Background: Lipid disorders are one of risk factors for cardiovascular diseases. The aim of the study was to determine the lipid profile in early childhood in the group of Polish children born small for gestational age (SGA). Materials and Methods: The study included 140 children (93 SGA and 47 controls) aged 5 to 11 years. All children underwent a physical examination and blood tests for the glucose and lipid profile. SGA group was divided in subgroups: symmetrical and asymmetric intrauterine growth restriction (IUGR). Results: Blood sample analysis revealed higher levels of total cholesterol levels (SGA group 190.61 +/- 24.66 mg/dl vs control 143.23 +/- 23.90; p<0.001). The analysis of particular fractions of cholesterol showed significantly higher mean values of triglycerides, LDL-cholesterol as well as lower mean values of HDL-cholesterol in children born as SGA. Children in both groups did not differ significantly according to weight and body mass index. A statistically significantly higher glucose concentration was obtained in the group of children with IUGR with symmetrical type of IUGR. Conclusions: Children born SGA even in their early childhood, without overweight or obesity, have abnormal lipid profile, which may be a risk factor of cardiovascular diseases in adulthood.

One of the major concerns in structural health management (SHM) is the early detection of a growing crack. Using this, future damage due to crack propagation can be mitigated or eliminated by implementing proper repair and maintenance. Acoustic Emission (AE) is a non-destructive testing (NDT) method with potential applications for locating and monitoring fatigue cracks. The research presented in this paper focuses on SHM using AE. A novel AE signal analysis approach was proposed in order to detect crack initiation and assess small crack lengths. Experimental investigation indicated that initiation of a crack could be identified through the statistical analysis of the resulting features of the AE signals. A probabilistic AE-based model for small fatigue crack sizing was developed and the uncertainties of the model were estimated. In addition, a probabilistic model validation approach was implemented to confirm accurate estimation of the results. The outcome of this research can be used to evaluate the integrity of structures under fatigue loading. The proposed approach can also be applied as an approach to manage health and assess prognosis of structures.

In an insightful article published in Nature human behavior on November 2020, the effectiveness of 46 “non-pharmaceutical interventions” (NPI) regarding Covid-19 pandemic have been compared¹. One of these 46 categories, the one which is ranked as the most effective measure, is named “small gatherings cancelation”. In the discussion section of that article, the authors introduce a list of what they probably assume to be representative examples of this category, namely, “closures of shops”, “closure of restaurants,” “mandatory home–working”, “gathering of 50 people or less” and so on. The name that the authors have given to this category could give rise to confusions and misunderstandings. We used corpus analysis to show that “small gathering” is commonly used to denote a planned or spontaneous “event”, and consequently does not convey what the authors intend this term to cover as its most representative instances i.e., Simultaneous presence of people (crowd) in shops or offices. Furthermore, taking a top-down approach, we focused on the information which was provided in reference material like CDC and WHO documents. The analysis showed that “small gatherings” is encoded in those sources to denote “events” and “small gatherings cancelation” is used to denote cancelling preplanned events. In conclusion, neither unspecialized language nor official/institutional discourse uses “small gathering” the way that the authors of the aforementioned article use it i.e., to refer to simultaneous presence of people (crowd) in shops or offices. Therefore, when language users come across this phrase, if they do not read the entire article, the only semantic frame that is evoked in their mind would be that of a festive or social “event” rather than of crowded shops or offices; this misunderstanding is cognitively justified and consequently changing this terminology is recommended.

A recent study has suggested that the age profiles for deaths due to COVID-19 variants differs between variants and shows male/female specificity. This study demonstrates the age and sex dependency is common among human pathogens. The often-reported higher susceptibility to infections among the young and elderly is true in general but does not apply to individual pathogens. Even among different types of pneumonia there are subtle differences in the age profile. The gender ratio between pathogens likewise shows wide variation from as low as 10% female admissions for leptospirosis to around 90% for gonococcal admissions. The observed age/sex variation observed for mortality due to COVID-19 variants is an expression of a far wider phenomenon with implications to the age/sex response to vaccines. We propose that such differences are likely to be controlled by small noncoding RNAs which act as potent regulators of gene expression leading to altered cell morphology, metabolism, immune function, and response to vaccines.

Since 2020 COVID-19 has caused serious mortality around the world. Given the ambiguity in es-tablishing COVID-19 as the direct cause of death we first investigate the effects of age and sex upon all-cause mortality during 2020 and 2021 in England and Wales. Since infectious agents have their own unique age profile for death, we explore several methods to adjust single year of age deaths in England and Wales during 2019 (the pre-COVID-19 base year) to a pathogen-neutral single year of age baseline. This adjusted base year is then used to confirm the widely reported higher deaths in males for most ages above 43 years in both 2020 and 2021. During 2020 (+ COVID-19 but no vac-cination) both male and female population-adjusted deaths were significantly increased above age 35. A significant reduction in all-cause mortality among both males and females aged 75+ could be demonstrated in 2021 during widespread COVID–19 vaccination, however, below age 75 deaths progressively increased. This finding arises from a mix of vaccination and year of age profiles of deaths for the different SARS-CoV-2 variants. In addition, specific effects for age around puberty were demonstrated where females had higher deaths rather than males. There is evidence that year-of-birth cohorts may also be involved, indicating that immune priming to specific pathogen outbreaks in the past may lead to lower deaths for some birth cohorts. To specifically identify the age profile for the COVID-19 variants in 2020 to 2023, we employ the proportion of total deaths at each age which are potentially due to or ‘with’ COVID-19. The original Wuhan strain, and the Alpha variant show somewhat limited divergence in the age profile with the Alpha variant shifted to a moderately higher proportion of deaths below age 84. The Delta variant specifically targeted persons below age 65. The Omicron variants showed significantly lower proportion of overall mortality, with markedly higher relative proportion of deaths above age 65 steeply increasing with age to a maximum around 100 years of age. A similar age profile for the variants can be seen in the age-banded deaths in US states – although slightly obscured by using age bands rather than single year of age. However, the US data shows that higher male deaths are greatly dependent on age and the COVID-variant. Deaths determined as ‘due to’ COVID-19 (as opposed to ‘involving’ COVID-19) in England and Wales were especially over-estimated in 2021 relative to the change in all-cause mortality. This arose as a by-product of an increase in COVID-19 testing capacity in late 2020. Potential structure-function mechanisms for the year of age specificity of SARS-CoV-2 var-iants are discussed. The question is posed as to whether vaccines based on different variants carry the specific age profile through into the vaccine.

Expression analysis of small noncoding RNA (sRNA), including microRNA, piwi-interacting RNA, small rRNA-derived RNA, and tRNA-derived small RNA, is a novel and quickly developing field. Despite a range of proposed approaches, selecting and adapting a particular pipeline for transcriptomic analysis of sRNA remains a challenge. This paper focuses on the identification of the optimal pipeline configurations for each step of human sRNA analysis, including reads trimming, filtering, mapping, transcript abundance quantification and differential expression analysis. Based on our study, we suggest the following parameters for analysis of human sRNA in relation to categorical analyses with two groups of biosamples: (1) trimming with the lower length bound = 15 and the upper length bound = \(Read\ length - 40\% Adapter\ length\); (2) mapping on a reference genome with bowtie aligner with one mismatch allowed (-v 1 parameter); (3) filtering by mean threshold > 5; and (4) analyzing differential expression with DESeq2 with adjusted p-value < 0.05 or limma with p-value < 0.05 if there is very little signal and few transcripts.

The mucopolysaccharidoses (MPS) are a group of 11 lysosomal storage diseases (LSDs) produced by mutations in the enzymes involved in the lysosomal catabolism of glycosaminoglycans. Most of the mutations affecting these enzymes may lead to changes in processing, folding, glycosylation, pH stability, protein aggregation, and defective transport to the lysosomes. The use of small molecules, called pharmacological chaperones (PCs), that can restore the folding, trafficking and biological activity of mutated enzymes has been extensively explored in LSDs as a therapeutic alternative. PCs have the advantage of wide tissue distribution, potential oral administration, lower production cost, and fewer issues of immunogenicity. In this paper, we will review the advances in the identification and characterization of PCs for the MPS. These molecules, mainly based in molecules mimicking the enzyme substrates, have been described for MPS II, IVA, and IVB, showing a mutation-dependent enhancement of the mutated enzymes. Although the results show the potential of this strategy, further studies should focus in the development of disease-specific cellular models that allow a proper screening and evaluation of the identified PCs. In addition, in vivo evaluation, both pre-clinical and clinical, should be performed, before they can become a real therapeutic strategy for the treatment of MPS patients.

In the rapidly evolving landscape of genetic engineering, the advent of CRISPR-Cas technologies has catalyzed a paradigm shift, empowering scientists to manipulate the genetic code with unprece-dented accuracy and efficiency. Despite the remarkable capabilities inherent to CRISPR-Cas sys-tems, recent advancements have witnessed the integration of small molecule to augment their functionality, introducing new dimensions to the precision and versatility of gene editing applica-tions. This review delves into the synergy between CRISPR-Cas technologies and small molecule drugs, elucidating the pivotal role of chemicals in optimizing target specificity and editing efficiency. By examining a diverse array of applications, ranging from therapeutic interventions to agricultural advancements, we explore how the judicious use of chemicals enhances the precision of CRISPR-Cas-mediated genetic modifications. In this review we emphasize the significance of small molecule drugs in fine-tuning the CRISPR-Cas machinery, which allows researchers to exert meticulous con-trol over the editing process. We delve into the mechanisms through which these chemicals bolster target specificity, mitigate off-target effects, and contribute to the overall refinement of gene edit-ing outcomes. Additionally, we discuss the potential of chemical integration in expanding the scope of CRISPR-Cas technologies, enabling tailored solutions for diverse genetic manipulation challenges. As CRISPR-Cas technologies continue to evolve, the integration of small molecule drugs emerges as a crucial avenue for advancing the precision and applicability of gene editing techniques. This re-view not only synthesizes current knowledge but also highlights future prospects, paving the way for a deeper understanding of the synergistic interplay between CRISPR-Cas systems and chemical modulators in the pursuit of more controlled and efficient genetic modifications.

The current trend in supply chain development requires the application of new knowledge to meet the challenges posed by new technologies. One such technology is blockchain, which facilitates supply chain solutions through the use of innovative data transfer, storage and verification systems. However, the use of blockchain can be challenging for certain stakeholders, such as small carriers, who may lack the necessary technical expertise or access to the technology. In this paper, we explore the potential for engaging small carriers that provide services within the blockchain supply chain but face technological barriers. We identify the barriers and opportunities for these carriers to participate, focusing on a case study of a small carrier that transports temperature-sensitive cargo. In addition, we introduce in-vehicle temperature measurement for use in cold chains and propose an ecosystem that can benefit different stakeholder groups.

We develop the theory of Heyting small spaces and prove a new version of Esakia duality for such spaces. To do this, we notice that spectral spaces may be seen as sober small spaces with all smops compact and introduce the method of the standard spectralification. This helps to understand open continuous definable mappings between definable spaces over o-minimal structures.

Background: The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer(ES-SCLC). Intergrated the clinical benefits of pembrolizumab and its high cost into account, this study aim to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the the US payer perspective. Methods: A Markov model was developed to compared the costs and quality-adjusted life-years (QALYs) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy, treatment utilization and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examined the robustness of our model. Results: Adding pembrolizumab to standard first-line EP, resulted in better effectiveness than the use of EP alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio(ICER) of $334,373/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerts no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide rang of willingness to pay were modest. Conclusion: From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compare with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary measure to improve its cost-effectiveness.

Small scale carp polyculture plays a key role for food supply in Bangladesh, however, factors including water pollution, limited infrastructure and inadequate disease management hinder its sustainability. This paper reports on a survey of 231 farmers across the 6 major carp producing regions in Bangladesh, analyzing factors including, farmers’ social aspects, farm characteristics, information on disease and approaches adopted to combat them, and biosecurity practices. Almost half (46.8%) of the farms surveyed experienced disease in carp species, with clear regional variations. Eighty four percent of farms reported carp mortalities during disease outbreak, with an average mortality level 10.23±11.81%. Clinical signs during outbreaks lasted between a week and a month, and there was a peak in disease outbreaks in two seasonal periods between June to July and October to December. Disease incidence was related to a range of factors including the farmer experience, ponds/farm type, stocked species, and biosecurity practice. A combination of disinfecting measures during pond preparation and measures during stocking, including discarding fingerling transport water off-farm, fingerling disinfection and check the health of fingerlings before stocking significantly reduced disease occurrence. Treatments involving the antibiotics, ciprofloxacin, erythromycin, and azithromycin were reported as ineffective, raising concerns about non-prudent use, inadequate dosing (perhaps without appropriate veterinary guidance) and the potential for further driving antimicrobial resistance in the environment. The research unveils a concerning pattern of disease high disease incidence across small-scale carp farms in Bangladesh and the significant potential for disease spread highlights the need for responsible disposal practices. The study emphasizes the need for improving training and awareness programs are vital for addressing biosecurity and disease management challenges, ensuring sustainable aquaculture and community well-being.

Entrepreneurial activities in economic and social domains are considered one of the conditional pillars for successful transformation of resource-rich countries to sustainable, knowledge-based and diversified economies. However, there is no, and cannot be, a single recipe for such a transformation as every country or region needs to develop its own strategy, policy toolbox and implementation plan depending on its historical and present socio-economic make up and trajectory. This paper advances the qualitative findings of a previously published work to delve deeper into the complexities of entrepreneurship within resource-based economies, with a particular focus on Qatar. Employing a mixed methodology that blends explanatory and quantitative analysis, this paper aims to validate and refine the entrepreneurship framework proposed previously, ensuring its relevance and adaptability to Qatar's unique economic and cultural context, and its extendibility to similar resource-rich country settings. It systematically focuses on discovering various social, economic, and environmental dimensions critical to fostering entrepreneurship in resource-rich countries. These include examining government policies, cultural and social factors, financial support mechanisms, innovation ecosystem, technology adaptation, and digitization. A primary component of this study is the methodological approach, which includes collecting and analyzing quantitative data through a survey developed based on previous findings on qualitative explorations. This approach allows for an objective assessment of the effectiveness of the proposed recommendations. The paper presents a set of detailed recommendations aimed at various stakeholders, including government bodies, supporting agencies, and entrepreneurs themselves. These recommendations encompass integrating entrepreneurship education into academic curricula, increasing easy access to business and market information, simplifying, unifying and streamlining policies and procedures, and adapting them into the legal system. Other important and unique recommendations include establishing a country-wide entrepreneurship free-zone (Ent-Q) and facilitating its operations though an online digital platform (Ryadah), allocating certain percentage of governmental ministries’, agencies’ as well as large corporations’ budgets into innovative small business development programs and preferred purchasing from small business. These initiatives are validated to become effective tools and avenues to create a conducive entrepreneurial environment, facilitating transformation into a diversified, knowledge-based and sustainable economy. The expected outcomes of implementing these recommendations include an increase in the efficiency of entrepreneurship-related policymaking, a rise in the number, quality and impact of entrepreneurs, and the sustained diversification of the economy into non-oil/gas sectors and actors. In conclusion, this paper provides a comprehensive set of strategies and recommendations expected to significantly contribute to the nurturing and growth of entrepreneurship in resource-based economies.

To verify the reliability of the proposed stitching linear scan method for roundness measurement of small cylindrical workpieces, measurement uncertainties of the workpieces with various dimension are conducted. The cross-sectional circle of a cylindrical workpiece is divided into several equal arcs to be measured. Thus, the arc profile can be characterized according to the measured arcs. The roundness profile of the cylindrical part can be obtained by stitching these arc profiles together. Firstly, the measurement uncertainty of the workpiece with a diameter 1.5 mm and length 5.8 mm is evaluated to be 0.095 μm which can meet the uncertainty target of 0.1 μm. Considering the uncertainty of θx and θz which are the alignment around X-axis and Z-axis respectively changing with workpiece dimension changing, relevant uncertainties are carried out. As a result, there is no limitation with respect to workpiece diameter theoretically If the alignment can reach θz = θx = ±0.1° without considering the measurable range of the machine.

We propose a new estimator for creating expansion factors for survey plots in the USDA Forest Inventory and Analysis program. This is a regularized version of the raking estimator widely used in sample surveys. The regularized raking method differs from other predictive modeling methods for integrating survey and ancillary data in that it produces a single set of expansion factors that can have general purpose use to produce small area estimates and wall-to-wall maps of any plot characteristic. This method also differs from other more widely used survey techniques, such of GREG estimation, in that it is guaranteed to produce positive expansion factors. We extend the previous method here to include cross-validation, and provide a comparison to expansion factors between the regularized raking and ridge GREG survey calibration.

EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, remission is transient, and no further effective treatment options are available for EGFR-TKI-advanced EGFR-mutant NSCLCs. Immunotherapy with immune checkpoint inhibitors (ICIs) induces sustained cancer remission in a subset of NSCLCs. However, ICI therapy exhibits limited activity in most EGFR-mutant NSCLCs. Mechanistically, the strong oncogenic EGFR signaling in EGFR-mutant NSCLCs contributes to the non-inflamed tumor immune microenvironment (TIME), characterized by a limited number of CD8+ T cell infiltration, a high number of regulatory CD4+ T cells and a high number of inactivated infiltrated T cells. Besides, EGFR-mutant NSCLC patients are generally non-smokers with low levels of PD-L1 expression and tumor mutation burden. However, current understanding only partially explains why a small population of EGFR-mutant NSCLCs durably respond to ICI therapy, resulting in many researchers actively working in this field. This review reviews the hope seen from pre-clinical studies and clinical trials which may be adopted to improve the outcome of ICI therapy in EGFR-mutant NSCLCs. Besides, the underlying mechanisms leading to the inferior clinical outcome of ICI therapy in EGFR-mutant NSCLCs are discussed.

Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for translating amino acids for protein synthesis. Their function in pathogen-derived infectious diseases has been well established, which has led to development of small molecule therapeutics. The applicability of ARS inhibitors for other human diseases such as fibrosis has recently been explored in the clinical setting. There are active studies to find small molecule therapeutics for cancers. Studies on central nervous system (CNS) disorders are burgeoning as well. In this regard, we present a concise analysis of the recent development of ARS inhibitors based on small molecules from the discovery research stage to clinical studies as well as a recent patent analysis from the medicinal chemistry point of view.

In general, remote sensing has proven to be a powerful tool in the overall understanding of natural and anthropogenic phenomena. Satellites have become useful tools for tasks such as characterization, monitoring, and the continuous prospecting of natural resources. This research aims to analyze spatial dynamic and destructive on coral reefs area and correlation between live coral reduction and population on small islands. Landsat MSS, TM, ETM, and OLI-TIRS are used to spatial analyze of coral reef dynamics from 1972 to 2016. The image processing includes gap-filling, atmospheric correction, geometric correction, image composite (true color), water column correction, unsupervised classification, reclassification, accuracy assessment. The statistical analysis identifies the relationship between dynamic population data with a reduction of live coral, namely Principal Component Analysis (PCA) and Multiple Regression Analysis. The effect of the population shows a positive correlation with the reduction in the area of live coral, although it is significant. The fact is the practice of coral destruction on an island; it is usually not only caused or carried out by residents who live on the island but also carried out by other residents of different islands.

In this study, we aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). We conducted a secondary analysis of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29 – 0.97). In multivariate analysis, patient age (p = 0.014) and gross tumor volume (GTV, p = 0.031) were significant factors associated with overall survival, while TLC reduction (p = 0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p = 0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, constraining the volume of the radiation dose to the whole heart must be prioritized to reduce TLC.

The massive amount of human biological, imaging and clinical data produced by multiple and diverse sources, necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels as well as their orchestration and links are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof of concept study cases. Personalized simulations over the actual anatomy of a patient have been carried out. The hypermodel has also applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin based clinical decision support system and the core of future in silico trial platforms, although additional retrospective adaptation and validation is necessary.

In Bangladesh, family businesses play a significant role in the country's business landscape because so few private companies are set up as large-scale, non-family ownership firms. Thus, it is vital to comprehend family businesses in order to comprehend Bangladeshi company dynamics. In this paper, authors attempted to survey the existing research in the area of family business in Bangladesh. It was found that the area as a research is totally an open field and a lot of new research can be done in the said area. Although a good number of studies can be classified as focused on the SME (small and medium enterprise) domain, a major shortcoming of those SME studies is that the SMEs themselves vary greatly in terms of size, scope, and technology. Whereas most of the family businesses can be predominantly put in the SME category, the particular issue of family business and family dynamics is not very common in those studies. This paper suggests that a good amount of research or studies can be done focusing on family business constitution, family members' participation norm, recruitment and promotion norm, family business succession rules and succession planning, training for family business leadership and management, training for board and directorial supervision, and so on.

The rampant misuse of drones poses a serious threat to national security and human life. Currently, the CNN method has been widely used in drone detection. However, there is a challenge that traditional CNN cannot cope with, which is small drone targets often have reduced amplitude or even lost features in infrared images. This paper proposes a Progressive Feature Fusion Network (PFFNet) that gradually increases the response amplitude of the target in the deep network. The Feature Selection Model (FSM) is designed to improve the utilisation of the output coding graph and enhance the feature representation of the target in the network. A lightweight segmentation head is also designed to achieve progressive feature fusion with multi-layer outputs. Experimental results show that the proposed algorithm can achieve low duration and high accuracy in drone target detection. On the public dataset, the IoU is improved by 2.53% and the detection time is reduced by 81.03%.

Plant pathogenic fungi are the largest group of disease-causing agents on crop plants and represent a persistent and significant threat to agriculture worldwide. Conventional approaches based on the use of pesticides raise social concern for the impact on the environment and human health and alternative control methods are urgently needed. The rapid improvement and extensive implementation of RNAi technology for various model and non-model organisms has provided the initial framework to adapt this post-transcriptional gene silencing technology for the management of fungal pathogens. In this review, we describe exogenous RNAi involved in plant pathogenic fungi and discuss small RNA production, formulation, and RNAi delivery methods. We explore some challenges with possible solutions. Furthermore, exogenous RNAi holds great potential for RNAi-mediated plant pathogenic fungal disease control.

This study investigated the roles of transactions cost in MSMEs access to finance. This was done by investigating the impact of transactions cost on access to credit from both MSMEs and financial institutions (commercial banks and microfinance banks). From the MSMEs’ side, borrowing experience, decision lag, firm size and borrowers’ distance to the loan office were investigated. On the financial institution’s side, the costs of information gathering, loan administration, monitoring and loan enforcement were investigated. We used the questionnaire survey method, in-depth interviews and case studies, as well as the annual financial statements of the banks. We identified interest rate and collateral value as constraints to access to finance for MSMEs. We also found financial institutions’ attitude to MSMEs access to credit was not friendly. Financial institutions need to do more to bring down transaction cost of lending. This hopefully can be achieved by investing more in agent banking which would lower operating costs, as well as spreading risk, and ultimately increase credit intermediation to small businesses.

We present the first evidence of lethal interspecific aggressive behavior against Burmeister’s porpoise Phocoena spinipinnis, in a non-predatory context, and the first indications of such behavior in a cetacean from Chilean waters. Two cases, both adult males, are described. Analysis of the fresh tooth rakes, specifically the inter-rake distance, points to common bottlenose dolphin Tursiops truncatus as aggressor. Interdental distances measured on skulls allowed us to exclude Orcinus orca, Globicephala melas, Lagenorhynchus obscurus and Pseudorca crassidens. Evidence of severe blunt trauma, including extensive subdermal hematomas, rupture of pleura and extrusion of lung parenchyma, underscores the level of violent aggression. The reason is unknown but Tursiops truncatus is well-documented to occasionally harass and kill harbour porpoises Phocoena phocoena in the Northern Hemisphere. Considering the scarce information available on the biology and behavioral ecology of Burmeister’s porpoises in Chile and elsewhere, we recommend more systematic field research. Also, as to help formulate effective management measures that can mitigate the main threat for this species in Chile (as in Peru), i.e. fisheries interactions. In Chile, P. spinipinnis is classified as Data Deficient (D.S. N°06-2017), so its real conservation status is unknown.

This manuscript critically reviews the design and delivery of spray-dried particles for the achievement of high total lung doses (TLD) with a portable dry powder inhaler. We introduce a new metric termed the product density, which is simply the TLD of a drug divided by the volume of the receptacle it is contained within. The product density is given by the product of three terms: the packing density (the mass of powder divided by the volume of the receptacle), the drug loading (the mass of drug divided by the mass of powder), and the aerosol performance (the TLD divided by the mass of drug). This manuscript discusses strategies for maximizing each of these terms. Spray drying at low drying rates with small amounts of a shell-forming excipient (low Peclet Number) leads to formation of higher density particles with high packing densities. This enables ultrahigh TLD (>100 mg of drug) to be achieved from a single receptacle. Emptying of powder from capsules is directly proportional to the mass of powder in the receptacle, requiring an inhaled volume of about 1 L for fill masses between 40 and 50 mg and up to 3.2 L for a fill mass of 150 mg.

Small RNAs (sRNA) and microRNAs (miRNAs) are small endogenous noncoding single-stranded RNAs that regulate gene expression in eukaryotes. Experiments in mice and humans have revealed that a typical small RNA can affect the expression of a wide range of genes, implying that small RNAs function as global regulators. Here, we used small RNA deep sequencing to investigate at how jararhagin, a metalloproteinase toxin produced from the venom of Bothrops jararaca, affected mmu-miRs expression in mice 2 h and 24 h after injection. The findings revealed that seven mmu-miRs were substantially differentially expressed (p-value (p (Corr) cut-off 0.05, FC 2) at 2h after jararhagin exposure, and that the majority of them were upregulated when compared to PBS. In contrast to these findings, a comparison of Jar 24h vs PBS 24hrs demonstrated that the majority of identified mmu-miRs were downregulated. Furthermore, the studies demonstrated that mmu-miR can target the expression of several genes involved in the MAPK signaling pathway. The steady antithetical regulation of mmu-miRs may correlates with the expression of genes that trigger apoptosis via MAPK in the early stages, and this effect intensifies with time. The findings expand our understanding of the effects of jararhagin on local tissue lesions at the molecular level.

[NiFe]-hydrogenases are gas-processing metalloenzymes that catalyze the conversion of dihydrogen (H2) to protons and electrons in a broad range of microorganisms. Within the framework of green chemistry, the molecular proceedings of biological hydrogen turnover inspired the design of novel catalytic compounds for H2 generation. The bidirectional “O2-sensitive” [NiFe]-hydrogenase from Escherichia coli HYD-2 has recently been crystallized; however, a systematic infrared characterization in the presence of natural reactants is not available yet. In this study, we analyze HYD-2 from E. coli by in situ ATR FTIR spectroscopy under quantitative gas control. We provide an experimental assignment of all catalytically relevant redox intermediates alongside the O2- and CO-inhibited cofactor species. Furthermore, the reactivity and mutual competition between H2, O2, and CO was probed in real time, which lays the foundation for a comparison with other enzymes, e.g., “O2-tolerant” [NiFe]-hydrogenases. Surprisingly, only Ni-B was observed in the presence of O2 with no indications for the “unready” Ni-A state. The presented work proves the capabilities of in situ ATR FTIR spectroscopy as an efficient and powerful technique for the analysis of biological macromolecules and enzymatic small molecule catalysis.

Background: It remains unclear whether transfer RNA-derived small RNAs (tsRNAs) play a role in pathological cardiac hypertrophy (PCH). We aimed to clarify the expression profile of tsRNAs and disclose their relationship to the clinical phenotype of PCH and the putative role. Methods: Small RNA sequencing was performed in the plasma of PCH patients and healthy volunteers. In a larger sample size and angiotensin Ⅱ (Ang II)-stimulated H9c2 cells, the data were validated by real-time qPCR. The atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were examined in Ang II-stimulated H9c2 cells. The role of tsRNAs in the pathogenesis of PCH was explored by bioinformatics analysis. Results: A total of 4185 differentially expressed tsRNAs were identified, of which 4 and 5 tsRNAs were observed to be significantly differentially upregulated and downregulated expressed. Of the 5 down-regulated tsRNAs, 4 of them were verified to be significantly down-regulated in the larger sample group, among which tRF-30-3JVIJMRPFQ5D, tRF-16-R29P4PE, tRF-21-NB8PLML3E, and tRF-21-SWRYVMMV0 had areas under the curve to diagnose concentric hypertrophy. The 4 down-regulated tsRNAs were negatively correlated with left ventricular posterior wall dimensions in PCH patients (r=-0.4227; r=-0.4517; r=-0.5567; r=-0.4223). The levels of ANP and BNP as well as cell size were decreased in Ang II-stimulated H9c2 cells with 21-NB8PLML3E mimic transfection. Bioinformatics analysis revealed that the target genes of tRF-21-NB8PLML3E were mainly enriched in the metabolic pathway and involved in the regulation of ribosomes. Conclusion: The plasma tsRNAs tRF-21-NB8PLML3E might be considered biomarkers in patients with PCH with early screening potential.

HIV-1 Tat protein interacts with TAR RNA and recruits CDK9/cyclin T1 and other host factors to induce HIV-1 transcription. Thus Tat-TAR RNA interaction, which is unique for HIV-1, represents an attractive target for anti-HIV-1 therapeutics. To target Tat-TAR RNA interaction, we used a crystal structure of TAR RNA with acetylpromazine bound to the bulge of TAR RNA, to dock compounds from Enamine database containing 1.6 million individual compounds. Docking identified 173 compounds that were analyzed for the inhibition of HIV-1 infection. Top ten inhibitory compounds with IC50 ≤ 6 µM were selected and the three least toxic compounds, T6780107 (IC50=2.97 μM), T0516-4834 (IC50=0.2 μM) and T5628834 (IC50=3.46 μM), were further tested for HIV-1 transcription inhibition. Only T0516-4834 compound showed selective inhibition of Tat-induced HIV-1 transcription, whereas T6780107 compound inhibited equally basal and Tat-induced transcription and T5628834 compound only inhibited basal HIV-1 transcription. The T0516-4834 compound also showed strongest inhibition of HIV-1 gag RNA expression and p24 production in CEM T cells infected with HIV-1 IIIB. Of the three compounds, only the T0516-4834 compound disrupted Tat-TAR RNA interaction indicating that it might target TAR RNA. Also, of the three tested compounds, T5628834 but not T6780107 or T0516-4834 disrupted Tat-CDK9/cyclin T1 interaction. Taken together, our study identified novel compound T0516-4834 that disrupted Tat-TAR RNA interaction and inhibited Tat-induced transcription and HIV-1 infection suggesting that this compound might serve as a new lead for anti-HIV-1 therapeutics.

Capsizing accidents are regarded as marine accidents with a high rate of casualties per accident. Approximately 89% of all such accidents occur in small ships (vessels with gross tonnage less than 10 tons). Stability calculations are critical for assessing the risk of capsizing incidents and evaluating a ship's seaworthiness. Despite the high frequency of capsizing accidents involving small ships, they are generally exempt from adhering to stability regulations, thus remaining systemically exposed to the risk of capsizing. Moreover, the absence of essential design documents complicates direct ship stability calculations. This study utilizes hull form feature data—obtained from the general arrangement of small ships—as input for a deep learning model. The model is structured as a multilayer neural network and aims to infer hydrostatic curves, which is required data for stability calculations.

The operation feasibility of small hydropower plants in mountainous sites is subjected to the run-of-river flow which is also depending on a high variability in precipitation and snow cover. Moreover, the management of this kind of systems has to be performed with some particular operation conditions of the plant (e.g. turbine minimum and maximum discharge) but also some environmental flow requirements. In this context, a technological climate service is conceived in tight connection with end users, perfectly answering the needs of the management of small hydropower systems in a pilot area, and providing forecast of river streamflow together with other operation data. This paper presents an overview of the service but also a set of lessons learnt related to features, requirements and considerations to bear in mind from the point of view of climate services developers. In addition, the outcomes give insight into how this kind of services could change the traditional management (normally based on the past experience), providing a probability range of future river flow based on future weather scenarios according to the range of future weather possibilities. This highlights the utility of the co-generation process to implement climate services for water and energy fields but also that seasonal climate forecast could improve the business as usual of this kind of facilities.

Still, the most common in vitro model for absorption, distribution, metabolism and excretion (ADME) purposes is the Caco-2 cell line. However, clear differences in gene- and protein expression towards the small intestine and an at best fair prediction accuracy of intestinal drug absorption restrict the usefulness as model for intestinal epithelial cells. To overcome these limitations, we evaluated a panel of low-passaged patient-derived colorectal cancer cell lines of the HROC collection concerning similarities to small intestinal epithelial cells and their potential to predict intestinal drug absorption. After initial screen of a larger panel, ten cell lines with confluent outgrowth and long-lasting barrier forming potential were further characterized in close detail. Tight junctional complexes and microvilli structures were detected in all lines, differentiated epithelial cells were abundant in 7/10. All lines expressed multiple transporter molecules, with expression levels in three lines being close to those of small intestinal epithelial cells. Compared to the Caco-2 model, three HROC lines demonstrated both higher similarity to jejunal epithelial tissue cells and higher regulatory potential of relevant drug transporters. In sum, these lines would be better suited human small intestinal epithelium models for basic and translational research; especially for ADME studies.

Exportin-1, the ubiquitous nuclear protein transporter, is widely confirmed as an active chemotherapeutic target in non-small cell lung cancer condition while Juglans mandshurica is a well-studied anticancer plant in some lung cancer cell lines. We intend to find novel exportin-1 inhibitor from Juglans mandshurica with better potential tolerability and pharmaco-dynamo-kinetic properties than the current selective inhibitors of nuclear export in non-small cell lung cancer treatment. Osiris property explorer DataWarrior, Glide standard precision docking, quantum mechanics polarized ligand docking, MMGBSA binding free energy calculations, Jaguar density functional theory analysis, and the online web-based SwissADME were employed respectively in this study to filter the retrieved compounds based on tolerability, toxicity, and Lipinsky’s rule of five violation potential, determine their druggability, establish relative stability of the lead compound in water solvation model, and evaluates druglikeness, lead-likeness, as well as synthetic accessibility of the lead compound. This study reveals eriodictyol as having higher binding free energy (-40 kcal/mol) than that of standard (-39.56 kcal/mol) in exportin-1 active site, better synthetic accessibility score (3.15 versus 3.29), high GI absorption, non-blood brain barrier permeant, lacks Brenk and PAINS alert, obeying Lipinski’s, Ghose’s, Veber’s, Egan’s, and Muegge’s rule of druglikeness and lead-likeness as well as non-cytotoxic to HepG2 cells. We therefore found eriodictyol as a lead-like, non-toxic exportin-1 inhibitor with good predictive stability and pharmacokinetic potential and thus provided data for further validation of eriodictyol as a candidate exportin-1 inhibitor in both preclinical and clinical studies involving lung cancer therapy.

The aim of this study is to provide the scientists with a straightforward correlation that can be applied for predicting the Fanning friction factor and consequently the pressure drop during blood flow in small caliber vessels. Due to the small diameter of the conduit, the Reynolds numbers are low and thus the flow is laminar. The study has been conducted using CFD simulations validated with relevant experimental data acquired using an appropriate experimental set-up. The experiments concern pressure drop measurement during the flow of a blood analogue that follows the Casson model, i.e. an aqueous glycerol solution that contains a small amount of xanthan gum and exhibits similar behavior to blood, in a smooth, stainless steel microtube (L=5.6cm and D=400 μm). The interpretation of the resulting numerical data led to the proposal of a simplified model that incorporates the effect of the flow rate, the hematocrit value (35-55%) and the vessel diameter (300-1800 μm) and predicts with better than ±10% the Fanning friction factor and consequently the pressure drop during laminar blood flow in small caliber vessels.

Traceability is the ability to determine the path of a product from purchase to consumption to determine when and where it originated. This paper aimed to determine the factors that influence fishers’ decision-making to participate in tuna traceability program, it also explores the determinants of fish catch for small-scale fishers and the feasibility of implementing tuna traceability in the Davao Gulf, Philippines. The result of the interview showed that the significant factors that highly affected the decision-making of fishers in implementating tuna traceability program: boat capacity, fishing hours and communication of fishers (P≤0.05). Household size, years in community, fishing hours, volume of fish sold, and the fishers' communication in the fishing ground (P≤0.05) were other factors that determined the daily catch of the fishers. The results of this study showed that fishers from the Davao Gulf were willing to be part of traceability program that would sustain and increase the value of their fish catch. Moreover, communication was shown to be critically needed in such programs adjusting it for the fish catch to remain fresh or of good quality. Our study will help in deterring and mitigating illegal, unregulated and unreported fishing (IUU) through fish catch traceability.

Computers and artificial intelligence affect every field of life nowadays. In medical image interpretation automatic decision making using algorithms are used increasingly in every sub-field and computer aided diagnosis (CAD) is one of the main tools available to medical science today. CAD systems are used as an augmented option for both the medical practitioner and the patients, with image analysis and interpretation being of primary importance. In particular, spatial relations are used in knowledge representation, and these relations can be used for effective medical image interpretation. In this paper, we put forth an algorithm for defining non-small cells lungs cancer (NSCLC) stages in lungs images interpretation using topological spatial relations. We show an application case study in event motion predictions for lung cancer staging scoring - tumor, nodes and metastasis (TNM) - with combined topological and directional relations.

Detecting rotational objects in remote sensing imagery is a significant challenge. These images typically encompass a broad field of view, featuring diverse and intricate backgrounds, with ground objects of various sizes densely scattered. As a result, identifying objects of interest within these images is a daunting task. While the integration of Convolutional Neural Networks (CNN) and Transformer networks leads to some advancements in rotational object detection, there is still room for improvement, particularly in enhancing the extraction and utilization of information related to smaller objects. To address this, our paper presents a multi-scale feature fusion module and a global feature context aggregation module. Initially, we fuse original, shallow, and deep features to reduce the loss of shallow feature information, thereby improving the detection performance of small objects in complex backgrounds. Subsequently, we compute the correlation of contextual information within feature maps to extract valuable insights. We name the newly proposed model the "Multiscale Feature Context Aggregation Module" (MFCA). We evaluate our proposed methodology on three challenging remote sensing datasets: DIOR-R, HRSC, and MAR20. Comprehensive experimental results show that our approach surpasses baseline models by 2.07\% mAP, 1.02\% mAP, and 1.98\% mAP on the DIOR-R, HRSC2016, and MAR20 datasets, respectively.

F-type ATP synthases play a key role in oxidative and photophosphorylation processes producing adenosine triphosphate (ATP) for most biochemical reactions in living organisms. In contrast to the mitochondrial FOF1-ATP synthases those of chloroplasts are known to be mostly monomers with approx. 15% fraction of oligomers interacting presumably non-specifically in a thylakoid membrane. To shed light to the nature of this difference we studied interactions of the chloroplast ATP synthases using small-angle X-ray scattering (SAXS) method. Here, we report evidence of I-shaped dimerization of solubilized FOF1-ATP synthases from spinach chloroplasts at different salinity. The structural data were obtained by SAXS and showed dimerization in response to changes in ionic strength. The best model describing SAXS data was two ATP-synthases connected through F1/F1’ parts, presumably via their δ-subunits, forming dimers with the “I” shape. Such I-shaped dimers might possibly connect the neighboring lamellae in thylakoid stacks assuming that the FOF1 monomers comprising such dimers are embedded in different thylakoid membranes. If this type of dimerization exists in nature, it might be one of the pathways of inhibition of chloroplast FOF1-ATP synthase for preventing of ATP hydrolysis in dark, when salinity in plant chloroplasts is rising. Together with a redox switch inserted into a γ-subunit of chloroplast FOF1 and lateral oligomerization, an I-shaped dimerization might comprise a subtle regulatory process of ATP synthesis and stabilize the structure of thylakoid stacks in chloroplasts.

Small hydro-power systems seem to be the best solution for energy generation through the use of pump as turbine (PAT) due to its low cost and lesser environmental hazards associated with it. Recently, PAT applications are gaining global attention in energy generation but its operation is not fully understood. The performance and flow behavior is affected by several operational conditions. This study seeks to investigate the effects of rotational speed on flow behavior and performance of a PAT. Rotational speed is an important physical parameter that affects the operation of a PAT. A selected centrifugal pump model of four blades and splitters was used for the study. Numerical simulations were carried out using k-ε turbulence model to solve the three-dimensional (3D) equations in both pump and PAT modes. The outcomes were then validated using experimental results in the pump mode to obtain overview flow physiognomies. The results predicted that the efficiency increases as the rotational speed increases in the pump mode whereas in turbine mode, higher rotational speed cannot convert hydraulic energy into mechanical energy. Thus, a rotational speed of 1500 rpm performed the highest efficiency of 69.8% at QBEP among the other rotational speeds selected. Moreover, the head performance in the turbine mode increases as the flow rate increases. This research provides useful information which will help improve PAT performance as well as selecting PAT for small hydro-power site.

In the last years, more and more studies highlight the advantages of complementing traditional master classes with additional activities that improve students´ learning experience. This combination of teaching techniques is specially advised in the field of structural engineering, where intuition of the structural response it is of vital importance to understand the studied concepts. This paper deals with the introduction of a new (and more encouraging) educational tool to introduce intuitively students in the dynamic response of structures excited with an educational shaking table. Most of the educational structural health monitoring systems use sensors to determine the dynamic response of the structure. The proposed tool is based on a radically different approach, as it is based on low-cost image-recognition techniques. In fact, it only requires the use an amateur camera, a black background and a computer. In this study, the effects of both the camera location and the image quality are also evaluated. Finally, to validate the applicability of the proposed methodology, the dynamic response of small-scale buildings with different typologies is analyzed. In addition, a series of surveys were conducted in order to evaluate the activity based on student´s satisfaction and the actual acquisition and strengthening of knowledge.

Small modular reactors (SMR) (&lt;300 MW) offer a potentially attractive nuclear energy option for the middle-east region (MER). Currently, the MER uses a significant amount of fossil fuel to process heat applications such as water desalination and in petroleum refineries and chemical plants, besides generating electricity. SMR technologies represent an opportunity to meet future energy demand in the MER. This paper discusses issues related to the future development and use of SMR technology in nuclear-renewable hybrid energy systems for application in the middle east. SMRs have also been examined as part of a resilient hybrid energy system that combines nuclear energy with renewable energy and traditional fossil energy to produce chemicals, fuels, and electricity. This paper presents the results of a techno-economic analysis of a Nuclear-Renewable-Conventional Hybrid Energy System. The paper concludes that SMR technology will be an essential feature of future hybrid energy systems for the MER.

Importance: The COVID-19 pandemic is currently accelerating. Patients with locally advanced non-small cell lung cancer (LA-NSCLC) may require treatment in locations where resources are limited and the prevalence of infection is high. Patients with LA-NSCLC frequently present with comorbidities that increase the risk for severe morbidity and mortality from COVID-19. These risks may be further increased by treatments for LA-NSCLC. Observation: We present expert thoracic oncology multidisciplinary (radiation oncology, medical oncology, surgical oncology) consensus of alternative strategies for the treatment of LA-NSCLC during a pandemic. The overarching goals of these approaches are to reduce the number of visits to a healthcare facility, reduce the risk of SARS-CoV-2 exposure, and attenuate the immunocompromising effects of lung cancer therapies. Patients with resectable disease can be treated with definitive non-operative management if surgical resources are limited or the risks of perioperative care are high. Non-operative options include chemotherapy, chemoimmunotherapy, and radiation therapy with sequential schedules. The order of treatments may be based on patient factors and clinical resources. Whenever radiation therapy is delivered without concurrent chemotherapy, hypofractionated schedules are appropriate. For patients who are confirmed to have COVID-19, usually cancer therapies may be withheld until symptoms have resolved with negative viral test results. Conclusions and Relevance: The risk of severe treatment-related morbidity and mortality is significantly elevated for patients undergoing treatment for LA-NSCLC during the COVID-19 pandemic. Adapting alternative treatment strategies as quickly as possible may save lives and should be implemented through communication with the multidisciplinary cancer team.

A sufficient amount of tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥ 1 mm2) and tumor content rate (≥ 30%) on the success rate of Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥ 1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.

Biological nanoparticles (NPs), such as extracellular vesicles (EVs), exosome-mimetic nanovesicles (EMNVs) and nanoghosts (NGs), are perspective non-viral delivery vehicles for all types of therapeutic cargo. Biological NPs are renowned for their exceptional biocompatibility and safety, alongside their ease of functionalization, but a significant challenge arises when attempting to load therapeutic payloads, such as nucleic acids (NAs). One effective strategy involves fusing biological NPs with liposomes loaded with NAs, resulting in hybrid carriers that offer the benefits of both biological NPs and the capacity for high cargo loads. Despite their unique parameters, one of the major issues of virtually any nanoformulation is the ability to escape degradation in the compartment of endosomes and lysosomes which determines the overall efficiency of nanotherapeutics. In this study, we fabricated all major types of biological and hybrid NPs and studied their response to acidic environment observed in endolysosomal compartment. In this study, we show that EMNVs display increased protonation and swelling relative to EVs and NGs in an acidic environment. Furthermore, the hybrid NPs exhibit an even greater response compared to EMNVs. Short-term incubation of EMNVs in acidic pH corresponding to late endosomes and lysosomes again induces protonation and swelling, whereas hybrid NPs are ruptured, resulting in the decline of their quantities. Our findings demonstrate that in an acidic environment, there is enhanced rupture and release of vesicular cargo observed in hybrid EMNVs that are fused with liposomes compared to EMNVs alone. This was confirmed through PAGE electrophoresis analysis of mCherry protein loaded into nanoparticles. In vitro analysis of NPs colocalization with lysosomes in HepG2 cells demonstrated that EMNVs mostly avoid endolysosomal compartment whereas hybrid NPs escape it over time. To conclude, (1) hybrid biological NPs fused with liposomes appear more efficient in the endolysosomal escape via the mechanism of proton sponge associated with scavenging of protons by NPs, influx of counterions and water, and rupture of endo/lysosomes, but (2) EMNVs are much more efficient than hybrid NPs in actually avoiding endolysosomal compartment in human cells. These results reveal biochemical differences across four major types of biological and hybrid NPs, and indicate that EMNVs are more efficient in escaping or avoiding endolysosomal compartment.

Infrared small target detection (ISTD) plays a crucial role in both civilian and military applications. The detection of small targets against dense cluttered backgrounds remains a challenging task, requiring the collaboration of false alarm source elimination and target detection. Existing approaches primarily focus on modeling targets while often neglecting false alarm sources. To address this limitation, we propose a Target and False Alarm Collaborative Detection Network to leverage the information provided by false alarm sources and the background. Firstly, we introduce a False Alarm Source Estimation Block (FEB) that estimates potential interferences present in the background by extracting features on multiple scales and employing stepwise upsampling for feature fusion. Subsequently, we propose a framework that employs multiple FEBs to eliminate false alarm sources across multiple scales. Finally, a Target Segmentation Block (TSB) is introduced to accurately segment the targets to produce the final detection result. Experiments on public datasets demonstrate that, compared to other methods, our model achieves high accuracy in segmenting targets while being able to extract false alarm sources which can be used for further studies.

Ship detection in large-scene offshore synthetic aperture radar (SAR) images is crucial in civil and military fields, such as maritime management and wartime reconnaissance. However, the problems of low detection rates, high false alarm rates, and high missed detection rates of offshore ship targets in large-scene SAR images are due to the occlusion of objects or mutual occlusion among targets, especially for small ship targets. To solve this problem, this study proposes a target detection model (TAC_CSAC_Net) that incorporates a multi-attention mechanism for detecting marine vessels in large-scene SAR images. Experiments were conducted on two public datasets, the SAR-Ship-Dataset and high-resolution SAR image dataset (HRSID), with multi-scene and multi-size, and the results showed that the proposed TAC_CSAC_Net model achieves good performance for both small and occluded target detection. Experiments were conducted on a real large-scene dataset, LS-SSDD, to obtain the detection results of subgraphs of the same scene. Quantitative comparisons were made with classical and recently developed deep learning models, and the experiments demonstrated that the proposed model outperformed other models for large-scene SAR image target detection.

Water quality retrieval for small urban waterbodies by remote sensing get used to be difficult due to coarse spatial resolution of the remote sensing imagery. The recently launched Sentinel-2 produces imagery with a spatial resolution of 10 m. It provides an opportunity to solve the problem of retrieving water quality for small waterbodies. Additionally, many water management issues also require fine resolution of imagery, e.g. illegal discharge to an urban waterbody. Since illegal discharges are an important issue for urban water management, chemical oxygen demand (COD), total phosphorous (TP), and total nitrogen (TN) were chosen as the target parameters for water quality retrieval in this study. COD, TP and TN, however, are non-optically active parameters. There were limited studies in the past to retrieve these parameters in comparison with optically active parameters, e.g. Chlorophyll-A etc. This study compared three machine learning models, namely Random Forest (RF), Support Vector Regression (SVR), and Neural Networks (NN), to investigate the opportunity to retrieve the above non-optically active parameters. Results showed that R² of TP, TN, and COD by NN, RF and SVR were 0.94, 0.88, and 0.86, respectively. The performances of water quality retrieval for these non-optically active parameters were significantly improved by the optimized machine learning models. These models hence solved the problem to use remote sensing data to retrieve these non-optically active water quality parameters and provided a new monitoring strategy for small waterbodies. Water quality mapping obtained by Sentinel-2 imagery provided a full spatial coverage of the water quality characterization for the entire water surface. Compared with water samples collecting and testing, it greatly reduced labor cost, reagents cost, and waste treatment cost. It also may help identify illegal discharges to urban waterbodies. The method developed in this research provides a new practical and efficient water quality monitoring strategy in managing water with consideration of environmental sustainability.

Self-selecting the intensity of aerobic training is a perspective that allows practitioners to develop autonomy (choice of pace), improve physical fitness and achieve weight loss. To compare the effect of four aerobic training protocols on cardiometabolic and psycho-affective responses in physically inactive adult men and women. The sample consisted of 11 individuals aged 56 ± 10 years and BMI 29.2 ± 2.4 kg/m2 performed four different treadmill aerobic training protocols, including: 1-individual with self-selected intensity (ISS), 2-individual with prescribed intensity (IPI) (64-76% of HR max), 3-small group with self-select. selected intensity (SGS) and 4-small group prescribed intensity (SGP) (64-76% of HR max). Heart rate (HR), lactate (LACT), perceived exertion (RPE), affective response (FS), activation scale (FAS), enjoyment (PACES) and intention to repeat the session (INT) were analyzed. Statistical analysis used ANOVA with Tukey's post hoc test (p&lt;0.05). HR, LACT and RPE analyzes did not show significant differences between protocols. The FS showed a smaller decline in the SI protocol (p&lt;0.05), and the intention to repeat the training session was greater in the SI protocol (p&lt;0.05). Conclusion: The data allow us to conclude that the SI training protocol produced superior results in affective response, pleasure and intention to repeat the session.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), with 10.4 million new cases per year reported in the human population. Recent studies on the Mtb transcriptome have revealed the abundance of noncoding RNAs expressed at various phases of mycobacteria growth, in culture, in infected mammalian cells and in patients. Among these noncoding RNAs are both small RNAs (sRNAs) between 50-350 nts in length and smaller RNAs (sncRNA) <50 nts. In this review, we provide an up-to-date synopsis of the identification, designation, and function of these Mtb-encoded sRNAs and sncRNAs. The methodological advances including RNA sequencing strategies, small RNA antagonists and locked nucleic acid sequence specific RNA probes advancing the studies on these small RNA are described. Initial insights into the regulation of the small RNA expression and putative processing enzymes required for their synthesis and function are discussed. There are many open questions remaining about the biological and pathogenic roles of these small non-coding RNAs, and potential research directions needed to define the role of these mycobacterial noncoding RNAs summarized.

Аnalysis of small RNA sequencing data across a range of biofluids is a significant research area, given the diversity of RNA types that holds potential diagnostic, prognostic, and predictive value. The intricate task of segregating the complex mixture of small RNAs from both human and other species, including bacteria, fungi, and viruses, poses one of the most formidable challenges in the analysis of small RNA sequencing data, currently lacking satisfactory solutions. This study introduces sRNAflow, a user-friendly bioinformatic tool with a web interface designed for the analysis of small RNAs obtained from biological fluids. Tailored to the unique requirements of such samples, the proposed pipeline addresses various challenges, including filtering potential RNAs from reagents and environment, classifying small RNA types, managing small RNA annotation overlap, conducting differential expression assays, analysing isomiRs, and presenting an approach to identify the sources of small RNAs within samples. sRNAflow also encompasses an alternative alignment-free analysis of RNA-seq data, featuring clustering and initial RNA source identification using BLAST. This comprehensive approach facilitates meaningful comparisons of results between different analytical methods. The source code can be accessed at https://github.com/zajakin/sRNAflow under the GPL3 licence.

This case study assessed marketing arrangements used by small scale farmers in the Lake Basin and Lower Eastern bean corridors of Kenya to determine which markets work for rural producers and what changes are needed to produce and supply sufficient quantities for trade. Using exploratory research, data was collected through focus group discussions with six farmer groups representing a total of 1255 bean farmers and key informant interviews with extension staff. The results indicated that 94% of the farmers produced beans before identifying buyers with only 6% participating in group marketing. Though spot-market transactions with brokers and traders provided ready cash for the farmers, formal buyers were perceived to be more reliable but difficult to find and, operated stringent requirements which were a barrier to entry. A theory of change to integrate smallholders into formal markets to sustainably produce and supply sufficient volumes for trade should entail a transformation agenda at four levels of the value chain: intensification of production through pure stand models with greater use of certified high yielding varieties; stable price guarantees; a market-driven research and extension service and; an enabling political, policy and business environment in the bean value chain. Further research is needed to pilot these changes in a case control study.

The World Health Organization (WHO) recently added snakebite envenoming to the priority list of Neglected Tropical Diseases (NTD). It is thought that ~75% of mortality following snakebite occurs outside the hospital setting, making the temporal gap between a bite and antivenom administration a major therapeutic challenge. Small molecule therapeutics (SMTs) have been proposed as potential pre-referral treatments for snakebite to help address this gap. Herein, we discuss the characteristics, potential uses and development of SMTs as potential treatments for snakebite envenomation. We focus on SMTs that are secretory phospholipase A2 (sPLA2) inhibitors and metalloprotease (MP) inhibitors.

Higher-risk myelodysplastic syndrome (HR-MDS) has a poor prognosis in the absence of efficient therapy. The evaluation of new therapies in animal models of HR-MDS is hampered by the absence of accurate in vivo biomarkers of the disease. In this study we compared [18F]Fluoro-desoxyglucose Positron Emission Tomography (FDG-PET) and [18F]Fluoro-thymidine (FLT)-PET imaging for disease follow-up in a triple transgenic MMTVtTA/TetoBCL-2/MRP8NRASD12 mouse model of HR-MDS. Normal control FVB/N mice (G1,n=9) and HR-MDS mice (G2,n=12) underwent both FDG- and FLT-PET procedures at 2-day intervals, on a dedicated small animal device. Blood cell counting, BCL-2 and Mac-1hi/Gr-1lo expression measurements in blood were performed before each PET procedure. Visually, PET images of G2 mice demonstrated homogeneous FDG uptake in the whole skeleton similar to that observed in G1 mice, and abnormal FLT hot spots in bone marrow not observed in G1 mice. The intensity of FLT hot spots in bone marrow was higher in 3-months old G2 mice than in 2-months old G2 mice, concordant with a higher percentage of cells expressing Mac-1hi/Gr-1lo and lower platelets counts. We conclude that FLT-PET/CT imaging is a more valuable surrogate non-invasive quantitative marker of HR-MDS bone marrow involvement than FDG-PET/CT in our mouse model of HR-MDS.

We performed Bayesian network meta-analysis (NMA) to suggest frontline treatments for patients with high PD-L1 expression (at least 50%). A total of 5,237 patients from 22 studies were included in this NMA. In terms of progression-free survival, immune checkpoint inhibitors (ICIs) plus bevacizumab plus chemotherapy had the highest surface under the cumulative ranking curve (SUCRA) value (98.1%), followed by ICI plus chemotherapy (82.9%). In terms of overall survival (OS), dual immunotherapy plus chemotherapy had the highest SUCRA value (79.1%), followed by ICI plus bevacizumab plus chemotherapy (73.4%). However, there was no significant difference of survival outcomes among treatment regimens combined with immunotherapy. Moreover, ICI plus chemotherapy failed to reveal a significant OS superiority to ICI monotherapy (hazard ratio = 0.978, 95% credible internal: 0.771-1.259). In conclusion, this NMA indicates that ICI plus chemotherapy with/without bevacizumab might to be the best options in terms of OS for NSCLC with high PD-L1 expression. Considering there was no significant difference of survival outcomes among treatment regimens incorporating immunotherapy and ICI plus chemotherapy failed to show significant survival benefits over ICI monotherapy, however, ICI monotherapy may be reasonable as first-line treatment for advanced NSCLC with high PD-L1 expression and no targetable aberrations.

The development of targeted therapeutics for cancer continues to receive intense research attention as laboratories and pharmaceutical companies seek to develop drugs and technologies that improve treatment efficacy and mitigate harmful side effects. In the aftermath of World War I, it was discovered that mustard gas destroys rapidly dividing cells and could be used to treat cancer. Since then, chemotherapy has remained a predominant treatment for cancer; however, the destruction of dividing cells throughout the body yields devastating side effects including off-target damage of the digestive tract, bone marrow, skin, and reproductive tract. Furthermore, the high mutation rate of cancerous cells often renders chemotherapy ineffective long-term. Therapies with improved specificity, localization, and efficacy are redefining cancer treatment. Herein, we define and summarize the principal advancements in targeted cancer treatment and briefly comment on the march towards personalized medicine in the treatment of human cancer.

The advent of RNA-sequencing (RNA-Seq) technologies has markedly improved our knowledge and expanded the compendium of small non-coding RNAs, most of which derive from the processing of longer RNA precursors. In this review article, we will discuss about the biogenesis and function of small non-coding RNAs derived from eukaryotic ribosomal RNA (rRNA), called rRNA fragments (rRFs), and their potential role(s) as regulator of gene expression. This relatively new class of ncRNAs remained poorly investigated and underappreciated until recently, due mainly to the a priori exclusion of rRNA sequences—because of their overabundance—from RNA-Seq datasets. The situation surrounding rRFs resembles that of microRNAs (miRNAs), which used to be readily discarded from further analyses, for more than five decades, because we could not believe that RNA of such a short length could bear biological significance. As if we had not yet learned our lesson not to restrain our investigative, scientific mind from challenging widely accepted beliefs or dogmas, and from looking for the hidden treasures in the most unexpected places.

Results from the phase III Keynote-024 clinical trial have established Pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR and ALK wild-type. However, given the differences between patients treated in routine clinical practice and within a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-up, we designed a retrospective observational study of patients with NSCLC who were treated with Pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were to assess PFS and OS using the Kaplan-Meier method, treatment response and safety. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression and smoking habit were prognostic factors for PFS, while age, sex, ECOG PS, smoking habit and histology had an impact on OS. Multivariable analysis confirms prognostic role of PD-L1 for PFS and ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of Pembrolizumab in the first-line setting as well as a safety profile consistent with the results of Keynote-042. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

Patient-derived tumor organoids (PDTOs) are a novel preclinical model of non-small cell lung cancer (NSCLC) for studying tumor biology and precision medicine, which recapitulates tumor morphology and gene expression profile. However, some issues such as low establishment rates, long-term production, and the loss of the immune microenvironment have hindered their widespread practical use. In this study, we investigated the efficacy of a recently introduced free-floating organoid production method to address these issues. The free-floating approach provided PDTO establishment success rate of over 90 % resulting in organoid formation within a short period of one week. These organoids retained the elements of the parental tumor morphology and contained stroma and immune cell populations, as confirmed by flow cytometry analysis. Importantly, we found that the cytokine and growth factor expression profiles of the free-floating organoids correlated with those of the original tumors in 58 % of cases, indicating the preservation of tumor-associated signaling pathways. Obtained organoids exhibited different responses to anticancer chemotherapeutics that might be a result of variable expression of drug resistance-associated genes. Considering the high establishment rate and short time of free-floating organoid production, this technique provides a valuable tool for a more accurate evaluation of therapeutic strategies and cancer biology studies.

UN 2030 Sustainable Development Goal 6 presents difficulties for small island developing states such as the Kingdom of Tonga, which relies on rainwater and groundwater lenses for freshwater supply. Planning and managing water resources to supply demands in dispersed small islands under variable climate and frequent extreme events is challenging. Tensions between water planning using top-down versus bottom-up processes have long been recognized. Tonga’s overarching national planning instrument is the Tonga Strategic Development Framework, 2015-2025 (TSDFII). This identifies desired national outcomes and is used to direct and resource Ministries and address international and regional commitments. Water supply was a low priority in the three-month consultations that led to TSDFII. Community Development Plans (CDPs), developed by rural villages throughout Tonga’s five Island Groups over nine years, involved participation from 80% of each village population who ranked local priorities. Analysis of priorities in 117 available village CDPs reveals improvements to village water supply was the highest overall priority in all five Island Groups and ranked within the top three priorities by 76% of all villages, with women, youth and men returning figures of 83%, 66% and 80% respectively. The mismatch between top-down and bottom-up priorities appears to result from an urban/rural divide.

Blockchain technology (BCT) has the potential for sustainable development, enhancing business efficiency, reducing costs, and strengthening data security. Despite its potential, adoption among small and medium-sized enterprises (SMEs) is low due to the need for significant changes in technology infrastructure and the challenge of interoperability. A cross-sectional survey was done with 226 Hong Kong SMEs. The PLS-SEM results highlighted favorable transformation conditions as the most critical factor for SMEs considering the adoption of BCT. These conditions address both internal and external readiness for adopting the disruptive strategy. Other contributing factors to BCT adoption include trust in BCT developers, perceived usefulness and ease of use, government support, and perceived security. The research results contributed to the literature on disruptive technology acceptance, adoption, transformation conditions, technology readiness, and SMEs’ technology adoption. Government-supported policies and initiatives can promote BCT adoption, including educational programs, case studies, and resources for readiness. Financial support and regulatory frameworks can further encourage adoption. BCT developers can demonstrate the value of their systems, effectively communicate potential ROI and cost savings, and provide user-friendly interfaces to increase SMEs’ intention to adopt BCT.

Plant diseases and pests reduce crop yields, accounting for global crop losses of 30% to 50%. In conventional agricultural production systems, these losses are typically controlled by applying chemical pesticides. However, public pressure is mounting to curtail agrochemical use. In this context, employing beneficial endophytic microorganisms is an increasingly attractive alternative to the use of conventional chemical pesticides in agriculture. A multitude of fungal endophytes are naturally present in plants, producing enzymes, small peptides and secondary metabolites due to their bioactivity, can protect hosts from pathogens, pests and abiotic stresses. The use of beneficial endophytic microorganisms in agriculture is an increasingly attractive alternative to conventional pesticides. The aim of this study was to characterize fungal endophytes isolated from apparently healthy, feral wine grapes in eastern Canada that have grown without agrochemical inputs for decades. Host plants ranged from unknown seedlings to long-lost cultivars not widely propagated since the 1800s. HPLC-MS was used to identify unique endophyte-derived chemical compounds in the host plants, while dual-culture competition assays showed a range in endophytes’ ability to suppress the mycelial growth of Botrytis, which is typically controlled in viticulture with pesticides. Twelve of the most promising fungal endophytes isolated were identified using multilocus sequencing and morphology, while DNA barcoding was employed to identify some of their host vines. These fungal endophyte isolates, which consisted of both known and putative novel strains, belonged to seven genera in six families and five orders of Ascomycota. Exploring the fungal endophytes in these specimens may yield clues to the vines’ survival and lead to the discovery of novel biocontrol agents.

Small bowel non-Meckelian diverticulosis is a rare condition with only few published cases despite being described over 200 years ago. In the midst of the COVID-19 pandemic, studies suggested that a lot of patients may experience gastrointestinal manifestations. Intestinal symptoms could worsen the inflammation and infection associated with small bowel diverticulitis. Here, we present two cases: one with inflammation and rupture in a COVID-19 patient and the other as an asymptomatic detection. Furthermore, we provide a mini-review of the literature to emphasize the importance of considering this entity in the differential diagnosis of an acute abdomen.

We previously showed that feeding mice a diet containing 1% mantle tissue decreased food consumption, leading to death. We also isolated and identified toxic substances in the mantle tissue. In the present study, we investigated the characteristics and stability of mantle tissue toxicity. Treatment of mantle tissue with 1 mM HCl, 1 mM NaOH, 1 mM dithiothreitol, and 1 mM H2O2 and heating did not reduce the toxicity of mantle tissue in mice. These results suggest that mantle toxins are stable in tissues, particularly when exposed to acidic and digestive enzymes. We examined whether mantle tissue exhibited acute toxicity. Diets containing 1% and 20% mantle extract showed similar levels of toxicity, demonstrating that feeding of mantle tissue does not lead to acute toxicity. Finally, we examined the toxicity of the mantle tissue against small intestinal tissue. Chronic feeding of mantle tissue to mice changed the color of the small intestine. Real-time PCR analysis showed that mantle tissue feeding caused changes of inflammation and endoplasmic reticulum stress markers in the small intestine. These results suggest that feeding of mantle tissue causes toxicity after causing initial damage to the small intestinal tissue.

Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. Hyperhomocysteinemia (HHcy) is typically defined as levels >15 micro mols/L. Elevated plasma levels of Hcy can be caused by the deficiency of either vitamin B12 or folate. The active role of homocysteine is quite ambivalent: many studies detected its potential impact on neurological events; others try to identify it as one of the possible risk factors of cardiovascular events, but with a complementary and secondary role. HHcy has been reported in many neurologic disorders, including cognitive impairment and stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. Nowadays, homocysteine could be considered as a possible link between a common vascular risk factor and potential alterations in degenerative neuronal disorders. HHcy-induced oxidative stress, endothelial dysfunction, inflammation, smooth muscle cell proliferation, and endoplasmic reticulum stress; all these aspects have been considered to play an essential role in the pathogenesis of several diseases, including atherosclerosis, major stroke, and vascular dementia. Specific models of astrocytes impairment in HHcy-mice, which mimic small vessel disease, have been developed with a three-step investigation (at 6, 10, 14 weeks of B6, B9, and B12 detrimental diet in wild type HHcy mouse). These studies found out that after ten weeks on a diet (at the most after 14 weeks), end-feet disruption occurs. This phenomenon is concomitant to reduced vascular labeling for aquaporin -4-water channels, lower protein/mRNA levels for Kir4.1, and BK potassium channels, associated with a higher expression of MMP-9. The most exciting finding is that microglial activation in this mice model was evident since the precocious time of observation (6-week time) and precedes astrocytic changes. Our research aims to review the possible role of HHcy in neurodegenerative disease and small-vessel disease and to understand its pathogenic impact.

Small-scale fishers are considered as one of the most vulnerable communities in Bangladesh but very few studies focused on the livelihood sustainability and vulnerabilities of this professional group. A fieldwork in lower Padma and upper Meghna hilsa sanctuaries identifies different livelihood characters and associated vulnerabilities of the fishers. A conceptual framework known as Sustainable Livelihood Approaches (SLA) has been introduced to analyses the qualitative and quantitative data. The insights of the livelihood strategies provide on small-scale fishers and fisheries management have been explained and explored. Fishers are found solely dependent on fishing, economically insolvent and neglected. In addition, some socio-economic abstractions such as low income, credit insolvency, lack of substitute earning flexibility make them more vulnerable. A number of effective suggestions are elicited from fishers’ perceptions, the implementation of which is crucial to ensure livelihood sustainability of the small-scale fishers.

Alfalfa, an important legume forage, is an ideal crop for sustainable agriculture and a potential bioenergy plant. Drought, one of the most common environmental stresses, substantially affects plants’ growth, development and productivity. MicroRNAs (miRNAs) are newly discovered gene expression regulators that have been linked to several plant stress responses. To elucidate the role of miRNAs in drought stress regulation of alfalfa, a high-throughput sequencing approach was used to analyze 12 small RNA libraries comprising of 4 samples, each with 3 biological replicates. We identified 348 known miRNAs, belonging to 80 miRNA families, from the 12 libraries and 281 novel miRNAs using Mireap software. 18 known miRNAs in roots and 12 known miRNAs in leaves were screened out as drought-responsive miRNAs. Except for miR319d and miR157a which were upregulated under drought stress, the expression pattern of drought-responsive miRNAs were different between roots and leaves in alfalfa. This is the first study discovering miR157a, miR1507, miR3512, miR3630, miR5213, miR5294, miR5368 and miR6173 are drought-responsive miRNAs. Target transcripts of drought-responsive miRNAs were computationally predicted. All 447 target genes for the known miRNAs were predicted using an online tool. This study provides a significant insight on understanding drought-responsive mechanisms of alfalfa.

The rural population percentage decreased from 82.7% to 68.9% in 2011, even though there is an increase in the total rural population, which stands at 833.7 million, and the rural population were now more than three times compared to the population seven decades ago. Another observation is the decrease in cultivators percentage from 71.9% to 45.1 %, while agriculture labour increase from 28.1% to 54.9% during the same period. Despite the increase in irrigated land and net area sown, the average holdings' size under the farmers is continuously decreasing, and it requires a study to look into the reasons. The research probes the role of Minimum Support Price (MSP) in supporting farmers and measuring market price above MSP needed to help marginal and small farmers remain above the poverty level. It explains how different market rates above MSP have a different impact on different categories of agriculture landholding. The study works on developing a common model that relates the impact of MSP on different farmers categories. The model can be generalized to all crops and regions and useful in designing policies that focus on uplifting the income of agricultural farmers.

For equivalent modeling of mixed wind farms (WFs), existing clustering indicators cannot consider the complex coupling characteristics between different types of wind turbines (WTs). This paper proposes a refined equivalent modeling method for mixed WFs based on artificial intelligence technology. Firstly, the electromechanical transient performance of mixed WFs is analyzed. The WT type, wind speed and direction, and voltage dip are considered the main factors affecting the external dynamic response of mixed WFs. Secondly, the equivalent node model is established, including the selection of independent and dependent variables. Then, the multiple artificial neural networks (ANNs) are trained one by one based on sample data, to explore the nonlinear relationship between the dependent variables and the independent variables. Finally, the electromechanical transient simulations of the power systems with a mixed WF is carried out by using the MATLAB platform. Simulation results show that the proposed model can reflect the external characteristics of the mixed WF in different wind scenarios and voltage dips.

The paper presents a new vision on the energy consumption management in the case of the Small and Medium Enterprises (SMEs), integrated into an advanced decision support platform, with technical and economic benefits on increasing the energy efficiency, which contains modules for database management, profiling, forecasting, and production scheduling. Inside each module, Artificial Intelligence and Data Mining techniques were proposed to remove the uncertainties regarding the dynamic of technological flows. Thus, the data management module includes the Data Mining techniques, that extract the technical details on the energy consumption needed in the development of production scheduling strategies, the profiling module uses an original approach based on clustering techniques to determine the typical energy consumption profiles required in the optimal planning of the activities, the forecasting module contains a new approach based on an expert system to forecast the total energy consumption of the SMEs, and production scheduling module integrates a heuristic optimization method to obtain the optimal solutions in flattening the energy consumption profile. The testing was done for a small enterprise from Romania, belonging to the domain of trade and repair of vehicles. The obtained results highlighted the advantages of the proposed decision support platform on the decrease in the intensity of energy consumption per unit of product, reduction of the purchase costs, and modification of the impact whom the energy bills have on the operational costs.

This paper proposes a compact planar Wi-Fi antenna with optimized radiation patterns for small uncrewed aerial vehicle (UAV) applications in both urban and open areas. It is suitable for mounting on the outermost side of the non-metallic wing of small UAVs. It has small dimensions of 16.5 mm (L) by 30.3 mm (W) by 1.6 mm (h), and the measured results of its prototype are in agreement with simulated data. Its impedance bandwidths over the two frequency ranges are 2.11 to 2.58 GHz and 5.06 to 7.5 GHz ( ). At 5.8 GHz, it has stronger radiation below the small UAV to reduce interference from rare-use directions. Its maximum radiations, the directions of the maximum radiation in each elevation plane, are below the UAV and between 14° and 29° from the horizontal plane. At 2.4 GHz, it has quasi-omnidirectional radiation to ensure a stable link in all directions, and its maximum radiations are near the horizontal plane. The optimized radiation patterns at 5.8 and 2.4 GHz can provide more antenna gain when the small UAV flies farther in urban and open areas, respectively. In addition, it has good vertically polarized radiation for long-distance applications.

Indian cities are increasingly becoming susceptible to PM10 induced health effects which have become a matter of concern for the policymakers of the country. Air pollution is engulfing the comparatively smaller cities as the rapid pace of urbanization, and economic development seems not to lose steam ever. A review of air pollution of 28 cities of India, which includes tier-I, II, and III cities of India, found to have grossly violated both WHO and NAAQS standards in respect of acceptable daily average PM10 concentrations by a wide margin. Predicting the city level PM10 concentrations in advance and accordingly initiate prior actions is an acceptable solution to save the city dwellers from PM10 induced health hazards. Predictive ability of three models, linear MLR, nonlinear MLP (ANN), and nonlinear CART, for one day ahead PM10 concentration forecasting of tier-II Guwahati city, were tested with 2016-2018 daily average observed climate data, PM10, and gaseous pollutants. The results show that the non-linear algorithm MLP with feedforward backpropagation network topologies of ANN class, giving the best prediction value when compared with linear MLR and nonlinear CART model. ANN (MLP) approach, therefore, may be useful to effectively derive a predictive understanding of one day ahead PM10 concentration level and thus provide a tool to the policymakers for improving decision-making associated with air pollution and public health.

Non-Small Cell Lung Cancer (NSCLC) is the most common pulmonary malignancy, most frequently diagnosed at an advanced stage (III/IV). Patients in the Locally-Advanced Stage Subgroup (IIIA) are relatively few, yet compose of heterogenic phenotypes posing a diagnostic and treating challenge, leading to lack of clinical guidelines regarding the optimal standard of care. Several approaches exist, with a general agreement that a combined oncological and surgical modality approach is required. In this current retrospective descriptive study, operable Stage IIIA NSCLC patients who underwent surgery between 2013-2020 were evaluated on several aspects, including initial diagnosis, neoadjuvant regimens, outcomes of surgical intervention, overall survival at 2-years and 5-years following treatment. A total of 35 patients had neoadjuvant oncological treatment (mostly chemoradiation therapy) prior to surgery, out of which 28 patients were diagnosed with Stage IIIA NSCLC. In post-operative assessment of pathological staging, downstaging was reported in 20 patients, of which 7 (25%) cases were defined as complete pathological response. The 2-years overall survival rate was 65% and the 5-years overall survival rate was 60%. The main pattern of disease recurrence was distant metastasis.

Recently, SMR (Small Modular Reactor) is expected to be able to operate flexibly in conjunction with a high renewable energy penetration grid as a result of improved safety and easy power control compared to large nuclear power plants. SMRs such as South Korea’s System-integrated Modular Advanced ReacTor (SMART) are designed to use canned motors (CMs) for their reactor coolant pumps (RCPs) to enhance safety. The CMs passively enhance the reactor’s safety by preventing leakage of radioactive reactor coolant. However, with motor sizes designed to be as small as possible, and the increased air gap of CMs between stator and rotor, starting torque may be insufficiently small compared to that of similar sized induction motors (IMs). Thusly, CMs may require variable frequency drives (VFDs) to start. This paper compares the torque characteristics of CMs with those of IMs for SMART’s RCPs. ETAP is then used to perform motor starting analysis for CMs started with and without VFDs. The results are presented and analyzed to find out if the VFDs deal with the CM starting torque issue.

During recent years UAVs have been increasingly used in agriculture and forestry research and application. Nevertheless, most of this work has been devoted to improving accuracy and explanatory power, often at the cost of usability and affordability. We tested a low-cost UAV and a simple workflow to apply four different greenness indices to the monitoring of pine (Pinus sylvestris and P. nigra) after-fire regeneration in a Mediterranean forest. We selected two sites and masured all pines within a pre-selected plot. Winter flights were carried out at each of the sites, at two flight altitudes (50 and 100 m). Automatically normalizing images entered an SfM based photogrammetric software for restitution and the obtained point cloud and orthomosaic processed to get a canopy height model and four different greenness indices. Sum of pine DBH was regressed on summary statistics of greenness indices and canopy height model. ExGI and GCC indices outperformed VARI and GRVI in estimating pine DBH, while canopy height model slightly improved the models. Flight altitude did not severely affect model performance. Our results show that low cost UAVs may improve forest monitoring after disturbance, even in those habitats and situations were resource limitation is an issue.

In the past decade, RNA fragments derived from full length small nucleolar RNAs (snoRNAs) have been shown to be specifically excised and functional. These sno-derived RNAs (sdRNAs) have been implicated as gene regulators in a multitude of cancers, controlling a variety of genes post-transcriptionally via association with the RNA-induced silencing complex (RISC). In this review, we have summarized the literature connecting sdRNAs to cancer gene regulation. SdRNAs possess miRNA-like functions, and are able to fill the role of tumor-suppressor or tumor-promoter in a tissue context-dependent manner. Indeed, there are many miRNAs that are actually derived from snoRNA transcripts, meaning that they are truly sdRNAs and as such are included in this review. As sdRNAs are frequently discarded from ncRNA analyses, we emphasize that sdRNAs are functionally relevant gene regulators and likely represent an overlooked subclass of miRNAs. Based on the evidence provided by the papers reviewed here, we propose that sdRNAs deserve more extensive study to better understand their underlying biology and to identify previously overlooked biomarkers and therapeutic targets for a multitude of human cancers.

Over the last three decades, special economic zones (SEZs) have given new impetus to the ever-growing export-oriented industrialization in developing countries. Where various economies have benefited from SEZs, many zones have ended up becoming enclaves with trifling advantage. The SEZs in Pakistan have experienced the same fate and failed to contribute to exports, employment and creating linkages with the domestic economy. Recently under China Pakistan Economic Corridor (CPEC), SEZs are proposed to be set up in Pakistan; with a hope to fuel the stuttering economy. However, it is pertinent to first understand the local context and device policies considering stakeholders' perspectives. This study aims to identify the factors for the successful implementation of SEZs derived from the regional context of Pakistan. In-depth interviews are conducted from most relevant stakeholders, who have been involved in the development of SEZs. The results pointed towards the removal of political influence over zones and government taking the lead role in deciding the types of industry to be invited in these zones. Each zone should have a clear vision of development based on its regional advantage. The zone promotions should be based on competitiveness rather than fiscal incentives. Joint ventures and PPP to be encouraged inside the zones for sustainable operations.

Craters are the most prominent geomorphological features on the surface of celestial bodies, which is playing a crucial role in studying the formation and evolution of celestial bodies, as well as in landing and planning for surface exploration. Currently, the main automatic crater detection models and datasets focus on the detection of large and medium craters. In this paper, we created 23 small lunar crater datasets for model training based on the Chang’E-2 (CE-2) DOM, DEM, Slope, and integrated data with 7 kinds of visualization stretching methods. And then, we proposed the YOLO-Crater model for Lunar and Martian small crater detection by replacing EioU and VariFocal loss to solve the crater samples imbalance problem and introducing a CBAM attention mechanism to mitigate interference from the complex extraterrestrial environment. The results show that the accuracy (P = 87.86%, R = 66.04%, and F1 = 75.41%) of the Lunar YOLO-Crater model based on the DOM-MMS (Maximum-Minimum Stretching) dataset is the highest and better than that of YOLOX model. And the Martian YOLO-Crater, trained by the Martian dataset from the 2022 GeoAI Martian Challenge, achieves good performance with P = 88.37%, R = 69.25%, and F1 = 77.65%. It indicates that the YOLO-Crater model has a strong transferability and generalization capability, which can be applied to detect small craters on the Moon and other celestial bodies.

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

Peste des Petits Ruminants (PPR) is one of the major transboundary animal diseases that severely impact livestock production and trade worldwide. An investigation was carried into the seroprevalence and risk factors of PPR in small ruminants, camels, and wild ruminants in Bahrain. A total of 1240 serum samples were collected from 119 sheep flocks and 1224 serum samples from 125 goat herds. In addition, 100 sera from camels and 38 sera from wild ruminants, were collected. Serum samples were tested for the presence of PPR specific antibodies using a competitive ELISA. Flock management and health information of the flocks and herds were collected using a semi-structured questionnaire. The individual prevalence of PPR in sheep and goats was 26% and 25.5%, respectively. The flock or herd level prevalence of PPR was 22.7% and 29.6% in sheep and goats, respectively. None of the tested camels or wild ruminants were positive for PPR-specific antibodies. Sheep and goats from the Northern governorate were more likely to be seropositive to PPR than in other governorates. On the individual animal level, the univariate analysis suggested; age (&lt;12 months), sex (male), and health status (weak animals) as risk factors for PPR seropositivity. On the flock/herd level, the multivariable logistic regression analysis identified large flock/herd size and semi-intensive farming as risk factors for PPR seropositivity.

Micro and small wood-processing enterprises represent the heart of the European forest-based industries, being among the key drivers of economic growth in rural, mountainous, and poor regions. Their economic efficiency is of fundamental importance for their existence and the pro-vision of income for the local population in rural areas. Data Envelopment Analysis (DEA) is nonparametric, linear-programming-based approach, commonly used to analyse the efficiency of organizational units. This method allows estimating the economic efficiency of a certain eco-nomic system without assumptions about the functional form between resources and products. Furthermore, DEA determines the efficiency frontier and gives results of whether an enterprise, i.e., a Decision Making Unit (DMU) is efficient or not. The main objective of this study was to investigate and evaluate the economic efficiency of micro and small wood-processing enterpris-es in the EU countries and reveal the hidden inputs that facilitate efficiency generation. The eco-nomic efficiency evaluation was carried out on the basis of the official statistical data for the mi-cro and small wood-processing companies in the EU member states for the period 2015-2020 by performing a two-stage DEA analysis. The data used were standardized by value per employee. In addition to the first stage of DEA, fractional regression probit and logit models with four contextual variables were used to reveal the influence of the hidden inputs in the model. The results showed that the micro and small wood-processing enterprises can be regarded as more scale-efficient than technically-efficient entities. The only contextual variable affecting the eco-nomic efficiency was Investments per Person Employed, improving the efficiency by 2% per 1% increase of the investments.

Recent advances in embedded antenna and sensor technologies for 5G communications have galvanized a response toward the investigation of their electromagnetic (EM) performance for urban context and civil engineering applications. This article quantitatively investigates the effects of material loading on an evolved antecedent-based design of a hexagonal-stubbed Complementary Split-Ring Resonator (CSRR)-loaded antenna through simulation and experimentation. The optimized antenna design is first conceptualized within a simulation environment to achieve EM resonance at 3.50 GHz before delving into the analysis of operational performance characteristics. As a proof-of-concept, a physical antenna prototype is fabricated on a printed circuit board for the in-situ evaluation of S11 parameter plot. Subsequently, a simulation-based parametric study is conducted on antenna prototypes embedded into Ordinary Portland Cement pastes with varying weight percentages of iron(III) oxide. Simulation-derived and experimental results are mutually verified, achieving a systemic downward shift in resonant frequency and corresponding variations in impedance matching induced by changes in the loading reactance. Finally, an inversion modeling procedure is employed using perturbation theory to extrapolate the relative permittivity of the dielectric embedding materials. Our proposed analysis contributes to optimizing concrete-embedded 5G antenna sensor designs and establishes a foundational framework for estimating unknown EM parameters of cement-based composites.

The pathogenesis of Cerebral Small Vessel Disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the aim of describing the pattern of endothelial activation. Plasma samples from 3 groups of young subjects have been tested: PTs (subjects affected by early stage CSVD); CTRLs (control subjects without abnormalities at MRI scanning); BDs (blood donors). Human Brain Endothelial Cells 5i (HBEC5i) were treated with plasma and total RNA was extracted. RNAs were pooled to reduce gene expression-based variability and NGS analysis was performed. Differentially expressed genes were highlighted comparing PTs, CTRLs and BDs with HBEC5i untreated cells. No significantly altered pathway was evaluated in BD related treatment. Regulation of p38 MAPK cascade (GO:1900744) was the solely pathway altered in CTRLs related treatment. Indeed, 36 different biological processes turned out to be deregulated after PTs treatment of HBEC5i, i.e., the cytokine-mediated signaling pathway (GO:0019221). Endothelial cells activate inflammatory pathways in response to stimuli from CSVD patients’ plasma, suggesting the pathogenetic role of neuroinflammation from the early asymptomatic phases of cerebrovascular disease.

Small molecule kinase inhibitors (SMKIs) are one of the heightened concerns in the field of drug research and development. There are seventy-nine (up to July 2023) small molecule kinase inhibitors have been approved by FDA and hundreds kinase inhibitors candidates in clinical trials, which shed light on the treatment of some major diseases. As an important strategy of drug design, computer-aided drug design (CADD) plays an indispensable role in the discovery of SMKIs. CADD methods, such as docking, molecular dynamic, pharmacophore have been applied to the design and optimization of small molecule kinase inhibitors. In the review, we provide an overview of recent advances in CADD and SMKIs; and the application of CADD for discovery of SMKIs.

Appropriate use of perioperative antimicrobials can significantly reduce the risk of postoperative infections. However, inappropriate antimicrobial use can result in the creation of multidrug resistant bacteria, increased costs, host flora disruption, side effects, and increased risk of hospital-acquired infections This survey evaluated the current perioperative use of antimicrobials in small animals by Spanish veterinarians using a web-based questionnaire. Responses were represented using descriptive statistics and a statistical analysis of the association between demographic data and perioperative antimicrobial use was performed. Preoperative antimicrobials were administered in clean surgery by up to 68.3% of participants, 81.0% in clean-contaminated surgery and 71.3% in dirty surgery, while in the postoperative period, antimicrobials were administered by up to 86.3% of participants in clean surgery, 93.2% in clean-contaminated surgery and 87.5% in dirty surgery. Factors considered “very important” for antimicrobial selection were the degree of wound contamination, patient immunosuppression, and use of prosthesis. The most frequently used antimicrobial was beta-lactamase-resistant penicillin. Postoperative antimicrobial use was associated with participants without postgraduate training. This study highlights an overuse of antimicrobials in perioperative procedures in small animal surgery in Spain. Therefore, evidence-based guidelines and further education regarding the correct use of antimicrobial prophylaxis are recommended.

Traditional camera sensors rely on human eyes for observation. However, the human eye 1 is prone to fatigue when observing targets of different sizes for a long time in complex scenes, and 2 human cognition is limited, which often leads to judgment errors and greatly reduces the efficiency. 3 Target recognition technology is an important technology to judge the target category in camera 4 sensor. In order to solve this problem, a small size target detection algorithm for special scenarios was 5 proposed by this paper. Its advantage is that this algorithm not only has higher precision for small 6 size target detection, but also can ensure that the detection accuracy of each size is not lower than the 7 existing algorithm. In this paper, a new down-sampling method was proposed, which could better 8 preserve the context feature information. The feature fusion network was improved to effectively 9 combine shallow information and deep information. A new network structure was proposed to 10 effectively improve the detection accuracy of the model. In terms of accuracy, it is better than: YOLOX, 11 YOLOXR, YOLOv3, scaled YOLOv5, YOLOv7-Tiny and YOLOv8.Three authoritative public data sets 12 were used in this experiment: a) On Visdron data sets (small size targets), DC-YOLOv8 is 2.5% more 13 accurate than YOLOv8. b) On Tinyperson data sets (minimal size targets), DC-YOLOv8 is 1% more 14 accurate than YOLOv8. c) On PASCAL VOC2007 data sets (Normal size target), DC-YOLOv8 is 0.5% 15 more accurate than YOLOv8.

Small RNAs (sRNA) are epigenetic regulators of essential biological processes that have been linked to the onset and progression of leukemia, including acute adult T-cell leukemia-lymphoma (ATLL) caused by the retrovirus Human T-lymphotropic virus type 1. Here, we describe the sRNA profile of a 30-year-old female with ATLL at diagnosis and after maintenance therapy, with the goal of correlating their expression levels with response to therapy.

The accumulation of process waste in the production line causes fluctuations, bottlenecks, and increased inventory in workstations disrupting process flow. In this paper, the aim is the use a simulated value stream mapping (SVSM) as a lean assessment tool for decision-making in the continuous improvement process to influence and provide consideration and consistency on productivity improvement in the production system. The proposed methodology applied discrete event simulation for production process operations improvement to eliminate non-value adding times and provides good quality products at the lowest cost and highest efficiency. The results are the analysis of the current state of the production system in a South African truck manufacturing industry small and medium enterprise (SMEs) as a potential solution for the production system future state. The identified non-value adding times in the 6 most critical workstations was eliminated by SVSM which resulted in a productivity improvement of 4%, most importantly bringing the productivity to 95% and total cycle time improvement to 451 for small units and 466 for large units. The results proposed combined VSM and Simulation techniques which enhance the LEAN application by DES to increase productivity and performance improvement to remain competitive in the global economy.

Medical and translational scientific research requires the use of animal models as an initial approach to the study of new therapies and treatments, but when the objective is an exploration of translational potentialities, classical models fail to adequately mimic problems in humans. Among the larger animal models that have been explored more intensely in recent decades, small ruminants, namely sheep and goats, have emerged as excellent options. The main advantages associated to the use of these animals in research works are related to their anatomy and dimensions very similar to those of humans in most physiological systems, in addition to their low maintenance and feeding costs, tendency to be docile, long life expectancies and few ethical complications raised in society. The most obvious disadvantages are the significant differences in some systems such as the gastrointestinal, and the reduced amount of data that limits the comparison between works and the validation of the characterization essays. Despite everything, recently these species have been increasingly used as animal models for diseases in different systems, and the results obtained open doors for their more frequent and advantageous use in the future. The purpose of this review is to summarize the general principles related to the use of small ruminants as animal models, with focus on regenerative medicine, to group the most relevant works and results published recently and to highlight the potentials for the near future in medical research.

Shrinking farm size and fragile farm resources pose a significant challenge to the sustainability of small-scale farms. Efficient resource utilization in small-scale farms is crucial to achieving farm sustainability through endogenous mechanisms. However, the precise mechanisms to integrate physical resources to achieve farm sustainability are not very clear yet. By capturing the interaction among farm resources as a network phenomenon, we identify the discrete resource interactions (RIs) in different types of small-scale farms of Indian Sundarbans, which are associated with higher farm sustainability. Thirty-two linkages, 11 reciprocal linkages, 22 triads, and three ‘core elements’ that occurred and cooccurred on highly sustainable farms are found to be critical in achieving farm sustainability. Using the properties of resource interaction networks as explanators of farm sustainability, we anticipate that sustainability in small-scale farms can be achieved by strategically creating new RIs on the farm. However, there may be limitations to such achievement depending on the nature of RI and type of farm. The analytical approach helps to understand the structural basis of sustainability in small-scale farms, and this approach can be used to achieve farm sustainability through the strategic integration of existing farm resources in the smallholder systems.

Although researchers have investigated widely the impact of IOD phases on human lives, only a few have examined such impacts on fisheries. In this study, we analyzed the influence of negative (positive) of IOD on a chlorophyll a (Chl-a) concentration as an indicator of phytoplankton biomass and small pelagic fish production in the eastern Indian Ocean (EIO) off Java. We also conducted field surveys in the EIO off Palabuhanratu Bay at the peak (October) and the end (December) of the 2019 positive IOD phase. Our findings show that the Chl-a concentration had a strong and robust association with the 2016 (2019) negative (positive) IOD phases. The negative (positive) anomalous Chl-a concentration in the EIO off Java associated with the negative (positive) IOD phase induced strong downwelling (upwelling), leading to the preponderant decrease (increasing) of small pelagic fish production in the EIO off Java.

We present a summary of our protocol for employment of small-molecule circadian rhythm modulators. The abilities of compounds to affect oscillations have received significant attention. We outline assessments of circadian changes using indirubin-3’-oxime (IO), 5-iodo-indirubin-3’-oxime (5I-IO), and 5-sulfonic acid-indirubin-3’-oxime (5SA-IO), analyzing effects on Bmal1 and Per2 oscillations and oncogenic features.

Sustainable Development Goal (SDG) 6.2 sets an ambitious target of leaving no one without adequate sanitation by 2030. The key concern is the lack of local human and financial capital to fund the collection of reliable information to monitor progress towards the goal. As a result, national and local records may be telling a different story of the proportion of safely managed sanitation that counts towards achieving the SDGs. This paper unveils such inconsistency in sanitation data generated by urban authorities and proposes a simple approach for collecting reliable and verifiable information on access to safely managed sanitation. The paper is based on a study conducted in Babati Town Council in Tanzania. Using a smartphone-based survey tool, city health officers were trained to map 17,383 housing units in the town. A housing unit may comprise of two or more households. The findings show that 5% practice open defecation, while 82% of the housing units have some forms of sanitation. Despite the extensive coverage, only 31% of the faecal sludge generated is safely contained, while 64% is not. This study demonstrates the possibility of using simple survey tools to collect reliable data for monitoring progress towards safely managed sanitation in the towns of global south.

Most pivotal clinical trials in advanced non-small cell lung cancer (NSCLC) have excluded patients with poor performance status (PS), and data on the efficacy and safety of pharmacotherapy have not been fully accumulated. For NSCLC patients with PS 2 and without druggable genetic alterations, monotherapy with cytotoxic agents or carboplatin-based combination therapy is usually administered based on the results of several randomized trials. However, the evidence of cytotoxic chemotherapy for patients with PS 2 is insufficient, with limited efficacy and toxicity concerns. Immune checkpoint inhibitors (ICIs) are a promising treatment for patients with PS 2 because of lower incidence of severe toxicity compared to cytotoxic chemotherapy. Meanwhile, several reports suggest that anti-PD-1 antibodies monotherapy is less effective for patients with PS 2, especially for those with PS 2 caused by disease burden. Although the combination therapy of nivolumab and ipilimumab is a promising treatment option, there is a divergence in efficacy data between clinical trials. The standard of care for advanced NSCLC with PS 2 has not been established, and future therapeutic strategies should take into account the heterogeneity of the PS 2 population.

The advent of immunotherapy has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC), improving the prognosis of this disease and becoming a key part of the treatment, especially in the population without an oncogenic driver mutation. Two different groups of immune checkpoint inhibitors (ICIs) are used in lung cancer: Anti- Cytotoxic T-lymphocyte antigen-4 (Anti-CTLA 4) and Anti- T-cell receptor programmed cell death-1 or its ligand (Anti-PD-1 and Anti PD-L1). Here in, we review an uptodate on the use of immunotherapy for advanced NSCLC.

Cogging torque is a pulsating, parasitic and undesired torque ripple intrinsic of the design of a permanent magnet synchronous generator (PMSG), which should be minimized due to its adverse effects: vibration and noise. In addition, as aerodynamic power is low during start-up at low wind speeds in small wind energy systems, the cogging torque must be as low as possible to achieve a low cut-in speed. A novel mitigation technique using compound pre-slotting, based on a combination of magnetic and non-magnetic materials, is investigated. The finite element technique is used to calculate the cogging torque of a real PMSG design for a small wind turbine, with and without using compound pre-slotting. The results show that cogging torque can be reduced by a factor of 48% with this technique, while avoiding the main drawback of the conventional pre-slotting technique: the reduction of induced voltage due to leakage flux between stator teeth. Furthermore, through a combination of pre-slotting and other cogging torque optimization techniques, 84%, cogging torque can be eliminated for a given design.

Vacuum drying can dehydrate materials further than dry heat methods while protecting sensitive materials from thermal degradation. Many industries have shifted to vacuum drying as cost- or time-saving measures. Small-scale vacuum drying, however, has been limited by high costs of specialty scientific tools. To make vacuum drying more accessible, this study provides design and performance information for a small-scale open source vacuum oven, which can be fabricated from off-the-shelf and 3-D printed components. The oven is tested for drying speed and effective-ness on both waste plastic polyethylene terephthalate (PET) and a consortium of bacteria developed for bioprocessing of terephthalate wastes to assist in distributed recycling of PET for both additive manufacturing as well as potential food. Both materials can be damaged when exposed to high temperatures, making vacuum drying a desirable solution. The results showed the open source vacuum oven was effective at drying both plastic and biomaterials, drying at a higher rate than a hot-air dryer for small samples or for low volumes of water. The system can be constructed for less than 20% of commercial vacuum dryer costs for several laboratory-scale applications including dehydration of bio-organisms, drying plastic for distributed recycling and additive manufacturing, and chemical processing.

In this study, we propose a radiomics-clinical probability weighted model for the prediction of prognosis for NSCLC. The model combines radiomics features extracted from RT planning images with clinical factors such as age, gender, histology, and tumor stage. CT images with radiotherapy structures of 422 NSCLC patients were retrieved from The Cancer Imaging Archive (TCIA). Radiomic features were extracted from gross tumor volume (GTV). Five machine learning algorithms, namely decision trees (DT), random forests (RF), extreme boost (EB), support vector machine (SVM) and generalized linear model (GLM), were optimized by a voted ensemble machine learning (VEML) model. A probabilistic weighted approach is used to incorporate the uncertainty associated with both radiomic and clinical features and to generate a probabilistic risk score for each patient. The performance of the model is evaluated using a receiver operating characteristic (ROC). Radiomic model, clinical factors model and combined radiomic-clinical probability weighted model demonstrated good performance in predicting NSCLC survival with AUC of 0.941, 0.856 and 0.949 respectively. The combined radiomics-clinical probability weighted enhanced model achieved significantly better performance than radiomic model in 1-year survival prediction (chi-square test, p<0.05). The proposed model has the potential to improve NSCLC prognosis and facilitate personalized treatment decisions.

The multivariate Gaussian random fields with matrix-based scaling laws are widely used for inference in statistics and many applied areas. In such contexts interests are often in symmetry and in the rates of change of spatial surfaces in any given direction. This article analyzes the almost sure sample function behavior for operator fractional Brownian motion, including multivariate fractional Brownian motion. We obtain the estimations of small ball probability and the strongly locally nondeterministic for operator fractional Brownian motion in any given direction. Applying these estimates we obtain Chung's laws of the iterated logarithm for spatial surfaces of operator fractional Brownian motion. Our results show that the precise rates of change of spatial surfaces are completely determined by the self-similarity exponent.

Effective biomarkers are essential to the early diagnosis of non-small cell lung cancer (NSCLC). Herein, a retrospective study of 49 newly diagnosed and recurrent NSCLC patients, 31 patients with benign pulmonary disease and 24 healthy volunteers was conducted, to evaluate the diagnostic value of circulating rare cells for NSCLC. The expression of circulating tumor cells (CTCs) and circulating tumor-derived endothelial cells (CTECs) in peripheral blood were measured by subtraction enrichment-immunostaining-fluorescence in situ hybridization (SE-iFISH). The level of CTCs (P＜0.001) and CTECs (P＜0.001) was significantly higher in NSCLC group than that in benign pulmonary disease group. The proportion of small CTCs (P＜0.001) and CTECs (P＜0.0001) significantly increased from benign lung disease individuals to NSCLC patients. The AUC of ROC curves of total CTCs and CTECs were 0.815 (95%CI: 0.722~0.907), 0.739 (95%CI: 0.618~0.860), respectively. The cut-off values for discriminating NSCLC with benign lung disease patients were total CTCs 11.5 units/6ml and total CTECs 10.5 units/6ml, with sensitivity and specificity being 67.3% and 83.9%, 77.6% and 77.4%, respectively. When CTCs and CTECs were combined, predictive value significantly increased to 82.6% as measured by the area under the curve. Small CTCs and triploid CTCs had high positive predictive value (PPV) and positive likelihood ratio (LR+) of the diagnosis of NSCLC in early stage. CTCs and CTECs can not only be used as new biomarkers for the diagnosis of NSCLC, but can also improve diagnostic performance of the early stage NSCLC. Moreover, the combined examination of CTCs and CTECs is be superior to the single.