1960 to 2021, and the range of change in the extreme precipitation indexes from 1990 to 2021 was lower than that from 1960 to 1989. Moreover, their high-value areas and high climate tendency areas are mainly concentrated in the northern and western parts of Xinjiang, with upward trends all accounting for over 71.00% of the entire region. The research results provide theoretical foundations for formulating climate risk strategies in the northwest region of China.

Productivity has been modest in construction due to many reasons, especially project-specific operations and fragmentation. The main aim of this research is to map the challenges towards industrialization in construction through a comparative study of the manufacturing industry. An inductive approach and a qualitative method are followed by applying semi-structured inter-views, and node-based thematic analysis. The key elements of industrialization in mature man-ufacturing companies are benchmarked. The findings indicate a specific order of steps for indus-trialization in construction. Data and information management with achieved systematization have been sources of productivity in manufacturing companies. However, the systematization starts from the offering, construction companies need to define their offering, that is the products, and define their respective data. Only accurate and good quality data on products enables the systematization of order delivery processes, which are the engine for a company’s success or failure. Continuous efficiency improvement is only possible with systematized processes and respective data related to the processes. The originality involves clarifying the industrialization of construction companies via products, respective data, and processes considering industrialized manufacturing companies.

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

We study a two-echelon supply chain made up of a supplier and a manufacturer, both of which can reduce their component/product carbon emissions. With the vertical technology spillovers, we explore the optimal decisions of centralized and decentralized supply chains with price dependent demand and propose coordination strategy for the decentralized supply chain. Considering the cost contraction effectiveness of the technology spillovers, the centralized and decentralized game theoretic models of a two-echelon supply chain are developed to investigate optimal decisions of pricing and carbon emissions reduction. Through a systematic comparison and numerical analysis, we show that the profits of both players and the entire supply chain improve with the effect of technology spillovers increasing. Carbon emissions reduction will be taken by various protective measures so that the supplier and the manufacturer who do not innovate can hardly share the results of innovating via the “free-riding” methods when the technology spillover is relatively small. We also propose a revenue-cost sharing contract through bargaining to enhance the performance of the decentralized supply chain.

By introducing environmental mediator, for avoiding randomness in selecting indicators and subjectivity in deciding interaction path coefficients to reveal interaction mechanism among forest industry, ecology and environmental capacity, structural Pressure–State–Impact–Response (PSIR) and quantitative Structural Equation Modeling (SEM) are utilized with data on thirty–one provinces of China. We can find that: (i) forest industry has a negative influence on ecology, whereas ecology has a positive influence on industry; (ii) the destructive influence that industry has on ecology is much greater than the positive effect ecology has on industry; and (iii) environmental capacity plays a partial mediating role between industry and ecology. According to these results we can conclude that: (i) forest industry and ecology are not in a symbiotic relationship and have not reached a level of ecological security; (ii) the interaction between industry and ecology is in a period of transition from antagonistic to beneficial; and (iii) industry dominates ecology. However, we prospect the following advice: (i) methods of forest industry should be changed; (ii) new modes of industrial integration and circular economy should be developed; and (iii) the ability of the environment to sustain itself should be enhanced. The level of forest ecological security to discuss the symbiotic mechanism of industry and ecology will propose to be measured in future.

Despite being stored at 113 K and atmospheric pressure, LNG cold potential is not exploited to reduce green ships’ energy needs. An innovative system based on three Organic Ranking Cycles integrated into the regasification equipment is proposed to produce additional power and recover cooling energy from condensers. A first-law analysis identified ethylene and ethane as suitable working fluids for the first and the second ORC making available freshwater and ice. Propane, ammonia and propylene could be arbitrarily employed in the third ORC for air-conditioning. An environmental analysis that combines exergy efficiency, ecological indices and hazard aspects for marine environment and ship’s passengers, indicated propylene as safer and more environmentally friendly. The exergy analysis confirms more than 20% of the LNG potential can be recovered from every cycle to produce a net clean power of 76 kW, whereas 270 kW can be saved by recovering condensers' cooling power to satisfy some ship needs. Assuming the sailing mode, a limitation of 162 kg in LNG consumptions was determined, avoiding the emission of 1584 kg of CO2 per day. Marine thermal pollution is reduced by 3.5 times by recovering the working fluids' condensation heat for the LNG pre-heating.

Driving factors of smart city construction are exploratively studied by grounded theory method based on text sources from journal papers in SCI and CSSCI databases. Initial scale of driving factors about smart city construction is obtained on the basis of above analyses. This paper modifies measuring items of the initial scale with a small sample pretest and reliability test, then forms final items by exploratory factor analysis. According to the above scale, questionnaires are designed to obtain empirical data, and confirmatory factor analysis is used to verify further validity and reliability of the scale. The results show that driving factors of smart city construction include three main dimensions: problem-oriented factors, business- or technology-driven factors and endogenous development requirements.

Background. The Stanford Health Assessment Questionnaire-Disability Index (HAQ) is widely used to measure functional ability in persons with Rheumatoid Arthritis (RA). The instrument was developed with limited involvement from persons with RA, and their perception of the instrument has not been studied in depth. The aim of this study was to explore how persons with RA experience the use of the HAQ in care. Methods. Forty persons with RA were purposefully recruited to participate in semi-structured interviews. The interviews were then analyzed qualitatively using thematic analysis. Results. The participants questioned the relevance of the HAQ but nevertheless experienced that the instrument had a profound effect on their understanding of health and how care is delivered. The analysis resulted in three themes: Problems with individual items, meaning of the summative score, and effects on care and health perceptions. Conclusions. To make the HAQ relevant to persons with RA, it needs to be revised or to include an option to select items most meaningful to the respondent. To ensure relevance, the HAQ update should preferably be co-created by researchers, clinicians and persons with RA.

Recycling waste products is an environmental-friendly activity that can bring benefits to accompany, saving manufacturing costs and improving economic efficiency. For the beer industry, recycling bottles can reduce manufacturing costs and reduce the industry's carbon footprint. This paper presents a model for a multi-objective collection-distribution center location and allocation problem in a closed loop supply chain for the beer industry, in which the objective is to minimize total costs and transportation pollution. Uncertainties in the form of randomness and fuzziness are jointly handled in this paper to ensure a more practical problem solution, for which returned bottle sand unusable bottles are considered fuzzy random variables. A heuristic algorithm based on priority-based global-local-neighbor particle swarm optimization (pb-glnPSO) is applied to ensure reliable solutions for this NP-hard problem. A case study on a beer operation company is conducted to illustrate the application of the proposed model and demonstrate the priority-based global-local-neighbor particle swarm optimization.

The wellness economy has developed rapidly recently, particularly in wellness tourism. Wellness tourism transforms sustainable strategy through the availability of extended multi-actor engagement in service innovation to further the tourism experience. Therefore, when operating a wellness tourism destination, it is necessary to encourage multi-actor engagement in service innovation to achieve sustainable development. This paper introduces a mixed research method with the SWOT-AHP-QSPM, as it qualitatively analyzes the advantages, disadvantages, opportunities, and threats, constructs an evaluation index system, conducts quantitative analysis using the analytic hierarchy process, determines the index weight and weighted score, and calculate the sustainable development strategy, which is appropriate for wellness development of Chongqing Tea Mountain and Bamboo Forest National Forest Park. Purposive field surveys and personal interviews were conducted in Chongqing forest tourism destinations, involving 356 effective respondents. The research reveals that multi-actor engagement significantly enhances sustainable development. These findings bridge service innovation knowledge gaps and provide valuable insights for forest tourism destination management and sustainable policy strategies to elevate multi-actor engagement in forest sites.

Prostate cancer (PC) is a common malignancy of elderly men, characterized by great heterogeneity in its clinical course, ranging from an indolent to a highly aggressive disease. The aggressive variant prostate cancer (AVPC) clinically shows an atypical pattern of disease progression, similar to that of small cell PC (SCPC), and also shares the chemo-responsiveness of SCPC. The term AVPC does not describe a specific histologic subtype of PC but rather the group of tumors that, irrespective of morphology, show an aggressive clinical course, dictated by androgen receptor (AR) indifference. AR indifference represents an adaptive response to androgen deprivation therapy (ADT), driven by epithelial plasticity, an inherent ability of tumor cells to adapt to their environment by changing their phenotypic characteristics in a bi-directional way. The molecular profile of AVPC entails combined alterations in tumor suppressor genes retinoblastoma protein 1 (RB1), tumor protein 53 (TP53) and phosphatase and tensin homolog (PTEN). The understanding of the biologic heterogeneity of castration-resistant PC (CRPC) and the need to identify the subset of patients that would potentially benefit from specific therapies necessitate the development of prognostic and predictive biomarkers. This review aims to discuss the possible pathophysiologic mechanisms of AVPC development and the potential use of emerging tissue-based biomarkers in clinical practice.

Venoms are a rich source of bioactive compounds, and among them is leberagin-C (Leb-C), a disintegrin-like protein derived from the venom Macrovipera lebetina transmediterrannea snakes. Leb-C has shown promising inhibitory effects on platelet aggregation. Previous studies have demonstrated that this SECD protein specifically targets α5β1, αvβ3 and αvβ6 integrins through a mimic mechanism of RGD disintegrins. In our current study, we focused on exploring the potential effects of Leb-C on metastatic breast cancer. Our findings revealed that Leb-C disrupted the adhesion, migration, and invasion capabilities of MDA-MB-231 breast cancer cells and its highly metastatic D3H2LN sub-population. Additionally, we observed significant suppression of adhesion, migration, and invasion of Human Umbilical Vein Endothelial Cells (HUVECs). Furthermore, Leb-C demonstrated a strong inhibitory effect on fibroblast growth factor 2-induced proliferation of HUVEC. We conducted in vivo experiments using nude mice and found that treatment with 2 µM of Leb-C resulted in a remarkable 73% reduction in D3H2LN xenograft tumor size. Additionally, quantification of intratumor microvessels revealed a 50 % reduction in tumor angiogenesis in xenograft after 21 days of twice-weekly treatment with 2 µM of Leb-C. Collectively, these findings suggest the potential utility of this dinsintegrin-like protein for inhibiting aggressive and resistant metastatic breast cancer.

Natural gas hydrate, also known as combustible ice and mainly composed of methane, it is identified as the potential clean energy in the 21th century. Due to its large reserves, gas hydrate can ease problems caused by energy resource shortage and has gained attention around the world. In this paper, we focus on the exploration and development of gas hydrate as well as discussing its status and future development trend in China and abroad, then we analyze its opportunities and challenges in China from four aspects: resource, technology, economy and police with five forces model and PEST method. The results show, China has abundance gas hydrate resource; however the backward technologies and inadequate investment has seriously hindered the future development of gas hydrate, so China should establish relevant cooperation framework and intuitional arrangement to attract more investment as well as breaking through technical difficulties to make gas hydrate commercialization as soon as possible.

Pancreatic neuroendocrine neoplasms (pNENs) are rare tumors accounting for only 1-2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2 and neuroendocrine carcinoma: NEC) on the basis of Ki-67 proliferation index and mitotic count according to the 2010 WHO classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as MEN1, DAXX and ATRX, whereas NECs have an inactivation of TP53 and RB1, and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic backround together with preclinical studies to develop new agents, including those already under investigation for SCLC, will be needed to improve the prognosis.

The increasing availability of longitudinal data (repeated numerical observations of same units at different times) requires the development of flexible techniques to automatically detect common errors in such data. Besides obvious and easily identifiable cases, such as missing or out-of-range data, large longitudinal dataset often present problems not easily traceable by the techniques used for generic datasets. In particular, elusive and baffling problems are i) inversion of one or more values from one unit to another; ii) anomalous jumps in the series of values, iii) errors in the timing of the values due to a recalculation operated by the data providers to compensate previous errors. This work proposes a statistical-mathematical approach based on a system of indicators that is able to capture the complexity of the described problems by working at the formal level, regardless of the specific meaning of the data. The proposed approach identifies suspect erroneous data and is applicable in a variety of contexts. We implement this approach in a relevant database of European Higher Education institutions (ETER) by analyzing Total academic staff, that is one of the most important variables, used in empirical analysis as proxy of size and also considered by policy makers at European level.

The European Union Water Framework Directive (2000/60/EC; WFD) aims to achieve a good ecological and chemical status of all bodies of surface water by 2027. The development of an integrated guidance on surface water chemical monitoring (e.g. WFD Guidance Document No. 7/19) has been transferred into national German law (Ordinance for the Protection of Surface Waters, OGewV). For the majority of compounds, this act requires a monthly sampling frequency to assess the chemical water quality status of a surface water body. To evaluate the representativeness of the sampling strategy under the OGewV, high-frequency online monitoring data is investigated under different sampling scenarios and compared with current, monthly grab sampling strategy. About 23 million data points were analyzed for this study, three chemical parameters (dissolved oxygen, nitrate-nitrogen, chloride concentration) and discharge data were selected from four catchment of different sizes ranging from 51391 km² to 84 km² (Elbe, Vereinigte Mulde, Neiße and two stations at Lockwitzbach). In this paper we proposed short-term online-monitoring (STOM) as a sampling alternative. STOM considers the placement of online sensors over a limited duration and return interval. In general we: (I) compare the results of conventional grab sampling with STOM, (II) investigate the different performance of STOM and grab sampling using discharge data as proxy for analyzing event-mobilized pollutants and (III) investigate the related uncertainties and costs of both sampling methods. Results show, that STOM outperforms grab sampling for parameters where minimum/maximum concentrations are required by law as the probability to catch a single extreme value is higher with STOM. Furthermore, parameters showing a pronounced diurnal pattern, like dissolved oxygen, are also captured considerably better. The performance of STOM showed no substantial improvements for parameters with small concentration variability, as nitrogen-nitrate The analysis of discharge events as a proxy parameter for event-mobilized pollutants proved that the probability of capturing samples during events is significantly increased by STOM.

Urbanization is considered as a main indicator of regional economic development due to its positive effect on promoting industrial development; however, many regions, especially developing countries, are troubled by its negative effect — the aggravating environmental pollution. Many researchers have indicated that rapid urbanization stimulated the expansion of industrial production scale and increased industrial pollutant emissions. However, this judgement contains a grave deficiency in that urbanization not only expands industrial production scales but can also increase industrial labour productivity and change the industrial structure. To modify this deficiency, we first decompose the influence which urbanization impacts on industrial pollutant emissions into the scale effect, the intensive effect and the structure effect by using the Kaya Identity and the LMDI Method; second, we perform an empirical study of the three effects’ impacts by applying the spatial panel model with data from 282 Chinese cities between 2003 and 2013. Our results indicate that (1) there are significant reverse U-shapes between Chinese urbanization rate and its industrial pollutant emissions; (2) the scale effect and the structure effect have aggravated Chinese industrial waste water discharge, sulphur dioxide emissions and soot (dust) emissions, while the intensive effect has generated a decreasing and ameliorative impact on that aggravated trend. The definite relationship between urbanization and industrial pollutant emissions depends on the combined influence of the scale effect, the intensive effect and the structure effect; (3) there are significant spatial autocorrelations of industrial pollutant emissions between Chinese cities, but the spatial spillover effect from other cities does not aggravate local urban industrial pollutant emissions, we offer an explanation to this contradiction that the vast rural areas surrounding Chinese cities have served as sponge belts and have absorbed the spatial spillover of cities’ industrial pollutant emissions. According to the results, we argue that this type of decomposition of the influence into three effects is necessary and meaningful, it establishes a solid foundation for understanding the relationship between urbanization and industrial pollutant emissions, and effectively helps to meet relative policy making.

Under the development mode of deep blending of emerging technologies, major projects are important for enhancing China's comprehensive national strength and independent innovation capability. Based on the social benefits of major projects, and considering the influence of reputation factors, an evolutionary game model composed of a general contractor and subcontractor of major projects is established. This paper studies the influence of various factors including the income distribution coefficient of collaborative innovation, and MATLAB simulation software is analyzed the influence of factors on an evolutionary path. The results show that a reasonable income distribution coefficient can promote the game behavior of both parties to the direction of active collaborative innovation; The reduction of innovation cost and the improvement of spillover technology absorption capacity can make innovation subjects tend to choose active collaborative innovation strategies. In addition, reputation loss above a specific threshold can effectively inhibit free-riding behavior and encourage innovation subjects to choose active collaborative innovation strategies. The research results provide reference for promoting major projects' technology innovation.

The p53 tumor suppressor protein is an activator of transcription. Diverse stress factors lead to various sets of posttranslational modifications of p53 what results in different sets of upregulat-ed genes. We noticed that actinomycin D and nutlin-3a (A+N) synergize in inducing activating phosphorylations of p53 and upregulation of selected p53-target genes. Here we found that one of these genes is DUSP13, which codes for poorly-studied, dual-specificity phosphatase having at least two isoforms, one expressed in testis and the other in skeletal muscles. In cancer cells ex-posed to A+N, DUSP13 is expressed from an alternative promoter in intron, what results in ex-pression of isoform named TMDP-L1. The luciferase reporter tests demonstrated that this pro-moter is activated by both endogenous and ectopically expressed p53. We showed for the first time that mRNA expressed from this promoter actually produces the protein, which can be de-tected by Western blotting in all examined cancer cell lines with wild-type p53 exposed to A+N. In some cell lines it is also induced by clinically relevant camptothecin or by nutlin-3a acting alone. This isoform, fused with green fluorescent protein localizes in perinuclear region of cells. Thus, TMDP-L1 isoform may be an important element of p53-regulated stress response system.

Accurate forecasting of icing thickness has a great significance for ensuring the security and stability of power grid. In order to improve the forecasting accuracy, this paper proposes an icing forecasting system based on fireworks algorithm and weighted least square support vector machine (W-LSSVM). The method of fireworks algorithm is employed to select the proper input features with the purpose of eliminating the redundant influence. In addition, the aim of W-LSSVM model is to train and test the historical data-set with the selected features. The capability of this proposed icing forecasting model and framework is tested through the simulation experiments using real-world icing data from monitoring center of key laboratory of anti-ice disaster, Hunan, South China. The results show that the proposed W-LSSVM-FA method has a higher prediction accuracy and it may be a promising alternative for icing thickness forecasting.

1) Background: When women receive a diagnosis of a gynecologic malignancy, they can have questions about their diagnosis or treatment that can result in voice queries to virtual assistants. Recent advancement in artificial intelligence (AI) has transformed the landscape of medical information accessibility. The Google virtual assistant (VA) outperformed Siri, Alexa, and Cortana in voice queries presented prior to the explosive implementation of AI in early 2023. The efforts presented here focus on determining if advances in AI in the last 12 months improved the accuracy of Google VA responses related to gynecologic oncology. (2) Methods: Previous questions were utilized to form a common basis for queries prior to 2023 and responses in 2024. Correct answers were obtained from the UpToDate medical resource. Responses related to gynecologic oncology were obtained using Google VA, as well as the generative AI chatbots Google Bard/Gemini and Microsoft Bing-Copilot. (3) Results: The AI narrative responses varied in length and positioning of answers within the response. Google Bard/Gemini achieved an 87.5% accuracy rate, while Microsoft Bing-Copilot reached 83.3%. In contrast, the Google VA’s accuracy in audible responses improved from 18% prior to 2023 to 63% in 2024. (4) Conclusion: While the accuracy of the Google VA has improved in the last year, it underperformed Google Bard/Gemini and Microsoft Bing-Copilot so that there is considerable room for further improved accuracy.

The geographical environment, food culture, and dietary habits are substantially different between the southern and northern regions in China. We investigated the associations with dietary patterns and metabolic syndrome between Chinese adult from the southern and northern regions (North: 1249; South: 1849) using data from the Chinese Health and Nutrition 2009 survey. Respectively, four dietary patterns were identified by factor analysis in the two regions. Each dietary pattern of factor score was calculated for three groups by tertile (T1<T2<T3). In the northern region, the association between the Alcohol and Western pattern and the risk of abdominal obesity (OR: 1.31; 95%:1.01, 1.68), hypertriglyceridemia (OR: 1.35; 95%:1.05, 1.74), high fasting blood glucose (OR: 1.37; 95%: 1.05, 1.80), and hypertension (OR: 1.55; 95%: 1.45, 1.99) was increased. In the southern region, the Convenience Food pattern was positively associated with hypertriglyceridemia (OR: 1.53; 95%: 1.03, 2.26), low HDL-cholesterol (OR: 1.96; 95%: 1.12, 3.43), and metabolic syndrome (OR: 1.79; 95%: 1.03, 3.11). The Alcohol dietary pattern was positively associated with high fasting blood glucose (OR: 1.83, 95%: 1.13, 2.97). There are some dietary pattern differences in the two regions. It is necessary to consider the factors of food culture and food intake habits in order to provide nutrition education to Chinese individuals from different regions in the future.

Accurately distinguishing between indolent and aggressive tumors is a crucial unmet need in the clinical management of prostate cancer (PCa). The traditional Gleason grading system has been utilized for this purpose; however, there is often ambiguity in classifying tumors with a Gleason grade of 7. Clinicians commonly resort to using secondary Gleason grades, such as 3+4 or 4+3, to classify these tumors as indolent or aggressive, respectively. Unfortunately, such classifications are prone to misinterpretation, leading to erroneous diagnoses and prognoses. To address this challenge, we investigated the application of Machine Learning (ML) techniques to classify PCa patients based on gene expression data sourced from The Cancer Genome Atlas. By comparing gene expression levels between indolent and aggressive tumors, we sought to identify distinctive features for developing and validating a range of ML algorithms and stacking techniques. The stacking based model achieved an impressive accuracy of 96% for all samples encompassing primary Gleason grades 6 to 10. Notably, when excluding Gleason grade 7 from the analysis, the accuracy further improved to 97%. This study underscores the effectiveness of the stacked ML algorithm for accurately classifying indolent versus aggressive PCa. Leveraging gene expression data and employing a combination of classifiers, this approach offers a powerful solution to address the unmet need in robustly distinguishing between different types of PCa tumors. Future implementation of this methodology may significantly impact clinical decision-making and patient outcomes in the management of prostate cancer.

Local food has continued to become more popular in both the home and as featured ingredients in all segments of food service. Numerous studies have explored the motivating factors for consumer purchasing motivators. However, no known study has explored if there is a correlation between ego and intent to buy local foods. This study adopted a modified version of the Theory of Trying and surveyed a sample of 237 food service buying agents in South Carolina to examine their perceptions of buying local. Results suggest that ego is a predictor of trying to purchase local foods for restaurants. It was also found that the modified model is an acceptable model for predicting buyer intent. These findings support the majority of the studies looking at ego-centric behaviors with green purchases and could potentially help local food suppliers to better market their products to foodservice establishments. This study could also act as the foundation for future studies to explore the full extent of ego’s motivational effect on purchasing intentions in the food service industry.

Expression of miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA. In addition, expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3′-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.

Assessment of extreme events and climate change on reservoir inflow is important for water and power stressed countries. Projected climate is subject to uncertainties related to climate change scenarios and Global Circulation Models (GCMs’). Extreme climatic events will increase with the rise in temperature as mentioned in the AR5 of the IPCC. This paper discusses the consequences of climate change that include extreme events on discharge. Historical climatic and gauging data were collected from different stations within a watershed. The observed flow data was used for calibration and validation of SWAT model. Downscaling was performed on future GCMs’ temperature and precipitation data, and plausible extreme events were generated. Corrected climatic data was applied to project the influence of climate change. Results showed a large uncertainty in discharge using different GCMs’ and different emissions scenarios. The annual tendency of the GCMs’ is bi-vocal: six GCMs’ projected a rise in annual flow, while one GCM projected a decrease in flow. The change in average seasonal flow is more as compared to annual variations. Changes in winter and spring discharge are mostly positive, even with the decrease in precipitation. The changes in flows are generally negative for summer and autumn due to early snowmelt from an increase in temperature. The change in average seasonal flows under RCPs’ 4.5 and 8.5 are projected to vary from -29.1 to 130.7% and -49.4 to 171%, respectively. In the medium range (RCP 4.5) impact scenario, the uncertainty range of average runoff is relatively low. While in the high range (RCP 8.5) impact scenario, this range is significantly larger. RCP 8.5 covered a wide range of uncertainties, while RCP 4.5 covered a short range of possibilities. These outcomes suggest that it is important to consider the influence of climate change on water resources to frame appropriate guidelines for planning and management.

The effects of climate change health impacts on urban health care systems and vulnerable populations are a researched topic with foundations on urban risk management, urban health methodologies, and sustainable urbanization. As climate change is a dynamic and transformative global issue the gap between adaptation and mitigation efforts and urban planning relies, among other things, in the limitations of previous studies of risk management structures tailored to the existing strategy to calculate the uncertainties and predict their influence on urban systems and subsystems. Moreover, as climate and health is a well-researched issue, it is also complex as the methodologies and strategic approach to minimize health risks of climate change is intrinsically contingent to risk methodologies and policy-making processes that are efficient with support of knowledge-based information. This paper emphasis the need for focusing on urban health risk management methods that serves to identify potential opportunities, and then manage and take action to prevent adverse health effects. It also emphasizes the probability of events and their consequences, which are measurable both qualitatively and quantitatively.

Motivated by empirical observations, we propose a possible extension of Gibrat's law. By applying it into the random growth theory of income distribution (Gabaix, 2009), we find that the income distribution is described by a generalized Pareto-type distribution (GPD) with three parameters. We observe that there is a parameter /elta in the GPD that plays a key role in determining the shape of income distribution. By using the Kolmogorov-Smirnov test, we empirically show that, for typical market-economy countries, /elta is close to 0 significantly, such that the income distribution is characterized by a two-class pattern in which the bottom 90% of the population is approximated by an exponential distribution and the richest 1%~3% is approximated by an asymptotic power law. However, we empirically find that, for China both in planned economy period and in early stages of market reformation (from 1978 to 1990), /elta is significantly deviated from 0, such that the bottom of the population no longer conforms to an exponential distribution.

Electricity price forecasting has become a crucial element for both private and public decision-making. This importance has been growing since the wave of deregulation and liberalization of energy sector worldwide late 1990s. Given these facts, this paper tries to come up with a precise and flexible forecasting model for the wholesale electricity price for the Italian power market on an hourly basis. We utilize artificial intelligence models such as neural networks and bagged regression trees that are rarely used to forecast electricity prices. After model calibration, our final model is bagged regression trees with exogenous variables. The selected model outperformed neural network and bagged regression with single price used in this paper, it also outperformed other statistical and non-statistical models used in other studies. We also confirm some theoretical specifications of the model. As a policy implication, this model might be used by energy traders, transmission system operators and energy regulators for an enhanced decision-making process.

Splines and quasi-interpolation operators are important both in approximation theory and applications. In this paper, we construct a family of quasi-interpolation operators for the bivariate quintic spline spaces S₅³ (∆_mn⁽²⁾). Moreover, the properties of the proposed quasi-interpolation operators are studied, as well as its applications for solving two-dimensional Burgers’ equation and image reconstruction. Some numerical examples show that these methods, which are easy to implement, provide accurate results.

The strong competition in the automotive industry has required manufacturers to implement lean production, both with methods and techniques specific to Industry 4.0. At the same time, universities must provide graduates with specific skills for applying these new production methods and techniques. In this context, a Lean Learning Factory was developed in the Pitesti University Center, which allows students to learn, experiment, and research, in an environment similar to that of enterprises, the new Lean Manufacturing methods and techniques, and Industry 4.0. The research presented in this study had as its objective identifying the minimum number of repetitions necessary to train operators who serve two differently organized workstations, one classic, the other including digital techniques, but on which the same assembly operation is performed. Several indicators were considered in the analysis, such as the number of errors, the number of stops, the effective duration of the work cycle, and the percentage ratio between the standard duration of cyclical activities and the effective duration of the work cycle. The evolution of these indicators was mathematically modelled by regression functions, using the least squares method. The obtained results also highlight the usefulness of applying the DOJO method as a Lean manufacturing-specific learning technique and the efficiency of implementing digital techniques in work organization.

In the drive towards environmental restoration and sustainable energy solutions, effective utilization and management of agricultural crop residues are vital to mitigate greenhouse gas (GHG) emissions and waste accumulation. Converting biogenic wastes into biofuels and bioproducts has the potential to tackle the energy crisis and contribute to environmental remediation. In this investigation, teff husk, primarily generated in Ethiopia during teff production within the agro-industrial sector, is used as the feedstock for the slow pyrolysis process. In Ethiopia, it is estimated that over 1.75 million tons of teff husk are generated annually, with a significant portion being incinerated in the fields, resulting in substantial environmental pollution. This study focuses on assessing teff husk as a potential material for slow pyrolysis, a crucial stage in biochar production, to tap into its biochar-producing potential. To determine the composition of the biomass, the teff-husk was initially analyzed by thermogravimetry. The significant presence of fixed carbon indicates that teff husk is a viable candidate for pyrolytic conversion into biochar particles. The process of slow pyrolysis took place at three varied temperatures—specifically, at 400, 450, and 500 °C. Process parameters of slow pyrolysis such as reaction time, temperature, and heating rate were enhanced to obtain maximum biochar yields. The highest biochar yield of 43.4 wt% was recorded at optimized reaction time, temperature, and heating rate of 120 min, 400 °C, and 4.2 °C/min, respectively. Furthermore, biochar's physicochemical, SEM-EDX, FTIR, and TGA characterization were performed. The thermal stability and carbon content of biochar were found to rise at higher temperatures. Unlike fuel recovery, the results suggest that teff-husk can be used as a feedstock for biochar production.

Biodiversity has become an issue of global anxiety over the past decades due to its rapid decline worldwide. Bangladesh as one of the most densely populated countries in the world is no more exception. The country, although, was once very rich in biodiversity, during the last few decades as a consequence of the rapid reduction in forest area, urbanisation, habitat modification, unsustainable natural resources use and collection and overall climate change it has decreased alarmingly. Of late, the government, as a signatory of various regional and international conservation treaties, has taken various initiatives to improve country’s dwindling biodiversity. This paper reviews the present situation of biodiversity in Bangladesh, management trends and major causes of biodiversity loss. A separate statutory body is fundamental to ensure conservation, sustainable use and equitable sharing of benefits arisen from biodiversity in the country.

Elizabethkingia anophelis is an opportunistic pathogen causing lifethreatening infections in humans, particularly in immunocompromised patients, neonates and elderly. Infections caused by this species are exceptionally challenging to treat due to its multiresistance to antimicrobials. We report a case of central line-associated bloodstream infection by E. anophelis in a 2.5-year-old girl with acute lymphoblastic leukemia successfully treated with a combination of piperacillin/tazobactam and amikacin. The literature was also reviewed on paediatric infections caused by E. anophelis. Accurate identification with MALDI-TOF, or using molecular techniques, is crucial because of varying susceptibilities among species. Early, accurate diagnosis and prompt effective treatment optimize outcomes.

We propose a novel unsupervised semantic segmentation method for fast and accurate flood area detection utilizing color images acquired from Unmanned Aerial Vehicles (UAVs). To the best of our knowledge, this is the first fully unsupervised method for flood area segmentation in color images captured by UAVs, without the need of pre-disaster images. The proposed framework addresses the problem of flood segmentation based on parameter-free calculated masks and unsupervised image analysis techniques. First, a fully unsupervised algorithm gradually excludes areas classified as non-flood utilizing calculated masks over each component of the LAB colorspace, as well an RGB vegetation index and the detected edges of the original image. Unsupervised image analysis techniques, such as distance transform, are then applied, producing a probability map for the location of flooded areas. Finally, flood detection is obtained by applying the hysteresis thresholding segmentation. The proposed method is tested and compared with variations, and other supervised methods in two public datasets, consisting of 953 color images in total, yielding high-performance results, with 87.4% and 80.9% overall accuracy and F1-Score, respectively. The results and computational efficiency of the proposed method show that it is suitable for on board data execution and decision-making during UAVs flight.

The Circular Bioeconomy (CBE) combines the concepts of bioeconomy and circular economy. As an alternative concept to the current fossil-based, linear economy, it de-scribes an economy based on the efficient valorization of biomass. It is regional in nature and aims to improve sustainability. An analysis of the transition process, by identifying its success criteria and assessing its impacts through the modelling of technology-specific scenarios is necessary to ensure that CBE concepts are sustainable. However, a compre-hensive consideration of regional influences on both is lacking. Based on extensive literature research and an expert survey, we (i) present a compre-hensive catalog of CBE success criteria and discuss their region-specific character and (ii) develop a methodology based on evaluation matrices that enable to match CBE technolo-gies with regions. The matrices support the evaluation of technological and regional characteristics influencing the successful CBE implementation. The results show that the success criteria "biomass resources", "technological", and "social" are perceived as highly important, and that most of the success criteria are both region- and technology-specific, highlighting the relevance of developing matrices to match them. We describe such matrices indicatively for the two broadest and most im-portant success criteria clusters “social acceptance” and “biomass supply chain”. With this, we substantiate the regional nature of CBE and raise the awareness on the importance of considering regional conditions in CBE transition processes. Furthermore, we provide practical guidance on how regional conditions can be reflected in the selection of technologies, e.g. in regional CBE technology scenarios.

Pain is frequently reported during cancer disease, and still remains poorly controlled in 40% of patients. Recent developments in oncology have helped to better control pain. Targeted treatments may cure cancer disease and significantly increase survival. Thereby, a novel population of patients (cancer survivors) has emerged, also enduring chronic pain (27.6% moderate to severe pain). The present review discuss the different options currently available to manage pain in (former) cancer patients in the light of progress made in the last decade. Major progress in the field are recent development of a chronic cancer pain taxonomy now included in International Classification of Diseases (ICD-11) and update of WHO analgesic ladder. Until recently, cancer pain management has mostly relied on pharmacotherapy, opioids being considered as mainstay. The opioids crisis has prompted the reassessment of opioids use, both in cancer patients and cancer survivors. The review focuses on the current utilization of opioids, on the neuropathic pain component often neglected and on techniques and non-pharmacological strategies available which help to personalize patient’s treatment. Cancer pain management is now closer to the management of chronic non-cancer pain i.e. “an integrative pain care” aiming to improve patient’s quality of life.

The concept of a Social License to Operate (SLO) has become increasingly important in the sustainability literature in recent years. Having its origins in the business discourse of the mining industry with respect to limiting opposition to mining projects, the notion of a social contract above and beyond legal requirements has since become applied across a number of different industries. Despite the concepts adoption confusion exists over the practices and outcomes of SLO, and particularly the nature of engagement. Given this situation it is surprising that not more attention to the role of marketing, and social marketing in particular, in operationalizing the concept. The paper discusses the potential of social marketing to contribute to SLO. Economic, political and social relations are complex in SLO and exchange is intricate in such relational environments. A community-based social marketing orientation is proposed as a means to improve exchange relations and enhance engagement. Seven models of SLO related social marketing models are discussed with community-based social marketing and adaptive co-marketing models being regarded as the most positive for the achievement of an SLO. Potential barriers to adoption of these approaches are noted.

The main objective of this study was to compare the removal efficiency of nutrients using Lactuca sativa, Medicago sativa and Phragmites australis in subsurface flow constructed wetlands with horizontal flow. In order to test water quality, fabricated reactors designed and the plants cultivated in the soil while their root were inside the wastewater. A long time study carried out from spring till end of autumn (9 months) in order to evaluate the difference in removal rate based on the seasonal changes. The highest removal rate was during summer which followed by spring and autumn. Thus, the effect of plants on the removal efficiency of organic matter (COD, BOD), TSS and nutrient (P and TN) appeared to be dependent on the seasonal growth. Phragmites australis the most sensitive species in order the removal of nutrient from wastewater.

The use of haptic devices in rehabilitation of impaired limbs has become rather popular, given the proven effectiveness in promoting recovery. In a standard framework, such devices are used in rehabilitation centers, where patients interact with virtual tasks, presented on a screen. To track their sessions, kinematic/dynamic parameters or performance scores are recorded. However, as Internet access is now available at almost every home, and in order to reduce the hospitalization time of the patient, the idea of doing rehabilitation at home is gaining wide consent. Medical care programs can be synchronized with the home rehabilitation device; patient data can be sent to the central server that could redirect to the therapist laptop (tele-healthcare). The controversial issue is that the recorded data do not actually represent the clinical conditions of the patients according to the medical assessment scales, forcing them to frequently undergo clinical tests at the hospital. To respond to this demand, we propose the use of a bilateral master/slave haptic system that could allow the clinician, who interacts with the master, to assess remotely and in real time the clinical conditions of the patient that uses the home rehabilitation device as the slave. In this paper, we describe a proof of concept to highlight the main issues of such an application, limited to one degree of freedom, and to the measure of the stiffness and range of motion of the hand.

The economic, social and environmental benefits generated by the use of urban public transportation infrastructure constitute a complex dynamic urban public transportation infrastructure utilization benefit system. This paper evaluates the coupling coordination among these three benefits taking four Chinese autonomous municipalities as an example. These four cities have large-scale urban public transportation infrastructures but their utilization has many serious problems. The basic function of urban public transportation infrastructure has not been fully played in these cities. Whether the different benefits of urban public transportation infrastructure have been developed in harmony or not is unclear. We analyzed the coordinated development among three benefits by constructing coupling coordination degree model and used Gini coefficient to study the difference of coordinated development among three benefits of four cities. The result shows that the levels of coordinated development among three benefits of urban public transportation infrastructure were lower in these four cities and have positive correlation with it of urban public transportation infrastructure utilization benefit. Raising the level of urban public transportation infrastructure utilization benefit is the most crucial solution of promoting the coordinated development among three benefits.

This paper aims to develop a hierarchical risk assessment model using the newly-developed evidential reasoning (ER) rule, which constitutes a generic conjunctive probabilistic reasoning process. In this paper, we first provide a brief introduction to the basics of the ER rule and emphasize the strengths for representing and aggregating uncertain information from multiple experts and sources. Further, we discuss the key steps of developing the hierarchical risk assessment framework systematically, including (1) formulation of risk assessment hierarchy, (2) representation of both qualitative and quantitative information, (3) elicitation of attribute weights and information reliabilities, (4) aggregation of assessment information using the ER rule and (5) quantification and ranking of risks using utility-based transformation. The proposed hierarchical risk assessment framework can potentially be implemented to various complex and uncertain systems. A case study on the fire/explosion risk assessment of marine vessels demonstrates the applicability of the proposed risk assessment model.

Neuroblastoma (NB) is a childhood cancer with heterogeneous characteristics, posing challenges to effective treatment. NBs express somatostatin receptors that facilitates the use of somatostatin analogs (SSTAs) as tumor-seeking agents for diagnosis and therapy. High-risk (HR) NBs often have gain-of-function mutations in the receptor tyrosine kinase anaplastic lymphoma kinase (ALK). Despite intensive multimodal treatment, survival rates remain below 40% for children with HR-NB. The aim of this work was to investigate the combined effect of the SSTA 177Lu-octreotide with the ALK inhibitor lorlatinib. Mice bearing human HR-NB CLB-BAR tumors were treated with lorlatinib, 177Lu-octreotide, combination of these pharmaceuticals or saline (control). Tumor volume was monitored and tumor samples were evaluated for cleaved caspase-3 and expression of 84 human genes involved in apoptosis. Combination treatment with 177Lu-octreotide and lorlatinib demonstrated synergistic antitumor effects. Increased number of cleaved caspase 3-positive cells was observed in tumors from mice treated with 177Lu-octreotide alone and in combination with lorlatinib. Modulation of Bcl-2 family gene expression was observed only in the presence of both 177Lu-octreotide and lorlatinib, with BID downregulated and HRK upregulated on days 2 and 7, respectively. The data suggests that ALK signaling pathway inhibition may contribute to radiosensitization in radionuclide therapy with 177Lu-octreotide.

ABSTRACT After locavore was chosen as “the best word of the year” in 2007, its popularity increased gradually. Today great number of locavores consciously prefer locally produced food for the benefit of themselves and their community. Undoubtedly this conscious movement has its consequences in marketing discipline. Accordingly, this paper is purposed to examine the how locavore perceptions affect loyalty towards retailers that sell locally produced food. In this context, a survey was applied to people residing in Istanbul and Kocaeli districts to measure the robustness of these effects. Furthermore, attitude towards locavore is used as a control variable to reveal to what extend locavorism affects these proposed connections. According to results, for participants with low attitude, Social Responsibility and Health Consciousness variables have significant effect on local retailer shopping loyalty. However, for participants with high attitude, all independent variables proved to have substantial effect on local retailer shopping loyalty. As the first empirical study in Turkey on the subject, this paper will provide important insight to academia and practicioners due to today’s ever-increasing consciousness in green marketing.

The aim of the article is to verify differences in the perception of selected factors of sustainability among small and medium-sized enterprises (SMEs) in Central Europe. The subjects of analysis are factors such as corporate social responsibility (CSR), business risk sources (market, financial, personnel, and operational), reputation and social media, national support, social changes, and crisis events in business. The questionnaire was completed by 1,090 SMEs from the business environments of Visegrad Group countries. Statistical hypotheses were verified using Z-scores for two population properties. The most negatively perceived factors among owners and managers in the SME segment are national support and legislative changes. The most positively perceived factor is reputation and social media. The country of doing business is a significant factor. The perception of crisis events in business is most negative among Czech SMEs. More than 80% of Hungarian SMEs perceive their companies as sustainable. In comparison with Slovak and Polish SMEs, Hungarian perceptions are more positive in the context of sustainability. The country of doing business is the strongest factor in evaluating CSR indicators. The positive perception of CSR in Czech SMEs (43.9%) is lower than in other countries.

1) Landsat operational land imager (OLI) data and consequent laboratory measurements were used to predict Chlorophyll-a (Chl-a) concentration and the trophic states for an inland lake within the East Kolkata Wetland, India; 2) The most suitable band ratio was identified by performing Pearson correlation analysis between Chl-a concentrations and possible OLI band and band ratios from the study points; 3) The results showed highest correlation coefficient from the band ratio OLI5/OLI4 with an R value of 0.85. The prediction model was then developed by applying regression analysis between the band ratio OLI5/OLI4 and Chl-a concentration of the study points. The reflectance ratios of the validation points were given as input on the prediction model and the model output was considered as predicted Chl-a values of the validation points to check the efficiency of the prediction model. The regression model between laboratory-derived Chl-a value and model-fitted Chl-a value of the validation points revealed a high correlation with an R² value of 0.78. Trophic State Index (TSI) of the lake was also calculated from laboratory-derived Chl-a value and model-fitted Chl-a value of the validation points. The study presented a high correlation of TSI determined from predicted data with TSI from laboratory reference data (R = 0.88). The TSI values of the lake ranged from 65 to 75 which indicate that the lake is appeared to be eutrophic to hypereutrophic conditions. 4) This empirical study showed that Landsat 8 OLI imagery can be effectively applied to estimate Chl-a levels and trophic states for inland lakes.

Achieving the dual development of rural revitalization and urbanization is an important strategic goal of China’s current modernization. Rural population and settlements are the main components of the countryside in traditional agricultural areas, and play an important role in the development of the countryside itself in terms of urban and rural land use and in the formation of urban and rural development patterns. This study analyzes the spatial and temporal changes in rural populations and settlements at the township level, as well as the degree and type of coupled development. A framework for urban–rural development relationships based on different types of coupled development is proposed, and a model of urban–rural forces is constructed to derive the spatial pattern of urban–rural development at the township level that may be formed in the future. Our study shows that the rural population and settlements in the study area are characterized by significant spatial and temporal dynamics, indicating that traditional rural areas are in a process of rapid development and change. The results of the township-level coupling measurements present four types of development in terms of the spatial pattern of urban–rural development: A-type is most likely to produce new cities or satellite towns in the Jixi–Harbin–Qiqihar area in the future; B-type is the fastest dying area in the future, located in the Harbin and Qitaihe clusters, with a tendency to merge into Harbin; C-type is the area to be focused on in the future to attract population and strictly control the growth of the rural settlement area to avoid it turning into B-type; D-type may develop regional township centers in the future in the combined area of Jiamusi City, Suihua City and Mudanjiang City. The results of the study provide experience in realizing rural revitalization according to local conditions. The new spatial pattern of urban–rural development provides an important reference for formulating land use policies, optimizing urban–rural land allocation and realizing integrated urban–rural development strategies.

During choriogenesis in insects, chorion (eggshell) is formed by surrounding follicular epithelial cells in ovarioles. However, the regulatory endocrine factor(s) activating choriogenesis and the chemical components on eggshell deserve further exploration. In two representative Coleopterans, a Coccinellid Henosepilachna vigintioctopunctata and a Chrysomelid Leptinotarsa decemlineata, genes encoding the 20-hydroxyecdysone (20E) receptor heterodimer, ecdysone receptor (EcR) and ultraspiracle (USP), and two chitin biosynthesis enzymes UDP-N-acetylglucosamine pyrophosphorylase (UAP) and chitin synthase (ChS1), were highly expressed in ovaries of the young females. RNA interference (RNAi)-aided knockdown of either HvEcR or Hvusp in H. vigintioctopunctata inhibited oviposition, suppressed the expression of HvChS1, and lessened the positive signal of Calcofluor staining on the chorions, which suggests the reduction of a chitin-like substance (CLS) deposited on eggshells. Similarly, RNAi of LdEcR or Ldusp in L. decemlineata constrained oviposition, decreased the expression of LdUAP1 and LdChS1, and declined CLS contents in the resultant ovaries. Knockdown of LdUAP1 or LdChS1 caused similar defective phenotypes, i.e., reduced oviposition and CLS contents in the L. decemlineata ovaries. These results, for the first time, indicate that 20E signaling activates choriogenesis in two Coleopteran species. Moreover, our findings propose the deposition of a CLS on the chorions.

In Taiwan, mountainous areas account for approximately two-thirds of the total area. The steep terrain and concentrated rainfall during typhoons cause landslides, which pose a considerable threat to mountain settlements. Therefore, models for analyzing rainfall-induced landslide hazards are urgently required to ensure adequate land use in mountainous areas. In this study, focusing on Pingtung County in southern Taiwan, we developed a landslide hazard index (IRL) to land use. Using FORMOSA-2 and SPOT-5 satellite images, data were collected before and after four typhoons (one in 2009 and three in 2013). The ArcGIS random tree classifier was used for interpreting satellite images to explore surface changes and disasters, which were used to analyze slope disturbances. The product of the maximum 3-h rolling rainfall intensity and effective accumulated rainfall was used as a rainfall trigger index (IRT). Considering environmental and slope disturbance factors, an index of slope environmental strength potential (ISESP) was developed through logistic regression (LR). Landslide hazard to land use was estimated using IRT and ISESP. The average coefficient of agreement (Kappa) was approximately 0.71 (medium to high accuracy); the overall accuracy of slope environmental strength potential analysis was approximately 80.4%. At a constant ISESP, IRT increased with the increasing hazard potential of rainfall-induced landslides. Furthermore, IRT and ISESP were positively correlated with landslide occurrence. When large ISESP values occur (e.g., fragile environment and high land development intensity), small IRT values may induce landslides.

Managing a portfolio whose value closely tracks an index by trading only in a subset of the index constituents involves an NP-hard optimisation problem. In the prior literature, it has been suggested to solve this problem using sequential Monte Carlo (SMC, a.k.a. particle filter) methods. However, this literature does not take transaction costs into account, although transaction costs are the primary motivation for attempting to replicate the index by trading in a subset, rather than the full set of index constituents. This paper extends the SMC approach to index tracking to allow for proportional transaction costs and implements this extended method on empirical data for a variety stock indices. In addition to providing a more practically useful tracking strategy by allowing for transaction costs, we find that including a penalty for transaction costs in the optimisation objective can actually lead to better tracking performance.

The aims of this study are to measure the technical efficiency (TE) of Cambodian household’s rice production and trying to determine its main influencing factors using the stochastic frontier production function. The study utilized primary data collected from 301 rice farmers in three selected districts of Battambang by structured questionnaires. The empirical results indicated the level of household rice output varied according to differences in the efficiency of production processes. The mean TE is 0.34 which means that famers produce 34% of rice at best practice at the current level of production inputs and technology, indicates that rice output has the potential of being increased further by 66% at the same level of inputs if farmers had been technically efficient. Furthermore, between 2013-2015 TE of household’s rice production recorded -14.3% decline rate due to highly affected of drought during dry season of 2015. Moreover, evidence reveals that land, fertilizer, and pesticide are the major influencing input factors of household’s rice production, while disaster, education of household head, family size and other crops’ cultivated area are core influencing factors decreasing TE. Conversely, the main influencing factors increasing TE are irrigated area, number of plot area and sex of household head.

The aims of this study are to measure the technical efficiency (TE) of Cambodian household’s rice production and trying to determine its main influencing factors using the stochastic frontier production function. The study utilized primary data collected from 301 rice farmers in three selected districts of Battambang by structured questionnaires. The empirical results indicated the level of household rice output varied according to differences in the efficiency of the production processes. The mean TE is 0.34 which means that famers produce 34% of rice at best practice at the current level of production inputs and technology, indicates that rice output has the potential of being increased further by 66% at the same level of inputs if farmers had been technically efficient. Furthermore, between 2013-2015, TE of household’s rice production recorded -14.3% decline rate due to highly affected of drought during dry season of 2015. Moreover, evidence reveals that land, fertilizer, and pesticide are the major influencing input factors of household’s rice production, while disaster, education of household head, family size and other crops’ cultivated area are core influencing factors decreasing TE. Conversely, the main influencing factors increasing TE are irrigated area, number of plot area and sex of household head.

The present study aims to measure the technical efficiency and establish core factors effecting rice production in Cambodia. Four-years dataset generated from the central government document “Profile on Economics and Social” of entire 25 provinces between 2012-2015 and the stochastic production frontier model (SFA) was applied. The results indicated that the level of output (quantity) of Cambodian rice production varied according to the different level of capital investment in agricultural machineries, total rice actual harvested area, and technically fertilizers application within provinces. Furthermore, evidence revealed the overall mean efficiency of rice production is 78.4% implies that there is still room to further improve technical efficiency by given the same level of inputs and technology. More importantly, the findings revealed that irrigation, production technique and amount of agricultural supporting staffs are being as the most important influencing factors of rice production’s technical efficiency in Cambodia. In conclusion, present study strongly recommends the development of irrigation systems and good water management practices to be considered and bring into more effective actions by the central government as well as related agencies for improving rice production in Cambodia in addition to capital investment and improving technical skills of supporting staffs and rural farmers.

This paper draws upon the theory of turbulence in physics to explore the similarities and differences between volatility in financial markets and turbulent phenomena at a statistical physics level. By analogizing the dynamics of financial markets with fluid turbulence, we have developed an innovative analytical framework aimed at deepening the understanding of the complexity inherent in financial markets. Our research methodology includes a comparative analysis of simulated time series data for the Standard & Poor's 500 Index and fully developed turbulent velocity time series. We focus on the similarities in key statistical physical properties, including probability distributions, correlation structures, and power spectral densities. Furthermore, we have established a model of capital flow in financial markets and proposed corresponding solutions. Through computational simulations and data analysis, we find that while financial market volatility shares some statistical characteristics with turbulent phenomena, significant differences exist in the shapes of probability distributions and the temporal scales of correlations. This suggests that although financial markets exhibit patterns akin to turbulence, the behavior of this complex, multi-variable driven system does not completely correspond to natural turbulence, highlighting the limitations of directly applying turbulence theory to financial market analysis. Our study offers a new perspective for the theories of financial markets and the field of econophysics, providing fresh insights into the complexity of financial markets and contributing to the prevention and management of financial risk.

Strategic intelligence covers the examination of what impacts and influences the business and the related SWOT analysis, (strengths, weaknesses, opportunities, and threats mapping). Through this research, leaders will be able to properly allocate and re-route resources, identify areas of improvement, and ensure that strategic initiatives are aligned with the organization's mission. Strategic intelligence is, therefore, effective through the use of critical thought and data-driven decisions and seeing the outcomes of different positioned alternatives. It must also form and support a culture of cooperation and open communication within the organizations, stimulating employees' inputs and learning curves. The article's subject is the necessity for strategic intelligence, a crucial competence for leaders, managers, and companies striving to remain competitive, to be utilized and best leveraged in today's volatile and dynamic business contexts. It helps the leadership turn proactive, foresee trends, and make correct, agile decisions that enforce companies' long-term growth and success. This study follows a research design that includes a thorough literature review and bibliometric research, executed via VoSViewer, illustrating the concept of strategic intelligence from a leadership point of view as a driver of competitive advantage. Further, the article points out that the limitations are acknowledged because the literature on the matter is limited, as strategic intelligence is relatively new to the business sector; moreover, more research is required to fully understand and use the potential of strategic intelligence in business growth. By overcoming these limitations and continuing to study this concept, businesses can gain a competitive edge and make informed decisions that fuel their success in an ever-evolving market. As a result, this study contributes to developing strategic intelligence in leadership and business and paves the road for further research and applications of strategic intelligence theories in organizational contexts.

To improve carbon efficiency for urban logistics service system composed of a third-party logistics service provider (3PLs) and an e-business enterprise, low-carbon operation game between them was studied. Considering low carbon technology investment cost and sales expansion effect of low carbon level, profit functions for both players were constituted. Based on their different bargaining capabilities, totally 5 types of game scenarios were designed. Through analytical solution, Nash Equilibria under varied scenarios were obtained. By analyzing these equilibria, 4 major propositions were given, in which, some key variables and system performance index were compared. Results show that the best system yields could only be achieved under the fully cooperative situation; limited cooperation only for carbon emission reduction would not benefit the system performance improvement; E-business enterprise-leading game’s performance overtook 3PLs-leading ones.

The purpose of this study is to establish whether digital literacy and insurtech adoption influence insurance inclusion in Uganda. Principally, we sought to determine whether insurtech adoption mediates the nexus between digital literacy and insurance inclusion. This study adopted a cross-sectional and quantitative correlational approach. The study’s sample was 391 individuals who had used digital platforms such as mobile phones and computers to access insurance products and services in Uganda. Data were collected using structured survey questionnaires. Partial Least Squares Structural Equation Modelling (PLSEM) was employed to test the hypothesised relationships. The results demonstrate that both digital literacy and insurtech adoption significantly and positively influence insurance inclusion. We also found digital literacy to be a significant and positive determinant of insurtech adoption. Markedly, it was found that insurtech adoption mediates the association between digital literacy and insurance inclusion in Uganda. However, this study was conducted in a developing country with an underdeveloped insurance market and with low technological advancement. This may affect generalisation of the study findings. This study’s novelty lies in establishing how digital literacy and insurtech adoption interplay to influence insurance inclusion in Uganda. This is the first study to examine the effect of digital literacy and insurtech adoption on insurance inclusion.

Routing a person through a traffic network presents a tension between selecting a fixed route that is easy to navigate and selecting an aggressively adaptive route that minimizes the expected travel time. We propose to create non-aggressive adaptive routes in the middle-ground seeking the best of both these extremes. Specifically, these routes still adapt to changing traffic conditions, however we limit the number of adjustments made in the route. This improves the user experience, by providing a continuum of options between saving travel time and minimizing navigation. We design strategies to model single and multiple route adjustments, and investigate enumerative techniques to solve these models. To alleviate the intractability with handling real-life traffic data, we develop efficient algorithms with easily computable lower and upper bounds. We finally present computational experiments highlighting the benefits of limited adaptability in terms of reducing the expected travel time.

Human papillomavirus (HPV) uses the cellular trafficking machinery to reach the cell nucleus and initiate a successful infection. The HPV capsid consists of two proteins: L1 (the major capsid protein) and L2 (minor capsid protein), and L2 is known to be responsible for trafficking the viral genome to the nucleus. From previous studies, we know that many cellular proteins interact with L2 and are involved in the trafficking process at different stages of the infectious entry process. To further investigate how HPV-16 achieves successful viral entry, we have performed a mass spectrometry analysis to identify novel interacting proteins that associate with incoming HPV-16 virions. We show that HPV-16 pseudovirions interact with a group of cellular cargo proteins (COPI), and here we confirm that this is mediated by the direct binding of L2, but not L1, to the COPB1 subunit. We also show that the ability of L2 to interact with COPB1 is conserved in both low- and high-risk HPV types. Furthermore, we also show that the interaction is essential for successful infection entry of multiple HPV types, thereby identifying a novel constituent of the infectious entry pathway of the HPV.

The article presents a model for optimizing biomass supply chains using the linear programming framework integrated with a Geographic Information System. Based on the distance from a given type of biomass resource, its calorific value, price, and transportation costs, the model identifies the optimal source of biomass, allowing it to cover the demand for the required total energy value with the lowest possible costs. The case study includes the Połaniec power plant in southeastern Poland and potential sources of forest biomass and agricultural straw within 100 km of the plant. Unit costs of biomass varied depending on biomass availability and energy demands. For energy demand on the level of 1 PJ yearly, the lowest unit costs of biomass (4.08 €/MJ) were when all kinds of biomass were available, and the highest (5.47 €/MJ) was when only stacked wood was available. As energy demand increased, unit costs increased, and the ability to meet this demand with just one type of biomass decreased. The energy biomass sector can utilize the model to benefit both biomass producers and their final buyers.

Taiwan’s auditors have suffered from processing excessive audit data, including drawing audit evidence. This study advances sampling techniques by integrating machine learning with sampling. This machine learning integration helps avoid sampling bias, keep randomness and variability, and target the risker samples. We first apply a Naive Bayes classifier to classify data into some classes. Next, a user-based, item-based, or hybrid approach is employed to draw audit evidence. The representativeness index is the primary metric for measuring the representativeness of audit evidence. The user-based approach denotes the selection of samples between two percentiles in a class as audit evidence. It may be equivalent to a combination of monetary and variable sampling methods. The item-based approach represents the choice of risky samples as audit evidence. It may be identical to a combination of non-statistical and monetary sampling methods. Auditors can hybridize those user-based and item-based approaches to balance representativeness and riskiness in selecting audit evidence. Three experiments show that sampling using machine learning integration has the benefits of drawing unbiased samples, handling complex patterns, correlations, and unstructured data, and improving efficiency in sampling big data. However, the limitations are the classification accuracy output by machine learning algorithms and the range of prior probabilities.

Aortic valve stenosis and malignancy frequently coexist and share the same risk factors as atherosclerotic disease. Data reporting the prognosis of patients with severe aortic stenosis and cancer are limited. Tailoring the correct and most optimal care for cancer patients with severe aortic stenosis is complex. Cancer patients may be further disadvantaged by aortic stenosis if it interferes with their treatment by increasing the risk associated with oncologic surgery and compounding the risks associated with cardiotoxicity and heart failure (HF). Nowadays, several therapeutic options are available for aortic valve stenosis (surgical valve replacement , transcatheter valve implantation, balloon valvuloplasty, or medical therapy), but in presence of malignancy, the use of one of these versus the others should be decided on a case-by-case approach, depending on cancer stage and associated treatment, expected outcome, comorbidities and after an accurate physical examination and Doppler-echocardiography which are the key tools for diagnosing and evaluating aortic stenosis. The current review considers the available data on the association between aortic stenosis and cancer, and therapeutic options.

Melanoma is the most aggressive form of skin cancer. In the advanced stage of development it is resistant to currently available therapeutic modalities. Increased invasiveness and metastatic potential depend on a number of proteins involved in various signal transduction pathways. Hippo signaling plays an important role in malignant transformation. Dysfunctions of the Hippo pathway initiate the expression of tumor growth factors and is associated with tumor growth and metastasis formation. This review summarizes the recent achievements in studying the role of the Hippo pathway in melanoma pathogenesis and points to the potential specific targets for anti-melanoma therapy.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

Background: Periodontitis is a disease that leads to serious functional and aesthetic dysfunctions resulting in impairment of life quality; it exists in different forms and its etiology is related with multiple component causes. Angiogenesis, together with inflammatory infiltrate, are two key processes in the evolution of inflammatory processes involving gingival tissues. The aim of this study was to evaluate their alterations in relation to some important periodontal diseases-associated factors (i.e. smoke, sex, age, plaque, pus, probing pocket depth) in patients with diagnosis of Generalized Aggressive Periodontitis (GAP). Methods: Eighteen subjects with GAP were enrolled for this study. Percentage of inflammatory cells and vascular area were measured and evaluated in relation with each periodontal diseases-associated factor. Results: The results showed a significant decrease of the percentage of vascular area in association with almost all the periodontal diseases-related factors (smoke, age, PPD, plaque) and not significant differences in the percentage of inflammatory cells. Conclusions: Data suggest that, even if these factors are often commonly related to worsening of periodontal status, they did not affect inflammatory and vascular pattern, as we can assume. For the future, additional studies, aimed to evaluated each singular factor in a wider sample size, should be planned.

Land use and cover change (LUCC) is an important method to investigate the causes of global environment change. We utilized the emergy ecological footprint (EEF) model to construct a land-use change model to be used as a systematic measuring tool for monitoring sustainable development trends. In particular, we estimated the eco-security of the Cing-jing region as a case study so that responsible agencies can use it to maintain a balance between ecological preservation and tourism development. The results indicated the following: First, the ecological environment of the Cing-jing region satisfied the safety standard in 2008–2014; however, the related indices increased considerably. Second, the grey model predicted a decrease in 2015–2024 ecological carrying capacities of Cing-jing and a large increase in capita EFs, resulting in a larger ecological deficit and higher EFI. The eco-security from 2015–2024 was higher compared to 7 years ago and is predicted to reach the Grade 2 intermediate level in 2022; thus the Cing-jing region is gradually becoming ecologically unsustainable. Strengths of our study included the use of EEF theory in a quantitative analysis of slope lands for the effective evaluation of ecological security. Finally, we expanded our research to include ecological security issues.

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopment disorder frequently co-occurring with Attention-Deficit/Hyperactivity Disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage ASD core symptoms, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend neuroleptics to reduce psychomotor agitation in people with ASD. However, since children with ASD are often drug-resistant, alternative treatments are often justified. Reports from literature showed that intra-venous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with lower frequency of adverse events compared to convention-al treatments. However, since findings are occasionally inconsistent, IV-VPA is not an approved option in clinical psychiatry. We aim at improving the knowledge on the IV-VPA treatment option in emergency psychiatry in the pediatric age. Methods: We report the case of a 11-year-old boy suffering from a complex neurodevelopmental condition, who experienced a psychotic episode with severe aggressive and disruptive behaviors, successfully treated with IV-VPA. Besides, we conducted an up-dated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. On the contrary, IV-VPA led to a safe and prompt clinical success, in line with other reports. Based on our literature review, IV-VPA can be highly effective and can reduce the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.

Innovation is an essential key factor in the technology development history. Past research on innovation focused more on the innovation behavior of technology, but seldom described knowledge assets which also influence innovation behavior greatly. The effect of knowledge assets attribute and result on disruptive innovation is therefore regarded as the research topic in this study, where disruptive innovation is divided into outbound and inbound to combine combination-embeddednessandmajor business specificityof knowledge assets as the research model. Manufacturing enterprises in China are proceeded the questionnaire survey, and 173 valid copies are collected. The empirical analysis shows that combination-embeddedness of knowledge assets presents significantly positive effects on major business specificity and outbound innovationof an enterprise but reveals remarkably negative effects on inbound innovation. Enterprises are suggested to constantly accumulate knowledge assets with low major business specificity before disruptive innovation in order to reduce ineffective inbound innovation.

The Infierno glacier is located in Aragon (Spain), Pyrenees mountain range, southern slope, the only one in this country that still preserves white glaciers. These are the southernmost glaciers in Europe and are currently in rapid regression. The work analyzes the evolution of the glacier between 2016 and 2022 (taking as "year zero" or starting point, 2015). In addition to the observations on the glacier itself, the variables (precipitation, temperatures, snow volumes and thicknesses) that allow understanding this evolution are studied. The results offer strong regression, with thickness losses in that period of 4.6 m and retreat of its front of 14.9 m. The evolution has frequent trend changes, linked to the interannual climatic irregularity characteristic of this mountain range. The main explanatory factor is the thermal increase. The thermal anomalies with respect to the average reference values have increased, in this period, +0.55° C. The year 2022 has been particularly warm and has recorded the greatest regression of the glacier (between May and August, the thermal anomalies were between +4° C and +2° C). Regarding precipitations, they have irregular tendencies and show a decreasing trend (-9% in the same period of time).

Despite significant advances in tumor biology and clinical therapeutics, metastasis remains the primary cause of cancer-related deaths. While RNA-seq technology has been used extensively to study metastatic cancer characteristics, challenges persist in acquiring adequate transcriptomic data. To overcome this challenge, we propose MetGen, a generative contrastive learning based on deep learning model. MetGen generates synthetic metastatic cancer expression profiles using primary cancer and normal tissue expression data. Our results demonstrate that MetGen generates comparable samples to actual metastatic cancer samples, and we discuss the learning mechanism of MetGen. Additionally, we demonstrate MetGen's interpretability using metastatic prostate cancer and metastatic breast cancer. MetGen has learned highly relevant signatures in cancer, tissue, and tumor microenvironment, such as immune response and the metastasis process, which potentially fosters a more comprehensive understanding of metastatic cancer biology. The development of MetGen represents a significant step toward the study of metastatic cancer biology by providing a generative model that identifies candidate therapeutic targets for the treatment of metastatic cancer.

Pancreatic cancer (PC) is considered one of the most challenging and formidable malig-nancies to treat because it is usually diagnosed at terminal stage, thus it is characterized with a poor prognosis with 5% of patients living over 5 years. The late diagnosis leads to a lower suc-cess rate of resectability, hence chemotherapy or chemoradiotherapy are the only hopes for most PC patients. However, the available drug combinations for PC treatment did not provide satisfactory clinical outcomes. There is a pressing and urgent need to discover new chemothera-peutics which fight PC with tolerable side effects and less liability for resistance. Pentacyclic triterpenes (PTs) are privileged structures with a multitude of biological activities mitigating several ailments, particularly in neoplasm field. They are characterized by a high therapeutic window and their activity can be highly enhanced through structural modifications. Indeed, several parent PTs such as oleanolic acid, ursolic acid, lupeol, betulinic acid, and celastrol proved effective against different PC phenotypes inhibiting their proliferation, invasion, and metastasis mainly via KRAS modulation. Some PTs worked as adjuvant chemosensitizers in gemcitabine-resistant or TRAIL-resistant cells. Owing to their potential in PC treatment, we pre-sent this review article summarizing PC pathogenesis and the promising role of PTs in the man-agement of PC when used either solely or in combination with other chemotherapies such as gemcitabine and 5-Fluorouracil.

As a new plant slope protection technology, living stumps can effectively improve slope stability. The current study attemptes to investigate the mechanical characteristics of the root system of living stumps and their reinforcement mechanism on slopes by carrying out a three-dimensional living stump slope modeling test. Using ABS materials, a 3D model of a living elm stump was created by 3D printing and a slope model test was carried out. The reinforcement mechanism of the living stump was studied through a combination of model testing and numerical simulation. The results indicate that, due to the presence of living stumps in the lower and middle parts of the slope, the maximum shear stress area of the soil moved to a deeper direction. The stress state of the soil around the living stump was effectively improved due to the existence of the lateral root system.Living stumps in the lower part of the slope cross the potential sliding surface and transferred the soil shear stress gradually to the root system through root-soil interaction. Moreover, the tap roots and lateral roots of living stumps form a robust spatial structure that bears the shear stress of soil together, thus increasing the stability of the slope.

Developing effective trend estimators is a main method to solve the online portfolio selection problem. Although the existing portfolio strategies have demonstrated good performance through the development of various trend estimators, it is still challenging to determine in advance which estimator will yield the maximum final cumulative wealth in online portfolio selection tasks. This paper studies an online ensemble approach for online portfolio selection by leveraging the strengths of multiple trend estimators. Specifically, a return-based loss function and a cross-entropy-based loss function are first designed to evaluate the adaptiveness of different trend estimators in a financial environment. On this basis, a passive aggressive ensemble model is proposed to weigh these trend estimators within a unit simplex according to their adaptiveness. Extensive experiments are conducted on benchmark datasets from various real-world stock markets to evaluate the performance. The results show that the proposed strategy achieves the state-of-the-art performance including efficiency and cumulative return.

The ongoing challenge to ensure a sustainable and affordable energy supply forces industrial companies to implement appropriate measures. These measures typically lead to an increased system complexity, which has to be addressed during operation. Whereas existing approaches from the field of supervisory and optimal control appear to be capable of mastering this issue, these are still not adopted in industry. Therefore, this work presents a procedure model for the systematic development of application-oriented operating strategies for industrial energy supply systems. The procedure model combines research approaches from the fields of sequencing control and approximate MPC to extract rule-based operating strategies. By splitting the procedure model into five phases, expert knowledge can be integrated in a target-oriented manner. Subsequently to the description, the procedure model is exemplary applied to the example of an industrial heating supply system. Throughout an optimization study, the developed operating strategy is compared to a MPC strategy as well as a baseline strategy. Whereas the conventional MPC approach is the upper bound with regard to optimality, the developed operating strategy is able to generate comparable results. Compared to the baseline strategy, a relative reduction in operating expenses of 5.4 % to 37.0 % are achieved in this specific use case.

In this study the impact of terrorist attacks on exchange rate is estimated. Particularly, the study focuses on Turkish terrorist attacks and its implication on Turkish lira versus pound sterling exchange rate. In order, to find the causal effect the study employed Autoregressive distributive lag (ARDL) bound testing approach as an estimation technique. Accordingly, the analysis reveals that terrorist attack has a negative impact on the exchange rate in both short and long-run. However, the negative effect of terrorism tends to be small in both the short-run and long-run. More precisely, terrorist attack depreciates the exchange rate between Turkish lira and pound sterling by approximately 0.00072 in the next trading day. The long-term effect also shows that terrorist attack depreciates the exchange rate on average by 0.00212.

Air pollution, climate change and global warming show direct linkage. Introduction - Background: Research in the field has proposed and demonstrated their link to increased allergenicity in plants, leading to increased allergic diseases. Allergen patterns are changing in response to climate change. Across Europe, up to 12% of the population suffers from allergic diseases (bronchial asthma and allergic rhinitis) caused by the pollen grains. The medical costs of these types of allergies are enormous and are increasing with the spread of common ragweed - Ambrosia artemisiifolia* in Europe. In practice, more and more patients are turning to allergists. Methods: Based on these data, the research aims to identify safety measures and specific legislation to control and eradicate common ragweed in the countries most affected by the spread of this plant in Europe, increase in population exposure in countries affected by the presence of common ragweed and the socio-economic impact of allergic rhinitis and bronchial asthma at European level.[1][2] Our database search did not reveal any other research that has addressed this topic to date. Results: This research identifies specific legislation to the countries most affected by the spread of this plant pollen grains at European level, changes in allergen patterns and monitoring/safety eradication measures decided by local authorities, and data on the spread of common ragweed over the last two decades, costs per treatment, increased allergic rhinitis and bronchial asthma morbidity in the most affected areas. Conclusions: At European level, there are no universally valid models for eradicating this weed. Various methods can be used to limit the spread of common ragweed and its pollen production (e.g. mowing once or twice a year of overgrown land, ploughing, chemical control, public information, etc.). Local and regional cooperation should be considered essential to promote phytosanitary &amp; safety measures and exchange of information on methods to identify and manage the spread of common ragweed. Unified legislation at European level would help all affected countries; reduce morbidity from respiratory allergic diseases and the costs of treating these diseases.

Reactive NO_x is one of the major air pollutants, which also plays a key role as greenhouse gas. Many research efforts have been devoted to not only detection of NO_x in air but also abatement of NO_x emission. The aim of this mini review is to provide a panoramic snapshot of the electrochemical analysis methods for the emission and detection of NO_x in atmosphere, with special emphasis on NO_x sensor. The electrochemical detecting mechanism and materials for fabricating electrochemical gas sensors are discussed and the prospects and challenges in this area are also evaluated. This work will serve as a useful source to inform the interested audience of the latest developments and applications in the field of NO_x emission and electrochemical detection.

Aggressive mature T-cell lymphoma (TCL) is a disease that carries a poor prognosis. The mechanism, at the functional protein level, of the resistance to therapy of TCL has not yet been well clarified. To comprehensively clarify the mechanism, we first reviewed the literature, as mentioned in the Introduction section, on 22 types of representative functional proteins reported as being potentially associated with treatment resistance, mainly in hematologic tumors. Next, we retrospectively analyzed the tumor cell expressions of these 22 functional proteins in 16 randomly selected patients with TCL who had received CHOP (cyclophosphamide, hydroxyl doxorubicin, oncovin, and prednisolone) therapy as first-line treatment. As a result, we propose a new three-group prognostic classification of TCL (the TCL Urayasu Classification) based on the mechanism of resistance to treatment of these tumors. The study subjects included 7 patients (44%) with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), 6 patients (38%) with angioimmunoblastic T-cell lymphoma (AITL), and 3 patients (19%) with anaplastic large T-cell lymphoma (ALCL). Immunohistochemistry was performed in paraffin-embedded tumor tissue sections prepared from these patients as antigens using antibodies against the 22 previously reported treatment-resistance-related proteins to determine the tumor cell expression statuses of these proteins. Log-rank test was performed to compare the overall survival (OS) after CHOP therapy of the patients showing positive and negative immunostaining for these proteins, as well as among patients grouped based on other factors. Overall, the median OS of the TCL patients was about 33.5 months. When compared by the disease type, the prognosis was found to be worse in the order of ALCL, AITL, and PTCL. A multivariate analysis showed that expression of glucose-regulated protein 94 (GRP94), a protein that serves as a pro-survival component under endoplasmic reticulum (ER) stress in the tumor microenvironment, was significantly associated with shortened survival. No significant difference was observed for the conventional poor prognostic factors: high-risk International Prognostic Index (IPI) and high-risk Prognostic Index for peripheral T-cell lymphoma, unspecified (PTCL-U) (PIT). However, when GRP94 was combined with six other factors, listed below, as survival-shortening factors, significant differences were observed. The 6 factors were 1) programmed cell death-ligand 1 (PD-L1) and 2) programmed cell death 1 (PD-1), which are involved in immune surveillance; 3) aldo-keto reductase family 1 member C3 (AKR1C3), which is an enzyme that inactivates HO (hydroxyl doxorubicin [H] and oncovin [O]) of CHOP; 4) P53, a tumor suppressor; 5) Glucose-regulated protein 78 (GRP78), an ER stress protein; 6) thymidine phosphorylase (TP), which is an enzyme involved in thymidine catabolism. Based on the combination of GRP94 and the six other factors expressed in the tumors, we propose a new prognostic classification system for TCL (TCL Urayasu classification). Group 1 (group with a relatively good prognosis): GRP94-negative (n = 6; median OS, 88 months; p < 0.01); Group 2 (group with a poor prognosis): GRP94-positive, plus expression of 2 of the 6 aforementioned factors (n = 5; median OS, 25 months; p > 0.05); and Group 3 (group with a very poor prognosis): GRP94-positive, plus expression of at least 3 of the 6 aforementioned factors (n = 5; median OS, 10 months; p < 0.01). Thus, the TCL Urayasu prognostic classification is a simple, useful, and innovative classification that also explains the mechanism of resistance to treatment for each functional protein. Accumulation of more cases and further analyses are expected in the future to enable clinical application, such as use of a stratified treatment approach and treatment using inhibitors.

In 2022, the new WHO Classification of Endocrine and Neuroendocrine Tumors, Fifth Edition (beta version) (WHO 5th) was published. The importance of understanding the molecular genetics of thyroid tumors as revealed by large-scale genomic analyses such as The Cancer Genome Atlas (TCGA). Consequently, the WHO 5th was fundamentally revised, resulting in a systematic classification based on tumor cell-of-origin and clinical risk. This paper outlines following critical points of the WHO 5th. 1. Genetic mutations in follicular cell-derived neoplasms (FDN) highlight the role of mutations in the MAP kinase pathway, including RET, RAS, and BRAF, as drivers of carcinogenesis. Differentiated thyroid cancers such as follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) have specific genetic alterations that correlate with morphological classifications: RAS-like tumors (RLTs) and BRAF p.V600E-like tumors (BLTs), respectively. 2. The Framework for benign lesions have revised. The WHO 5th introduces new categories such as "developmental abnormalities" and "thyroid follicular nodular disease" in benign FDN. 3. Low-Risk Tumors include NIFTP, TT-UMP, and HTT. 4. PTC histological variants are reclassified as "subtypes" in the WHO 5th. 5. The concept of high-grade carcinomas is introduced, encompassing poorly differentiated thyroid carcinoma (PDTC), differentiated high-grade thyroid carcinoma (DHGTC), and high-grade medullary thyroid carcinoma (MTC). 6. Squamous cell carcinoma is included in anaplastic thyroid carcinoma (ATC) in the WHO 5th due to shared genetic and prognostic features. 7. Hürthle cell adenoma/carcinoma is renamed oncocytic thyroid adenoma/carcinoma. 8. Other miscellaneous tumors are classified into salivary gland-type carcinomas of the thyroid, thyroid tumours of uncertain histogenesis, thymic tumours within the thyroid, and embryonal thyroid neoplasms. The WHO 5th thus emphasizes the importance of classifying tumors based on genetic abnormalities together with histomorphology, aiding in accurate pathological diagnosis and treatment selection, including molecular-targeted therapies.

Introduction: Signet-ring cells are typically associated with mucin-secreting epithelium thus most commonly found in a gastrointestinal tract, however not exclusively. Primary signet ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. Clinical case: In June of 2023 a 54-year-old Caucasian male came to the hospital complaining of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma st. IV. Unfortunately, the patient with the disease this advanced, PE, and third-degree thrombocytopenia was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. Discussion: Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results which may contribute to its late diagnosis which together with inconsistent immunohistochemical findings and unpredictable response to hormonal treatment pose both diagnostic and therapeutic challenges that negatively affect the prognosis. Conclusion: The study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease which may positively influence the prognosis.

The Himalaya is well known for high diversity and ethnobotanical uses of medicinal plants. However, not all areas of the Himalayas are well studied. In particular, studies on ethnobotanical uses of plants from the Eastern Himalayas are rare and lacking for many tribes. Past studies primarily focused on listing plants name and their traditional medicinal uses. However, studies on traditional ethnopharmacological practices on medicine preparation had not yet been reported in published literature from the Eastern Himalaya. In this study, we are reporting the first time ethnopharmacological used 24 medicines, their procedures of preparation and listed 53 plant species used for those medicines for Monpa tribe. Such documentations had not yet been done for other tribes in India. Our research demonstrates the urgent need to documents traditional medicine preparation procedures from the local healers before rapid cultural modernization forgets them in transforming country like India. This study should motivate national and international researchers to do more works on ethnopharmacology and bioprospecting.

The purpose of this paper is to examine the role and impact of public governance on European supranational public policies that seek to foster scientific and economic growth within innovation ecosystems (IEs) through the PITCCH initiative. The PITCCH is a European innovation development initiative funded by Horizon 2020 under the 'Innovation in SMEs' measure.The research methodology for this study is based on a 10-month real-time ethnographic field study of the PITCCH project, which allowed for the observation of the project governance and the capture of the perspectives of innovation-driven small and medium enterprises (i-SMEs) in their engagement with IE stakeholders.The findings of this research demonstrate the role of public governance in providing result-oriented practical support to the IE through the lens of i-SMEs, and they contribute to the existing literature on regional economic growth supported by supranational public policies. These findings have both academic and practical applications. They enrich the current literature on this topic and provide insights for policymakers and governing representatives seeking to implement effective public policies.

Structural variations (SVs) play a key role in the pathogenicity of hematological malignancies. Optical genome mapping (OGM) is an emerging technology that enables genome-wide detection of all classes of SVs at a high resolution and sensitivity. Identification of cryptic SVs leading to gene disruption or predicted novel gene fusions could be important drivers for cancer development and/or portend a prognostic relevance, which could be used to modify the treatment plan. A cohort of 106 consented cases that had a successful OGM analysis performed were included in the study. Demographic, clinical, laboratory and treatment data were collected. Routine diagnostic and prognostic testing were done on the peripheral blood and bone marrow aspirate as indicated. Additional samples of peripheral blood and/or bone marrow were sent for OGM testing. OGM led to a change in risk stratification in 17/66 (25.75%) of patients with hematological malignancies, the majority of these patients (15/66, 22.72%), having their risk stratification upgraded with a resulting change in treatment of 14 patients. This study highlights the ability of OGM to detect rare, cryptic and clinically relevant variants that potentially impact disease diagnosis, risk stratification and actionable treatment targets.

To investigate the impact of electrode structure on Electrical Stimulation Therapy (EST) for chronic wound healing, this study designed three variants of flexible microelectrodes (FMs) with Ag-Cu coverings (ACCs), each exhibiting distinct geometrical configurations: hexagonal, cross-shaped, and serpentine. These were integrated with PPY@PDA/PANI (3/6) hydrogel dressings. Comprehensive animal studies, coupled with detailed electrical and mechanical modeling and simulations, were conducted to assess their performance. Results indicated that the serpentine-shaped FM outperformed its counterparts in terms of flexibility and safety, exhibiting minimal thermal effects and a reduced risk of burns. Notably, FMs with metal coverings under 3% demonstrated promising potential for optoelectronic self-powering capabilities. Additionally, simulation data highlighted the significant influence of hydrogel non-uniformity on the distribution of electrical properties across the skin surface, providing critical insights for optimizing EST protocols when employing hydrogel dressings.

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying non-invasive biomarkers in body fluids such as blood and urine. A source of biomarkers in these biofluids are extracellular vesicles (EVs), nanosized vesicles that contain a wide array of molecular cargo, including small non-coding RNA such as microRNA and transfer RNA-derived fragments (tRF). Here we performed small-RNA next-generation sequencing for urine EVs, serum EVs and serum supernatant from 41 patients with non-muscle invasive BC (27 stage Ta, 14 stage T1) and 15 non-cancer patients (NCP) with benign cystoscopy findings. Serum and urine samples were collected before transurethral resection of bladder tumors (TUR-b) and at routine postsurgery check-ups. Expression levels of tRFs in presurgery samples were compared to those at postsurgery check-ups and to NCPs. To strengthen the reliability of our results, samples from 10 patients with stage T1 disease were resequenced. When comparing tRF expression in urine EVs between BC patients with stage T1 disease and NCPs, 14 differentially expressed tRFs (DEtRFs) were identified. In serum supernatant, six DEtRFs were identified among stage T1 patients when comparing presurgery to postsurgery samples, and four DEtRFs were found when comparing presurgery samples to NCPs. By performing a blast search, we found that sequences of DEtRFs aligned with genomic sequences pertaining to processes relevant to cancer development, such as enhancers, regulatory elements and CpG islands. Our findings display a number of tRFs that may hold potential as biomarkers for the diagnosis and recurrence-free survival of BC.

This study addresses the challenge of treating skin cancer effectively, especially in visible areas like the face, where traditional methods may be undesirable. Current options, including surgery and radiation therapy, have limitations such as complexity, expense, and imprecise dose delivery. The proposed solution involves additively manufacturing personalized patches using diagnostic imaging data, offering a targeted and controlled dose of beta-emitting isotopes like Y-90. The patches, tailored to the tumor's shape and depth, aim to minimize damage to healthy tissues and structures. Through 3D printing technology we demonstrated the feasibility of creating individualized applicators filled with radioisotopes, that have the potential to deliver therapeutic doses while ensuring patient comfort and affordability. This innovative approach, based on radiation delivery simulations, offers a promising future alternative to conventional radiation therapy methods. Clinical trials are required to validate its efficacy and safety, but the potential for reduced radiation exposure and enhanced treatment precision positions this personalized and targeted therapy as a valuable advancement in skin cancer treatment.

This study focuses on understanding how global auto parts companies manage innovation by analyzing keywords in CEO messages from their reports. The study involved three key phases: (1) extraction of innovation-related keywords emphasized in CEO messages, (2) comparison of innovation-related keyword usage between high-performing (upper group) and low-performing (lower group) companies, and (3) analysis of the characteristics of innovation management via internal meaning and the structural interpretation of keywords. A comparison between the upper and lower groups revealed distinct differences in the emphasized keywords. The mapping of open innovation success factors, based on keywords extracted according to eigenvector centrality, identified Provision of Resources and Governance as central to innovation management in the upper group. These findings serve as a benchmark for establishing the direction, vision, and strategy of innovation management in the lower group.

Tumor microenvironment including cancer-associated fibroblasts (CAF) has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell – tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles. There is evidence that miRs have very similar roles in activating hepatic (HSC) and pancreatic stellate cells (PSC) as part of precancerous fibrotic diseases. In summary, deregulated miRs affect various intracellular functional complexes, such as transcriptional factors, extracellular matrix, cytoskeleton, EMT/MET regulation, soluble factors, tyrosine kinase and G-protein signaling, apoptosis and cell cycle & differentiation, but also formation and composition of the extracellular microenvironment. These processes result in the clinical appearance of desmoplasia involving CAFs and fibrosis characterized by deregulated stellate cells. In addition, modulated release of soluble factors can act as (auto)activating feedback loop for transition of NFs into their pathological counterparts. Furthermore, epigenetic communication between CAFs and cancer cells may confer to cancer specific functional readouts and transition of NF into their pathological counterparts. MiR related epigenetic regulation with many similarities should be considered as key factor in development of cancer and fibrosis specific environment.

Good governance in natural resource management (NRM) is one of the most challenging issues in developing countries that often inappropriately embedded in national policies and political agendas. It is, in fact, even more important for countries like Bangladesh with exceptionally high pressure and dependence on its natural resources for sustaining rural livelihoods. Globally, nowadays, good governance is considered as one of the key factor for achieving the goal of sustainable development and biodiversity conservation. Bangladesh, of late has responded to that global zeal by involving local communities in the management of country’s declining forest and other natural resources. The colonial legacy of the forestry sector of Bangladesh was planned and, managed as interim projects through donors’ prescriptions. Thus, institutions, management processes and conservation outcomes were problematic. The conventional approach adopted by colonial and post-colonial regimes for forest management also proved to be inefficient due to its top-down management system. The absolute dependency on donor support, and their prescription sometimes worsened the situation both ecologically and socially. Global, regional and local trends supported the need for a different dimension in the governance paradigms. The introduction of a pluralistic approach, known as co-management in protected areas (PAs) is an example of an attempt whereby shared governance mechanism are implemented to attain the desired goals of conservation that will also address the livelihoods and aspirations of communities living in and around PAs of the country. However, in designing future forest and PA regimes the concern of the external aid support and attached conditions remain a reality that needs to be addressed. Adequate attention should be given to our vanishing biodiversity, culture and community livelihoods through devising an appropriate governance mechanism recognizing and supporting local rights, access and participation in the environmental management. It is now time to mainstream the adhoc nature of governance according to our national conservation strategy and policy frameworks in order to achieve the goals and objectives of the Bangladesh NRM sector addressing the human and community right of people in the specific context of forest protected areas management.

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumour distribution of fenretinide, a synthetic retinoid chemically related to all-trans-retinoic acid, after administration of a novel oral nanoformulation of fenretinide, called bionanofenretinide (BNF). BNF was developed to overcome the major limitation of fenretinide: its poor aqueous solubility and bioavailability due to its hydrophobic nature. The method proved to be reproducible, precise, and highly accurate for the measurement of the drug and the mains metabolites. The lower limit of quantification resulted 1 ng/mL. The curve range of 1-500 ng/mL and 50-2000 ng/mL, for plasma and tumor homogenate respectively, was appropriate for the analysis, as demonstrated by the accuracy between 96.8% and 102.4% for plasma and 96.6-102.3% for tumor. The inter-days precision and accuracy determined on quality controls at 3 different levels were in ranges of 6.9%-7.5% and 99.3-101.0% and 0.96-1.91% and 102.3-105.8% for plasma and tumour, respectively.

Predictive biomarkers for immune checkpoint inhibitors (ICI), such as PD-L1 expression (TPS), remain limited in clinical applications. Improved novel ICI predictive biomarkers are urgently needed. We evaluated a live single-cell functional liquid biopsy cytokine profiling platform to track immunotherapy treatment response and outcomes. Peripheral blood mononuclear cell samples of healthy donors and NSCLC patients undergoing ICI-based therapies were collected longitudinally pre-/post-treatment under IRB-approved protocols. Samples were enriched for CD4+ and CD8+ T-lymphocytes and analyzed on the IsoLight platform. The single T-cells were captured in microchambers on IsoCode chips for cytokines profiling. Functional polyfunctionality data from 55,775 single cells were analyzed using the IsoSpeak software, kappa coefficient, and Kaplan-Meier survival plots. We found a significant difference between responders and non-responders in CD8+ T-cells’ changes in overall polyfunctionality and polyfunctional strength index (ΔPSI). ΔPSI score in CD8+ T-cells performed better than PD-L1 TPS and, when combined with PD-L1 TPS, strongly correlated with early ICI treatment response with a kappa coefficient of 1.0 (p=0.003). High CD4+ T-cells ΔPSI predicted a strong trend of improved PFS (3.9-fold) and OS (3-fold). In conclusion, single peripheral T-cell polyfunctionality dynamics analysis is a promising liquid biopsy profiling platform as NSCLC ICI predictive biomarker regardless of oncogene-addiction status.

Recombinant α1-microglobulin (A1M) is proposed as protector during 177Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of 177Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but, the radioprotecting action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after 177Lu-octreotate and/or A1M administration. Mice were injected with 177Lu-octreotate and/or A1M, while control mice received saline or A1M vehicle solution. Bone marrow, kidney medulla, and kidney cortex were sampled after 24 hours or 7 days. Differential protein expression was analyzed with tandem mass spectrometry. Dosimetric estimation was based on 177Lu activity in kidney. PHLDA3 was the most prominent radiation responsive protein in kidney tissue. In general, no statistically significant difference in expression of radiation-related proteins was observed between the irradiated groups. Most canonical pathways were identified in bone marrow from the 177Lu-octreotate+A1M group. Altogether, tissue-dependent proteomic response followed exposure to 177Lu-octreotate alone or together with A1M. Combining 177Lu-octreotate with A1M did not inhibit the radiation induced protein expression early after exposure, and late effects should be further studied.

The paper examines the impact of inward remittances flows on per capita GDP growth in Bangladesh during 1976-2012. We find that the growth effect of remittances is negative at first but becomes positive at a later stage, an evidence of a non-linear. Unproductive use of remittances was rampant in the beginning when they were received by migrant families but better social and economic investments led to more productive utilisation of remittances receipts at later periods. This was the possible mechanism behind the U-shaped relationship. Unlike what is suggested in the literature that the effect of remittances is more pronounced in a less financially developed economy, our evidence do not show that the effect of remittances on per capita GDP growth in Bangladesh is conditional on the level of financial development.

The paper combines two new original concepts about eco-energetic systems. The first one is related to the M.E.N. (Mega-Eco-Nega-Watt) paradigm, which is based on three different but complementary ecological economic spaces: MEGAWATT, as needed energy, ECOWATT, as ecological energy, and NEGAWATT, as preserved energy, even the renewable energies and technologies, in the context of electrical energy production. The second concept presented in this paper is the eco-energetic efficiency, introduced in order to facilitate a correlation between the energetic efficiency of the system and a necessary, new defined ecological coefficient. The proposed formula for eco-energetic efficiency enables an interesting form of reporting to the different situations in which the input energy, output energy, lost energy and externalities, involved in an energetic process interact to produce energy in a specific energetic system, in connection with the circular economy model. Finally, is presented an original diagram of the energetic chains to produce electricity in a resilience regim, with high eco-energetic efficiency from originating in different primary energetic sources as external (gravitation & solar sources), fuels (classical & radioactive), internal sources and others. Even what kind of energetic sources are used to obtain electricity, as coals, gas, wood, hydropower, nuclear power, wind power, biomass, solar systems, and others, the entire process should be sustainable in what is the transdisciplinary integration of the different representative spheres as energy, socio-economy, ecology (environment), with the main core, sustainable education, inclueding the law and administrative aspects, as necessary fields of the knowledge based society/economy.

The aim of this article is to evaluate and compare, retrospectively, the efficacy of two regenerative periodontal procedures in patients suffering from aggressive periodontitis (AgP). Twenty-eight patients were diagnosed with AgP, suffering from multiple intra-bony defects (IBD); that were treated by one of two regenerative modalities of periodontal therapy randomly assigned to each patient: a. guided tissue regeneration (GTR) or b. an application of enamel matrix derivatives (EMD) combined with DBX. The monitoring of the treated sites included recordings of probing depth (PD), clinical attachment level (CAL), and gingival recession. Pre-treatment and follow-up (up to 10 years from the surgery) recordings were analyzed statistically within and between groups. A significant reduction was shown at time on PD and CAL values, however, not between subject groups. CAL values decreased in all sites. At EMD group (44 sites) CAL gain was 1.92 mm (±1.68) from pre-treatment to follow-up (p<0.001) and at the GTR group (12 sites) CAL gain of 2.27 (±1.82) mm. In conclusion, 1-10 years observations have shown that surgical treatment of AgP patients by either GTR or by application of EMD/DBX results in similar successful clinical results.