One mechanism by which fructose could exert deleterious effect in metabolism and inflammation is via its potency vis-à-vis de Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin to test the hypothesis that indeed AGEs are formed by fructose during simulated digestion of an ubiquitous food protein with intrinsic allergenic potential and under model physiological conditions. Methods: OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100 mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370 nm, Emission: λ 440nm. Results: AGE adducts form between fructose and OVA which can be found in peptide fractions (< 5 kDa) at times (30 min) and concentration ranges (10 mM) plausibly found in the intestines, whereas no reaction occurs with glucose. The reaction is inhibited by chlorogenic acid at concentrations compatible with those found in the gut. The reaction is inhibited by AG, a specific antiglycation agent. Conclusion: Our proof of principle study shows that fructose-AGE formation on an ubiquitous allergenic protein indeed occurs in one hour and thereby may pave the way for the study of yet another mechanism by which the excess fructose in our Western diets is contributing to disease: intestinal AGE formation, absorption and RAGE engagement.

Based on PVDF (piezoelectric sensing techniques), this paper attempts to study the propagation law of shock waves in brittle materials during the process of three-wavelength laser irradiation of polysilicon, and discusses the formation mechanism of thermal shock failure. The experimental results show that the vapor pressure effect and the plasma pressure effect in the process of pulsed laser irradiation lead to the splashing of high temperature and high density melt. With the decrease of the laser wavelength, the laser breakdown threshold decreases and the shock wave is weakened. Because of pressure effect of the laser shock, the brittle fracture zone is at the edge of the irradiated area. The surface tension gradient and surface shear wave caused by the surface wave are the result of coherent coupling between optical and thermodynamics. The average propagation velocity of laser shock wave in polysilicon is 8.47×103m/s, and the experiment has reached the conclusion that the laser shock wave pressure peak exponentially distributes attenuation in the polysilicon.

Elevated carbon dioxide (eCO₂) stimulates wheat grain yield, but simultaneously reduces protein (N) concentration. Also other essential nutrients are subject to change. This study is a comprehensive synthesis of wheat experiments with eCO₂, estimating effects on N, minerals (B, Ca, Cd, Fe, K, Mg, Mn, Na, P, S, Zn), and starch. Analysis was made by i) deriving response functions for the relative effect on element concentration in relation to CO₂ concentration, ii) meta-analysis to test the magnitude and significance of observed effects, and iii) relating CO₂ effects on minerals to effects on N and grain yield. Responses range from zero to strong negative effects of eCO₂ on mineral concentration, with largest reductions for the nutritionally important elements N, Fe, S, Zn and Mg. Together with the positive but small and non-significant effect on starch concentration, the large variation in effects suggests that CO₂-induced responses cannot be explained by a simple dilution model. To explain the observed pattern, uptake and transport mechanisms may have to be considered, along with the link of different elements to N uptake. Our study shows that eCO₂ has a significant effect on wheat grain stoichiometry, with implications for human nutrition in a world of rising CO₂.

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

The main objective of this work is to investigate the temporal variation of PM10 concentrations within the urban area of Athens during the years 2001-2015. For this purpose, the time series of the particulate matter with aerodynamic diameter less than 10μm (PM10) is recorded for a 15-year period (2001-2015) in two different monitoring stations located in the urban area of Athens. The results show a totally different behavior of PM10 concentrations between the Athens city center and the suburban areas. It seems that in the city center the main sources of PM10 are traffic and heating systems especially during the cold period of the year. Furthermore, in the city center a significant seasonal variation was found with high concentrations during the cold period of the year and lower concentrations during the warm period of the year. Moreover, it was found that during the weekends, there is a decrease in PM10 concentrations probably due to the fact that majority of people do not use their vehicles. Finally, for both locations a significant temporal decreasing trend of the mean annual PM10 concentrations was found which indicates that during the last years, there have been improvements towards a better air quality.

The weight coefficients of the diaphragm spring depend on experiences in the traditional optimization. However, this method not only cannot guarantee the optimal solution but it is also not universal. Therefore, a new optimization target function is proposed. The new function takes the minimum of average compress force changing of the spring and the minimum force of the separation as total objectives. Based on the optimization function, the result of the clutch diaphragm spring in a car is analyzed by the non-dominated sorting genetic algorithm (NSGA-II) and the solution set of Pareto is obtained. The results show that the pressing force of the diaphragm spring is improved by 4.09%by the new algorithmand the steering separation force is improved by 6.55%, which has better stability and steering portability. The problem of the weight coefficient in the traditional empirical design is solved. The pressing force of the optimized diaphragm spring varied slightly during the abrasion range of the friction film, and the manipulation became remarkably light.

Brain is the most complex organ in the human body and it is divided into two hemispheres - left and right hemispheres. Left hemisphere is responsible for control of right side of our body whereas right hemisphere is responsible for control of left side of our body. Brain image segmentation from different neuroimaging modalities is one of the important parts in clinical diagnostic tools. Neuroimaging based digital imagery generally contain noise, inhomogeneity, aliasing artifacts, and orientational deviations. Therefore, accurate segmentation of brain images is a very difficult task. However, the development of accurate segmentation of brain images is very important and crucial for a correct diagnosis of any brain related diseases. One of the fundamental segmentation tasks is to identify and segment inter-hemispheric fissure/mid-sagittal plane, which separate the two hemispheres of the brain. Moreover, the symmetric/asymmetric analyses of left and right hemispheres of brain structures are important for radiologists to analyze diseases such as Alzheimer's, Autism, Schizophrenia, Lesions and Epilepsy. Therefore, in this paper we have analyzed the existing computational techniques used to find brain symmetric/asymmetric analysis in various neuroimaging techniques (MRI/CT/PET/SPECT), which are utilized for detecting various brain related disorders.

Accurate and consistent rainfall observations are vital for climatological studies in support of better planning and decision making. However, estimation of accurate spatial rainfall is limited by sparse rain gauge distributions. Satellite rainfall products can thus potentially play a role in spatial rainfall estimation but their skill and uncertainties need to be under-stood across spatial-time scales. This study aimed at assessing the temporal and spatial performance of seven satellite products (TARCAT (Tropical Applications of Meteorology using SATellite and ground-based observations (TAMSAT) African Rainfall Climatology And Time series), Climate Hazards Group InfraRed Precipitation with Station data (CHIRPS), Tropical Rainfall Measuring Mission (TRMM-3B43), Climate Prediction Center (CPC) Morphing (CMORPH), the Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks- Climate Data Record (PERSIANN-CDR), CPC Merged Analysis of Precipitation (CMAP) and Global Precipitation Climatology Project (GPCP) using gridded (0.05o) rainfall data over East Africa for 15 years(1998-2012). The products’ error distributions were qualitatively compared with large scale horizontal winds (850 mb) and elevation patterns with respect to corresponding rain gauge data for each month during the ‘long’ (March-May) and ‘short’ (October-December) rainfall seasons. For validation only rainfall means extracted from 284 rain gauge stations were used, from which qualitative analysis using continuous statistics of Root Mean Squared Difference, Standard deviations, Correlations, coefficient of determinations (from scatter plots) were used to evaluate the products’ performance. Results revealed rainfall variability dependence on wind flows and modulated by topographic influences. The products’ errors showed seasonality and dependent on rainfall intensity and topography. Single sensor and coarse resolution products showed lowest performance on high ground areas. All the products showed low skills in retrieving rainfall during ‘short’ rainfall season when orographic processes were dominant. CHIRPS, CMORPH and TRMM performed well, with TRMM showing the best performance in both seasons. There is need to reduce products’ errors before applications.

The way people innovate and create new ideas and bring them to the market is undergoing a fundamental change from closed innovation to open innovation. Why and how do firms perform open innovation? Firms’ open innovation is measured through the levels of firms’ joint patent applications. Next, we analyze network structures and characters of firms’ joint patent applications such as betweenness and degree centrality, structure hole, and closure. From this research, we drew conclusions as follows. First, the structure of collaboration networks has both direct and indirect effects on firms’ innovative performance. Second, in the process of joint patent applications, there is a long tail phenomenon in networks of joint patent applications. Third, the number of patents and International Patent Classification (IPC) subclasses together constitute a meaningful measure of the innovation performance of firms.

It is a well-established fact that inadequate Vitamin D (Vit-D) levels have negative effects on the development and progression of malignant diseases, mainly cancer. The purpose of this paper was to elucidate the effects of Vit-D intake and serum 25-hydroxyvitamin-D (25(OH)D) levels on cancer incidence and mortality, the current evidence in this field, and the biases of this evidence using the meta-meta-analysis method. Meta-analyses focusing on Vit-D intake, serum 25(OH)D levels, and cancer risk/mortality were identified. A structured computer literature search was performed in PubMed/Medline, Web of Science (WoS), and Scopus electronic databases using predetermined keyword combinations. Primary and secondary meta-meta-analyses were carried out, combining odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) for outcomes reported in selected meta-analyses. A total of 35 eligible meta-analyses assessing the association between Vit-D and cancer incidence and/or mortality were included in this study. In the pooled analysis, higher Vit-D intake and serum 25(OH)D levels were associated with lower cancer risk (OR = 0.93, 95% CI: 0.90-0.96, p < 0.001; OR = 0.80, 95% CI: 0.72-0.89, p < 0.001, respectively) and cancer-related mortality (RR = 0.89, 95% CI: 0.86-0.93, p < 0.001; RR = 0.67, 95% CI: 0.58-0.78, p < 0.001, respectively). When meta-analyses whose primary reports included only randomized controlled trials were pooled, there was no significant association between Vit-D intake and cancer risk (OR = 0.99, 95% CI: 0.97-1.01, p = 0.320). In subgroup analysis, Vit-D consumption was associated with a significant decrease in colorectal and lung cancer incidence (OR = 0.89, 95% CI: 0.83-0.96, p = 0.002; OR = 0.88, 95% CI: 0.83-0.94, p < 0.001, respectively). Taken together, both Vit-D intake and higher 25(OH)D levels may provide remarkable benefits in terms of cancer incidence and mortality, however, careful evaluation according to cancer types is critically important and recommended.

Introduction. Self-sampling has the potential to increase cervical cancer screening (CCS) among women living with HIV (WLWH) in low and middle-income countries (LMICs). However, our understanding of how HPV self-collection studies have been conducted in WLWH is limited. The purpose of this scoping review was to examine the extent to which the HPV self-sampling has been applied among WLWH in LMICs. Method: We conducted multiple searches in several databases for articles published between 2000 and January 2022. With the combination of keywords relating to HPV self-sampling, LMICs, and WLWH, we retrieved over 9,000 articles. We used pre-defined inclusion and exclusion criteria to select relevant studies for this review. Once a study met the inclusion criteria, we created a table to extract each study’s characteristics and classified them under common themes. We used a qualitative descriptive approach to summarize the scoping results. Results: A total of 12 articles were included in the final review. Overall, 3,178 women were enrolled in those studies and 2,105 (66%) of them were WLWH. The self-sampling participation rate was 92.6%. The findings of our study show that 43% of the WLWH in 8 of the studies reviewed tested positive for high-risk HPV (hr-HPV) genotypes, indicating 4 out of 10 WLWH in the studies are at risk of cervical cancer. The prevalence of the hr-HPV in WLWH was 18% higher than that of HIV-negative women. Most women in the study found the self-sampling experience acceptable, easy to use, convenient, and comfortable. Self-sampling performance in detecting hr HPV genotypes is comparable to clinician-performed sampling. However, limited access (i.e., affordability, availability, transportation), limited knowledge about self-screening, doubts about the credibility of self-sampling results, and stigma remain barriers to wide acceptance and implementation of self-sampling. In conclusion, the findings of this review highlight that (a) cervical cancer is a threat to every sexually active woman but for WLWH the threat increases, (b) self-sampling laboratory performance is similar to clinician performed sampling, (c) self-sampling is associated with an increase in cervical cancer screening uptake and (d) WLWH reported a positive experience with self-sampling. However, personal, environmental, and structural barriers challenge the application of self-sampling in LMICs, and these need to be addressed. Keywords: keyword 1; keyword 2; keyword 3 (List three to ten pertinent keywords specific to the article yet reasonably common within the subject discipline.)

Rett syndrome (RTT) is an X-linked neurodevelopment disorder associated with the single monogenic mutation in methyl-CpG binding protein 2 (MeCP2) in up to 95% of cases. The growing number of genome-wide association studies and incomplete concordance for autoimmune diseases in monozygotic twins concur to support the involvement of environmental factors, like infectious agents or chemicals, in the breakdown of tolerance leading to autoimmunity. In fact, the coexistence of a perturbation of the immune system in RTT patients has been previously hypothesized. We herein explored the hypothesis that an autoimmune component derived from environmental bacterial infection of non typeable Haemophilus influenzae may coexist in RTT. At this purpose we screened sera from RTT syndrome patients, non-RTT pervasive developmental disorders patients and healthy controls with the hyperglucosylated adhesin protein HMW1ct(Glc) used as a precise antigen in ELISA in order to identify specific antibodies to N-glucosylation sites. Results showed that HMW1ct(Glc) is able to significantly discriminate antibodies among RTT sera and controls. Competitive ELISA confirmed the specific interaction between antibodies characteristic of RTT syndrome and the N-glucosylation motifs of the bacterial adhesin protein HMW1ct(Glc).

The emergence of drug-resistant mycobacteria has rendered many clinical drugs and regimens ineffective, imposing significant economic and healthcare burden on individuals and society. Repurposing drugs intended for treating other diseases is a time-saving, cost-effective, and efficient approach for identifying excellent anti-mycobacterial candidates or lead compounds. This study is the first to demonstrate that rupatadine (RTD), a drug used to treat allergic rhinitis, possesses excellent activity against mycobacteria without detectable resistance, particularly Mycobacterium tuberculosis and Mycobacterium marinum, with a minimal inhibitory concentration as low as 3.13 µg/mL. Furthermore, RTD exhibited moderate activity against nonreplicating M. tuberculosis with the minimal inhibitory concentrations lower than drugs targeting the cell wall, suggesting that RTD has the great potential to be modified and used for the treatment of nonreplicating M. tuberculosis. Additionally, RTD exhibits partial synergistic effects when combined with clofazimine, pretomanid, and TB47 against M. tuberculosis, providing the theoretical foundation for the development of treatment regimens. Transcriptomic profiling leads us to speculate that eight essential genes may be the targets of RTD or may be closely associated with the mycobacterial resistance to RTD. In summary, RTD may be a promising hit for further anti-mycobacterial drug or regimen optimization, especially in case of nonreplicating mycobacteria.

Increased anthropogenic pressure on forest resources leads to deforestation and forest degradation, significantly limiting the regeneration capacity of native woody species and consequently the restoration of miombo woodlands in anthropized habitats within the rural area of Lubumbashi. This study assessed the diversity and natural regeneration capacity of miombo species through floristic inventories in three different habitats (unexploited forests, degraded forests, and post-cultivation fallows). The results reveal that for the adult’s stratum unexploited and degraded forests exhibit higher dendrometric (density, mean square diameter, basal area) and floristic parameter (taxa, genera, families) values compared to post-cultivation fallows. Furthermore, the regeneration of miombo woody species is higher in degraded forests (21 taxa; 105 juveniles/plot). However, regarding the sapling’s stratum (1 cm ≤ dbh &lt; 10 cm), the three habitats display nearly similar situations. Additionally, the floristic composition and diversity of unexploited and degraded forests show a significantly higher similarity (76.50%) among them compared to these habitats and the post-cultivation fallows (56.00%). These findings indicate that miombo woodlands have the potential to regenerate and maintain floristic diversity. To sustain this natural regeneration capacity of miombo woody species and promote the restoration of forest mass and its floristic diversity, it is imperative to determine the rotation period after habitat exploitation and regulate anthropogenic activities and late bush fires, particularly in anthropized habitats at the village level.

Timely and accurate acquisition of information on distribution of the crop planting structure in Loess Plateau of eastern Gansu Province, one of the most important agricultural areas in western China, is crucial for promoting fine management of agriculture and ensuring food security. In this study, the Object-Based Image Classification (OBIC), the Random Forest (RF) and Convolutional Neural Network (CNN) models were employed to classify the crop planting structure of four representative test areas in Qingyang City in a precise manner. Firstly, different optimal segmentation scales for various crops were selected using the Estimation of Scale Parameter 2 (ESP2) tool and the Ratio of Mean Difference to Neighbors(ABS) to Standard Deviation (RMAS)model. The images were then segmented through multiresolution segmentation combined with the Canny Edge Detection algorithm. Secondly, the L1 regularized logistic regression model was utilized to select and optimize 39 spatial feature factors including spectral, textural, geometric, and index features, in conjunction with phenological factors. Lastly, under the multi-level classification framework, the Random Forest (RF) classifier and Convolutional Neural Network (CNN) model, combined with object-based multiresolution segmentation, was used to classify the crop planting structure. The findings show that: Thanks to the Canny Edge Detection algorithm, we can obtain a more complete boundary of the segmented objects and improve the separability. The optimal segmentation scales for corn, vegetables, and buckwheat were found to be 55, 70, and 35, respectively, while wheat and apple had optimal segmentation scales of 65. In addition to phenological characteristics, the number of selected spatial features for corn, vegetables, buckwheat, wheat, and apple were 9, 7, 16, 12, and 10, respectively. The CNN model demonstrated high consistency with the RF model in the classification results, but the accuracy of RF model is higher than that of CNN model on the whole. The overall accuracy of classification using RF model in four test areas registered 91.93%, 94.92%, 89.37% and 90.68%, respectively. This paper introduced crop phenological factors, effectively improving the extraction precision of shattered agricultural planting structure in the Loess Plateau of eastern Gansu Province. Its findings have important application value in crop monitoring, management, food security and other related fields.

The presence of anti SARS-CoV2-RBD antibody (Anti-RBD) prevents severe COVID-19. We aimed to determine the accuracy of a point-of-care Anti-RBD test implemented in person living with HIV (PLWH), systemic lupus erythematosus (SLE), and chronic kidney disease (CKD). We enrolled 182 non-comorbid subjects and 335 persons with comorbid (PLWH, SLE, CKD) to test anti-RBD assay compared to surrogate viral neutralization (SVNT) as the reference test. We performed linear correlation analysis between anti-RBD vs SVNT and a ROC analyses to ascertain anti-RBD cut-off at 30%, 60%, and 90% inhibition of SVNT to calculate accuracy. Correlations of anti-RBD to SVNT among all groups were excellent with R= 0.7903, R=0.7843, R=0.8153 among non-comorbid, SLE and CKD groups, respectively, with significantly higher correlation among the PLWH group (R=0.8877; p-value=0.0072) compared to non-comorbid group. The accuracy of the anti-RBD test among PLWH and CKD group was similar with the non-comorbid but showed lower sensitivity in the SLE group (p=0.000014). The specificity of the test remained high in all groups. In conclusion, the Anti-RBD test had excellent correlation to SVNT. The persistently high specificity in all groups suggests that this test can be reliably utilized to detect presence of low neutralization capacity, prompting additional vaccination.

Introduction. Intra-abdominal cystic formations represent heterogeneous pathologies with varied localization and clinical manifestation. The first challenge of a giant intra-abdominal cystic lesion is identifying the organ of origin. The clinical presentation of intra-abdominal cystic lesions varies from acute manifestations to non-specific symptoms or accidental discovery. Case presentation: A 2-year-old girl presents to the emergency unit with a fever of 38.5 Celsius, loss of appetite, and apathy. The investigations showed a gigantic intra-abdominal mass whose organ belonging could not be specified. Postoperatively, a giant mesenteric lymphangioma was evident, which was completely excised. Discussions Giant cystic formations modify the anatomical reports and become space-replacing formations, and the starting point is even more challenging to assess preoperatively. Nevertheless, the careful evaluation of the characteristics of the formation, the effect on the adjacent organs, the age of the patient, and the clinical picture can provide elements of differential diagnosis.

A new Mg-Zn-Zr-Ca alloy in powder state was obtained via mechanical alloying method, from pure elemental powder. Further, the obtained powder-alloy was processed by selective laser melting (SLM) procedure to obtain 3D printed samples for small biodegradable implants. A series of microstructural, mechanical and corrosion analysis were performed. The SEM analysis of powder-alloy reveal a good dimensional homogeneity, with uniform colored, no agglutinated and almost rounded particles, suitable for selective laser melting procedure. Further, the SLM samples reveal a robust and unbreakable morphology, with a suitable porosity and without undesirable balling effect. The tested Young’s modulus of the SLM samples, of 42 GPa, is close to cortical bone one, of 30 GPa. The corrosion tests performed in PBS (Phosphate-buffered saline) solution show that the corrosion parameters have a satisfactory evolution.

This study outlines the development of an innovative method utilizing UHPLC-PDA for the simultaneous identification of polyphenols and bitter acids (alpha-acids, beta-acids, and iso-alpha-acids) in beer samples. The resulting chemical profiles were leveraged to distinguish the characteristics of four bergamot-flavored beers, each representing distinct styles (IPA, Lager, Blanche, and ALE), produced on a pilot-scale plant. In a streamlined 29-minute analysis, twenty-nine polyphenols and fourteen bitter acids were successfully identified under optimized separation conditions. Rigorous validation, encompassing parameters such as Limit of Detection (LOD), Limit of Quantification (LOQ), R-squared (R2), repeatability, and reproducibility, was conducted for polyphenol quantification using constructed calibration curves with seven levels. Exploring polyphenolic components as potential discriminators among different beer styles, a total of thirty-two polyphenolic compounds were identified and quantified, including characteristic bergamot peel polyphenols like neoeriocitrin, naringin, and neohesperidin. The determination of bitter units and total phenols further aided in style differentiation. Multivariate analysis provided additional insights into variations among specific beer styles, revealing discrepancies in the presence or relative concentrations of specific compounds linked to brewing ingredients and processes. This research enhances to trace the fingerprinting of the chemistry governing beer quality through a straightforward and cost-effective analytical approach, readily applicable in common laboratories.

The literature offers limited information on the effect of obesity on the rate of force development, a critical parameter for mobility in older adults. The objectives of this study were; to explore the influence of obesity on RFD in older adults and to examine the association between this neuromuscular parameter and walking speed. 42 older adults were classified into two groups: the control group (CG, n=22; age=81.13±4.02 years; Body mass index (BMI)=25.13±3.35 kg/m²), and the obese group (OG, n=20; age=77.71±2.95 years; BMI=34.46±3.25 kg/m²). Walking speed (m/s) was measured using the 10-meter walking test. Neuromuscular parameters of the plantar flexors were evaluated during a maximal voluntary contraction test using a dynamometer. The RFD was calculated from the linear slop of the force – time curve in two phases: from the onset of the contraction to 50 ms (RFD50-100) and from 100 to 200 ms (RFD100-200). The gait speed was lower in the OG compared to the CG (p

A reduction in population sodium (as salt) consumption is one of the most cost-effective strategies to reduce the burden of cardiovascular disease and it is a global health priority. High potassium intake is also recommended to reduce cardiovascular disease. To establish effective policies for setting targets and monitoring effectiveness within each country, the current level of consumption should be known. Greece lacks data on actual sodium and potassium intakes. The aim of the present study was therefore to assess dietary salt (using sodium as biomarker) and potassium intakes in a sample of healthy adults in northern Greece and to determine whether adherence to a Mediterranean diet is related to different sodium intakes or sodium-to-potassium ratio. A cross-sectional survey was carried out in Thessaloniki greater metropolitan area (northern Greece) (n=252, aged 18-75 years, 45.2% males). Participants’ dietary sodium and potassium intakes were determined by 24h urinary sodium and potassium excretions. In addition, we estimated their adherence to Mediterranean diet by the use of an 11-item MedDietScore (range 0-55). The mean sodium excretion was 175 (SD 72) mmol/day, equivalent to 4,220 (1,745) mg of sodium or 10.7 (4.4) g of salt per day and potassium excretion was 65 (25) mmol/day, equivalent to 3,303 (1,247) mg/day. Men had higher sodium and potassium excretions compared to women. Only 5.6% of the sample had salt intake <5g/d, which is the target intake recommended by the WHO. Mean sodium-to-potassium excretion ratio was 2.82 (1.07). There was no significant difference in salt or potassium intake or their ratio across MedDietScore quartiles. No significant relationships were found between salt intake and adherence to Mediterranean diet, suggesting that the perception of the health benefits of the Mediterranean diet does not hold when referring to salt consumption. These results suggest the need for a larger nation-wide survey on salt intake in Greece and underline the importance of continuation of salt reduction initiatives in Greece.

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 and 30 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90 and CD105 were analyzed by flow cytometry and stem cell transcription factors NANOG, SOX2 and OCT3/4 were detected by immunoblotting and Real-Time PCR. NANOG, SOX2 and OCT3/4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT3/4. NANOG silencing induced a significant OCT 3/4 (70% ± 0.05) and SOX2 (75% ± 0.03) down-regulation whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency and plasticity.

Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.

Cell membrane-derived liposomes, termed Memposomes, serve as promising carriers for drug delivery due to their ability to closely mimic cells and efficiently target specific cells. Liposomes derived from cancer cell membranes, in particular, exhibit homologous targeting capabilities, making them potential candidates for cancer-specific drug delivery. However, the underlying mechanisms and specific proteins responsible for this homologous targeting phenomenon remain debated. This study focuses on the role of E-cadherin, a cell adhesion molecule implicated in homophilic adhesion, in influencing the homologous targeting ability of Memposomes derived from cancer cell membranes. E-cadherin expression patterns were assessed in various cell lines, categorizing them into E-cadherin-positive and -negative groups. Memposomes were produced for each group, and their targeting tendencies were evaluated. The study confirmed that E-cadherin expression significantly influenced the homologous targeting ability of Memposomes. Cell lines with higher E-cadherin expression levels exhibited a more pronounced homologous targeting effect. This research demonstrates that cell adhesion molecules, particularly E-cadherin involved in homophilic adhesion, play a pivotal role in influencing the cell targeting ability of Memposomes. The study further validates the stability, safety, and purity of Memposomes, emphasizing their potential as effective drug delivery vehicles for the development of cell-specific therapies.

Luminal breast cancer has a high incidence worldwide and is a severe health threat. Estrogen receptor alpha (ER-α) is activated by 17β-estradiol (E2), and its overexpression promotes cancerous characteristics. Luminal breast cancer is an epithelial type; however, the cytokine IL-6 secreted by cells from the tumor microenvironment stimulates the epithelial to mesenchymal transition (EMT) and promotes metastasis. Also, IL-6 decreases ER-α levels, favoring the tamoxifen (TMX) resistance development. However, genes under E2 regulation continue expressing even though this receptor is absent. GPR30 is an alternative E2 receptor present in both luminal and aggressive triple-negative breast cancer and is related to TMX resistance and cancer progression. The roles of GPR30 and IL-6 on metastasis have been individually established; however, their interplay remains unexplored. This study aims to elucidate the role of GPR30 in IL-6-induced metastatic properties in MCF-7 luminal breast cancer cells. Results showed that GPR30 contributes to the E2-induced MCF-7 proliferation because its inhibition with the antagonist G15 and the Pertussis toxin (PTX) diminished it. Besides, GPR30 upregulated vimentin and downregulated E-cadherin levels in MCF-7 and in TMX-resistant (R-TMX) cells and is also involved in the IL-6-induced migration, invasion, and TMX resistance in MCF-7 cells. In addition, in MDA-MB-231 triple-negative cells, both basal and IL-6-induced metastatic properties were related to GPR30 activity. These results indicate that the GPR30 receptor regulates the EMT induced by IL-6 in breast cancer cells.

Identifying the primary site of origin of metastatic cancer is vital for guiding treatment decisions, especially for patients with cancer of unknown primary (CUP). Despite advanced diagnostic techniques, CUP remains difficult to pinpoint and is responsible for a considerable number of cancer-related fatalities. Understanding its origin is crucial for effective management and potentially improving patient outcomes. This study introduces a machine learning framework ONCOfind-AI that leverages transcriptome-based gene set features to enhance the accuracy of predicting the origin of metastatic cancers. By ensuring compatibility between RNA-sequencing and micro-array data, we were able to construct a more comprehensive training dataset. Integrating data from different platforms improved the accuracy of our machine learning models for predicting cancer origins. Our method was validated using external data from clinical samples collected through Kangbuk Samsung Medical Center and the Gene Expression Omnibus. The external validation results demonstrated a top-1 accuracy ranging from 0.80 to 0.86, with a top-2 accuracy of 0.90. This study highlights that incorporating biological knowledge through curated gene sets can merge gene expression data from different platforms, enhancing the compatibility needed for more effective machine learning prediction models.

In this multicenter, retrospective study we evaluated the added value of magnetic resonance dispersion imaging (MRDI) to standard multiparametric MRI (mpMRI) for PCa detection. The study included 76 patients - 51 with clinically significant prostate cancer (csPCa), who underwent radical prostatectomy and had an mpMRI including dynamic contrast enhanced-MRI. Two radiologists performed three separate randomized scorings based on mpMRI, MRDI and mpMRI+MRDI. Radical prostatectomy histopathology was used as the reference standard. Imaging and histopathology were both scored according to the Prostate Imaging-Reporting and Data System V2.0 sector map. Sensitivity and specificity for PCa detection were evaluated for mpMRI, MRDI and mpMRI+MRDI. Inter- and intra-observer variability for both radiologists were evaluated using Cohen’s Kappa. On a per patient level, sensitivity for csPCa for radiologist 1 (R1) for mpMRI, MRDI and mpMRI+MRDI were 0.94, 0.82 and 0.94, respectively. For the second radiologist (R2) these were 0.78, 0.94 and 0.96. R1 detected 4% additional csPCa cases using MRDI compared to mpMRI and R2 detected 20% extra csPCa cases using MRDI. Inter-observer agreement was significant only for MRDI (Cohen’s kappa = 0.4250, p=0.004). The results of this study show the potential of MRDI to improve interobserver variability and the detection of csPCa.

Prostate Cancer remains a prevalent health concern, emphasizing the critical need for early diagnosis and precise treatment strategies to mitigate mortality rates. Accurate prediction of cancer grade is paramount for timely interventions. This paper introduces an approach to prostate cancer grading, framing it as a classification problem. Leveraging ResNet models on multi-scale patch-level digital pathology and the Diagset dataset, the proposed method demonstrates notable success, achieving an accuracy of 0.999 in identifying clinically significant prostate cancer. The study contributes to the evolving landscape of cancer diagnostics, offering a promising avenue for improved grading accuracy and, consequently, more effective treatment planning. By integrating innovative deep-learning techniques with comprehensive datasets, our approach presents a step forward in the pursuit of personalized and targeted cancer care.

Background: Fine-needle aspiration cytology (FNAC) is widely used to diagnose and monitor thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is the standard for interpreting FNAC specimens. The risk of malignancy in Bethesda III nodules also known as Atypia of Undetermined Significance (AUS) varies significantly throughout several studies published worldwide. This retrospective study examines the risk of cancer in thyroid FNAC categorized as Bethesda III, as identified in the final histopathology of thyroidectomy specimens at a single endocrine surgery center. Methods: This retrospective cohort analysis included 1038 consecutive patients who underwent elective thyroid surgery with complete follow up data between January 2020 and March 2024. Preoperative data on clinical and pathological characteristics have been collected. The final histopathology report from the thyroidectomy specimen was compared to the results of the preoperative FNAC on nodules that were judged to be Bethesda category III. Statistical methods were performed using SPSS version 29. Results: A total of 670 ultrasound-guided FNACs (64.5%) performed during the study period were included in the final analysis. The study population was predominantly female, represented by 79.6% of patients with a mean age of 42.5 (SD 12.1), while 20.4% were male and significantly older with mean age 45.13 years (p = 0.02). The FNAC inadequacy rate was 5.1%, which was associated with a high risk of malignancy (6 out of 34, 17.6%). Out of the total sample size of 170 patients classified as group III, 57 were found to have malignancies in final surgical histopathology, representing 33.5% of the cases within this category. The secondary gender-related outcome analysis showed that female patients classified under the Bethesda II category had a significantly higher risk of malignancy, with a rate of 21.2%, compared to males who had a malignancy rate of 3.4% in the same Bethesda category (p = 0.001, chi square test). However, female had more better prognostic non-invasive tumors than male (p = 0.02, chi square test). Conclusion: The study's results indicate that Bethesda categories II and III are associated with a higher risk of malignancy in comparison to the reports of the first and third editions of the TBSRTC, particularly for female patients classified under category II.

Our study optimized MET ex14 skipping mutation detection by analyzing 223 Oncomine Focus Assay (OFA)-positive cases using Pan Lung Cancer PCR Panel (AmoyDx) and reverse transcription (RT)-PCR. Among the 11 MET ex14 skipping mutation-positive cases (average read counts: 1,390), two with OFA read counts of 2540 and 10177 were positive on all platforms. Those with OFA read counts ranging from 179–612 tested negative elsewhere. Specimens with low ratios (average ratio: 0.12% for nine cases) may yield false-positive results. Our results suggested monitoring read counts and ratios, and validating results with RT-PCR, is crucial to prevent false positives.

Background: Cancer therapy-related cardiac dysfunction (CTRCD) is a growing concern for public health, with a growing incidence due to improved survival rates for patients with hematological malignancies due to diagnostic and therapeutic advances. Identification of patients at risk CTRCD is vital to develop preventive strategies. Methods: A single-center retrospective cohort study was conducted between 1 January 2017 and 15 February 2023. Medical records of patients with lymphoma treated with first-line anthracyclines were reviewed. Demographic data, cardiovascular risk factors, biomarkers of myocardial damage and echocardiographic information were collected. Results: A total of 200 patients were included. The incidence of CTRCD was 17.4 % (35/200). Patients with CTRCD were older than those without CTRCD, with a mean age of 65.17 years vs 56.77 (p = 0.008). Dyslipidemia (DL) (31.4% vs 13.4% p = 0.017) and previous cardiovascular disease (40% vs 13.3%, p< 0.001) were more frequent in the group who developed an event. Mean baseline NT-proBNP levels in the subgroup with cardiovascular events were 388.73 kg /L ± 101.02, and 251.518 kg /L ± 26.22 in those who did not (p = 0.004). Differences in Troponin I levels were identified during and after treatment without exceeding the laboratory’s upper reference limit. Patients were followed for a median of 51.83 months (0.76-73.49). The presence of a CTCRD event had a negative impact on overall mortality from any cause (HR = 2.23 (95% CI 1.08-2.93), p = 0.031). Conclusions: Early identification of risk factors is crucial to manage patients at risk for CTRCD.

Tumor infiltrating lymphocytes (TILs) are an emerging biomarker predictive of response to immunotherapy across a spectrum of solid organ malignancies. The characterization of TILs in gastric cancer (GC) treated with contemporary, multiagent neoadjuvant chemotherapy (NAC) is understudied. In this retrospective investigation, we analyzed the degree of infiltration, phenotype, and spatial distribution of TILs via immunohistochemistry within resected GC specimens treated with or without NAC at a Western center. We hypothesized that NAC executes immunostimulatory roles evidenced by an increased number of anti-tumor TILs in the tumor microenvironment. We found significantly elevated levels of conventional and memory CD8+ T cells, and total TILs (CD4+, CD8+, Treg, B cells) within chemotherapy-treated tumors compared to chemotherapy-naïve specimens. We also revealed important associations between survival and pathologic response with enhanced TIL infiltration. Taken together, our findings advocate for an immunostimulatory role of chemotherpy and underscore the potential synergistic effect of combining chemotherapy with immunotherapy in resectable gastric cancer.

Colorectal cancer (CRC) is the second cause of cancer-related death where the CpG-island methylation pathways (CIMP) is associated to KRAS/BRAF mutations, two oncogenes rewiring cell metabolism, worst prognosis and resistance to classical chemotherapies. Despite this, the question of a possible metabolic rewiring in CIMPs has never been asked. Here we asked if metabolic dysregulations were associated to the methylation status of tumours by evaluating the transcriptome of CRC tumours. CIMP-high patients were found to present a hyper-metabolism activating mainly carbohydrates, folates, sphingolipids and arachidonic acid metabolic pathways. A third of these genes had epigenetic targets of Myc in their proximal promoter, activating carboxylic acid, tetrahydrofolate interconversion, nucleobase, and oxoacid metabolisms. Amongst the Myc signature, the expression of GAPDH, TYMS, DHFR, TK1 was enough to predict methylation levels, microsatellite instability (MSI) and mutations in the mismatch repair (MMR) machinery, which are strong indicators of responsiveness to immunotherapies. Finally, we discovered that CIMP patients harboured an increase in genes involved in the one-carbon metabolism, a pathway critical to provide nucleotides for cancer growth and methyl donors for DNA methylation which was associated to worse prognosis. Transcriptomics could hence become a tool to help clinicians stratify their patients better.

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

The persistent threat of cancer remains a significant hurdle for global health, prompting the exploration of innovative approaches in the quest for successful therapeutic interventions. Cyclin-dependent kinase 9 (CDK9), a central player in transcription regulation and cell cycle progression, has emerged as a promising target to combat cancer. Its pivotal role in oncogenic pathways and the pressing need for novel cancer treatments has propelled CDK9 into the spotlight of drug discovery efforts. This article presents a comprehensive study that connects a multidisciplinary approach, combining computational methodologies, experimental validation, and the transformative PROTAC (Proteolysis-Targeting Chimera) technology. By uniting these diverse techniques, we aim to identify, characterize, and optimize a new class of degraders targeting CDK9. We explore these compounds for kinase inhibitory properties and potential to induce targeted protein degradation, offering a novel and potentially more sustainable approach to cancer therapy. This cohesive strategy expresses the interface between computational predictions and experimental insights, with the ultimate goal of advancing the development of effective anticancer therapeutics targeting CDK9.

The following narrative review embarks on a comprehensive exploration of the pivotal role played by the gut microbiome within the Diet-Microbiota-Immunity (DMI) tripartite, aiming to enhance anti-cancer immunotherapy efficacy. While revolutionizing cancer treatment, resistance to immunotherapy and immune-related adverse events (irAEs) remain challenges. The tumor microenvironment (TME), shaped by cancer cells, influences immunotherapy resistance. The gut microbiome, influenced by genetics, environment, diet, and interventions, emerges as a critical player in TME reshaping, thereby modulating immune responses and treatment outcomes. Dietary patterns like the Mediterranean diet, caloric restriction modifications, and specific nutritional components show promise in influencing the tumor microenvironment and gut microbiome for better treatment outcomes. Antibiotics, disrupting gut microbiota diversity, may compromise immunotherapy efficacy. This review emphasizes the need for tailored nutritional strategies to manipulate microbial communities, enhance immune regulation, and improve immunotherapy accessibility while minimizing side effects. Ongoing studies investigate the impact of dietary interventions on cancer immunotherapy, pointing towards promising developments in personalized cancer care. This narrative review synthesizes existing knowledge and charts a course for future investigations, presenting a holistic perspective on the dynamic interplay between dietary interventions, the gut microbiome, and cancer immunotherapy within the DMI tripartite.

The Hippo pathway plays crucial roles in governing various biological processes during tumorigenesis and metastasis. Within this pathway, upstream signaling stimuli activate a core kinase cascade, involving MST1/2 and LATS1/2, which subsequently phosphorylates and inhibits the transcriptional co-activators YAP and its paralog TAZ. This inhibition modulates the transcriptional regulation of downstream target genes, impacting cell proliferation, migration, and death. Despite the acknowledged significance of protein kinases in the Hippo pathway, the regulatory influence of protein phosphatases remains largely unexplored. In this study, we conducted the first gain-of-functional screen for protein tyrosine phosphatases (PTPs) regulating the Hippo pathway. Utilizing a LATS kinase biosensor (LATS-BS), a YAP/TAZ activity reporter (STBS-Luc), and a comprehensive PTP library, we identified numerous novel PTPs that play regulatory roles in the Hippo pathway. Subsequent experiments validated PTPN12, a master regulator of oncogenic receptor tyrosine kinases (RTKs), as a previously unrecognized negative regulator of the Hippo pathway effectors, oncogenic YAP/TAZ, influencing breast cancer cell proliferation and migration. In summary, our findings offer valuable insights into the roles of PTPs in the Hippo signaling pathway, significantly contributing to our understanding of breast cancer bi-ology and potential therapeutic strategies.

Ganoderma lucidum, commonly known as the "Lingzhi" or "Reishi" mushroom, has long been recognized for its potential health benefits, and medicinal properties in traditional Chinese medicine. In recent years, the emerging field of nanotechnology has opened up new possibilities in order to use the remarkable properties of G. Lucidum at the nanoscale. The unique combination of bioactive compounds present in G. Lucidum, such as triterpenoids, polysaccharides, and peptides, has inspired interest in leveraging their therapeutic potential through nanotechnological approaches. Various nanomaterials, including nanoparticles, nanofibers, and nanocomposites, have been employed to encapsulate and deliver these bioactive components to target cells or tissues, enhancing stability, controlled release, and consequently their bioavailability. Nanotechnology-based strategies have been investigated for the efficient extraction and purification of bioactive compounds from G. Lucidum. The use of nanoscale materials has facilitated the extraction process, enhancing the yield and purity of the active components. Additionally, nanocarriers and nanoformulations have been developed to protect these sensitive bioactive compounds from degradation, ensuring their stability during storage and transportation. The use of G. Lucidum-based nanomaterials has shown promising results in several biomedical applications. Nanoparticles loaded with bioactive compounds derived from G. Lucidum have exhibited potent anticancer activity by targeting cancer cells, inducing apoptosis, and inhibiting tumor growth. Additionally, nanotechnology-based formulations have demonstrated immunomodulatory effects, promoting the activation of immune cells and enhancing the body's defense mechanisms. GL, combined with the potential of nanotechnology, presents an exciting frontier in the development of novel therapeutic and biomedical applications. The utilization of nanomaterials for extraction, delivery, and integration of bioactive compounds from G. Lucidum has shown immense potential for improving drug delivery, tissue engineering, and disease treatment. Further research and development in this interdisciplinary field are warranted to fully exploit the synergistic benefits offered by G. Lucidum, and nanotechnology, ultimately leading to innovative solutions for human health and well-being.

Background: Thyroid cancer incidence has increased globally in recent decades, especially in females, although its trends in Taiwan have not been studied extensively. This study aimed to investigate changes in female incidence and possible causes of thyroid cancer in Taiwan. Methods: Using the Taiwan Cancer Registry (TCR) Database, age-standardized incidence rates, age-specific incidence rates and birth cohorts were calculated. Correlation between female thyroid cancer incidence and cohort fertility rates were examined. Results: Thyroid cancer incidence increased in Taiwanese female, with age-adjusted rates per 100,000 people increasing from 7.37 during 1995-1999 to 20.53 during 2015-2019, APCs were 5.9% (95% CI, 5.3-6.5). Age-specific incidence rates increased with age, with peak rates occurring at younger ages. The APCs in the 50-54 age group were the highest (6.8%, 95% CI, 6.1-7.5). Incidence rates also increased with later birth cohorts. We observed a significant negative correlation between thyroid cancer incidence and fertility rates in the same birth cohort. Conclusion: We hypothesize that overdiagnosis may be a main reason for the rapidly increasing thyroid cancer incidence in Taiwanese female. Notably, we observed a strong negative correlation between fertility and thyroid cancer incidence. The associations with fertility will be an important subject for future thyroid cancer research.

Different prognostic scores have been applied to identify patients with non-small cell lung cancer who have a higher probability of poor outcome. In this study we evaluated whether Naples Prognostic Score, a novel index which considers both inflammatory and nutritional values, was associated with long-term survival. The study is a retrospective propensity score matching analysis of patients who underwent curative surgery for non-small cell lung cancer from January 2016 to December 2021. The score considered four pre-operative parameters: neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio, serum albumin and total cholesterol. Kaplan-Meier method and Cox regression analysis were performed to evaluate the relation between the score and disease-free survival, overall survival and cancer-related survival. A total of 260 patients were selected for the study, reduced to 154 after propensity score matching. Post-propensity Kaplan-Meier analysis showed a significant correlation between Naples Prognostic Score and overall survival (p=0.018) and cancer-related survival (p=0.007). Multivariate Cox regression analysis further validated the score as an independent prognostic indicator for both these survivals (p=0.007 and p=0.010 respectively). Naples Prognostic Score proved to be an easily achievable prognostic factor of long-term survival in patients with non-small cell lung cancer after surgical treatment.

Background: Malnutrition was associated with worse survival outcomes, impaired quality of life, and deteriorated performance status across various cancer types. We aimed to identify risk factors for malnutrition in patients with epithelial ovarian(EOC) and impact on survival. Methods: In our prospective study, we included the patients with primary and recurrent EOC, tubal or peritoneal cancer conducted. We assessed serum laboratory parameters, body mass index, nutritional risk index, nutritional risk screening score(NRS-2002), and bio-electrical impedance analysis. Results: We recruited a total of 152. Patients >65 years-old, with ascites of >500 ml, or with platinum-resistant EOC showed statistically significant increased risk of malnutrition when evaluated by NRS-2002(p-values = 0.014, 0.001, and 0.007, respectively). An NRS-2002<3 was an independent predictive factor for complete tumor resectability (p=0.009). The patients with NRS-2002≥3 had a median overall survival(OS) of seven months (95% CI=0-24 months), as compared to the patients with NRS-2002<3 where median OS was 46 months(p=0,001). Phase angle(PhAα)≤ 4.5 was the strongest predictor of OS. Conclusion: Malnutrition is an independent predictor of incomplete cytoreduction in study population. It is an independent prognostic factor for poor OS. Preoperative nutritional assessment is an effective tool in identification of high-risk groups within EOC characterized by poor clinical outcome.

Endocrine-disrupting chemicals (EDCs) may impact the development of Prostate Cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in controlling tumor growth is not known, EDCs may inhibit steroidogenic enzymes such as Cytochrome P450 c17 (CYP17A1) or aromatase (CYP19A1) involved in the production of Androgens or Estrogens. High levels of circulating androgens are linked to PCa in men and Polycystic Ovary Syndrome (PCOS) in women. Essential Oils or their metabolites (EOs) like lavender oil and tea tree oil have been reported to act as potential EDCs and contribute towards sex steroid imbalance in case of prepubertal gynecomastia in boys and premature thelarche in girls due to the regular exposure to lavenderbased fragrances among Hispanic population. We screened a range of EO components to determine their effects on CYP17A1 and CYP19A1 Computational docking was performed to predict the binding of EOs with CYP17A1 and CYP19A1 and functional assays were done using the radiolabeled substrates or Liquid Chromatography high-resolution Mass Spectrometry and cell viability assays were carried out in LNCaP cells. Many of the tested compounds bind close to the active site of CYP17A1, and (+)-Cedrol had the best binding with CYP17A1 and CYP19A1. Eucalyptol, Dihydro-β-Ionone & (-)-α-pinene showed 20% to 40% inhibition of dehydroepiandrosterone production; and some compounds also effected CYP19A1. Extensive use of these EOs in various beauty and hygiene products is common, but only a limited knowledge about their potential detrimental side effects exists. Our results suggest that prolonged exposure to some of these essential oils may result in steroid imbalances. On the other hand, due to their effect on lowering androgen output, ability to bind at the active site of steroidogenic cytochrome P450s, these compounds may provide design ideas for the novel compounds against hyperandrogenic disorders such as PCa and PCOS.

The Surgical Complexity Score (SCS) has been widely used to describe the surgical effort during advanced stage epithelial ovarian cancer (EOC) cytoreduction. Referring to a variety of multi-visceral resections, it best combines the numbers with the complexity of the sub-procedures. Nevertheless, not all potential surgical procedures are described by this score. Lately, the European Society for Gynaecological Oncology (ESGO) has established standard outcome quality indicators pertinent to achieving complete cytoreduction (CC0). There is a need to define what weight all these surgical sub-procedures comprising CC0 would be given. Explainable Artificial Intelligence (XAI) could explain the impact of real-time features on the CC0 prediction. We analyzed prospectively collected data from 560 consecutive patients with FIGO-stage III-IV who underwent cytoreductive surgery between Jan 2014 and Dec 2019 at a UK tertiary referral centre. Following adaptation of the structured ESGO ovarian cancer report template, we employed the eXtreme Gradient Boosting (XGBoost) algorithm to model an exhaustive list of surgical sub-procedures. We applied the Shapley Additive explanations (SHAP) framework to provide global (cohort) explainability. We used Cox regression for survival analysis and constructed Kaplan-Meier curves. The XGBoost model predicted CC0 with an acceptable accuracy (area under curve [AUC] = 0.70; 95% confidence interval [CI] = 0.63–0.76). Visual quantification of the feature importance for the prediction of CC0 identified upper abdominal peritonectomy (UAP) as the most important feature, followed by regional lymphadenectomies. The UAP best correlated with bladder peritonectomy and diaphragmatic stripping (Pearson’s correlations &gt; 0.5). Clear inflection points were shown by pelvic and para-aortic lymph node dissection and ileocecal resection/right hemicolectomy, which increased the probability for CC0. When UAP was solely added to a composite model comprising of engineered features, it substantially enhanced its predictive value (AUC = 0.80, CI = 0.75-0.84). The UAP was predictive of poorer progression-free survival (HR=1.76, CI 1.14- 2.70, P:0.01) but not overall survival (HR=1.06, CI 0.56-1.99, P:0.86). The SCS did not have significant survival impact. Machine Learning allows for operational feature selection by weighting the relative importance of those surgical sub-procedures that appear to be more predictive of CC0. Our study identifies UAP as the most important procedural predictor of CC0 in surgically cytoreduced advanced-stage EOC women. The classification model presented here can potentially be trained with a larger number of samples to generate a robust digital surgical reference in high output tertiary centres. The upper abdominal quadrants should be thoroughly inspected to ensure that CC0 is achievable.

(1) Background: The aim of this study is to investigate the diagnostic-therapeutic problem of pelvic recurrence of rectum cancer, highlighting current surgical standards and the possible role of the minimally invasive approach. This retrospective analysis of our surgical case study wishes to enter this debate while suggesting a possible line of action, based on the site of recurrence; (2) Methods: We examined, retrospectively, all the patients diagnosed, between 2008 and 2018, with cancer of the rectum at the "Pietro Valdoni" Department of Surgery and monitored their follow-up for 5 years. The sample consisted of 368 patients with rectal neoplasm, 136 females and 232 males, with an average age of 65.8 (ranging from 37 to 86); (3) Results: In 103 of the cases, the neoplasm was located in the upper rectum (28%), in 119 cases in the middle rectum (32.3%), in 102 cases in the lower rectum (27.7%), in 31 cases (8.4%) at the level of the right/sigma junction and in 13 cases it was not possible to define the site with certainty (3.5%); (4) Conclusions: The discussion re-mains open as to which approach is best at surgical level, whether laparoscopic, robotic or open-air. Our experience informs us that the most dangerous site remains on the anastomotic site.

Homologous recombination deficiency (HRD) has become an important prognostic and predictive biomarker for patients with high-grade serous ovarian cancer who may benefit from poly-ADP ribose polymerase inhibitors (PARPi) and platinum-based therapies. HRD testing provides relevant information to personalize patients’ treatment options, and it has been progressively incorporated in diagnostic laboratories. In this study, we evaluated the feasibility of in-house HRD testing deployable in a diagnostic clinical setting, comparing results from two commercially available next-generation sequencing (NGS)-based tumor tests (SOPHiA DDMTM HRD Solution and AmoyDx HRD Focus Panel) with the reference assay from Myriad MyChoice CDx. A total of 85 ovarian cancer samples were subjected to HRD testing. An overall strong correlation was observed across the three assays evaluated, regardless of the different underlying methods employed to assess genomic instability, with the highest pairwise correlation between Myriad and SOPHiA (R=0.87, p-value=3.39x10-19). The comparison of the assigned HRD status to the reference Myriad’s test revealed a positive predictive value (PPV) and negative predictive value (NPV) of 90.9% and 96.3% for SOPHiA’s test, while AmoyDx’s test achieved 75% PPV and 100% NPV. This is the largest HRD testing evaluation using different methodologies and provides a clear picture of the robustness of NGS-based tests currently offered in the market. Our data show that the implementation of in-house HRD testing in diagnostic laboratories is technically feasible and it can be reliably performed with commercial assays. Also, the turnaround time is compatible with clinical needs, being an ideal alternative to offer to a broader number of patients, while still maintaining high-quality standards at more accessible price tiers.

Today, numerous studies have shown that the physical environment in hospitals can significantly influence patients' well-being, comfort, and recovery. However, this is currently neglected in hospitals in the Global South. Therefore, there is an urgent need to increase the awareness to make it more applicable worldwide. Thus, this study focuses on improving the healing environment standards, by exploring the impact of evidence-based design and patient-centred care in hospitals for cancer patients; particularly the architectural space quality, on patient health outcomes as well as hospital staff health and wellbeing. In Global North countries, such as the UK, the Achieving Excellence Design Evaluation Toolkit (AEDET), is used by its National Health Services, to assess the effectiveness of various environmental attributes. However, these toolkits have not been designed for and do not work well within Global South countries, such as Northern Cyprus. To examine and compare the effectiveness of different physical environmental attributes and to evaluate user responses, the Post-Occupancy Evaluation Method and the AEDET toolkit have been used in the study. These were applied to both public and private hospitals in Northern Cyprus, involving cancer patients, staff, and professionals (n=220). The findings reveal the strength and weaknesses in terms of environmental comfort based on the aspects of evidence-based design of the hospitals such as natural light, air quality, noise, view, infection control, etc., to create a more optimal physical environment for better psychological outcomes. This is the first study to propose an adaptation of the AEDET toolkit to assist architects in designing healthcare facilities that are responsive to the requirements of hospital patients and staff; and to promote the quality of healing environment for improved health and well-being outcomes.

Breast cancer is the most common malignancy in women worldwide. The pathogenesis of this disease is closely related to the estrogen receptor alpha subtype (ERα). Therefore, it is of great importance to develop effective inhibitors of ERα activity for the treatment of breast cancer. In this paper, we propose a novel ensemble machine learning model for quantitative structure-activity relationship of anti-breast cancer drugs, which can effectively predict drug activity in small samples with multiple characteristic variables. To avoid the problem of over-fitting caused by low-correlation independent variables, the scoring mechanism of random forest was improved by incorporating three relevance indicators, including the maximum mutual information number, Pearson correlation coefficient and distance correlation coefficient, and 20 optimal molecular descriptors were selected. The Bayesian hyperparameter optimization method was used to optimize the parameters of multiple linear regression (MLR), support vector regression (SVR), and extreme gradient boosting (XGBoost), respectively. The AdaBoost strong learner was constructed by combining the weak learner with the weighted linear addition method. The results show that the proposed ensemble learning model has the best prediction performance compared to the three basic learner models and the CNN-LSTM combination prediction model. The root mean square error was reduced by 7.60%-26.51%. The mean relative error was reduced by 6.46%-30.92%. Goodness of fit increased by 9.57%-36.94%. Finally, the biological activities of 50 candidate compounds for ERα inhibitors were predicted, and it was found that 4-[2-benzyl-1-[4-(2-pyrrolidin-1-ylethoxy)phenyl]but-1-enyl]phenol had an excellent biological activity value pIC50, which had the potential to be an ERα inhibitor. The model proposed in this paper has good prediction accuracy, which can provide an effective reference for the discovery and development of anti-breast cancer drugs.

: Immune checkpoint inhibitors (ICI) cemiplimab and pembrolizumab have revolutionized the treatment of advanced cutaneous squamous cell carcinoma (cSCC). We aimed to evaluate the effectiveness and safety of ICI in a real-world cSCC population, including patients with conditions which would exclude clinical trial participation. In this single-center, retrospective cohort study, we included all non-trial patients with advanced cSCC treated with ICI between 2017 and 2022. We evaluated investigator-assessed best overall response (BOR) and immune-related adverse events (irAEs). We correlated survival outcomes with age, performance status, immune status and irAEs. For the 36 patients identified, best overall response (BOR) to ICI was partial response (PR) in 41.7%, complete response (CR) in 27.8%, and stable disease in (SD) 13.9% of patients. The PFS rate at 1 year was 63%; median PFS was not reached (NR). The median OS was 38.6 months (95% CI 25.4-NR). Immune compromised patients, ECOG performance 2-3, and age ≥75 years were not significantly associated with PFS or OS. IrAE grade 3-4 were seen in 13.9% of patients. In our Canadian experience with real-world patients, ICI was an effective and safe treatment for advanced cSCC patients. Patients achieved great benefit with ICI regardless of age, immune status or ECOG performance status.

Video capsule endoscopy (VCE) is increasingly used to decrease the discomfort among patients owing to its small size. However, VCE has a major drawback of not having narrow band imaging (NBI) functionality. The current VCE has the traditional white light imaging (WLI) only, which has poor performance in the computer-aided detection (CAD) of different types of cancer compared with NBI. Specific cancers, such as esophageal cancer (EC), do not exhibit any early biomarkers, making their early detection difficult. In most cases, the symptoms are unnoticeable, and EC is diagnosed only in later stages, making its 5-year survival rate below 20% on an average. NBI filters provide particular wavelengths that increase the contrast and enhance certain features of the mucosa, thereby enabling early identification of EC. However, VCE does not have a slot for NBI functionality because its size cannot be increased. Hence, NBI image conversion from WLI can be achieved only in post-processing at present. In this study, a complete arithmetic assessment of the decorrelated color space was conducted to generate NBI images from WLI images for VCE of the esophagus. Three parameters, namely, structural similarity index metric (SSIM), entropy, and peak-signal-to-noise ratio (PSNR), were used to asses the simulated NBI images. Results show the good performance of the NBI image reproduction method, with SSIM, entropy difference, and PSNR values of 93.215%, 4.360, and 28.064 dB, respectively.

The accurate identification of the primary tumor origin in metastatic cancer cases is crucial for guiding treatment decisions and improving patient outcomes. Copy Number Alterations (CNA) have emerged as valuable genomic markers for predicting the origin of metastases. This research article presents a comprehensive analysis of CNA-based prediction models in metastatic cancer. The study utilizes a dataset comprising CNA profiles from twenty different cancer types and employs advanced AI-based techniques for prediction. The research workflow consists of two models. The first is convolution network-based, while the other is a multi-stage model. In the first stage, a RELU model is developed to differentiate between 16 cancer types, considering their CNA, chromosome location, strand, and overall location. The second stage involves building specialized models to detect differences between cancer types within the same location or organs, such as brain lower-grade glioma and glioblastoma multiforme. Both generalized models achieve an overall accuracy of over 90%, while the specialized models achieve an accuracy of approximately 95% with minimal loss values. The results demonstrate the potential of AI-based approaches utilizing CNA data for improved diagnosis and personalized treatment strategies in metastatic cancer. This research establishes a solid foundation for future advancements in the field, paving the way for more effective and targeted approaches in metastatic cancer management.

Prostate cancer is the most occurred malignant disease in the male population in over one-half of the countries and still constitutes the fifth leading cause of death in 2020, worldwide. Metastatic prostate cancer is a lethal malignancy that mostly is terminated within several years through the patient's death. Researchers should focus on the phenomenon which is rigorously appertaining to metastatic cascade and operating as an initiator of metastases to provide the knowledge needed to solve the problem of diagnostics and treatment of advanced prostate cancer patients. The epithelial-mesenchymal transition is one such phenomenon. The current review is based mainly on three papers published in 2021, which describe the most important tissue-specific factors managing epithelial-mesenchymal transition and are discussed with scientific papers published in acknowledged journals. The effect of the current review is the specification of profiles of precise tissue factors predicting the progression of the prostate neoplasm to its metastatic stage in a new edition.

Prostate cancer (PCa) Lung metastases are rarely resected, therefore PCa lung metastases are insufficiently molecularly characterized. We recently identified carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as a potential driver of pulmonary metastatic spread. Here, we show the biological significance of CEACAM6 in PCa cell proliferation, apoptosis and migration. CEACAM6 was silenced by siRNA in PC3 cells. Functional assessment of apoptosis, cell viability, proliferation and migration were performed in siRNA-CEACAM6 PC3 cells. Non-treated and scrambled (scr) RNA PC3 cells were used as control. Following a specific knockdown of CEACAM6 in PC3 cells, the expression of CEACAM6 protein was significantly decreased in comparison to controls. Cell viability and cell counts decreased in CEACAM6 silent PC3 cells. In contrast, caspase-3 activity was highly elevated in siRNA-CEACAM6 PC3. Furthermore, by performing a cell scratch assay, the migration ratio in siRNA-CEACAM6 PC3 cells were significantly diminished compared with the control group after 48 hours of post transfection incubation. CEACAM6 as a cell adhesion molecule has been implicated in promoting metastatic disease in several solid tumours such as colorectal or gastric cancer. We could show that silencing of CEACAM6 has a significant functional effect on PCa cells. CEACAM6 might play an important role in fostering metastatic spread to the lung of PCa patients via enhancing proliferation and suppressing apoptosis. CEACAM6 might therefore pose an attractive therapeutic target to prevent metastatic disease.

Background and Objectives: The aim of this study is to investigate the diagnostic-therapeutic prob-lem of pelvic recurrence of rectum cancer, highlighting current surgical standards and the possi-ble role of the minimally invasive approach. This retrospective analysis of our surgical case study wishes to enter this debate while suggesting a possible line of action, based on the site of recur-rence. Materials and Methods: We examined, retrospectively, all the patients diagnosed, between 2008 and 2018, with cancer of the rectum at the "Pietro Valdoni" Department of Surgery and monitored their follow-up for 5 years. The sample consisted of 368 patients with rectal neoplasm, 136 females and 232 males, with an average age of 65.8 (ranging from 37 to 86). In 103 of the cases, the neo-plasm was located in the upper rectum (28%), in 119 cases in the middle rectum (32.3%), in 102 cases in the lower rectum (27.7%), in 31 cases (8.4%) at the level of the right/sigma junction and in 13 cases it was not possible to define the site with certainty (3.5%). Results: We examined all patients diagnosed with cancer of the rectum between 2008 and 2018 at the "Pietro Valdoni" Department of Surgery retrospectively and monitored their follow-up for 5 years. The sample consists of 368 patients with rectal neoplasm, 136 females and 232 males. Conclusions: The discussion remains open as to which approach is best at surgical level, whether laparoscopic, robotic or open-air. Our experience informs us that the most dangerous site remains on the anastomotic site.

Background: Currently, many detection methods have high sensitivity to the diagnosis of lung cancer. However, some postoperative patients with pulmonary nodule were eventually diagnosed as benign nodules. The ideal evaluation of an individual with a pulmonary nodule would expedite therapy for a malignant nodule and minimize testing for those with a benign nodule.Methods: This case-control study is designed to explore the relationship between ACE1 rs4646994 polymorphism and the risk of lung cancer in patients with pulmonary nodules, 400 individuals with lung cancer and benign pulmonary nodules were included. A DNA extraction kit was used to extract plasm DNA from peripheral blood. The relationship between ACE1 rs4646994 and the risk of lung cancer in patients with pulmonary nodules was determined by chi-square test, logistic regression analysis and cross analysis. Results: The results showed that the DD genotype of ACE1 rs4646994 may increase the risk of lung cancer in patients with pulmonary nodules, and this correlation was more significant in the female subgroup. In the age stratification analysis, it was found that the risk of lung cancer was significantly increased in the DD genotype of ACE1 rs4646994 in the older subgroup (&gt; 45 years). In addition, the possibility of EGFR mutation in lung adenocarcinoma patients with ACE1 rs4646994 DD genotype was lower than that of II or ID genotype carriers. Conclusions: Our study indicated that ACE1 rs4646994 polymorphism increases the risk of lung cancer in patients with pulmonary nodules from China.

Prostate cancer (PCa) is one of the most prevalent cancers among men in India. Although studies on PCa have dealt with the genetics, genomics, and the environmental influence in causality of PCa, not many studies employing the next generation sequencing (NGS) approaches of PCa have been carried out. In our previous study, we have identified some causal genes and mutations specific to Indian PCa using Whole-Exome Sequencing (WES). In the recent past, with the help of different cancer consortiums such as The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), along with differentially expressed genes (DEGs), many cancer-associated novel non-coding RNAs have been identified as biomarkers. In this work, we attempt to identify DEGs as well as long non-coding RNAs (lncRNAs) associated with signature pathways from an Indian PCa cohort using RNA-sequencing (RNA-seq) approach. From a cohort of 60, we screened 6 patients who underwent prostatectomy; we performed a whole transcriptome shotgun sequencing (WTSS)/RNA-sequencing to decipher the DEGs. We further normalized the read counts using fragments per kilobase of transcript per million mapped reads (FPKM) and analyzed the DEGs using a cohort of downstream regulatory tools, viz. GeneMANIA Stringdb, Cytoscape-Cytohubba, cbioportal to map the inherent signatures associated with PCa. By comparing the RNA-seq data obtained from the pairs of normal and PCa tissue samples using our benchmarked in-house cuffdiff pipeline, we observed some important genes specific to PCa such as STEAP2, APP, PMEPA1, PABPC1, NFE2L2, HN1L and some other important genes known to be involved in different cancer pathways such as, COL6A1, DOK5, STX6, BCAS1, BACE1, BACE2, LMOD1, SNX9, CTNND1 etc. We also identified a few novel lncRNAs such as LINC01440, SOX2OT, ENSG00000232855, and ENST00000647843.1 that need to be characterized further. Deregulation of SOX2OT is observed in various tumors, including lung cancer, gastric cancer, esophageal cancer, breast cancer, hepatocellular carcinoma, ovarian cancer, pancreatic, laryngeal squamous cell carcinoma, osteosarcoma, nasopharyngeal carcinoma, and glioblastoma. It would be interesting to characterize its function in PCa as well. In comparison with publicly available datasets, we have identified characteristic DEGs and novel lncRNAs implicated in signature PCa pathways in an Indian PCa cohort which have perhaps not been reported. As a pilot study, this has set a precedent for us to validate further experimentally, and we firmly believe this will pave a way towards discovery of biomarkers and development of novel therapies.

This study assesses the efficacy of a microwave colonoscopy algorithm to detect colorectal cancer precursors or polyps in an ex-vivo human colon model. The algorithm works with a device composed of a cylindrical ring-shaped switchable antenna array, which can be attached to the tip of a conventional colonoscope as an accessory. The accessory is connected to an external processing unit that generates an acoustic signal when a polyp is detected. Nowadays, 22% of polyps go undetected with conventional colonoscopy and the risk of cancer after a negative colonoscopy can be up to 7.9%. Fifteen ex-vivo freshly excised human colons with cancer (n=12) or polyps (n=3) were examined with the microwave-assisted colonoscopy system simulating a real colonoscopy exploration. Successive measurements of the colon were taken with the microwave-based colonoscopy device and processed with a microwave imaging algorithm. After the experiment, the dielectric properties of the specimens were measured with a coaxial probe and finally the samples underwent a pathology analysis. The results show that all the neoplasms were detected with a sensitivity of 100% and specificity of 87.4%.

Several therapeutic monoclonal antibodies are approved by FDA against the PD-1/PD-L1 (programmed death-1/programmed death ligand-1) immune checkpoint, which has been a great success in cancer treatment. However, existing therapeutics, including small molecules inhibitors against PD-L1 checkpoint have certain drawbacks such as high cost and drug resistance that challenge the current available anti-PD-L1 therapy. Thereof, this study presents the screening of 32552 compounds from Natural Product Atlas database against PD-L1, including three steps of structure-based virtual screening and binding free energy refinement for the selection of potent PD-L1 inhibitors. Subsequently, five natural compounds, i.e., Neoenactin B1, Actinofuranone I, Cosmosporin, Ganocapenoid A, and 3-[3-hydroxy-4-(3-methylbut-2-enyl)phenyl]-5-(4-hydroxybenzyl)-4-methyldihydrofuran-2(3H)-one, were collected based on the ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling and binding free energy (>-70 kcal/mol) for further computational investigation by comparison to co-crystallised ligand, i.e. JQT inhibitor. Based on interaction mapping, explicit 100 ns molecular dynamics simulation, and post binding free energy calculations, all the compounds exhibited intermolecular interactions (hydrogen and hydrophobic) with essential residues and substantial complex stability by comparison to the JQT inhibitor. Collectively, the calculated results advocate the selected natural compounds as the putative potent inhibitors of PD-L1 and, therefore, can be considered for further development of PD-L1 immune checkpoint inhibitor in cancer immunotherapy.

Cancer-associated fibroblasts (CAF) are highly prevalent cells in the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). CAFs exhibit a pro-tumor effect in vitro and have been implicated in tumor cell proliferation, metastasis, and treatment resistance. Our objective is to analyze the geospatial distribution of CAFs with proliferating and apoptotic tumor cells in the ccRCC tumor microenvironment and determine associations with survival and systemic treatment. Pre-treatment primary tumor samples were collected from 96 patients with metastatic ccRCC. Three adjacent slices were obtained from 2 tumor-core regions of interest (ROI) per patient, and immunohistochemistry (IHC) staining was performed for αSMA, Ki-67, and caspase-3 to detect CAFs, proliferating cells, and apoptotic cells, respectively. H-scores and cellular density were generated for each marker. ROIs were aligned, and spatial point-patterns were generated, which were then used to perform spatial analyses using a normalized Ripley's K function at a radius of 25μm (nK(25)). The survival analyses used an optimal cut-point method, maximizing the log-rank statistic, to stratify the IHC-derived metrics into high and low groups, and multivariable Cox regression analyses were performed accounting for age and International Metastatic RCC Database Consortium (IMDC) risk category. Survival outcomes included overall survival (OS) from the date of diagnosis, OS from the date of immunotherapy initiation (OS-IT), and OS from the date of targeted therapy initiation (OS-TT). Therapy resistance was defined as progression-free survival (PFS) <6 months, and therapy response was defined as PFS >9 months. CAFs exhibited higher cellular clustering with Ki-67+ cells than with caspase-3+ cells (nK(25): Ki-67 1.19; caspase-3 1.05; P = .04). The median nearest neighbor (NN) distance from CAFs to Ki-67+ cells was shorter compared to caspase-3+ cells (15 μm vs 37μm, respectively; P < .001). Multivariable Cox regression analyses demonstrated that both high Ki-67+ density and H-score were associated with worse OS, OS-IT, and OS-TT. Regarding CAFs, only a high H-score was associated with worse OS, OS-IT, and OS-TT. For caspase-3+, high H-score and density were associated with worse OS and OS-TT. Patients whose tumors were resistant to targeted therapy (TT) had higher Ki-67 density and H-scores than those who had TT response. Overall, this ex vivo geospatial analysis of CAF distribution suggests that close proximity clustering of tumor cells and CAFs potentiates tumor cell proliferation, resulting in worse OS and resistance to TT in metastatic ccRCC.

.Background: Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) showed promising results in patients with colorectal carcinoma at high risk of recurrence but still without clinically and radiologically evident signs of peritoneal spread. This study aims to analyze the feasibility of this proactive, early phase, multimodality approach. Methods: A mono-institutional, prospective, parallel, two-stage phase II trial enrolled 49 patients to standard surgery or surgery plus intraoperative HIPEC. Before the procedure and during surgery, patients received intravenous fluorouracil (and leucovorin to potentiate oxaliplatin activity. Data analysis included length of hospital stay, surgery duration, type of surgery and chemotherapy-related complications risk score. Results: No significant difference was seen in the median time spent in the hospital with a median stay of 7 days in both groups (p=0.5720). The surgical procedure's median duration was longer in the HIPEC group than in the control one. Side-effects and surgical complications did not cross at any time the Pocock-type boundary for side/effect monitoring (p=0.80, N.S.). Conclusions: The present prospective study results demonstrate the feasibility and safety of the colorectal surgery plus HIPEC treatment in patients with colorectal cancer patients at high-risk for peritoneal invasion, although clinically and radiologically undetectable.

Associations between blood cancer and genetic predisposition, including both inherited variants and acquired mutations and epimutations, have been well characterized. However, the majority of these variants affect noncoding regions, making their mechanisms difficult to hypothesize and hindering the translation of these insights into patient benefits. Fueled by unprecedented progress in next-generation sequencing and computational integrative analysis, studies have started applying combinations of epigenetic, genome architecture and functional assays to bridge the gap between noncoding variants and blood cancer. These complementary tools have not only allowed us to understand the potential malignant role of these variants but also to differentiate key variants, cell types and conditions from misleading ones. Here, we briefly review recent studies that have provided fundamental insights into our understanding of how noncoding mutations at enhancers predispose and promote blood malignancies in the context of spatial genome architecture.

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.

Background: The Micro Hand S robot is the first domestically produced surgical robot that has entered clinical use in China, and this is the first report of its application in colon cancer. Objective: This study aimed to validate the safety and efficacy of the domestically produced Chinese minimally invasive Micro Hand S surgical robot system in complex surgery, such as robotic complete mesocolic excision (R-CME). Methods: From March 2018 to December 2018, 30 patients with right hemicolon cancer underwent R-CME with the Micro Hand S robot system. The operative findings, morbidities, oncological findings and unique characteristics were summarizedwere analyzed. Result: 12 patients with right hemicolon cancer and 18 patients with sigmoid colon cancer underwent RCME with the Micro Hand S robot system. During the study period, the median operative duration was 209 (range, 180-255) min, and the median estimated blood loss volume was 35 (range, 25-75) ml. The median number of lymph nodes harvested was 42 (21-77), and the median postoperative hospital stay was 5 (range, 4-7) days. According to the Clavien-Dindo classification, there were no severe complications except for 7 cases of grade I complications and 5 cases of grade II complications. The conversion rate for all operations was 0%. There were no cases of 30-day readmission or 30-day mortality. Conclusion: Clinical application of domestically produced Chinese minimally invasive surgical robot system “Micro Hand S ” in selected colon cancer patients is technically feasible and safe.

Background: The Micro Hand S robot is the first domestically produced surgical robot that has entered clinical use in China, and this is the first report of its application in colon cancer.Objective: This study aimed to validate the safety and efficacy of the domestically produced Chinese minimally invasive Micro Hand S surgical robot system in complex surgery, such as robotic complete mesocolic excision (R-CME).Methods: From March 2018 to December 2018, 30 patients with right hemicolon cancer underwent R-CME with the Micro Hand S robot system. The operative findings, morbidities, oncological findings and unique characteristics were summarizedwere analyzed.Result: 12 patients with right hemicolon cancer and 18 patients with sigmoid colon cancer underwent RCME with the Micro Hand S robot system. During the study period, the median operative duration was 209 (range, 180-255) min, and the median estimated blood loss volume was 35 (range, 25-75) ml. The median number of lymph nodes harvested was 42 (21-77), and the median postoperative hospital stay was 5 (range, 4-7) days. According to the Clavien-Dindo classification, there were no severe complications except for 7 cases of grade I complications and 5 cases of grade II complications. The conversion rate for all operations was 0%. There were no cases of 30-day readmission or 30-day mortality. Conclusion: Clinical application of domestically produced Chinese minimally invasive surgical robot system “Micro Hand S ” in selected colon cancer patients is technically feasible and safe.

This study aimed to rank cancers based on the strength of the relationship between the comprehensive mRNA expression levels of the most harmful or protective genes and patient survival. Using The Cancer Genome Atlas dataset that includes the RNA sequencing and c linical data, we investigated not only gene specific prognostic availability, but also comprehensive prognostic availability of prognostic genes filtered by the Cox coefficient values, and ranked cancers using a specially designed prognostic indicator. Usi ng Kaplan Meier plots, we found that cancers vary in the strength of the influence of their prognostic genes, and can be ranked based on this finding. There is a high probability that the treatment developed by using methods that reduce or increase the exp ression levels of biomarkers, for cancers that ranked at the bottom will not be efficient. The results of this study could be used as scientific evidence for the same.

Breast cancer is the most common cause of death for women worldwide. Thus, the ability of artificial intelligence systems to predict and classify breast cancer is very important. In this paper, a hybrid ensemble method classification mechanism is proposed based on a majority voting mechanism. First, the performance of different state-of-the-art machine learning classification algorithms for the Wisconsin Breast Cancer Dataset (WBCD) were evaluated. The three best classifiers were then selected based on their F3 score. F3 score is used to emphasize the importance of false negatives (recall) in breast cancer classification. Then, these three classifiers, simple logistic Regression learning, stochastic gradient descent learning and multilayer perceptron network, are used for ensemble classification using a voting mechanism. We also evaluated the performance of hard and soft voting mechanism. For hard voting, majority-based voting mechanism was used and for soft voting we used average of probabilities, product of probabilities, maximum of probabilities and minimum of probabilities-based voting methods. The hard voting (majority-based voting) mechanism shows better performance with 99.42% as compared to the state-of-the-art algorithm for WBCD.

Background: Qazvin province has suffered a lot of natural disasters (earthquakes) for a long time. so, the establishment of the first industrial city in Iran, has always been a source of concern. One of these problems is the possibility of chlorine gas leaking from the chlorination system of drinking water and treatment plant the existing ones are on the health of the inhabitants of this region.Material and method: This analytical study was carried out in Novorossiysk district of Alborz in December 2012. Initially, chlorine gas leakage scenarios from these facilities were simulated by ALOHA and WISER software, and then using the Emergency Level System, according to the CCPS Consultative Center's Chemical Process Safety Advice, the Emergency Response Program was presented. Results: ALOHA software, in comparison with WISER software, has more precision to identify and address the consequences of chlorine gas leakage hazards and according to the simulation of this software in the event of a leak from the well and water resources unit at 8240 m from the area and at night 7520 meters will be affected. Due to the speed of delivering results through the WISER software, this software can be used at times when the operating speed is considered (incident time).Conclusion: According to the CCPS model, the emergency conditions were classified at levels 3 and 4, therefore, the relevant crisis management agencies (Qazvin Crisis Management Committee, Alborz City Health Center, Red Crescent and Firefighting Authority) should provide training maneuvers At Alborz city level, and informing people of cities and industrial companies, many efforts have been made to reduce human and environmental damage in case of possible leakage.

Significant recent advances in cancer immunotherapeutics include the vaccination of cancer patients with tumor antigen-associated peptide-pulsed dendritic cells (DCs). DC vaccines with homogeneous, mature, and functional activities are required to achieve effective acquired immunity; however, the yield of autologous monocyte-derived DCs varies in each patient. Priming with a low dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16–18 h prior to apheresis resulted in 50% more harvested monocytes, with a significant increase in the ratio of CD11c+CD80+ DCs/apheresed monocytes. The detection of antigen-specific cytotoxic T lymphocytes after Wilms’ tumor 1-pulsed DC vaccination was higher in patients treated with rhG-CSF than those who were not, based on immune monitoring using tetramer analysis. Our study is the first to report that DC vaccines for cancer immunotherapy primed with low-dose rhG-CSF are expected to achieve higher acquired immunogenicity.

Wnt pathway is involved in breast cancer (BC) progression. Our aim was to evaluate the expression of some components of the Wnt pathway (β-catenin, FZD4, LRP5, LRP6 and TCF1) in order to detect potential associations with NHERF1 protein. In addition, we assessed their impact on patients’clinical outcome. We evaluated 220 primary BC samples by immunohistochemistry (IHC) and protein localization by immunofluorescence. We found a significant correlation between NHERF1 and FZD4, LRP5, LRP6 and TCF1. Univariate analysis showed that β-catenin (p<0.0001), FZD4 (p=0.0001), LRP5, LRP6 and TCF1 over-expression (p<0.0001 respectively) was related to poor disease free survival (DFS). A Kaplan-Meier analysis confirmed univariate data and showed a poor DFS for cNHERF1+/FZD4+ (p=0.0007), cNHERF1+/LRP5+ (p=0.0002), cNHERF1+/LRP6+ (p<0.0001) and cNHERF1+/TCF1+ phenotypes (p=0.0034). In multivariate analysis, TCF1 and β-catenin expression were independent prognostic variable of worse DFS (p=0.009 and p=0.027, respectively). In conclusion, we found that β-catenin, FZD4, LRP5, LRP6 and TCF1 overexpression was associated to poor prognosis. Furthermore, we first identified TCF1 as independent prognostic factor of poor outcome, indicating it as a new potential biomarker for BC patients management. In addition, Wnt pathway proteins expression, both alone and in association with NHERF1, suggests original associations of biological significance for new studies.

The aim of the current study has been to assess externalizing problems from a gender perspective in the juvenile population. This objective has been evaluated though the Child and Adolescent Assessment System questionnaire (SENA), to measure the dimension of externalized problems. A total of 128 Spanish students took part in the survey, comprising 58 (45.3%) male and 67 (52.3%) female, aged between 12 and 16 years old (M= 13,7; Sd= 1,14). The sample was taken from three High- Schools (state and private-subsidized) in Madrid, Spain. The research for this study was conducted through a descriptive, inferential, quantitative, ex post facto design. The data analysis was performed using SPSS 27.0. The result revealed an increase in externalized problems: Attention (M= 2.65, Sd=.88), Anger Control (M= 2.27, Sd=.85) and Hyperactivity- Impulsivity (M= 2.26, Sd=.68). In addition, female students score highly in Attention Problems (F= 4.124; Sig.: .004), Hyperactivity-Impulsivity (F: 6.18; Sig.: <.001), and Anger Control (F: 2.3; Sig.: .062). This study highlights the impact and increase on students externalized mental health problems currently. It is essential to have a protective environment and promote the development of emotional intelligence, encouraging the mental health in young people. This article is part of the findings of the research project “Therapeutic Innovation Classroom for the accompaniment of teenager with Serious Mental Disorder” (Reference: 2021V/EU-UNED/02).

Recent technological advancements in conservation genetics and genomics have resulted in diverse tools for aiding conservation of species. The precision and resolution of high throughput sequencing technologies provide valuable insights to aid conservation decisions, but these technologies are often financially unfeasible or unavailable in resource constrained countries. Inter-Simple Sequence Repeat (ISSR) markers, when combined with sensitive automated detection systems, provide a simple, cheap means to investigate genetic diversity and discriminate closely related species. Here we apply this technology to assess genetic diversity and taxonomic delimitation in the Encephalartos eugene-maraisii species complex, a highly threatened, taxonomically dubious group of cycads in South Africa. Our analyses support taxonomic singularity of E. dyerianus, E. dolomiticus and E. eugene-maraisii. Relationships between E. nubimontanus and E. cupidus remain uncertain. E. middelburgensis samples showed no clustering but had poor amplification success. This study demonstrates the suitability of automated ISSR fingerprinting as a method for plant conservation studies, especially in resource-constrained countries, and we make recommendations as to how this methodology can be effectively implemented.

The importance of Muscovy ducks in industrial poultry production is growing; however, little is known about the physiology of their reproductive cycles. This study investigated the influence of male biostimulation on female ducks before the commencement of the laying phase. A total of 15 female Muscovites were kept in contact with a male duck until the point of laying, while 15 other females were kept without any contact with a male conspecific. Before reaching egg-laying maturity, the cloacae of 29 adult ducks were subjected to daily clinical assessments. The evaluations yielded four unique categories of outcomes, determined by assessing factors such as the degree of redness and protrusion of the mucous membrane, moisture level, and swelling of the cloacal sphincter muscle. In terms of biostimulation, the findings demonstrated that, on average, ducks in contact with males laid the first egg 16 days earlier than isolated ducks. Furthermore, there was no significant difference observed in the mean initial egg weight between both groups (p = 0.841). The changes in the cloacal morphology indicated significant morphological changes 25–26 days before laying. Efforts to improve Muscovy production and develop biotechnological techniques to modify the reproductive cycle will benefit from these advancements.

Delivering effective messages is critical to creating a more sustainable and resilient culture. The explosion of social media has enhanced information access but has often reinforced and polar-ized pre-existing viewpoints and norms. In contrast, digital signs are an “in your face in your space” technology that has the potential to deliver common content to a diverse local audience. Environmental Dashboard (ED) is a communications platform and set of content applications that combines information on current environmental conditions, real-time resource consumption, positive actions being taken by community members, and a community calendar. We conducted a longitudinal study to assess whether ED content delivered via digital signs in public locations would result in desirable psychological changes within a community. Participants completed surveys in six designated signage locations prior to installation (N = 174) and following two years of continuous exposure (N = 133). We observed: increases in pro-environmental social norms among people of color (a demographic emphasized); enhanced awareness of and sense of connection with the local community and ecology; increased self-reported electricity conservation; and increased perception of youth engagement (another demographic emphasized). Changes were mediated by exposure to digital signage. These findings support the hypothesis that content delivered through digital signs can strengthen pro-environmental and pro-social culture within communities.

The spread of micro- (MPs) and nanoplastics (NPs) in the environment has become a significant environmental concern, necessitating effective removal strategies. In this comprehensive scientific review, we examine the use of magnetic nanoparticles (MNPs) as a promising technology for the removal of MPs and NPs from water. We first describe the issue of MPs and NPs and their impact on the environment and human health. Then the fundamental principles of using MNPs for the removal of these pollutants will be presented, emphasizing that MNPs enable selective binding and separation of MPs and NPs from water sources. Furthermore, we provide a short summary of various types of MNPs that have proven effective in the removal of MPs and NPs. These include ferromagnetic nanoparticles, MNPs coated with organic polymers, as well as nanocomposites and magnetic nanostructures. We also review their properties, such as magnetic saturation, size, shape, surface functionalization and stability, and their influence on removal efficiency. Next, we describe different methods of utilizing MNPs for the removal of MPs and NPs. We discuss their advantages, limitations, and potential for further development in detail. In the final part of the review, we provide an overview of existing studies and results demonstrating the effectiveness of using MNPs for the removal of MPs and NPs from water. We also address challenges that need to be overcome, such as nanoparticle optimization, process scalability, and the removal and recycling of nanoparticles after the completion of the process. This comprehensive scientific review offers an extensive insight into the use of MNPs for the removal of MPs and NPs from water. With improved understanding and the development of advanced materials and methods, this technology can play a crucial role in addressing the issue of MPs and NPs and preserving a clean and healthy environment.

Carpels are a reproductive feature restricted to angiosperms, therefore they are a focus of many botanical studies. However, there are controversies over the nature of carpels. A reason underly-ing these controversies is mixing implications given by conflicting interpretations on fossil carpels in early fossil angiosperms from the Cretaceous. These controversies hinder a clear understanding of angiosperm evolution and systematics. A key to these questions is older fossil fruits bearing concerned information. Here we report a new fossil fruit, Xenofructus dabuensis gen. et sp. nov, from the Middle Jurassic of Liaoning, China. Unlike previously reported fruits of early angio-sperms that were interpreted as bearing seeds either on adaxial or abaxial margin by various au-thors, our fossil demonstrates clearly that the seeds in Xenofructus are neither borne on the adaxial nor abaxial margin of the fruit, instead the seeds of Xenofructus are borne on an axis positioned between two margins. This new feature implies that a placenta in carpels is an ovule/seed-bearing axis, a carpel is a composite organ comprising an enclosing leaf (fruit wall) and an axis (placenta). The adaxial or abaxial position of ovules/seeds frequently seen in fossil and extant angiosperms is a consequence derived through long time evolution (coalescence of placenta with either margin of fruits). Carpels can be taken as foliar structures enclosing their associated ovulate branches.

In this paper, a seamless connection between sensor technology and machine learning (ML) has been presented which has wide applicability in rehabilitation and physical medicine. The intent is to identify an ML algorithm which has a better performance, easy to deploy, and has less training time and consumes less computational resources. In short, we propose an algorithm which maximizes the synergy between a sensor and ML by maximizing classification performance and easy to do implementation, which is robust in computational power and lower in resource consumption. The premise of the work is to show the important considerations for evaluating ML algorithms for Upper-limb activity recognition for Physical medicine and rehabilitation field.

The process of developing therapies to treat rare diseases is fraught with financial, regulatory, and logistical challenges that have limited our ability to build effective treatments. Recently, a novel type of therapy called antisense therapy has shown immense potential for the treatment of rare diseases, particularly through single-patient N-of-1 trials. Several N-of-1 antisense therapies have been developed recently for rare diseases, including the landmark study of milasen. In response to the success of N-of-1 antisense therapy, the Food and Drug Administration (FDA) has developed unique guidelines specifically for the development of antisense therapy to treat N-of-1 rare diseases. This policy change establishes a strong foundation for future therapy development, and addresses some of the major limitations that previously hindered the development of therapies for rare diseases.

Quantum-dot cellular automata (QCA) is an emerging transistor-less field-coupled nanocomputing (FCN) approach to ultra-scale ‘nanochip’ integration. In QCA, to represent digital circuitry, electrostatic repulsion between electrons and the mechanism of electron tunnelling in quantum dots are used. QCA technology can surpass conventional complementary metal-oxide semiconductor (CMOS) technology in terms of clock speed, reduced occupied chip area, and energy efficiency. To develop QCA circuits, irreversible majority gates are typically used as the primary components. Recently, some studies have introduced reversible design techniques, using reversible majority gates as the main building block, to develop ultra-energy efficient QCA circuits. However, this approach resulted in time delays, an increase in the number of QCA cells used, and an increase in the chip area occupied. This work introduces a novel hybrid design strategy employing QCA irreversible, reversible, and partially reversible gates to establish an optimal balance between power consumption, delay time, and occupied area. The hybrid technique allows the designer to have more control over the circuit characteristics to meet different system needs. A combination of reversible, irreversible, and innovative partially reversible majority gates is used in the proposed hybrid design method. We have evaluated the hybrid design method by examining the half-adder circuit as a case study. We have developed four hybrid QCA half-adder circuits, each of which simultaneously incorporates various types of majority gates. The QCADesigner-E 2.2 simulation tool was used to simulate the performance and energy efficiency of the half-adders. This tool provides numerical results for the circuit input/output response and heat dissipation at the physical level, within a microscopic quantum mechanical model.

For their speed in data processing, low heights and cheapness, patch antennas are important to 5G networks. While there have been improvements in the area of bandwidth and size reduction; however, there are still problems that need to be fixed with regards achieving high data rates as well as wideband operation and compact sizes for 5G applications. In the coming years researchers should concentrate on materials optimization and feeding methods so that they can work efficiently at shorter wavelengths for next-generation systems while still covering all necessary bands.

In bacteria, enzymes usually comprise of enzymatic domains only. In eukaryotes/mammals, and here particularly in context of signal transduction, proteins with enzymatic functions contain additional modules promoting interactions with cooperating signaling proteins. Often such protein-protein interaction domains, such as SH2- and SH3-domains, help to localize the enzymatic function (e.g. kinase, phosphatase) to another protein, cellular compartment, or membrane nanodomain. In such cases, the interaction domain(s) serve(s) the enzymatic function. However, there are molecular situations in which an interaction domain fulfills its task completely independent of the protein´s enzymatic function and in this review, we call such function the adapter function of an enzyme. Though many stories can be told, we will concentrate on several proteins playing crucial roles in cells of the immune system, such as BTK, PI3K, and SHIP1, as well as in cancer cells, such as proteins of the RAS/ERK MAPK pathway. We will also discuss how these adaptor functions of enzymes determine or even undermine the efficacy of targeted therapy compounds, such as ATP-competitive kinase inhibitors, thereby highlighting the need to develop pharmacological approaches, such as PROTACs, that eliminate the entire protein. We also review how genetic kock-out and knock-in approaches can be leveraged to identify adaptor functions of signaling proteins.

The fractional advection-dispersion equation FADE plays an important role, especially in explaining the process of solute-transport in natural porous media with different degrees of heterogeneity. However, studies of the flow and transport of contaminants in the underground environment are based on the knowledge of many functional parameters of the subsoil. The delay factor caused by nonlinear absorption is one of these parameters inheriting significant ambiguities in its estimation in heterogeneous media. In the study, a fractional advection-dispersion FADE model was developed by the implicit Euler method, based on a Grunwald and Caputo-Liousville approximation to explicitly evaluate and simulate the transport mechanism of contaminants in media with unsaturated porous materials subjected to a nonlinear sorption model. Better solute mass retention was observed for fractional advection-dispersion FADE model. Moreover, the absorption parameter of the retardation coefficient has a better impact on the motion of the solute in a saturated porous medium. In other words, it has a significant effect on the dispersion of pollutants in aquifers. This study highlights the need to characterize the aquifer to predict solute transport in porous media.

Previous studies separately addressed the impact of urban expansion on vegetation cover and thermal conditions, as well as its effect on moisture and drought indicators, using geospatial techniques. Some studies, such as those by Malah et al. (2021) and Niu and Li (2020), focused on assessing urban environmental quality using an environmental quality index without considering urban expansion. Meanwhile, other studies, like those conducted by Indrawati et al. (2020), primarily focused on evaluating urban environ-ments using an integrated environmental index consisting of four indicators (greenness, moisture, drought, and cumulative clustering). The study by Zhu et al. (2019) applied the same integrated environmental index (IEI) and, by comparing it with temperature, re-vealed a negative correlation illustrating the effects of the environmental index on land surface temperature (LST). These two studies could be utilized to construct an index assessing the environmental condition in Riyadh. This is the case in the present study, where the addition of a temperature indicator due to the hot desert nature of the study area created the Urban Environmental Thermal Index to evaluate the urban en-vironment and provide results suitable to this region. It is expected that the present study will align with the findings of previous relevant studies, showing a negative im-pact of urban expansion on urban environmental components.

Diet-related diseases impact populations across the globe. While intertemporal preferences—a fundamental preference for the distribution of benefits across time—have been used to explain low-quality food choices, recent literature proposes another cause: inattention to future implications (or opportunity costs) of the options faced. Food choices tend to become habitual to conserve cognitive resources, rather than carefully modeling future health impacts. Both low discount rates for future benefits and attention to future health impacts predict healthier decisions. While intertemporal preferences are stable, attention may provide an opportunity to intervene in the decision process to promote healthier decisions. In this study, we test the impact of a simple message that highlights health during food choice on the healthiness of foods chosen and on health consideration and intertemporal preferences. Our results show that actively considering health outcomes and lower discount rates lead to healthier food choices. We find that messaging increases the consideration of health outcomes during food choice but does not affect intertemporal preferences, suggesting that simple prompts may be an effective way to promote decisions balancing short and long-term benefits by drawing attention to overlooked opportunity costs of choices.

This paper proposed emotion recognition methods for consecutive facial images, and implements the inference of neural network model on a field-programmable gate array (FPGA). The proposed emotion recognition methods are based on a neural network model architecture that combines convolution neural networks (CNNs), long short-term memory (LSTM), and fully connected neural networks (FCNNs), called CLDNN or ConvLSTM-FCN. This type of neural network mod-el can analyze the local feature sequences obtained through convolution of data, making it suita-ble for processing time-series data such as consecutive facial images. In this paper, sequences of facial images are sampled from videos corresponding to various emotional state of subjects. The sampled images are then pre-processed with the processes includes facial detection, greyscale conversion, resize, and data augmentation if necessary. The 2-D CNN in ConvLSTM-FCN is used for feature extraction for these pre-processed facial images. These sequences of facial im-age features are time sequences with dependent properties between the elements within them. The LSTM is then used to model these time sequences followed by fully connected neural net-works (FCNNs) for classification. The proposed consecutive facial emotion recognition method achieves an average recognition rate of 99.51% on RAVDESS dataset, 87.80% on BAUM-1s dataset and 96.82% on eNTERFACE’05 data set, using 10-fold cross-validation on the PC. Some com-parisons of recognition accuracies between the proposed method and the other existing related works are conducted in this paper. According to the comparisons, the proposed emotion recog-nition methods outperform the existing related researches. The proposed emotion recognition methods are then implemented on an FPGA chip using the neural network model inference algo-rithms in this paper, and the accuracies of the experiments conducted on the FPGA chip are iden-tical to those obtained on the PC. This verifies that the proposed neural network model imple-mented on the FPGA chip performs well.

For the first time, the effect of a significant change in the resistance of the aquatic environment of a population of protozoan microorganisms under the influence of radiofrequency electromagnetic radiation from cell phones has been experimentally studied. The results of the experiment demonstrate the biological nature of the changes occurring in the “water population of protozoa” system, which indicates that the impact of radiation directly affects the cell. This conclusion is confirmed by the same order of magnitude time of information exchange between individual individuals of the population in the calculation and in the experiment. An extremely low concentration of protozoa in the experiment was established, equal to 1000 pcs./liter, at which the indicated effect is observed.An unambiguous dependence of the biological effect in the “water – amoeba population” system on the average power of electromagnetic radiation of cell phones, both in standby mode and in talk mode, has been established. It is concluded that the presented method of changing the physical properties of the aquatic environment of a population of protozoa under the influence of electromagnetic fields can be a model experiment in identifying the mechanisms of interaction of biological systems with electromagnetic radiation, determining the response time of biological systems to external electromagnetic influence, and establishing the degree of influence of radiation in the 4G, 5G ranges.

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age representing the primary cause of anovulatory infertility. The nonapeptide oxytocin (OT) plays an important role in cognitive, emotional, and reproductive functions in human beings. Oxytocin receptors are expressed in several body parts including the ovaries. Despite this, the possible role played by oxytocin in symptoms of PCOS is not clear. The present systematic review aimed at understanding, the presence of possible oxytocin level alterations in PCOS, the connection between alterations of OT levels and the symptoms of PCOS, and the effect of oxytocin administration in PCOS. After a systematic search in the principal databases, seven studies, five human and two animal, were included. Most of the studies highlighted the role played by oxytocin in fertility issues related to PCOS. Studies that analyzed oxytocin basal levels in PCOS women agreed that PCOS is associated with a reduction in the serum level of oxytocin. Two studies found that in PCOS the serum levels of oxytocin were lower than healthy controls. One human and one animal study agreed about lower levels of PCOS, confirming a possible implication of a dysfunction of OT, in the pathogenesis of PCOS.

Today's city needs more than ever methodological devices that ensure a specific urbanism, in keeping with the complexity of relationships that occur in the urban space. Networks or systems of diverse nature must be activated to achieve a certain success of the city, even more so in its fragile central fabrics. The study is focused on the historic neighborhoods of the city of Jaén (Spain), which have a high vulnerability index. The aim is to establish a strategy to revitalize their urban and social capital and improve their articulation with the rest of the urban and territorial structure. A methodological proposal for the analysis of vulnerability factors and an urban and cartographic analysis of the public space is addressed through an interweaving of a triple network: environmental, social, and urban. For this purpose, the configuration of this overlapping network of analysis and formulation of criteria is presented, which considers the urban multiplicity and promotes new dynamics for the integrated urban regeneration of the area and for the activation of public and collective urban spaces.

Vaccines decrease morbidity and mortality. Nevertheless, their benefits depend on public response. During COVID-19, vaccine hesitancy and refusal were rampant, threatening public health. A thorough understand-ing of opponents' arguments is required to address the diffusion of unreliable information on social media and prevent vaccine hesitancy from developing into vaccine refusal. Accordingly, the article examines vac-cine opponents' justifications on social media. Textual content analysis of reader comments on three health-related Israeli Facebook pages was conducted. Data collection encompassed the Israeli COVID-19 vaccination period from October 2020 to May 2022. The comments were analyzed according to the health beliefs model (HBM). We found that vaccine opponents were characterized by low perceptions of the severity of the disease combined with high perceptions of the damages of the vaccine; low perceived benefits of vac-cine compliance; vaccine hesitancy and fear along with public distrust as barriers to change; and call for ac-tion to resist the vaccine and spread related anti-establishment views on the web. As vaccination hesitancy was found to develop into public distrust in the state systems and escalate into conspiracy beliefs and an-ti-vaccination activism, its early detection may prevent future vaccine resistance.

The main inhibitory neurotransmitter in the mammalian brain is 4-aminobutyric acid (GABA). Phthalimide acts as a sodium channel antagonist, one of the finest targets for treating epilepsy is the sodium channel and JNK kinase activity is inhibited to treat epilepsy. a novel compound with multiple targets of action for the treatment of epilepsy also anti-oxidant activity has been designed. The compounds are designed in two series aldehydes and aniline. Docking of all the designed compounds has been done with the suitable protein GABA-AT, sodium channel, JNK protein, and anti-oxidant from protein bank. QSAR was done for constructing many linear regression models. In combination with the developed Docking and QSAR outcomes, ADMET has been performed for the active compounds. The result shows that 11 of the compounds have excellent binding energy in docking with all the receptors and also have good QSAR results and follow the ADMET. The structural understanding of human GABA-AT inhibition was obtained from molecular dynamics simulation studies for compound no. 11 at 5 nanoseconds. Synthesis and pharmacological activity also suggest that the designed compound no.11 be considered the best Novel Compound.

Continuous technological progress places significant demands on the materials used in increasingly modern devices. An important parameter is often the long-term thermal resistance of the material. The use of heat-resistant polymer materials worked well in technologically advanced products. An economically justified direction in searching for new materials is the area of polymer nanocomposite materials. It is necessary to appropriately select both the polymer matrix and the nanofillers best able to demonstrate the synergistic effect. A promising area of exploration for such nanocomposites is the use of organosilicon polymers, which results from the unique properties of these polymers related to their structure. This review presents the results of the analysis of the most important literature reports regarding organosilicon polymer nanocomposites with increased thermal resistance. Particular attention was paid to modification methods of silicone nanocomposites focused on the increase of their thermal resistance related to the modification of siloxane molecular structure and by making nanocomposites using inorganic additives, carbon nanomaterials. Attention was also paid to such important issues as the influence of the dispersion of additives in the polymer matrix on the thermal resistance of silicone nanocomposites and the possibility of modifying the polymer matrix and permanently introducing nanofillers thanks to the presence of various reactive groups. The thermal stability mechanism of these nanocomposites was also analysed.

Bio-inspired gyroid triply periodic minimum surface (TPMS) lattice structures have been the focus of research in automotive engineering because they can absorb a lot of energy and have wider plateau ranges. The main challenge is determining the optimal energy absorption capacity and accurately capturing plastic plateau areas using finite element analysis (FEA). Using nTop's Boolean subtraction method, this study combined walled TPMS gyroid structures with normal TPMS gyroid lattice. This made a composite TPMS-gyroid lattice with relative densities ranging from 14% to 54%. Using the ideaMaker software and the fused deposition modeling (FDM) Raise3D Pro 2 3D printer to print polylactic acid (PLA) bioplastics in 1.75 mm filament made it possible to slice computer aided design (CAD) models and fabricate 36 lattices samples precisely layer by layer technique. Shimadzu 100kN testing equipment was utilized for the mechanical compression experiments. And the validation using finite element analysis (FEA). Further, CTG was examined using a field emission scanning electron microscope (FE-SEM) before and after compression testing. The composite TPMS gyroid lattice showed potential as shock absorbers for vehicles with relative densities of 33%, 38%, and 54%. The Gibson-Ashby model showed that the composite TPMS gyroid lattice deformed mainly by bending, and the size effect was seen when the relative densities were less than 15%. The lattice's relative density had a significant impact on its ability to absorb energy. The research also explored the use of these innovative foam-like composite TPMS-gyroid lattices in high-speed crash box scenarios, potentially enhancing vehicle safety and performance.

As matrix representations of magic labelings of related hypergraphs, magic squares and their various variants have been applied to many domains. Among various subclasses, trimagic squares have been investigated for over a hundred years. The existence problem for trimagic squares with singly even orders and orders 16n has been solved completely. However, very little is known for the existence of trimagic squares with other even orders except for the only three examples and three families. We construct normal trimagic squares by using product constructions, row-square magic rectangles, and trimagic pairs of orthogonal diagonal Latin squares. We give a new product construction: For positive integers p, q, and r having the same parity other than 1, 2, 3, 6, if normal p × q and r × q row-square magic rectangles exist, then a normal trimagic square with order pqr exists. As its application, we construct normal trimagic squares of orders 8q^3 and 8pqr for all odd integers q not less than 7 and p,r ∈ {7, 11, 13, 17, 19, 23, 29, 31, 37}. Our construction can easily be extended to construct multimagic squares.

Silencing of the fragile X mental retardation 1 (FMR1) gene and consequently lack of synthesis of FMR protein (FMRP) are associated with fragile X syndrome, which is one of the most prevalent inherited intellectual disabilities. FMRP is a multifunctional protein involved in many cellular functions in nearly all subcellular compartments under normal conditions and under conditions of cellular stress in both neuronal and non-neuronal cell types. This is achieved through its trafficking signals, nuclear localization signal (NLS), nuclear export signal (NES), and nucleolar localization signal (NoLS), as well as its RNA and protein binding domains, and is modulated by various post-translational modifications such as phosphorylation, ubiquitination, sumoylation, and methylation. This review summarizes recent advances in understanding the interaction networks of FMRP with a special focus on FMRP stress-related functions, including stress granule formation, mitochondrion and endoplasmic reticulum plasticity, ribosome biogenesis, cell cycle control, and DNA damage response.

Over the years, the need for autonomous systems such as drones, also known as unmanned aerial vehicles (UAVs), has significantly increased in popularity across several industries, including the military. The Internet of Battlefield Things (IoBT) represents a modern technological advancement that significantly enhances the operational efficacy of defense systems. It establishes an integrated military force by connecting individuals to intelligent technology in drones, radios, equipment, antennas and ground stations. This is achieved through the utilization of cloud and edge computing, sensors, mobile devices, embedded systems, and IoT-based systems. However, IoBT security is significantly compromised by enemies that exploit the vulnerabilities and malicious intrusions that specifically target the external environment or to obtain sensitive data. In addition, a comprehensive understanding of cyberattacks and countermeasures is essential for assuring the security of IoBT. On the other hand, as cyber threats get more complicated, trust becomes increasingly important for the security of digital systems. Within this context, the zero trust architecture contends that the security of a complex network is inherently vulnerable to internal and external threats. In defense, UAV security system applications, for example, the primary purpose of the zero trust architecture is to limit the vulnerability of military UAV systems to cyberattacks, hence reducing the possibility of data breaches and illegal entry. This study conducts a systematic review aimed at identifying different aspects of cybersecurity strategies for protecting UAV systems within the IoBT domain. Furthermore, zero trust architecture is presented in the study as an effective prospective solution to the security issues that develop in defense UAV systems.

This paper presents an innovative multi-agent, data-driven reinforcement learning (RL) approach to develop and utilize the thermal equivalent network model that represents the motor's thermal dynamics. A multi-agent reinforcement learning is designed and trained to adjust the model parameters using data from several motor driving cycles. To ensure the incoming driving cycle matches the historical data before employing the pre-trained RL agents, offline statistical analysis and clustering techniques are developed and used. Numerical simulations highlighted the RL agent's ability to develop strategies that effectively address the variability of driving cycles. The proposed RL framework showed its capability to accurately reflect the motor's thermal behavior under various driving conditions.

The wealth of data obtained during the past 20 years using Laser-Induced Breakdown Spectroscopy (LIBS) indicates that the technique is very promising to detect small chemical contents of alloying elements. The potential of LIBS was looked more seriously during the past two decades or so as more data were obtained on Aluminum and steel to study the phenomena in the condition of local thermodynamic equilibrium and time-delay between a Q-switch laser and an intensified CCD camera. Since the past decade, some data on compounds were also shown to be useful in determining small concentrations of harmful elements. This manuscript is intended to show that the technique of LIBS performance is very promising in fields such as micro-machining, in alloying element analysis, surface cleaning and environmental applications even with lightweight spectrometers having a relatively low resolution, which can potentially be air-borne.

As Artificial Intelligence (AI) technology, particularly Machine Learning algorithms, becomes increasingly ubiquitous, our abilities to understand and interpret AI and machine learning algorithms are becoming increasingly desirable. Visualization has been used as a common tool to view and understand complex machine learning processes. In this paper, we will focus on developing a general framework for the visualization of machine learning models as a scalar valued multi-dimensional function to help users understand how the models behave over different viewing spaces. We first give a formal definition of the visualization problem. Interpolation-based morphing and subspace sampling techniques are applied to generate various renderings through projections and cross-sections of the model space as 3D surfaces or heatmap images. This method will be applied to two real-world datasets and applications: the diagnosis of Alzheimer's Disease (AD) using a human brain networks dataset and a real-world benchmark dataset for predicting home credit default risks. The visualizations show that different machine learning algorithms can behave quite differently under different conditions.

The study investigated the usage of open data in public organizations, focusing on the motives, preferences, and governance ideals that determine their quality. The study shed light on how open data platforms are created and improved, as well as their influence on government operations. The primary goal was to understand the motivations behind the usage of open data, evaluate gov-ernance ideals, and examine institutions' efforts to standardize data formats. Hierarchical regres-sion analysis divides variables into core reasons and different preferences, demonstrating a need for "diversification" in order to use open data effectively. Efficiency, accountability, community impact, knowledge, and high-quality service delivery are all emphasized in governance value analysis. The institution's dedication to standardizing open data formats is evidenced by legislative measures and the integration of many technologies. The findings illustrate the institution's dual strategy of em-ploying traditional techniques and new technologies for effective data management. The report suggests increasing data openness and standardization, investing in ongoing training, upgrading alerting and awareness systems, and adopting specific regulations for open data use. Monitoring and feedback techniques are critical for adjusting and refining open data services to satisfy de-velopment needs. This study adds to the scientific knowledge of open data use by highlighting important motives, preferences, and governance ideals. The offered guidelines provide practical insights for public organizations looking to improve their open data platforms by promoting openness, efficiency, and community participation.

Monitoring of clients living with HIV encompasses a specific array of activities that routinely check on various aspects of ART following its initiation depending on the availability of resources in that particular state, among other factors as per guidelines from the World Health Organisation. This is a significant practice as it promotes positive health outcomes for patients and efficient utilisation of ART regimens to reduce resistance to the medication – hence it is a measure to guard avoidable costs. It also forms a basis on which decisions are made from. It can be done clinically by assessing for signs e.g., skin rash and symptoms e.g., nausea and vomiting, checking vital organ function and measuring weights across all populations, or can be also be done by assessing specimens for their respective viral loads, white blood cell count, pregnancy status or other infections such as hepatitis B. There have not been any special indications required for one to be eligible for monitoring during ART in developing countries; all qualify for routine monitoring even though some may be more frequent than others in cases of comorbidities such as renal failure where medications can be attributed to exacerbating the condition.

Underwater Sensor Networks (UWSNs) can enable a broad range of applications such as resource monitoring, disaster prevention, and navigation-assisted. It is especially relevant for sensor nodes location in UWSNs. Global Positioning System (GPS) is not suitable for using in UWSNs because of the underwater propagation problems. Hence some localization algorithms based on the precise time synchronization between sensor nodes have been proposed which are not feasible for UWSNs. In this paper, we propose a localization algorithm called Two-Phase Time Synchronization-Free Localization Algorithm (TP-TSFLA). TP-TSFLA contains two phases, namely, range-based estimation phase and range-free evaluation phase. In the first phase, we address a time synchronization-free localization scheme base on the Particle Swarm Optimization (PSO) algorithm to decrease the localization error. In the second phase, we propose a Circle-based Range-Free Localization Algorithm (CRFLA) to locate the unlocalized sensor nodes which cannot obtain the location information through the first phase. In the second phase, sensor nodes which are localized in the first phase act as the new anchor nodes to help realize localization. Hence in this algorithm, we use a small number of mobile beacons to help achieve location without any other anchor nodes. Besides, to improve the precision of the range-free method, an extension of CRFLA by designing a coordinate adjustment scheme is updated. The simulation results show that TP-TSFLA can achieve a relative high localization ratio without time synchronization.

Subnational governments play a key role responding to climate change risks in terms of policy strategies and instruments. This article analyzes how Brazilian municipal and state governments have developed and implemented public policies to mitigate and to adapt to climate change risks. We surveyed all cities’ and states’ climate policies within the country. The methodological approach includes five main points of analysis: 1. mitigation targets and intentions; 2. adaptation actions; 3. stakeholders’ participation; 4. policy implementation; 5. participation in networks related to climate change. Our results suggest that even though subnational climate policies in Brazil are isolated initiatives within the national context, they play an important role responding to climate change risks in different scales and levels. The strongest Brazilian policies with both mitigation and adaptation actions counted on previous mobilization for the climate issue involving different stakeholders from several segments of the society. These governments have also participated in transnational cooperation networks related to climate change.