In Philadelphia chromosome positive B-cell (Ph+) acute lymphoblastic leukemia (LLA), growing evidence has ac-cumulated about the efficacy of low-intensity and chemo-free regimens. Our objective was to analyze all recent trials evaluating these treatments and to compare them in terms of efficacy. We applied the Shiny method, an artificial intelligence technique, to analyze Kaplan-Meier curves and reconstruct patient-level data. Reconstructed patient data were then evaluated through standard survival statistics and subjected to indirect head-to-head treatment comparisons. The endpoint was progression-free survival (PFS). Based on 848 reconstructed patients, 9 trials were analyzed. The survival data from these trials were pooled into three types of treatments: i) treatments based on ty-rosine kinase inhibitors (TKIs) combined with reduced-intensity chemotherapy (denoted as TKICHE); ii) TKIs as-sociated to steroids with no chemotherapy (TKISTE); iii) chemotherapy-free combinations of blinatumomab plus TKIs (TKIBLI). According to the Shiny method, the three PFS curves were reported in a single Kaplan-Meier graph and subjected to survival statistics. In terms of PFS, TKIBLI ranked first, TKICHE second, and TKISTE third; the differences between these three regimens were statistically significant. This multi-treatment Kaplan-Meier graph, generated through the Shiny method, summarized the current evidence on these treatments in both qualitative and quantitative terms.

: In Philadelphia chromosome positive B-cell (Ph+) acute lymphoblastic leukemia (LLA), growing evidence has accumulated about the efficacy of low-intensity and chemo-free regimens. Our objective was to analyse all recent trials evaluating these treatments and to compare them in terms of efficacy. We applied the Shiny method, an artificial intelligence technique, to analyse Kaplan-Meier curves and reconstruct patient-level data. Reconstructed patient data were then evaluated through standard survival statistics and subjected to indirect head-to-head treatment comparisons. The endpoint was progression-free survival (PFS). Based on 562 reconstructed patients, 8 trials were analyzed. The survival data from these trials were pooled into three types of treatment: i) treatments based on tyrosine kinase inhibitors (TKIs) combined with reduced-intensity chemotherapy (denoted as TKICHE); ii) TKIs associated to steroids with no chemotherapy (TKISTE); iii) chemotherapy-free combinations of blinatumomab plus TKIs (TKIBLI). According to the Shiny method, the three PFS curves were reported in a single Kaplan-Meier graph and subjected to survival statistics. In terms of PFS, TKIBLI ranked first, TKICHE second, and TKISTE third; the differences between these three regimens were statistically significant. In conclusion, the multi-treatment Kaplan-Meier graph generated in this study has effectively summarized the current evidence on these treatments in comparative terms.

The symmetry properties of an ornament contain information about its civilisation and its interactions with other cultural sources. Two-dimensional periodic ornaments can be strictly classified into a limited set of 17 mathematical symmetry groups, also known as wallpaper groups. The collection of ornaments thus classified for a civilisation is characteristic of the cultural group and serves as a fingerprint to identify that group. If the distribution of wallpaper groups is available for several societies, mathematical methods can be applied to determine similarities and differences between the art practices of these communities. This method allows a systematic approach to the general ornamental practices within a culture and their interactions in the form of similarity of fingerprints. We test the feasibility of the method on examples of medieval Armenians, Byzantium, Seljuks first in Persia and then in Anatolia and among Arabs in the Middle East. For this purpose we present the distribution of the planar ornaments and calculate the Euclidean distances in pairs. We tested to what extend geographical and religious factors could account for the observed similarity of ornamental groups between cultures. The results suggest an intensive interaction between the Seljuk Turks and Arab craftsmen who produced the ornaments. Therefore the cultural interactions are religiously motivated.

The optimal timing for actively discontinuing immune checkpoint inhibitor therapy in long-term responders with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains unresolved. We conducted a retrospective study of 246 patients with R/M HNSCC treated with nivolumab to determine the optimal timing to actively discontinue nivolumab therapy. We examined the point at which progression-free survival (PFS) plateaued in all cases. We compared the prognosis of 19 (7.7%) ongoing cases and 227 (92.3%) discontinued cases and analyzed treatment duration and treatment-free interval (TFI). The 6-year overall survival was 11.8% (median, 12.1), and the 6-year PFS was 15.3% (median, 3.0). The PFS curve remained stable for 3 years. The median duration of nivolumab treatment was 2.9 months (range, 0.03–81.9): Ongoing group, 41.8 (5.6–81.9); Decision group, 36.8 (4.0–70.1); Toxicity group, 30.6 (2.8–64.8); and progressive disease group, 2.0 (0.03–42.9). TFI in the Decision group was 15.1 months (0.6–61.6) and 30.6 months (2.8–64.8) in the Toxicity group. Limited number of long-term responders in R/M HNSCC cases treated with nivolumab exists. Given that PFS plateaued at 3 years, we propose that the optimal duration of treatment for this subset of patients is 3 years.

Background: In the present study, we assessed the feasibility and success outcomes of voice prosthesis (VP) changes when performed by speech-language pathologist (SLP). Methods: Patients treated with total laryngectomy (TL) from January 2020 to December 2020 were prospectively recruited from our medical center. Patients benefited from tracheoesophageal puncture. The VP changes were performed by the senior SLP and the following data were collected for each VP change: date of placement; change or removal; VP type and size; reason for change or removal; and use of a washer for periprosthetic leakage. A patient-reported outcome questionnaire including 6 items was proposed to patients at each VP change (Appendix 1). Items were assessed with a 10-point Likert-scale. Results: Fifty-two VP changes were performed by the senior SLP during the study period. The mean duration of the SLP consultation, including patient history, examination and VP change procedure was 20 min (range: 15-30). The median prosthesis lifetime was 88 days. The main reasons for VP changes were transprosthetic (N=34; 79%) and periprosthetic (N=7; 21%) leakages, respectively. SLP successfully performed all VP changes. He did not change one VP but used a periprosthetic silastic to stop the periprosthetic leakages. In two cases, SLP needed the surgeon examination to discuss about the following indication: implant mucosa inclusion and autologous fat injection. The patient satisfaction was high according to the speed and the quality of care by the SLP. Conclusion: The delegation of VP change from the otolaryngologist-head and neck sur-geon to the speech-language pathologist (SLP) may be done without significant complications. The delegation of VP change procedure to SLP may be interesting in some rural regions with otolaryngologist shortage.

The purpose of this study was to elucidate patterns and mechanisms driving seasonal and inter-annual variations of carbon and nitrogen stable isotopes in the zooplankton crustacean commu-nity of Lake Maggiore (Italy), during the period 2009-2020. Different zooplankton taxa and groups revealed different ranges of d13C signatures, giving an insight into food sources and niche partition. In particular, cyclopoids had a restricted range with most negative d13C‰ values and increase in d13C fractionation with the establishment of water thermal vertical stratification, high-lighting the importance of vertical distribution as key factor for taxa coexistence in a vertically heterogenous environment. d13C of the zooplankton community and of Daphnia were positively related to water temperature (R2=0.58 p <0.0001 and R2=0.68 p <0.0001, respectively) and d13C Daphnia signature to chlorophyll-a (R2=0.32, p < 0.0001). Decomposition of time series data for zooplankton carbon and nitrogen signatures and environmental parameters identified increasing trends in water temperature, chlorophyll-a and water conductivity and decrease in nitrate, that matched changes in carbon isotopic signature trend in some zooplankton taxa (Bosmina, Daphnia and diaptomids). Overall, the observed patterns in zooplankton isotopic signatures were interpreted as integrations of climate warming effects in Lake Maggiore, affecting both food sources availability and environmental conditions.

OBJECTIVES: To assess the predictive value of serum trypsin and Trypsinogen Activation Peptide (TAP) for the severity of AP by means of a single center cohort study as well as a systematic review of the current literature. METHODS: The literature search was conducted using Medline (PubMed), EMBASE and the Cochrane Central Register. A total of 142 patients with acute pancreatitis (AP) were included in the cohort study and parameters of the revised Atlanta criteria of 2012 and the APACHE II were assessed. RESULTS: The review showed promising results for the predictive value of serum trypsinogen-2, but conflicting results for serum TAP and trypsin. In the cohort study, patients were observed for 4 days after diagnosis of AP: 9 patients had severe AP, 35 patients had moderate AP and 81 patients had mild AP. The ratio of the geometric mean of severe vs mild AP for trypsin was 0.72 (95% CI: 0.51-1.00), p=0.053 and for TAP 0.74 (95% CI: 0.54-1.01), p=0.055 respectively. CONCLUSION: The cohort study showed an inverse correlation of serum levels of TAP and trypsin with severity of AP. Serum TAP and trypsin have an inferior predictive value of severity of AP compared to the clinical APACHE II score.

Abstract: High step-up voltage gain nonisolated DC-DC converter have attracted much attention in photovoltaic, fuel cells and other renewable energy system applications. In this paper, by combining input current ripple-free boost cell with coupled-inductor voltage-doubler cell, an input current ripple-free high voltage gain nonisolated converter is proposed. In addition, passive lossless clamp circuit is adopted to recycle the leakage inductor energy and to reduce the voltage spike across the power switch. By utilizing voltage-doubler cell consisting of diode and capacitor, the voltage stress of switch is further reduced and the resonance between the leakage inductor and the stray capacitor of the output diode is eliminated. A low switch-on-resistance low-voltage-rated MOSFET can therefore be employed to reduce the conduction loss and cost. The reverse recovery loss of output diode is reduced, and the efficiency of converter can be improved. Furthermore, the proposed converter can achieve nearly zero input current-ripple and make the design of electromagnetic interference (EMI) filter easy. Steady state analysis and operation mode of the converter is performed. Finally, experimental results are presented to verify the analysis results of the proposed converter.

In recent years, there has been a notable rise in the incidence of breast cancer among young patients, who exhibit worse survival outcomes and distinct characteristics compared to the intermediate and elder patients. Therefore, it’s imperative to identify identify the specific features unique to young patients, which could offer insights into potential therapeutic strategies and improving survival outcomes. In our study, we performed an integrative analysis of bulk transcriptional and genomic data from extensive clinical cohorts to identify prognostic factors. Additionally, we analyzed the single-cell transcriptional data and conducted in vitro experiments. Our work confirmed that young patients exhibited higher grading, worse disease-free survival (DFS), a higher frequency of mutations in TP53 and BRCA1, a lower frequency of mutations in PIK3CA, and upregulation of eight metabolic pathways. Notably, galactose metabolism pathway showed upregulation in young patients and was associated with worse DFS. Further analysis and experiments indicated that galactose metabolism pathway may regulate the stemness of cancer cells and ultimately contribute to worse survival outcomes. In summary, our finding identified distinct clinicopathological, transcriptional, and genomics features and revealed a correlation between galactose metabolism pathway, stemness, and poor disease-free survival of breast cancer in young patients.

This paper addresses the input coupling problem for the shape memory alloy (SMA) actuated parallel platform with completely unknown nonlinear dynamics. The problem means that in a parallel platform with multiple SMA actuators acting together, the displacement of one of the actuators will simultaneously affect the remaining actuators to change. Due to the coupling problem and nonlinear characteristics of the SMA actuators, it is not easy to control the platform to achieve bi-directional swing with completely unknown nonlinear dynamics. Therefore, a model-free adaptive sliding mode control method is proposed to improve the control accuracy of the complex motion of the platform, avoiding the complex modeling process of the SMA actuated parallel platform. Based on the model-free adaptive control (MFAC) theory, a multiple input and multiple output (MIMO) dynamic linearized mathematical model of the parallel platform is established using the online input and output data of the system. Then, a sliding mode controller is designed based on the dynamic model. A rigorous theoretical analysis proves that the proposed model-free adaptive sliding mode controller is able to stably control the SMA actuated parallel platform, and its tracking error is uniformly ultimately bounded (UUB). Finally, experiments are conducted on the established SMA actuated parallel platform. The results show that the proposed model-free controller is feasible and effective, and can control the system well to achieve the complex motion of bi-directional swing.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of &lt;1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

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.

Tissue programmed death ligand-1 (PD-L1) protein expression is predictive of immune checkpoint inhibitor (ICI) benefit. However, tissue PD-L1 can be fraught with tissue acquisition and heterogeneity limitations. Plasma testing can overcome these limitations. However, the overall survival (OS) predictive benefit of plasma PD-L1 assays have not been well characterized. Patients with stage IV non-small cell lung cancer (NSCLC) and plasma cfRNA PD-L1 by PCR expression were identified and assessed for OS. 16 patients treated with front-line ICI-based regimens were assessed and represented a real-world patient population with over half with a performance status of 2 or greater. 10 contemporaneous patients at the same institution treated with chemotherapy alone were also identified and assessed. With a median follow-up of 33 months, median OS was 13 months with a 30% 3-year OS for the ICI treated patients compared to a median OS of 3 months and a 10% 3-year OS for those treated with chemotherapy alone. Comparative log-rank test p-value = 0.014 and a hazard ratio 0.376 (95%-CI 0.134-1.057). Plasma cfRNA PD-L1 was associated with a statistically significant survival benefit from ICI-based treatment compared to chemotherapy in the first line treatment of a real-world patient population of advanced NSCLC.

The one-dimensional MoS₂/carbon nanofibers (1D MoS₂/CNFs) are synthesized by electrospinning using exfoliated MoS₂ nanosheets and polyacrylonitrile as raw materials. The exfoliated MoS₂ nanosheets with size of about 150 nm are encapsulated in carbon nanofibers, and the free-standing MoS₂/CNFs can be easily cut into flexible tablet and directly used as binder-free anode for lithium storage. The resultant 1D MoS₂/CNFs exhibit a very high reversible capacity of 700 mAh g^-1 at 100 mA g^-1 after 50 cycles, high rate capacity (450 mAh g^-1 at 1000 mA g^-1 after 200 cycles) and good cycle stability.

Human Activity Recognition (HAR) technology enables continuous behavior monitoring, particularly valuable in healthcare. This study investigates the viability of using an ear-worn motion sensor for classifying daily activities, including lying, sitting/standing, walking, ascending stairs, descending stairs, and running. Fifty healthy participants (between 20 and 47 years old) engaged in these activities while under monitoring. Various machine learning algorithms, ranging from interpretable shallow models to state-of-the-art deep learning approaches designed for HAR, were employed for classification. Results demonstrate the ear sensor's efficacy, with deep learning models achieving 98% accuracy rate of classification. The obtained classification models are agnostic regarding which ear the sensor is worn and robust against moderate variations in sensor orientation (e.g., due to differences in auricle anatomy), meaning no initial calibration of the sensor orientation is required. The study underscores the ear's efficacy as a suitable site for monitoring human daily activity and suggests its potential for combining HAR with in-ear vital signs monitoring. This approach offers a practical method for comprehensive health monitoring by integrating sensors in a single anatomical location. This integration facilitates individualized health assessments, with potential applications in tele-monitoring, personalized health insights, and optimizing athletic training regimes.

Background: Non-surgical organ preservation protocols have known a large diffusion worldwide in the last decades. Their oncological and functional effectiveness in a real-world setting has been recently ques-tioned, also because of the high morbidity of salvage procedures. The aim of this study is to review the outcomes of post irradiation salvage total laryngectomy (STL) and reconstruction with pectoralis major flap. Methods: This retrospective observational study included 37 cases of STL in the period going from January 2015 to December 2021. Data for each patient were extracted from the hospital information system and reviewed. Results: The 3-year overall and disease specific survival are respectively 28% and 51%. All patients with recurrences died from the disease. Only 7 recurrences and 7 consequent deaths for cancer were rec-orded. The other 14 deaths derived from comorbidities, being diabetes the most significant predictive parameter for overall survival. Also low-er postoperative albumin levels were associated with a higher risk of death. Conclusions: Overall survival after STL and reconstruction with PMMF is low but most deaths are due to comorbidities and not to cancer progression or recurrence.

Surface initiated atom transfer radical polymerization (SI-ATRP) is one of the most versatile technique to modify the surface properties of material. Recent developed metal free SI-ATRP makes such technique more widely applicable. Herein photo-induced metal-free SI-ATRP of methacrylates, such as methyl methacrylate, N-isopropanyl acrylamide, and N,N- dimethylaminoethyl methacrylate, on the surface of SBA-15 was reported to fabricate organic-inorganic hybrid materials. SBA-15 based polymeric composite with adjustable graft ratio was obtained. The structure evolution during the SI-ATRP modification of SBA-15 was monitored and verified by FT-IR, XPS, TGA, BET, and TEM. The obtained polymeric composite showed enhanced adsorption ability for the model compound toluene in aqueous. This procedure provides a low cost, ready availability, and facile modification way to synthesize the polymeric composites without the contamination of metal.

We aimed to assess the prognostic value of BRAFV600E mutation in a series of 127 papillary thyroid carcinoma (PTC) cases as a single factor, as well as in synergic interaction with other standard risk factors. All cases were tested for BRAFV600E mutation by real-time PCR. Event-free survival (EFS) was calculated between the date of the first evaluation and the date of occurrence of an adverse event (tumor recurrence/distant metastasis) or the date of the last known status. The prevalence of BRAFV600E mutation was 57.2%. The Kaplan-Meyer analysis showed a significant reduction of EFS among cases harboring BRAFV600E mutation compared to non-mutated cases (p=0.010). In addition, BRAFV600E mutation was found to better predict adverse outcomes when associated with the following risk factors: age≥55 years-old (p<0.001), male gender (p<0.001), conventional (p=0.005) and tall cell (p=0.014) histology, tumor size&gt;40mm (p=0.001), extrathyroidal extension (p=0.001), multifocality (p=0.001) and lymph node metastasis (p&lt;0.001). In univariate analysis, a 3.74-fold increased risk for a reduced EFS (p=0.018) was found for BRAFV600E mutated cases. Our results highlight the prognostic value of BRAFV600E mutation in PTCs. Moreover, the synergic interaction between BRAFV600E mutation and other risk factors seems more valuable in terms of prognosis, compared to BRAFV600E mutation alone.

Studies in animal models have suggested that the ketogenic diet may be effective in the treatment of cancer. However, human cohort studies on the ketogenic diet have, thus far, failed to show benefits in cancer survival or in any other hard clinical endpoints of the disease. This paper presents a case report of a patient with glioblastoma multiforme. The patient had initially been treated with standard oncotherapy including surgery, radiotherapy and chemotherapy. Despite standard treatment, the patient experienced a recurrence of the glioblastoma seven months later. Subsequently, the patient refused radiotherapy and chemotherapy and opted to use the paleolithic ketogenic diet (PKD) as a stand-alone therapy. Following the adoption of the PKD, progression of the disease has been completely halted. At the time of writing, the patient has remained in remission for 48 months, is without side-effects and experiences an excellent quality of life without the use of any drugs.

Background: The proven efficacy of mTOR inhibitors (mTORI), tyrosine kinase inhibitors (TKI) or immune checkpoint inhibitors (ICI) therapies in metastatic renal cell carcinoma (RCC), suggested that these agents should be investigated as adjuvant therapy with the aim of eliminating any residual undetectable microscopic disease after curative resection. Our study aimed to compare the efficacy of these treatments through the application of an innovative method that reconstructs individual patient data. Methods: Nine phase III studies describing different treatment options for adjuvant RCC were selected. Individual patient data were reconstructed from Kaplan–Meier (KM) curves through the “IPDfromKM method”. Disease-free survival (DFS) were compared among combination treatments and control arm (placebo). Results were summarized as multi-treatment KM curves. Standard statistical testing was used, including hazard ratio and likelihood ratio tests for heterogeneity. Results: In the overall population, this study showed that two ICIs (pembrolizumab and nivolumab plus ipilimumab) and one TKI (sunitinib) showed superiority over placebo, whereas both TKI and mTORI did not. As we assessed DFS as the primary endpoint for the adjuvant comparison, the overall survival benefit remains unknown.. Conclusion: This novel approach to investigating survival has allowed us to conduct all of the indirect head-to-head comparisons between these agents in a context where no "real" comparative trials have been conducted.

As the development of high-throughput technologies, more and more high-dimensional or ultra high-dimensional genomic data are generated. Therefore, how to make effective analysis of such data becomes a challenge. Machine learning (ML) algorithms have been widely applied for modelling nonlinear and complicated interactions in a variety of practical fields such as high-dimensional survival data. Recently, the multilayer deep neural network (DNN) models have made remarkable achievements. Thus, a Cox-based DNN prediction survival model (DNNSurv model) , which was built with Keras and Tensorflow, was developed. However, its results were only evaluated to the survival datasets with high-dimensional or large sample sizes. In this paper, we evaluate the prediction performance of the DNNSurv model using ultra high-dimensional and high-dimensional survival datasets, and compare it with three popular ML survival prediction models (i.e., random survival forest and Cox-based LASSO and Ridge models). For this purpose we also present the optimal setting of several hyper-parameters including selection of tuning parameter. The proposed method demonstrates via data analysis that the DNNSurv model performs overall well as compared with the ML models, in terms of three main evaluation measures (i.e., concordance index, time-dependent Brier score and time-dependent AUC) for survival prediction performance.

This paper studies the duration patterns of unemployment spells for immigrants and the determinants of unemployment’s completion into one of a number of studied labour market states in Finland. We estimate a duration model for unemployment with competing risks of its terminating into employment, labour market training or economic inactivity. Taking into account the wide period of observation and opportunities to analyse processes of labour market integration during various periods of economic development in Finland, in combination with the individualistic character of the labour careers of immigrants, this research is beneficial owing to the many various findings concerning labour market integration of immigrants. The approach undertaken in this research has a dualistic “descriptive-dynamic” character under which integration is understood as a never-ending process, which is conditioned by a time period of long-term existence and a context of solitary action. We find that transitions out of unemployment spells have a cyclical character; after every new “cycle” in unemployment, the probability of terminating unemployment decreases further. We also find that ascriptive factors make sense in the process of job-placement of immigrants from unemployment. Therefore, the gender, education and age of immigrants, as well as the effect of the period in which first unemployment occurred, potentially predict transitions out of unemployment and further labour market integration of immigrants.

This paper investigates the impact of debt financing on dividend payments when they face the agency costs of free cash flow. Focusing on a sample of 120 firms listed on the Saudi Stock Exchange during the period 2011-2021. The study found a negative association between agency cost of free cash flow and dividend payment. More importantly, our research highlights the significant role of long-term debt in making more prudent use of free cash flow. The obligation to meet interest and principal payments acts as an incentive for them to steer clear of unprofitable expenses and risky investments. Concurrently, long-term debt imposes restrictive clauses in debt contracts, such as minimum dividend distribution requirements, which further encourage higher dividend payments. Since interest and debt repayments are fixed obligations, using free cash flow for dividend disbursement is considered a more profitable and beneficial approach for shareholders in the context of Saudi Arabia.

Tuberculosis (TB) remains a global health threat, necessitating innovative strategies for control and prevention. This comprehensive review explores the Mycobacterium tuberculosis Lysine Exporter (LysE) gene, unveiling its multifaceted roles and potential uses in controlling and preventing tuberculosis (TB). As a pivotal player in eliminating excess L-lysine and L-arginine, LysE contributes to the survival and virulence of M. tuberculosis. This review synthesizes findings from different electronic databases and includes 13 studies focused on the LysE of M. tuberculosis. The research unveils that LysE can be a potential drug target, a diagnostic marker for TB, and a promising candidate for vaccine development. The absence of LysE in the widely used BCG vaccine underscores its uniqueness and positions it as a novel area for TB prevention. In conclusion, this review underscores the significance of LysE in TB pathogenesis and its potential as a drug target, diagnostic marker, and vaccine candidate. The multifaceted nature of LysE positions it at the forefront of innovative approaches to combat TB, calling for sustained research efforts to harness its full potential in the global fight against this infectious disease.

The commercial oxygen-free copper sheets were cold-rolled with reduction rates ranging from 20% to 87% reduction rate and annealed at 400, 500 and 600 °C. The microstructure and texture evolution during cold-rolling and annealing processes were studied using optical microscopy (OM), the scanning electron microscopy (SEM) and the electron back-scattered diffraction (EBSD). The results show that the deformation textures of {123} (S) , {112} (Copper) and {110} (Brass) were continuously enhanced with the increase of cold-rolling reduction. The orientations along the α-oriented fiber converged towards Brass and the orientation density of β fiber obviously increased when the rolling reduction exceeded 60%. The recrystallization texture was significantly affected by the cold-rolling reduction. After 60% cold-rolling reduction, Copper and S textures components gradually decreased and {011} recrystallization texture component formed with the increase of annealing temperature. After 87% cold-rolling reduction, a strong Cube texture formed and other textures were inhibited with the increase of annealing temperature. The strong Brass and S deformation texture was conducive to the formation of a strong Cube annealing texture. The density of annealing twin boundary decreased with the increase of annealing temperature, and more annealing twin boundaries formed in the oxygen-free copper sheets with the increase of cold rolling reduction.

Aluminum wire is a common material for wire bonding due to its resistance to oxidation and low price. It does not melt when becoming a free air ball (FAB) during the electronic flame-off (EFO) process with wettability, and is applied by wedge bonding. This study used 20μm Zn-Coated Al-0.5wt.%Si (ZAS) wires to improve the FAB shape after the EFO process, while maintaining stability of the mechanical properties, including the interface bonding strength and hardness. In order to test circuit stability after ball bonding, the current-tensile test was performed. During the experiment, it was found that 80nm ZAS with wire bonding has lower resistance and higher fusing current. For the bias tensile test, the thicker Zn film diffused into the Al-Si matrix easily, after which the strength was reduced. The ball-bond interfaces had no change in their condition before and after the bias. Accordingly, ZAS could be a promising candidate for ball bonding in the future.

The present study aims to develop an efficient numerical method for computing the diffraction and radiation of water waves with horizontal long cylindrical structures, such as floating breakwaters. A higher-order scheme is used to discretize geometry of the structure as well as the relevant physical quantities. As the kernel of this method, Wehausen’s free-surface Green function is calculated by a newly-developed Gauss-Kronrod adaptive quadrature algorithm after elimination of its Cauchy-type singularities. To improve computational efficiency, a Chebyshev approximation approach is applied to a fast calculation of the Green function that needs evaluation thousands of times. In addition, OpenMP parallel technique is used to the formation of influence coefficient matrix, which significantly reduces CPU time. Finally, computations are performed on wave exciting forces and hydrodynamic coefficients for the long cylindrical structures, either floating or submerged. Comparison with other numerical and analytical methods demonstrates good performance of the present method.

The purpose of the present study was to investigate anti-staphylococcal activity of liposomal daptomycin, against four biofilm-producing S. aureus and S. epidermidis clinical strains, three of which are methicillin resistant. Neutral and negatively charged Daptomycin-loaded liposomes were prepared by three methods thin film hydration (TFH), DRV and microfluidic mixing (MM), and characterized for drug encapsulation (EE%), size distribution, zeta-potential, vesicle stability, drug release and drug integrity. Interestingly, whilst drug loading in THF and DRV nanosized (by extrusion) vesicles was around 30-35, very low loading (~4%) was possible in MM vesicles, requiring further explanatory investigations. Liposomal encapsulation protected daptomycin from degradation and preserve its bioactivity. Quantitative microtiter plate (crystal violet, CV), methylthiazoltetrazolium (MTT), and growth curve (GC) assays evaluated antimicrobial activity of neutral and negative charge daptomycin-liposomes towards planktonic bacteria and biofilms. Neutral liposomes exhibited dramatically enhanced inhibition of bacteria growth (compared to free drug) for all species studied, while negative charged liposomes were totally inactive. Biofilm prevention and treatment studies revealed high antibiofilm activity of liposomal daptomycin. Neutral liposomes were more active for prevention and negative charge ones for treating established biofilms. Planktonic bacteria as well as matured biofilms of low daptomycin susceptible MRSE and MRSA strains were almost completely eradicated by liposomal-daptomycin indicating the need for their further exploration as antimicrobial therapeutics.

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

Ependymoma is responsible for 8–10% of all pediatric brain tumors and constitutes the third most common brain tumor in children. No robust molecular markers are yet in routine clinical use. Surgical resection and adjuvant radiotherapy cure approximately 40-70% of pediatric patients with ependymoma. In our centre, we have been using prophylactic valproic acid treatment for brain tumor patients. Initial observations indicated that valproate could have a beneficial effect in the survival of patients. Recent observations by other authors have shown that patients with glioblastoma benefited from the treatment with valproic acid, a histone deacetylase inhibitor. We have used random survival forest, a novel ensemble survival modelling method to study a single- center, small number cohort of pediatric patients with ependymoma. This analysis has confirmed surgery resection extent and treatment with radiotherapy as independent predictors of overall survival. Treatment with valproic acid was also a predictor of higher survival in this cohort. These results highlight the potential usefullness of the random survival forest model in gathering information from retrospective data. More data is needed about the possible influence of histone deacetylase inhibition by valproic acid in the survival of patients with ependymoma.

To assess the community health workers’ (CHWs) knowledge, attitude, and practices (KAP) in type-2 diabetes (T2D) and hypertension (HTN) management. We thus also sought to assess the potential health system barriers for incorporating CHWs in T2D and HTN management. Mixed-method study comprised (1) a survey among 153 active CHWs to assess their KAP of T2D and HTN, and (2) semi-structured interviews with key informants to understand challenges of the health system and proposed solutions in incorporating CHWs in T2D and HTN management. The majority of CHWs correctly answered general knowledge questions on NCDs, risk factors, and prevention; however, only one-quarter correctly answered questions on smoking, family history, or tobacco use as risk factors. Most respondents appeared to have positive attitudes and have been practicing some activities related to T2D and HTN. Both financial and non-financial resource constraints were cited as challenges of the health system; therefore, re-structuring the role definition of CHWs and task of responsibilities, and assessment the need and workload have been proposed as ways forwards to effectively incorporate CHWs in T2D and HTN care. CHWs in Cambodia have shown their potential in T2D and HTN management; however, a well-designed strategy including technical training, clearly defined roles and responsibilities, and strong supporting structure are important to maximize their potential in the health system.

Aim: This study aimed to investigate whether baseline 18F-FDG PET-derived semiquantitative parameters could predict disease-free survival in patients with grade III breast cancer of different molecular subtypes undergoing neoadjuvant chemotherapy (NAC). Materials and Methods: Patients were retrospectively retrieved from the databases of two Italian hospitals (University of Padua and University Hospital of Ferrara). Inclusion criteria were: 1) histologically proven diagnosis of grade III breast cancer; 2) history of NAC; 3) execution of a baseline 18F-FDG PET/CT scan before the start of NAC; 4) adequate follow-up time to compute the 3Y-DFS. For each 18F-FDG-PET/CT scan, the following parameters were calculated in the primary tumor (SUVmax, SUVmean, MTV, TLG) and whole-body (WB_SUVmax, WB_MTV, and WB_TLG). Receiver operating characteristic (ROC) analysis was used for each parameter to assess the prediction capability for 3Y-DFS. DFS differences between groups were assessed using Kaplan-Meier curves and compared by log-rank test. Results: Ninety-five grade III breast cancer patients with different molecular types were retrieved (luminal A: 5; luminal B: 34; luminal B-HER2: 22; HER2-enriched: 7; triple-negative: 27). In the whole group of patients, WB_SUVmax was the best predictor of recurrence (AUC: 0.66; best cut-off: WB_SUVmax>9.43; SS: 96%; SP: 38.1%; p<0.008). Patients with luminal A and Her-2-enriched breast cancer types were excluded from the molecular subgroup analysis due to the small study samples (5 and 7, respectively). In luminal B patients (n=34), WB_MTV (AUC: 0.75; best cut-off: WB_MTV>195.33; SS: 55.56%, SP: 100%; p=0.002) and WB_TLG (AUC: 0.73; best cut-off: WB_TLG>1066.21; SS: 55.56%, SP: 100%; p=0.05) were the best predictors of 3Y-DFS. Patients had a higher probability of DFS in case of a WB_MTV≤195.33 (3429±210 vs. 446±144 days; p<0.001) or WB_TLG≤ 1066.33 (937.35±19 vs. 496±131 days; p<0.001). In luminal B-HER2 patients (n=22), WB_SUVmax was the only predictor of 3Y-DFS (AUC: 0.857; best cut-off: WB_SUVmax>13.12; SS: 100%; SP: 71.43%; p<0.001); patients with WB_SUVmax≤13.12 had a significantly longer DFS (3857 days) than patients with a WB_SUVmax >13.12 (1693±430 days; p<0.004). No parameter resulted significant in the prediction of 3Y-DFS in patients with grade III triple-negative cancer. Conclusion: Volume-based parameters, extracted from baseline 18F-FDG PET, seem to be promising tools in the prediction of recurrence within 3 years in patients with grade III luminal B and luminal B- HER2 breast cancer undergoing NAC. Larger study samples are needed to confirm these preliminary findings.

Candida glabrata is a yeast of increasing medical relevance, particularly in critically ill patients. It is the second most isolated Candida species associated with invasive candidiasis (IC) behind C. albicans. The attributed higher incidence is primarily due to an increase in the acquired immunodeficiency syndrome (AIDS) population, cancer, and diabetes patients. The elderly population and the frequent use of indwelling medical devices are also predisposing factors. The work aimed to review various virulence factors that facilitate the survival of pathogenic C. glabrata in IC. The available published research articles related to the pathogenicity of C. glabrata were retrieved and reviewed from four credible databases, mainly Google Scholar, ScienceDirect, PubMed, and Scopus. The articles highlighted many virulence factors associated with pathogenicity in C. glabrata, including adherence to a susceptible host surface, evading host defences, and producing hydrolytic enzymes (e.g., phospholipases, proteases, and haemolysins). The factors facilitate infection initiation. Other virulent factors include iron regulation and genetic mutations. Accordingly, biofilm production, tolerance to high-stress environments, and development of resistance to the antifungal drug, notably to fluconazole and other azole derivatives, were reported. The review provided evident pathogenic mechanisms and antifungal resistance associated with C. glabrata in ensuring its sustenance and survival.

This research was devoted to study the effect of the tacticity of PMMA on the surface physicochemical properties such as the London dispersive component of the surface energy of the polymer, the polar and dispersive free energies, the Lewis’s acid-base surface parameters, and the Lewis acid and base surface energies of atactic, isotactic and syndiotactic PMMAs as a function of the temperature. Inverse gas chromatography (IGC) at infinite dilution was used to determine the surface thermodynamic properties of PMMA at different tacticities. The experimental values of the net retention time and volume of model organic molecules adsorbed on the atactic, isotactic and syndiotactic PMMAs, were obtained by IGC technique at infinite dilution. The London dispersion interaction energy was used for the separation of the polar and dispersive energy of the different n-alkanes and polar solvents adsorbed on the different PMMA surfaces. The London dispersive surface energy γ_s^d (T) of PMMAs was determined by applying the Hamieh thermal model that took into account the effect of the temperature on the surface area of adsorbed molecules. The obtained results showed non-linear variations of γ_s^d (T) of atactic, isotactic, and syndiotactic PMMAs with three maxima characterizing the three transition temperatures of PMMAs, T_g, T_g and T_(liq-liq) with a shift of these temperatures with the isotactic and syndiotactic PMMAs. It was showed that the polar interaction free energy ∆G_a^p (T) also showed the presence of the three above transition temperatures of the polymers. The study showed an important non-linearity variation of the different acid-base parameters in the various polymer surfaces proving the highest effect of the temperature and the tacticity on these parameters. The determination of the enthalpic and entropic Lewis’s acid-base parameters showed an amphoteric character for the different PMMAs. The basicity of the atactic PMMA was about four times larger than its acidity outside the neighborhood of the transition temperatures of the polymer. Whereas, the isotactic PMMA was about 2 to 2.5 times more basic than acid, while the syndiotactic PMMA exhibited the highest basicity by showing a surface 5 to 8 times more basic than acid. However, the Lewis acid-base parameters strongly depended on the temperature and sudden variations of these surface parameters were observed around the transition temperatures largely depending on the PMMA tacticity. The determination of the polar acid and base surface energies of the three PMMAs led to the same previous transition temperatures with an important effect of the tacticity of PMMA on the values of these acid-base surface energies.

Naturally fermented dairy products are an important component of the human diet. They are a valuable source of nutrients as well as vitamins and minerals. Their importance as a source of probiotic bacterial strains should not be overlooked. A number of studies highlights the positive effects of species of the Lactobacillacea on the intestinal microbiota, the overall homeostasis of the body, as well as a complementary treatment for some diseases. However, data on the effects on intestinal epithelial cells of postmetabolites released by bacteria are incomplete. This is likely due to the fact that these effects are species and strain specific. In the present study, we investigated the effects of postmetabolites produced by a pre-selected candidate probiotic strain Limosilactobacillus fermentum on HT-29 intestinal epithelial cells. Our data showed a pronounced proliferative effect, evaluated by flow cytometry, quantification of cell population, and determination of mitotic index. This was accompanied by stabilization of the cell monolayer, measured by increase of TEER (trans epithelial electric resistance) and reorganization of actin filaments. The data obtained are a clear indication of the positive effects, that the products secreted by L. fermentum strain 53 have on the intestinal epithelial cells.

The aim of this study was characterization of some dairy drinks based on Milk Serum regarding major whey proteins (WP) and free amino acids (FAAs) using reversed phase high performance liquid chromatographic (RP-HPLC) methods. The studied WP, -lactalbumin (-La), bovine serum albumin (BSA), -lactoglobulin A (-Lg A) and -lactoglobulin B (-Lg B) were separated on Aeris XB-C18 column at 214 nm detection. The RP-HPLC method was validated by selectivity, linearity (R2 ≥0.99), sensitivity (LOQ, 1.35–10.08 µg mL−1), accuracy (recovery 96.79-103.07%) and precision (% RSD ≤ 4.13%). The total studied WP in studied dairy drinks varied between 1.42 and 3.047 g·L-1. The chromatographic profile of FAAs (aspartic acid, glutamic acid, serine, histidine, arginine, glycine, threonine, alanine, tyrosine, cysteine, tryptophan, methionine, valine, phenylalanine, isoleucine, leucine and lysine) was determined in lyophilized concentrate of Milk Serum by RP-HPLC using pre-column derivatization reaction with orthophthalaldehyde (OPA). The total studied FAAs in studied samples varied between 1.103 and 1.119 mg·g-1. Moreover, the Milk Serum showed bacteriostatic activity against two bacterial strains Escherichia coli and Staphylococcus aureus. The obtained results confirm that dairy drinks based on the Milk Serum constitutes a valuable sources of bioactive components with benefits for human healthy nutrition.

One of the central criteria for free will is “Could I have done otherwise?” But because of a temporal asymmetry in human choice, the question makes no sense. The question is backward-looking, while human choices are forward-looking. At the time when any choice is actually made, there is as of yet no action to do otherwise. Expectation is the only thing to contradict (do other than). So the ability to do something not expected by the ultimate expecter, Laplace’s demon, is a better criterion for free will. If human action is fundamentally unpredictable, then we have free will. Scientists have studied a form of fundamental unpredictability, known as undecidability. The features that make a system capable of undecidable dynamics have been identified: program-data duality; potential to access an infinite computational medium; and the ability to implement negation. Humans have all three of these features, so we very likely are fundamentally unpredictable, so we have free will.

Survival of Medulloblastoma (MB) depends on various factors, including the gene expression profiles of MB tumor tissues. In this study, we identified 967 MB survival related genes (SRBs) using the gene expression dataset of Cavalli et al. (2017) and the Cox proportional hazards regression model. Notably, the SRGs were over-represented on chromosomes 6 and 17, known for the abnormalities monosomy 6 and isochromosome 17 in MB. The most significant SRG was HMGA1 (high mobility group AT-hook 1), which is a known oncogene and a histone H1 competitor. High expression of HMGA1 was associated with worse survival, primarily in the Group 3γ subtype. The high expression of HMGA1 was unrelated to any known somatic copy number alteration. Most SRGs on chromosome 17p were associated with low expression in Group 4β, the MB subtype with 93% deletion of 17p and 98% copy gain of 17q. Pathway analysis showed that both chromosomes 6 and 17 included SRGs related to telomere maintenance and provide a rationale for testing telomerase inhibitors in Group 3 MBs. We conclude that HMGA1, along with other SRGs on chromosome 6 and 17 warrant further investigation as potential therapeutic targets in selected subgroups or subtypes of MB.

This paper focuses on a joint model to analyse longitudinal proportion and survival data. After transforming the longitudinal proportional data by a logit function, we adopt a partially linear mixed-effect model for it, in which nonlinear function of time is fitted via using B-splines technique and a centered Dirichlet Process Mixture Model (CDPMM) is specified for a general distribution of random effects. The survival data is assumed to a Cox proportional hazard model, the sharing random effects joint model is developed for the two types of data. Combining the Gibbs sampler and the Metropolis-Hastings algorithm, we propose a Bayesian Lasso (BLasso) method to simultaneously estimate unknown parameters and select important covariates. Simulation studies are conducted to investigate the finite sample performance of the proposed methods. An example from the MA.5 research experiment is used to illustrate the proposed methodologies.

Background: Overall survival is the most important outcome for treatment response in feline chronic kidney disease (CKD). Beraprost has been shown to reduce the kidney function decline in cats with International Renal Interest Society (IRIS) stage 2 and 3 CKD. However, association with prolonged survival has not yet been examined. Objective: To assess the relationship between beraprost and overall survival in cats with CKD in real clinical practice. Animals: Client-owned cats with IRIS stage 3 CKD (n = 134), evaluated between 2017 and 2020. Methods: Retrospective cohort study based on data from electronic medical records of one hospital. Results: Multivariable Cox regression models on all treatment effects showed that beraprost only was related to better survival (P = 0.028). The cohort was divided into “beraprost therapy” and “no beraprost therapy” groups, and survival analyses revealed that overall survival was significantly longer in the beraprost therapy group, using Kaplan-Meier curves (P = 0.004). However, baseline phosphate is known to be an important prognostic indicator and was not well balanced between the two groups. Therefore, a subcohort of 97 cats was selected (those having baseline phosphate < 6.0 mg/dL) that allowed for this parameter to be balanced between groups. The survival data in this subcohort was consistent with that of the overall study cohort. Conclusions: In feline patients with CKD, beraprost therapy was associated with better overall survival.

The study of rare diseases is important not only for the individuals affected but also for the advancement of medical knowledge and a deeper understanding of human biology and genetics. The wide repertoire of structural information now available from reliable and accurate prediction methods provides the opportunity to investigate the molecular origins of most of the rare diseases reviewed in the Orpha.net database. Thus, it has been possible to analyze the topology of the missense mutations found in the 2,535 proteins involved in Mendelian rare diseases (MRD), which form the database for our structural bioinformatics study. The amino acid substitutions responsible for MRD show different mutation site distributions at different three-dimensional protein depths. We then predicted the depth-dependent effects of mutations for the 20,248 pathogenic variants that are present in our database. The results of this structural bioinformatics investigation are relevant, as they provide additional clues to mitigate the damage caused by MRD.

Background Gliomas are the most prevalent primary malignant brain tumors worldwide. Recent studies highlight the potential of long non-coding RNAs (lncRNAs) in tumor progression, with LINC01354 being upregulated in various malignancies. This study investigates the role of LINC01354 in glioma prognosis to provide novel insights for early prognosis prediction.Methods This study involved four cohorts of low-grade glioma tissue samples collected from hospitals in Xinjiang, Beijing, and Guangzhou, China. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was used to measure LINC01354 expression levels. Clinical information and survival data were analyzed using Cox regression and ROC analysis to evaluate the association between LINC01354 expression and overall survival. Clinical comparisons were conducted to identify potential discrepancies in clinical parameters across different cohorts.Results Elevated LINC01354 levels were associated with poorer overall survival in the West China cohort (Xinjiang) but not in the North (Beijing) or South China (Guangzhou) cohorts. Clinical parameter comparisons revealed no significant differences among the cohorts that could explain the regional discrepancy. Further analysis within the West China cohort indicated that LINC01354's prognostic value was consistent across Han and non-Han ethnic groups and unaffected by dietary staples. However, LINC01354's prognostic significance was more pronounced in patients born in Xinjiang compared to those born elsewhere. A prognostic model incorporating LINC01354 expression and birth location demonstrated good predictive accuracy with ROC AUC values of 0.777 in the training cohort and 0.757 in the validation cohort.Conclusion LINC01354 is a potential prognostic biomarker for low-grade glioma in the West China population, particularly among patients born in Xinjiang.

The implementation of green roofs as sustainable urban drainage systems provides benefits for stormwater control and the environment and is always more encouraged. In this paper, the estimation of the probability of vegetation survival without irrigation has been proposed as a guide to choose the proper values for the design parameters; in particular the growing medium thickness has been related to the average return interval of the water content at the end of the dry period. Moreover the study represents an improvement of the analytical probabilistic approach since a chain of consecutive rainfall events has been considered, in order to take into account the possibility that the storage capacity is not completely available at the beginning of each event because of the pre-filling from more than one previous rainfall as typically happens for green roofs. Finally, developed equations have been validated by means of their application to two case studies, respectively in northern and southern Italy.

The detection of SARS-Cov-2 in the sewage and water resources has increased the awareness among the people about the possibility survival of SARS-Cov-2 in the environment and the potential to transmit into the human through food chain or water resources. Moreover, the surface contaminated by the virus need to be disinfected frequently by using an effective disinfectant, the current chapter discussed the efficiency of the most traditional treatment process of the sewage and wastewater, and their role in the elimination of the virus as well as the sterility assurance level concept. Moreover, the chemical disinfectant used currently and their temporary efficiency has been reviewed.

The COVID-19 pandemic has revealed many knowledge gaps with implications toward the speed and nature of our response to contain, assess and mitigate risk. The routine discharge of treated and untreated wastewater into rivers and coastal waters has placed SARS-CoV-2 viability in wastewater at the centre of an emerging hazard and potential risk to water industry workers and the public who come into contact with sewage-impacted water. Here we provide a review of the Severe Acute Respiratory Syndrome coronavirus primary literature that presents the evidence base pertaining to the key questions of whether the SARS-CoV-1 and SARS-CoV-2 is shed in stool and urine, is recoverable, and infectious in wastewater. We discuss the challenges posed by the current literature base and the extent to which the current evidence is fit for the purpose of informing robust human and environmental risk assessments.

Long-term, multi-decade research on planted tree survival in urban settings is sparse. One understudied urban environment is highway rights-of-way (ROW), lands adjacent to high-speed, unsignalized roadways. We conducted a re-inventory of tree planting cohort in northern Illinois, U.S. on a 48 km-long highway near Chicago which were 10-, 21-, and 30-years old to evaluate long-term patterns of survival and diversity. Using each randomly selected planting site along the highway as a unit of observation and analysis, we compared the number of trees documented in record drawing to the number of trees currently alive to determine percent survival. We evaluated 224 planting sites which originally contained 2,944 trees and collected data about the planting site location. For the oldest cohort, 26% of trees were still alive in 2018 (median survival by species = 16%, Q1 = 0%, Q3 = 48%), while 31% of the 21-year-old cohort (med. = 6%, Q1 = 0%, Q3 = 47%) and 86% of the 10-year-old cohort were still alive (med. = 85%, Q1 = 74%, Q3 = 96%). The survival of the 21- and 30-year-old cohort matches urban tree survival estimates by other researchers, while the 10-year-old survival is higher than expected. The only planting location characteristic that significantly affected survival was traffic islands (areas between the highway and entrance/exit ramps). Species with low drought tolerance were less likely to be alive for the 10-year-old cohort. Waterlogging tolerant species were more likely to be alive in the 10-year-old cohort. Since some species in the 21- and 30-year-old cohorts had very low survival, the tree species richness and diversity s in study areas declined between the initial record drawings and reinventory. This study demonstrates the challenges of maintaining long-term survival and diversity in the highway ROW and emphasizes the importance of species selection.

Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammatory mediators that lead to the development of remote organ damage after trauma remain obscure. HMGB1 and inflammatory mediators were analyzed in plasma from 54 combat casualties, collected on admission to a military hospital in Iraq, and at 8 and 24 hours after admission. Forty-five (83%) of these patients had traumatic brain injury (TBI). Nine healthy volunteers were enrolled as controls. HMGB1 plasma levels were significantly increased in the first 8 hours after admission, and were found to be associated with systemic inflammatory responses, injury severity score, and presence of TBI. These data provided the rationale for designing experiments in rats subjected to blast injury and hemorrhage, to explore the effect of HMGB1 inhibition by CX-01. Animals were cannulated, then recovered for 5-7 days before blast injury in a shock tube and volume-controlled hemorrhage. Blast injury and hemorrhage induced an early increase in HMGB1 plasma levels that coincided with severity of tissue damage and mortality. CX-01 inhibited systemic HMGB1 release, decreased local and systemic inflammatory responses, significantly reduced tissue and organ damage, and tended to increase survival. These data suggest that CX-01 has potential as an adjuvant treatment for traumatic hemorrhage.

Nobel Prize-winning physicist Sir Roger Penrose and Stuart Hameroff, a renowned American physician and scientist, have put forward an innovative theory that the human brain has a quantum mechanism located in the microtubular protein system within neurons, known as the "Orch OR" theory. According to the researchers, this mechanism is responsible for the brain's non-computational actions such as consciousness and free will. This theory has been criticized by several researchers from both the biological and physical sides. The purpose of this paper is to examine whether there is a possible basis for this theory in the philosophy of science.

This is a report on a dynamic autonomous magnetic interaction which does not depend on polarities resulting in short ranged repulsion involving one or more inertial bodies and a new class of bound state based on this interaction. Both effects are new to the literature, found so far. Experimental results are generalized and reported qualitatively. Working principles of these effects are provided within classical mechanics and found consistent with observations and simulations. The effects are based on the interaction of a rigid and finite inertial body (an object having mass and moment of inertia) endowed with a magnetic moment with a cyclic inhomogeneous magnetic field which does not require to have a local minimum. Such a body having some DoF involved in driven harmonic motion by this interaction can experience a net force in the direction of the weak field regardless of its position and orientation or can find stable equilibrium with the field itself autonomously. The former is called polarity free magnetic repulsion and the latter magnetic bound state. Experiments show that a bound state can be obtained between two free bodies having magnetic dipole moment. Various schemes of trapping bodies having magnetic moments by rotating fields are realized as well as rotating bodies trapped by a static dipole field in presence of gravity. Also, a special case of bound state called bipolar bound state between free dipole bodies is investigated.

Background: Gluten and casein-containing foods could aggravate the symptoms of children and adolescents with autism spectrum disorder (ASD), and subsequently impact their quality of life. However, there is a mixed opinion among researchers concerning the impact of alternative diet on reducing ASD symptoms. Objective: This scoping review aimed at examining the impact of the ‘’gluten-free, casein-free’’ (GFCF) diet on health outcomes and the quality of life among autistic children and adolescents. Methods: A scoping review of the literature was performed following the Joanna Briggs Institute (JBI) guidelines. Four databases including EbscoHost, Medline, CINAHL and ProQuest were used to obtain subject-specific studies relevant to the research question and published between July 2013 and March 2024. A comprehensive search using keywords such as “autism spectrum disorder”, “gluten-free diet”, and “casein-free diet” was conducted to obtain articles related to the research focus area. Only full-text, peer-reviewed, written in English articles were selected. Data extraction and data analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses- extension to Scoping Review (PRISMA-ScR) protocol. Results: From the initial 586 studies a total of 27 articles were included in the final analysis of the review. The thematic analysis included ‘GFCF diet and improvement of the core autistic symptoms’’, “the gut-brain link’’, ‘’dietary interventions and autism’’, ‘’possible side effects due to the GCFC diet’’, and ‘’ inconclusive studies and mixed opinions’’. Majority of the studies showed positive effect of the GFCF diet on a variety of autistic symptoms including positive changes in cognitive skills, behaviour, and gastrointestinal symptoms while some showed conflicting evidence. Conclusion: The currently available evidence on the impact of ‘GFCF’’ diet on the quality of life of autistic children and adolescents may warrant potentially effective interventions for alleviating symptoms of autism spectrum disorders. However, this scoping review highlighted the need for more research to provide more reliable evidence on the health outcomes and quality of life of ASD sufferers to guide practice.

Persons who inject drugs (PWIDs) represent an important reservoir of hepatitis C virus (HCV) infection, hence therapeutic communities (TCs) are promising points of care for the identification and treatment of HCV-infected PWIDs. We evaluated the effectiveness and efficacy of an HCV micro-elimination program targeting PWIDs in the context of a drug-free TC applying Cascade of Care (CoC) evaluation by calculating frequencies of infection diagnosis, confirmation, treatment and achievement of a sustained virological response (SVR). We also evaluated the risk of reinfection of PWIDs achieving HCV eradication, by collecting follow-up virologic information of previously recovered individuals and eventual relapse in drug use, assuming the latter as a potential source of reinfection. We considered all PWIDs (aged 18+ years) residing in the San Patrignano TC at the beginning of the observation period (Jan/2018–Mar/2022) or admitted thereafter, assessing for HCV and HIV serology and viral load by standard laboratory procedures. Ongoing infections were treated with direct acting antivirals (DAA), according to the current national guidelines. Out of the 792 individuals tested on admission, 503 (63.5%) were found to be seropositive for antibodies against HCV. 481 of these 503 individuals (95.6%) underwent HCV-RNA testing. Out of the 331 participants positive for HCV-RNA, 225 were ultimately prescribed a DAA treatment with a Sustained Viral Response (SVR), which was achieved by 222 PWIDs (98.7%). 186 of 222 PWIDs (83.8%) with SVR remained HCV-free on follow-up (with a median follow-up of 2.73 years after SVR ascertainment). The CoC model in our TC proved efficient in implementing HCV micro-elimination, as well as in preventing reinfection and promoting retention in care of individuals, which aligns with the therapeutic goals of addiction treatment.

The purpose of this study is to provide an accurate formula for calculating entropy for short DNA sequences and to demonstrate how to use it to examine leukemia patient surviving. We used IDIBAPS leukemia patient’s data base with 117 anonymized records. The generalized form of the Robust Entropy Estimator (EnRE) for short DNA sequences was proposed and key EnRE futures was showed. The Survival Analysis has been done using statistical package IBM SPSS. Entropy EnRE were calculated for leukemia patients for two samples: A. 2 groups divided by median EnRE and B. 2 groups of patients were formed according to their belonging to 1st and 4th quartiles of EnRE. The result of survival analysis are statistically significant: A. p &lt; 0.05; B. p &lt; 0.005. The death hazard for a patient with EnRE below median is 1.556 times that of a patient with EnRE over median and that the death hazard for a patient of 1st quartile (lowest EnRE) is 2.143 times that of a patient of 4th quartile (highest EnRE). The transition from median to quartile patients’ groups with more EnRE differentiation confirmed the unique significance of the entropy of DNA sequences for leukemia patients surviving.

Glioblastoma (GBM) is a very aggressive malignant brain tumor with the vast majority of patients surviving less than 12 months (Short-term survivors [STS]). Only around 2% of patients survive more than 36 months (Long-term survivors [LTS]). Studying these extreme survival groups might help in better understanding GBM biology. This work aims at exploring application of machine learning methods in predicting survival groups(STS, LTS). We used age and gene expression profiles belonging to 249 samples from publicly available datasets. 10 Machine learning methods have been implemented and compared for their performances. Hyperparameter tuned random forest model performed best with accuracy of 80% (AUC of 74% and F1_score of 85%). The performance of this model is validated on external test data of 16 samples. The model predicted the true survival group for 15 samples achieving an accuracy of 93.75%. This classification model is deployed as a web tool GlioSurvML. The top 1500 features which retained classification efficiency (Accuracy of 80%, AUC of 74%) were studied for enriched pathways and disease-causal biomarker associations using the HumanPSD^TM database. We identified 199 genes as possible biomarkers of GBM and/or similar diseases (like Glioma, astrocytoma, and others). 57 of these genes are shown to be differentially expressed across survival groups and/or have impact on survival. This work demonstrates the application of machine learning methods in predicting survival groups of GBM.

ZIKV is the latest addition to an ever-growing list of arboviruses that are causing outbreaks with serious consequences. 14 mild cases were recorded between 1960 and 1980 until the first major outbreak was recorded in 2007 on Yap island followed by more severe outbreaks in French Polynesia (2013) and Brazil (2015) leading to a 20-fold increase in GBS and Microcephaly cases respectively. Various transmission methods have been recorded ranging from Aedes mosquito vector transmission to sexual and vertical transmission. No current vaccines or treatments are available but recent studies have taken interest in the NS5 protein which has both the RdRp & MTase domains making it important for viral replication alongside other important functions such as inhibiting the innate immune system thus ensuring virus survival and replication. Structural studies can help design inhibitors while biochemical studies can help understand the various mechanisms utilized by NS5 thus counteracting them can inhibit or abolish the viral infection. Drug repurposing has proven to be an effective tool since hundreds of thousands of compounds can be screened in-silico thus saving time and resources while also having information available on such compounds especially if they are already used to treat other ailments.

Background: Malnutrition commonly affects patients with oral squamous cell carcinoma (OSCC), which contributes to worsening prognosis. Moreover, specific strategies for diagnosing and managing malnutrition in OSCC are lacking. Methods: This retrospective study included 52 consecutive patients with OSCC who underwent surgery at the University Hospital of Palermo (I) from Jan 2020 to May 2023. In-hospital nutritional support was provided by a dedicated team. The patients were compared with a historical control group of 11 patients. The nutritional treatment consisted of standard oral (ON) or artificial nutrition (AN). Traditional measurements, including bioimpedance-derived body composition and volumetric reconstruction of the posterior paraspinal muscles at the C3 level based on magnetic resonance imaging (MRI-C3), were obtained in 16 patients to investigate sarcopenia. Results: The patients were categorized according to TNM stage: groups A (TNM stages I-III) and B (IVa-IVc). The prevalence of group A patients was 59.6% in the case group and 90.9% in the control group (P

Genetic, developmental, biochemical, and environmental variables interact intricately to produce sex differences. The significance of sex differences in cancer susceptibility is being clarified by numerous studies. Epidemiological research and cancer registries have revealed over the past few years that there are definite sex variations in cancer incidence, progression, and survival. However, oxidative stress and mitochondrial dysfunction also have a significant impact on the response to treatment of neoplastic diseases. Young women may be more protected from cancer than men because most of the proteins implicated in the regulation of redox state and mitochondrial function are under the control of sexual hormones. In this review, we describe how sexual hormones control the activity of antioxidant enzymes and mitochondria, as well as how they affect several neoplastic diseases. The molecular pathways that underlie the gender-related discrepancies in cancer that have been identified may be better understood, which may lead to more effective precision medicine and vital information on treatment options for both males and females with neoplastic illnesses.

The real-world outcomes of patients with metastatic prostate cancer (mPCa) are largely unexplored. We investigated the improvements in overall survival (OS) and cancer-specific survival (CSS) in patients with de novo mPCa in latest years. The USA SEER Research Data (2000-2017) were analyzed using the SEER*Stat software. The Kaplan-Meier method and Cox regression were used. Patients with de novo mPCa were allocated to 3 cohorts based on year of diagnosis: A (2000-2003), B (2004-2010), C (2011-2014). Maximum follow-up was fixed to 5 years. Overall, 26434 patients were included. Age, race and metastatic stage significantly affected OS and CSS. After adjustment for age and race, patients in cohort C showed 9% reduced risk of death (HR:0.91 [95% CI, 0.87-0.95], p&lt;0.001) and 8% reduced risk of cancer-specific death (HR:0.91 [95% CI, 0.87-0.95], p&lt;0.001) compared to those in cohort A. After adjustment for age, race and metastatic stage, patients in cohort C showed an improvement in OS and CSS compared to cohort B (HR:0.94 [95% CI, 0.91-0.97], p=0.001 and HR:0.89 [95% CI, 0.85-0.92], p&lt;0.001). Patients with M1c disease had a more pronounced improvement in OS and CSS compared with the other stages. No differences were found between cohort B and C. In conclusion, the prognosis of de novo mPCa remains poor with a median OS of 30 months and a median CSS of 35 months. Limited OS and CSS improvements were observed in latest years.

It has been suggested that particle size plays an important role in determining the genotoxicity of gold nanoparticles (GNPs). The purpose of this study was to compare the potential radio-sensitization effects of two different sized GNPs (3.9 and 37.4 nm) fabricated and examined in vitro in Lewis Lung carcinoma (LLC) as a model of non-small cell lung cancer through use of comet and clonogenic assays. After the treatment of 2Gy X-ray irradiation, both particle sizes demonstrated increased DNA damage when compared to treatment with particles only and radiation alone. This radio-sensitization was further translated into a reduction in cell survival demonstrated by clonogenicity. This work indicates that GNPs of both sizes induce DNA damage in LLC cells at the tested concentrations, whereas the 37.4 nm particle size treatment group demonstrated greater significance in vitro. The presented data aids in the evaluation of the radiobiological response of Lewis Lung carcinoma cells treated with gold nanoparticles.

The canonical decomposition of a bipartite graph is a new decompositionmethod that involves three operators, parallel, series and K+S. The class of weak bisblit graphs is totally decomposable with respect of these operators, and the class of bicographs is totally decomposable with respect of parallel and series operators. We prove in this paper that the class of bipartite (P_6,C_6)-free graphs is exactly the class of bipartite graphs that are totally decomposable with respect of parallel and K+S operators. We simplify the recognition algorithm of weak-bisplit graphs to adepte with bipartite (P_6,C_6)-free graphs. As a result of this adapted algorithm, we prsent efficient solutions in this class of graphs for two optimization graph problems, the first is the maximm balanced bi-clique problem and the the second is the maximum independent set problem.

Spatial crowdsourcing emerges as a new computing paradigm that enables mobile users to accomplish spatio- temporal tasks in order to solve human-intrinsic problems. Existing crowdsourcing systems critically use centralized servers for interacting with workers and making task assignment decisions. These systems are hence susceptible to issues such as the single point of failure and the lack of operational transparency. Prior work, therefore, turns to blockchain-based decentralized crowdsourcing systems, yet still suffers from problems of lacking efficient task assignment scheme, requiring a deposit to an untrusted system, low block generation speed, and high transaction fees. To address these issues, we design a blockchain-based decentralized framework for spatial crowdsourcing, which we call SC-EOS. Our system does not rely on any trusted servers, while providing efficient and user-customizable task assignment, low monetary cost, and fast block generation. More importantly, it frees users from making a deposit into an untrusted system. Our framework can also be extended and applied to generic crowdsourcing systems. We implemented the proposed system on the EOS blockchain. Trace-driven evaluations involving real users show that our system attains the comparable task assignment performance against a clairvoyant scheme. It also achieves 10× cost savings than an Ethereum-based implementation.

The free energy principle states that self-organization occurs through minimization of free energy, which is a measure of potential thermodynamic work. By minimizing free energy, the organism happens to also minimize surprise over its boundary, promoting chances of survival. We discuss the ethical implications of the cognitive goal in detail from an empirical point of view, highlighting the principle of least action as a physical basis of Occam's razor, the universality of the free energy principle, and its explanation of natural selection. We explain that the free energy principle extends to groups of organisms and helps us understand group-scale adaptations and selection in biology. The free energy principle applies to all scales of organization in the organism from single cells to the entire nervous system. When this principle is taken to its logical extremes of modeling groups, populations and ecosystems, we uncover a new, evolutionarily sensible path at explaining puzzling aspects of human motivation and judgement, including ethical decisions. To minimize free energy, populations have to act to maximize gathering of information, while building effective models at mitigating changes to its dynamic structure. The free energy principle thus provides a naturalistic explanation of some of our deepest ethical intuitions, and valuable principles of social behavior. We interpret the cognitive goal that corresponds to the principle as seeking a dynamic, fruitful, yet peaceful activity that sustains the organism. This state of mind is interestingly similar to the Buddhist intuition of mental equanimity; the organism's final goal is to be at peace and harmony with the environment. Another immediately relevant aspect is that assemblies must form to promote symbiotic, synergistic, positive feedback loops, which coincides with the findings of ecologists. Therefore, ethics naturally emerges in self-organizing systems. Assemblies of organisms must ultimately unite in macro-minds to achieve the greatest reduction in free energy, as well as building technological extensions of themselves to improve their capacity to do such, therefore the principle also predicts a post-singularity world-mind composed mostly of artificial intelligence.

A series of novel sulfonylurea benzothiazoline were designed by splicing active groups and bioisosterism. A solvent-free synthetic route was developed for the sulfonylurea benzothiazoline derivatives via the cyclization and carbamylation. All the compounds were characterized by IR, 1H-NMR, 13C-NMR, HRMS. The biological activity tests indicated the compounds could protect maize against the injury caused by chlorsulfuron to some extent. The molecular docking result showed that the new compound competed with chlorosulfuron to bind with the herbicide target enzyme active site to attain detoxification.

Product innovation is a crucial factor in enterprise survival. Even though there are sources from strategic theory that guides the clear comprehension towards appreciating the nexus between these two variables (product innovation and enterprise survival), there are still many lacunas that should be addressed and filled. Consequently, the need for additional empirical corroboration or support is pertinent. This study aimed at verifying the nexus between product innovation and enterprise survival, and how they are affected by the existence of antecedent variables such as competitive intensity and competitive advantage. In the methodology, this study adopts the conduct of explanatory and cross-sectional investigations through the use of structural equation modelling (SEM) to a sample of selected food and beverages enterprises in Lagos, Nigeria. Regarding the food and beverage enterprises in Lagos, Nigeria, this study discovered that competitive intensity has huge positive implication on product innovation at (0.39; t = 5.69, p < 0.05). This gives numerical evidence that, in the face of more market competition, enterprises will be pressured to adopt the model of costs reduction on products which will enhance the reduction of product prices, and will have significant impact on profit. However, the findings reveal that there is no significance between competitive advantage and product innovation at (0.002; t = 0.203, p > 0.05), and there is no significance between product innovation and enterprise survival at (-0.035; t = -1.583, p > .05). As a result, the food and beverage enterprises should concentrate more on product innovation so that they will be able to stand the intensity of competition. The results emanated from the study is germane as it make significant contribution to literature and the body of knowledge and on strategic management by enlightening that competitive intensity is a necessary inducement for product innovation.

A theoretical account of development in mesocortical anatomy is derived from the free energy principle, operating in a neural field with both Hebbian and anti-Hebbian neural plasticity. An elementary structural unit is proposed, in which synaptic connections at mesoscale are arranged in paired patterns with mirror symmetry. Exchanges of synaptic flux in each pattern form coupled spatial eigenmodes, and the line of mirror reflection between the paired patterns operates as a Markov blanket, so that prediction errors in exchanges between the pairs are minimized. The theoretical analysis is then compared to the outcomes from a biological model of cortical neurodevelopment, in which neuron precursors are selected by apoptosis for cell body and synaptic connections maximizing synchrony and also minimizing axonal length. It is shown that this model results in patterns of connection with the anticipated mirror symmetries, at micro-, meso- and inter-arial scales, among lateral connections, and in cortical depth, explaining the spatial organization and functional significance of neuron response preferences, and compatible with features of both columnar and noncolumnar cortex. Multi-way interactions of mirrored representations provide a preliminary anatomically realistic model of cortical information processing.

Systemic AL amyloidosis is a challenging disease for which many patients are considered frail in daily clinical practice. However, no study has so far addressed frailty and its impact on the outcome of these patients. We built a simple score to predict mortality based on three frailty-associated variables: age, ECOG performance status (&lt;2 vs. 2) and NT-proBNP (&lt;8500 vs. 8500 ng/L). Four-hundred and sixteen consecutive newly diagnosed patients diagnosed at ten sites from the Spanish Myeloma Group were eligible for the study. The score was developed in a derivation cohort from a referral center, and it was externally validated in a multicenter cohort. On multivariate analysis the three variables were independent predictors of survival. The score was able to discriminate four groups of patients in terms of overall survival and early mortality in both cohorts. Comorbidity was also analyzed with the Charlson comorbidity index, but it did not reach statistical significance in the model. A nomogram was created to easily estimate the mortality risk of each patient at each time point. This score is a simple, robust, and efficient approach to dynamically assess frailty-dependent mortality both at diagnosis and throughout the follow-up. The optimal treatment for frail AL amyloidosis patients remains to be determined but we suggest that the estimation of frailty-associated risk could complement current staging systems, adding value in clinical decision-making in this complex scenario.

Approximately half of head and neck squamous cell carcinoma (HNSCC) cases recur, and most of them recur within the first two years after treatment. Although it has been suggested that the interval to recurrence after radical treatment and prognosis in patients with HNSCC are associated, investigations are insufficient. In this study, patients diagnosed with HNSCC at Kyushu University Hospital were retrospectively analyzed (n = 500). A total of 234 patients experienced recurrence, with 110 and 124 patients experiencing early recurrence (ER) (recurrence within 2–6 months) and late recurrence (LR) (recurrence after 7 months), respectively. There were two independent risk factors for poor prognosis in the multivariate analyses: ER (hazard ratio [HR] = 3.200, 95% confidence interval [CI] = 1.570–6.521, p = 0.001) and no radiotherapy (HR = 0.374, 95% CI = 0.191–0.733, p = 0.004). In patients with recurrent HNSCC, a short interval to recurrence is a risk factor for poor prognosis and survival. This study demonstrated the prognostic value of ER in patients. During the selection of treatment for patients with recurrence, the recurrent area, initial treatment content, and strategy of changing salvage therapy depending on the recurrence status should be considered.

Endothelial function is regulated by a myriad of complex pathways. In our previous study, the expression of miR-378a-3p was shown to inhibit endothelial autophagy and impair endothelial function. However, the mechanism underlying the effect of miR-378a-3p in endothelial cells remains to be elucidated. By employing an in silico approach, Protein Disulfide Isomerase 4 (PDIA-4) was identified as a target of miR-378-3p; however, its’ role in endothelial cells is not known. We here report that endothelial cell-specific loss of PDIA-4 leads to impaired autophagic flux accompanied by loss of endothelial function and apoptosis. Endothelial cell-specific loss of PDIA-4 also induced marked changes in endothelial cells’ architecture, accompanied with the loss of endothelial markers and gain of mesenchymal markers consistent with endothelial-to-mesenchymal transition (EndMT). Loss of PDIA-4 activates TGF-signaling, and inhibition of TGF-signaling inhibits EndMT in PDIA-4 silenced endothelial cells in vitro. Our findings help elucidate the role of PDIA-4 in endothelial autophagy and endothelial function and provide a potential target to modulate and/or limit autophagy and EndMT in (patho-)physiological conditions.

Background and aims: Despite recent advances in advanced prostate cancer treatments, there are no clinically useful biomarkers or treatments for men with such cancers. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to characterize BRD9, currently understudied in prostate cancer, and investigate its co-expression with other genes to assess its potential as a biomarker and therapeutic target in human prostate cancer. Materials and methods: Omics data from a total of 2053 prostate cancer patients across 11 independent datasets were accessed via Cancertool and cBioPortal. mRNA expression and co-expression, mutations, amplifications, and deletions were assessed with respect to key clinical parameters including survival, Gleason grade, stage, progression and treatment. Network and pathway analysis was carried out using Genemania, and heatmaps were constructed using Morpheus. Results: BRD9 is overexpressed in prostate cancer patients, especially those with metastatic disease. BRD9 expression did not differ in patients treated with second generation antiandrogens versus those who were not. BRD9 is co-expressed with many genes in the SWI/SNF and BET complexes, as well as those in common signaling pathways in prostate cancer. Summary and conclusions: BRD9 has potential as a diagnostic and prognostic biomarker in prostate cancer. BRD9 also shows promise as a therapeutic target, particularly in advanced prostate cancer, and as a co-target alongside other genes in the SWI/SNF and BET complexes, and those in common prostate cancer signalling pathways. These promising results highlight the need for wider experimental inhibition and co-targeted inhibition of BRD9 in vitro and in vivo, to build on the limited inhibition data available.

Student retention is one indicator of accountability in the implementation of educational programs. Achievement of student retention rates indicates the performance of the quality objectives of an institution or college. To get an accurate picture of the factors related to retention, we need to do modeling. The retention variable is the time response variable measured in semester units. One of the statistical analyzes that can be used to analyze response data in time is survival analysis. The selection of an accurate analytical method in modeling will produce valid conclusions and impact making policies that are right and on target. This paper presents alternative modeling of student retention in distance education using survival analysis. The method used is a literature review. This paper also briefly describes distance education, open and distance education, distance education students' characteristics, distance education student retention, and survival models for modeling student retention in distance education.

Phagocytosis (and endocytosis) is an unusual cellular process which results in the formation of a novel subcellular organelle, the phagosome. This phagosome contains not only the internalised target of phagocytosis, but also the external medium, creating a new border between extracellular and intracellular environments. The boundary at the plasma membrane is, of course, tightly controlled and exploited in ionic cell signalling events. Although there has been much work on the control of phagocytosis by ions, notable Ca2+ ions influxing across the plasma membrane, increasing our understanding of the mechanism enormously, very little work has been done exploring the phagosome/cytosol boundary. In this paper, we have explored the changes in the intra-phagosomal Ca2+ ion content which occur during phagocytosis and phagosome formation in human neutrophils. Measuring Ca2+ ion concentration in the phagosome is potentially prone to artefacts as the intra-phagosomal environment experiences changes in pH and oxidation. However, by excluding such artefacts, we conclude that there are open Ca2+ channels on the phagosome, which allow Ca2+ ions to ‘drain’ into the surrounding cytosol. This conclusion was confirmed by monitoring the translocation of intracellularly expressed YFP-tagged C2 domain of PKC-γ. This approach marked regions of membrane at which Ca2+ influx occurred, the earliest being the phagocytic cup, and then the whole cell. This paper therefore presents data which has novel implications for understanding phagocytic Ca2+ signalling events, such as peri-phagosomal Ca2+ hotspots, and other phenomena.

Formation of the excited doublet (D) and quartet (Q) states of free radicals under their photoexcitation is discussed. Relative positions of D and Q states are compared to the positions of photoexcited states of organic molecules (Jablonsky diagram). A number of representative cases of the detected by emission or absorption excited is presented. A special case of the population lowest Q-state in some radicals of is discoursed. Spin-statistical factor in the reactions of Q and D is debated.

One of the most popular techniques for determining electrical properties of material is the free-space measurement technique. With the potential for new applications requiring efficient, accurate and broadband material measurement systems using higher millimeter-wave and terahertz frequencies, the free-space measurement method has received renewed interest. This is mainly due to its simplicity, favorable properties as a non-destructive method, and it allows transmission and reflection measurements without any physical contact with the sample. This paper reviews and discusses state- of-the-art free space material measurement systems, starting with the different measurement techniques available for material characterization, their important concepts, post-processing in determining their properties, and progress towards expanding their use at higher frequencies. Also, this paper reviews dielectric material characterization using the free space method focusing on their application extension towards the higher frequencies. Besides, the algorithms for conversion methods and usage of lens in free space material measurement system was discussed in this paper. Finally, a future perspective on the outlook of this free space method is presented prior to the conclusion.

Cell free systems are a widely used research tool in systems and synthetic biology and a promising platform for manufacturing of proteins and chemicals. In the past, cell free biology was primarily used to better understand fundamental biochemical processes. Notably, E. coli cell free extracts were used in the 1960s to decipher the sequencing of the genetic code. Since then, the transcription and translation capabilities of cell free systems have been repeatedly optimized to improve energy efficiency and protein yield. Today, cell free systems, in combination with the rise of synthetic biology, have taken on a new role as a promising technology for just in time manufacturing of therapeutically important biologics and high-value small molecules. They have also been implemented in an industrial scale for the production of antibodies and cytokines. In this review, we discuss the evolution of cell free systems, advancements in cell free protein synthesis, and cell free metabolic engineering, and conclude with discussing the importance and feasibility of mathematical modeling in cell free systems.

We explore the class of positive integers n that admit idempotent factorizations n=pq such that lambda(n) divides (p-1)(q-1), where lambda(n) is the Carmichael lambda function. Idempotent factorizations with p and q prime have received the most attention due to their cryptographic advantages, but there are an infinite number of n with idempotent factorizations containing composite p and/or q. Idempotent factorizations are exactly those p and q that generate correctly functioning keys in the RSA 2-prime protocol with n as the modulus. While the resulting p and q have no cryptographic utility and therefore should never be employed in that capacity, idempotent factorizations warrant study in their own right as they live at the intersection of multiple hard problems in computer science and number theory. We present some analytical results here. We also demonstrate the existence of maximally idempotent integers, those n for which all bipartite factorizations are idempotent. We show how to construct them, and present preliminary results on their distribution.

Using insights from cybernetics and an information-based understanding of biological systems, a precise, scientifically inspired, definition of free-will is offered and the essential requirements for an agent to possess it in principle are set out. These are: a) there must be a self to self-determine; b) there must be a non-zero probability of more than one option being enacted; c) there must be an internal means of choosing among options (which is not merely random, since randomness is not a choice). For (a) to be fulfilled, the agent of self-determination must be organisationally closed (a `Kantian whole'). For (c) to be fulfilled: d) options must be generated from an internal model of the self which can calculate future states contingent on possible responses; e) choosing among these options requires their evaluation using an internally generated goal defined on an objective function representing the overall `master function' of the agent and f) for `deep free-will', at least two nested levels of choice and goal (d-e) must be enacted by the agent. The agent must also be able to enact its choice in physical reality. The only systems known to meet all these criteria are living organisms, not just humans, but a wide range of organisms. The main impediment to free-will in present-day artificial robots, is their lack of being a Kantian whole. Consciousness does not seem to be a requirement and the minimum complexity for a free-will system may be quite low and include relatively simple life-forms that are at least able to learn.

Early detection of neurological conditions is critical for timely diagnosis and treatment. Identifying cellular-level changes is essential for implementing therapeutic interventions prior to symptomatic disease onset. However, monitoring brain tissue directly through biopsies is invasive and high-risk. Bodily fluids such as blood or cerebrospinal fluid contain information in many forms, including proteins and nucleic acids. Particularly, cell-free DNA (cfDNA) has potential as a versatile neurological biomarker. Yet, our knowledge of cfDNA released by brain tissue and how cfDNA changes in response to deleterious events within the brain is incomplete. Mapping changes in cfDNA to specific cellular events is difficult in vivo, where many tissues contribute to circulating cfDNA. Organoids are tractable systems for examining specific changes consistently in a human background. However, few studies have investigated cfDNA released from organoids. Here, we examined cfDNA isolated from cerebral organoids. We found that cerebral organoids release quantities of cfDNA sufficient for downstream analysis with droplet-digital PCR and whole-genome sequencing. Further, gene ontology analysis of genes aligning with sequenced cfDNA fragments revealed association with terms related to neurodevelopment and autism spectrum disorder. We conclude that cerebral organoids hold promise as tools for the discovery of cfDNA biomarkers related to neurodevelopmental and neurological disorders.

Complex-structured polymeric microparticles hold significant promise as advance in next-generation medicine mostly due to demand from developing targeted drug delivery. However, the conventional methods for producing these microparticles of defined size, shape and sophisticated composition often face challenges in scalability, reliance on specialized components such as micro-patterned templates, or have limited control over particle size distribution and cargo release kinetics. In this study, we introduce a novel and reliably scalable approach for manufacturing microparticles of defined structures and sizes with variable parameters. The concept behind this method involves the deposition of a specific number of polymer layers on a substrate with low surface energy. Each layer can serve as either the carrier for cargo or a programmable shell-former with predefined permeability. Subsequently, this layered structure is precisely cut into desired-sized blanks using a laser. The manufacturing process is completed by applying of heat to the substrate what results on sealing the edges of the blanks. The combination of the high surface tension of the molten polymer and the low surface energy of the substrate enables the formation of discrete particles, each possessing semi-spherical or other designed geometries determined by their internal composition. Such anisotropic microparticles are envisaged versatile applications.

Surrogate model based optimization method is widely-used to accelerate the design and optimization process~\cite{marler2004survey}. The input of regression model used in the surrogate model are numbers, which requires users to parametrize the geometries. In this paper, a new parameterization-free surrogate model is introduced and its corresponding uncertainty quantification and sensitivity analysis method are discussed. The input of new surrogate model methods is surface mesh of simulation domain. \Gls{gnns} is used to extract geometric information, and \Gls{cnns} is used to predict contours. This framework bypasses parameterization,as a consequence, uncertainties introduced by manual parameterization is reduced. However, such changes compared with conventional surrogate model methods impose great challenge on uncertainties quantification and sensitivity analysis. Uncertainties quantification in this paper means the error bar of prediction results, which is calculated by Gaussian Process Regression method in current surrogate method. In this paper, a new quantification method achieved by Kullback-Leibler divergence (KLD) is introduced. And the sensitivity analysis is conducted by Automatic Differentiation, which gives a Jacobian matrix of inputs. The method and analysis mentioned above are demonstrated by a low-pressure steam turbine rotator and its exhaust system.

The mechanisms of natural oscillations and resonance are described, considering the peculiarities of the transformation of elastic and kinetic energy in the implementation of the law of conservation of energy in local and integral volumes of the body, using the concept of mechanics based on the concepts of space, time and energy. When describing the motion in the Lagrange form, the elastic deformation energy of the particles is determined by the quadratic invariant of the tensor, whose components are the partial derivatives of Euler variables with respect to Lagrange variables. The increment of the invariant due to elastic deformation is represented as the sum of two scalars, one of which depends on the average value of the relative lengths of the edges of the particles in the form of an infinitesimal parallelepiped, the second is equal to the standard deviation of these lengths from the average value. It is shown that each of the scalars can be represented in the form of two dimensionless kinematic parameters of elastic energy, which participate in different ways in the implementation of the law of conservation of energy. One part of the elastic energy passes into kinetic energy and participates in the implementation of the law of conservation of energy for the body as a whole, considering external forces. The second part is not converted into kinetic energy but changes the deformed state of the particles in accordance with the equations of motion while maintaining the same level of the part of the elastic energy of the particles used for this. The kinematic parameters differ from the volume density of the corresponding types of energy by a factor equal to the elastic modulus, which is directly proportional to the density and heat capacity of the material and inversely proportional to the volume compression coefficient. Transverse, torsional, and longitudinal vibrations are considered free and under resonance conditions. The mechanisms of transformation of forced vibrations into their own after the termination of external influences and resonance at the superposition of free and forced vibrations with the same or similar frequency are considered. The formation of a new free wave at each cycle with an increase in the amplitude, which occurs mainly due to internal energy sources, and not external forces, is justified.

Background: Donor shortage limits the utilization of heart transplantation making it available for only a fraction of the patients on the transplant wait list. Continuous flow left ventricular assist devices have therefore risen in importance as a standard of care for end-stage heart failure. Short, mid and long-term survival rates as well as quality of life are now being studied with newer and more sophisticated machines. This study attempts to assess the impact of several commonly associated risk factors on long-term survival of LVAD recipients. Methods The TriNetX dataset comprises de-identified patient information across healthcare organizations. The study assesses the impact of demographics, infections, comorbidities, types of cardiomyopathies, arrhythmias, and end-organ dysfunction on long-term LVAD survival. The Log-rank test was used to assess post-implant survival effects, while Cox regression was used in univariate analysis to obtain Hazard Ratio (HR). Patients with unknown lab results were removed before the univariate analysis and K-M survival curves were generated. Samples with missing values or data errors (e.g., implantation is after recorded death) were excluded. All analyses were conducted using the Python programming language and the lifelines library. This study is IRB-exempt Results This study identified common risk factors that significantly impact survival such as CMV, hepatitis A exposure, atrial fibrillation, paroxysmal ventricular tachycardia, ischemic cardiomyopathy, renal dysfunction, diabetes, COPD, mitral valve disease, and hypertension. Conclusions This is the first report of a detailed long-term survival assessment of several risk factors that impact the LVAD population.

Tumor heterogeneity is a major obstacle in cancer therapy. We offer a novel perspective on tumor heterogeneity, informed by expanding upon the current view on tumor evolution. It is commonly known that in cancer, it is the advantageous genes and mutations that drive tumor capacities and the progression. We recognize an earlier, often overlooked, but necessary thus crucial step preceding the activation of advantageous genes functionality, namely, cellular response. We suggest that cancer is driven by an adaptive action taken by any organism when confronted with adversity - a cellular response to generate specific cancer capacities demanded to overcome survival threat - the responses that prompt the utilization of the functionality of advantageous genetic mutations and genes to attain these capacities and drive the disease. The ongoing development of cancer capabilities, as cells endeavor to obtain a competitive advantage, results in increased molecular chaos, observed as tumor heterogeneity. When the evolutionary drive for survival is impeded by therapeutic inhibition of critical genes, cell death occurs, a phenomenon thus termed oncogene addiction. We summarize the implications of this new framework for understanding tumor evolution and anti-cancer drug discovery, as well as understanding of basic cancer biology.

The relationship between human health and gut microbiota is becoming more apparent. It is now widely believed that healthy gut flora plays a vital role in the overall well-being of the individual. There are spatial and temporal variations in the distribution of microbes from the esophagus to the rectum throughout an individual's lifetime. Through the development of genome sequencing technologies, scientists have been able to study the interactions between different microorganisms and their hosts to improve the health and disease of individuals. The normal gut microbiota provides various functions to the host, whereas the host, in turn, provides nutrients and promotes the development of healthy and resilient microbiota communities. Thus, the microbiota provides and maintains the gut's structural integrity and protects the gut against pathogens. The development of the normal gut microbiota is influenced by various factors. Some of these include the mode of delivery, diet, and antibiotics. In addition, the environment can also affect the development of the gut microbiota. For example, one of the main concerns of antibiotic use is the alteration of the gut microbiota, which could lead to the development of multidrug-resistant organisms. When microbes are disturbed, it can potentially lead to various diseases. Depending on the species' ability to adapt to the human body's environment, the fate of the microbes in the host and their relationship with the human body are decided. This review aims to provide a comprehensive analysis of microbe, microbes-host immune interactions, and factors that can disturb their interactions.

The trace element copper (Cu) is part of our nutrition and essentially needed for several cuproenzymes that control redox status and support the immune system. In blood, the ferroxidase ceruloplasmin (CP) accounts for the majority of circulating Cu and serves as transport protein. Both Cu and CP behave as positive, whereas serum selenium (Se) and its transporter selenoprotein P (SELENOP) behave as negative acute phase reactants. In view that coronavirus disease (COVID-19) causes systemic inflammation, we hypothesized that biomarkers of Cu and Se status are regulated inversely, in relation to disease severity and mortality risk. Serum samples from COVID-19 patients were analysed for Cu by total reflection X-ray fluorescence and CP was quantified by a validated sandwich ELISA. The two Cu biomarkers correlated positively in serum from patients with COVID-19 (R=0.42, p&lt;0.001). Surviving patients showed higher mean serum Cu and CP concentrations in comparison to non-survivors ([mean+/-SEM], Cu; 1475.9+/-22.7 vs. 1317.9+/-43.9 µg/L; p&lt;0.001, CP; 547.2.5 +/- 19.5 vs. 438.8+/-32.9 mg/L, p=0.086). In contrast to expectations, total serum Cu and Se concentrations displayed a positive linear correlation in the patient samples analysed (R=0.23, p=0.003). Serum CP and SELENOP levels were not interrelated. Applying receiver operating characteristics (ROC) curve analysis, the combination of Cu and SELENOP with age outperformed other combinations of parameters for predicting risk of death, yielding an AUC of 95.0%. We conclude that the alterations in serum biomarkers of Cu and Se status in COVID-19 are not compatible with a simple acute phase response, and that serum Cu and SELENOP levels contribute to a good prediction of survival. Adjuvant supplementation in patients with diagnostically proven deficits in Cu or Se may positively influence disease course, as both increase in survivors and are of crucial importance for the immune response and antioxidative defence systems.

Diamidophosphate has been identified as a possible prebiotic compound used in the precursor membranes of the first ‘life’. Compounds such as these will be helpful in developing novel biomimetic approaches in synthetic chemistry. Thermochemical data for this type of compounds are not available. Hess’ law and estimates from calorimetric measurements used by Wakefield in the 1970s for other amido phosphates have been used to estimate the thermochemical values for the diamido and monoamido-phosphoric acid. Enthalpy of formation at 298.15 ^oC is calculated as – 821.9 kJ/mol and the free energy of formation calculated as -813.5 kJ/mol for the diamidophosphoric acid. The calculated enthalpy of formation of monoamidic phosphoric acid is -1117.1 kJ/mol and its free energy of formation is - -1105 kJ/mol.

The study is aimed at developing a resilient benchmarking system for small hotels in Ukraine, designed to ensure their survival and growth amid global disruptions and local crises. Given the severe challenges associated with the COVID-19 pandemic and military actions, the resilience of the regional tourism business becomes particularly relevant. The methods used in the study, including factor and cluster analysis, the method of taxonomy, and dendrograms, have enabled the development of development programs for two clusters of hotels: those located in areas with increased military risk and those in relatively safe territories. The taxonomic analysis revealed significant differences in managerial practices and operational efficiency, largely determined by the geographic location of the hotels. Hotels in active combat zones experience a 40% reduction in tourist flow and financial instability, while hotels in safe areas demonstrate a 30% higher level of customer satisfaction. The application of advanced security systems and modern marketing techniques has led to a 40% reduction in incidents.

We have designed cell penetrating peptides that target the leucine zipper transcription factors ATF5, CE-BPB and CEBPD and that promote apoptotic death of a wide range of cancer cell types, but not normal cells, in vitro and in vivo. While such peptides have the potential for clinical application, their mechanisms of action are not fully understood. Here, we show that one such peptide, Dpep, compromises glucose uptake and glycolysis in a cell-context-dependent manner (in about 2/3 of cancer lines assessed). These actions are dependent on induction of tumor suppressor TXNIP (thioredoxin interacting protein) mRNA and protein. Knockdown studies show that TXNIP significantly contributes to apoptotic death in those cancer cells in which it is induced by Dpep. The metabolic actions of Dpep on glycolysis led us to explore combinations of Dpep with clinically approved drugs metformin and atovaquone that inhibit oxidative phosphorylation and that are in trials for cancer treatment. Dpep showed additive to synergistic activities in all lines tested. In summary, we find that Dpep induces TXNIP in a cell-context-dependent manner that in turn sup-presses glucose uptake and glycolysis and contributes to apoptotic death of a range of cancer cells.

Background: Metastatic triple-negative breast cancer (TNBC) is aggressive with a poor median overall survival (OS), ranging from 8 to 13 months. There exists considerable heterogeneity in the survival at the individual patient level. To better understand the survival heterogeneity and improve risk stratification, our study aims to identify the factors influencing survival utilizing a large patient sample in the National Cancer Database (NCDB). Methods: Women diagnosed with metastatic TNBC from 2010 to 2020 in the NCDB were included. Demographic, clinic-pathological, treatment data, and overall survival (OS) outcomes were collected. Kaplan-Meier curves were used to estimate OS. The log-rank test was used to identify OS differences between groups for each variable in the univariate analysis. For the multivariate analysis, the Cox proportional hazard model with backward elimination was used to identify factors affecting OS. Adjusted hazard ratios and 95% confidence intervals are presented. Results: 2,273 women had a median overall survival of 13.6 months. Factors associated with statistically significantly worse OS included older age, higher comorbidity scores, specific histologies, higher number of metastatic sites, presence of liver or other site metastases in those with only one metastatic site (excluding brain metastases), presence of cranial and extra-cranial metastases, lack of chemotherapy, lack of immunotherapy, lack of surgery to distant sites, lack of radiation to distant sites, and receipt of palliative treatment to alleviate symptoms. In the multivariate analysis, comorbidity score, histology, number of metastatic sites, immunotherapy, and chemotherapy had a statistically significant effect on the OS. Conclusions: Through NCDB analysis, we have identified prognostic factors for metastatic TNBC. These findings will help improve prognostication at diagnosis, optimize treatment strategies, and facilitate patient stratification in future clinical trials.

Background: The incidence of spinal metastatic disease has risen with improved cancer survivorship. Separation surgery, the current standard surgical treatment, does not fully address spinal deformity. Advances in operative management warrant reevaluating maximal tumor resection and anterior column reconstruction with corpectomy. Methods: An IRB-approved retrospective single-center review of 63 patients was performed. Demographics, tumor characteristics, clinical and radiographic data, treatments, and neurological and survival outcomes were analyzed. Results: The mean age at presentation was 63.5 ± 9.6 years (range, 37-84 years) and 28 patients (44.4%) were female. Functional outcomes, measured by KPS, RAND-36 survey scores and Oswestry Disability Index all improved postoperatively (pre- vs postop: 70 to 80 (p=0.0056), 26.5 to 46.4 (p=0.0081), and 28.9 to 16.9 (p=0.0613), respectively). Spinal alignment also improved, with Cobb angle measurements showing a reduction in spinal kyphosis from -5 to 0 (p=0.021). Nine patients (14.5%) had non-fatal postoperative complications. The median OS for this cohort was 14.4 months (range, 0.6-145.0 months) with median follow-up time of 15.5 months. Conclusion: In oligometastatic spinal disease patients with good functional status, corpectomy for decompression of neural elements, deformity correction, and spinal stabilization is associated with improvements in pain and functional outcomes without overwhelming morbidity.

Alterations in microRNA (miRNA) expression have been reported in different cancers. We assessed the expression of 754 oncology-related miRNAs in esophageal adenocarcinoma (EAC) and evaluated their correlations with clinical parameters. We found that miR-221 and 483-3p were consistently upregulated in EAC cases vs. controls (Wilcoxon signed rank test: miR-221 P<0.0001; miR-483-3p P<0.0001). Kaplan‒Meier analysis showed worse cancer-related survival in patients expressing high miR-221 or miR-483-3p levels in all EACs (log-rank P=0.0025 and P=0.0235, respectively). Higher miR-221 or miR-483-3p levels also correlated with advanced tumor stages (Mann‒Whitney P=0.0195 and P=0.0085, respectively). Moreover, we found that overexpression of miR-221 was associated with worse survival in the low-risk EAC group. A significantly worse outcome was associated with the combined overexpression of miR-221 and miR-483-3p (log-rank P=0.0410). To identify target genes modified by miRNAs, we evaluatedtheir expression in different EAC cell lines, we transfected the corresponding mimic RNA (miRVANA) for either miR-221 or miR-483-3p and performed RNA-seq analysis. We found converging dysregulated genes involved in cancer progression, apoptosis, ATP synthesis and angiogenesis in miRNA-overexpressing cell lines, including a long non-coding RNA associated with oncogenesis, i.e., MALAT1. In conclusion, miR-221 and 483-3p overexpression in EAC correlated with low cancer-related survival, indicating that they might be considered new biomarkers for patient stratification.

(1) Background: Breast cancer is the second leading cause of cancer death among women. The accurate prediction of survival intervals will help physicians make informed decisions on treatment strategies or the use of palliative care for patients; (2) Methods: The gene expression is predictive and correlates to patient prognosis. To establish a reliable prediction tool, we collected the RNA-seq data of breast cancer patients, a total of 1187 RNA-seq data (median age 58 years), in FPKM format from the TCGA database. Among them, 144 RNA-seq data with date of death information was selected to establish the SaBrcada-AD dataset. We first normalized the SaBrcada-AD dataset to transcripts per million (TPM) to build survival prediction model SaBrcada. After normalization and dimension raising, the differential gene expression data were used for testing eight different deep learning architectures. Among them, GoogLeNet performed the best. Considering the effect of age on prognosis, we examined all ages between the lower and upper quartiles of patient age for a stratified random sampling test; (3) Results: Stratifying by age based on a cut-off of 61 years of age improved the accuracy of SaBrcada compared to previous findings, resulting in an accuracy of 0.798. We also built a free website tool to provide 5 kinds of predicted survival period information for clinician reference; (4) Conclusions: We established a breast cancer survival analysis prediction model, SaBrcada, and a website tool with the same name. Through this highly reliable survival analysis model and website tool, information on survival intervals will be provided for clinicians as part of precision medicine.

The apple leaf-curling midge, Dasineura mali Kieffer (Diptera: Cecidomyiidae), is an invasive pest of apple. To provide crucial information for its pest risk analysis, forecast and management, we investigated the effects of temperatures (5, 10, 15, 20 and 25°C) and daylengths (10, 11, 12, 13, 14 and 15 hrs) on its development and survival. The midge could not complete its development at 10°C or lower. After transferred from 20°C to 10°C, mature larvae could survive for about two months and develop to adults. Pupation and emergence rates were significantly higher at 20°C than at 10°C and 25°C. Daylength had no effect on these parameters. The low temperature threshold and thermal requirement to complete development from eggs to adults were 3.7°C and 627 degree-days, respectively. The midge had significantly lower thermal requirement for completion of its lifecycle at 20°C (614.5 degree-days) than at 15°C (650.1 degree-days) and 25°C (634.8 degree-days). The thermal model developed in this study provided accurate predictions of the number of D. mali generations and adult emergence time in each generation in different regions of New Zealand. We suggest that the model could be used to predict population dynamics of this pest in other parts of the world.

The experiment was conducted to determine the effects of different substrate on the survival, growth and total number of moulting in juvenile red claw, Cherax quadricarinatus for aquaculture purposes. In the present study, there is a problem in culturing juvenile stage of C. quadricarinatus especially for survival and growth. Thus, a substrate was used to improve the survival and growth of C. quadricarinatus especially for the intensive system due C. quadricarinatus need a large space to survive. C. quadricarinatus with initial body weight from 1.10 to 2.90 g, total length 2.82 to 4.36 cm were placed in tanks (80 L in volume capacity) with 55L in water and there are eight juveniles in each tank. Treatment tanks were introduced with coral as treatment 2 and pipe as treatment 3. While, tank without shelters was set as control (treatment 1). Black nets were installed on top of each for circumventing foreign objects enter the tank and protect from direct sunlight. Besides, C. quadricarinatus were acclimatized for seven days before started the experiment. The experiment was done in duplicate and conducted for 60 days and C. quadricarinatus were fed twice daily (morning and evening) based on 5% of body weight. From the total of two replications, C. quadricarinatus for treatment 2 (coral) were significantly in survival (81.25±8.84%), weight gain (347.36 ±6.04%), specific growth rate (2.50±0.02%), carapace length (32.93 ± 0.93 %) and total number of moulting (55.00±2.93%) compared to other treatments. Besides, the control treatment (treatment 1) has a lower percentage in survival (37.50±8.84%) weight gain (122.60±20.51%) specific growth rate (1.33±0.15%), carapace length (25.84±0.33 %) and total number of molting (29.00±0.71%). As a conclusion, usage of coral as the substrate in the rearing tank showed improvement in survival, weight gain, specific growth rate, carapace length and total number of molting in C. quadricarinatus. The coral can use in rearing tank for increase the growth and survival for a small scale and not for commercial. In addition, in the environmental aspect, the present study showed the benefit of replacing the use of PVC pipes with the natural structure of dead coral.

Solid tumors display complex biology and most therapies including chemotherapy cannot prevent therapy resistance and relapse. Most therapeutics target cancer cells, but recent data suggest the presence of cancer stem cells as cells with self-renewal and tumorigenic abilities. Cancer stem cell markers have been suggested to have prognostic value and can be targeted during cancer treatment and in resistant disease. CSCs have been postulated to play significant contextual roles in tumor initiation, progression, therapy resistance and metastasis. CSCs have thus been targeted by new generation cancer drugs. The transcriptional expression of several CSC markers in different cancers was evaluated by searching publicly available The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. We report here new findings on expression and prognostic significance of CSC markers in several cancers by examining the expression of CSCs markers in tumor tissues versus the adjacent normal tissues. We found that CSC markers were mostly highly expressed various tumors such as colon, lung, pancreatic and esophageal cancers. No CSC marker is expressed in the same pattern in all cancers and individual CSC marker expression was not linked to patient survival. This analysis calls for continued research on CSCs and clinical evaluation of the CSC markers in relation to prognosis of cancers in large population samples. Novel cancer drugs ought to target CSCs, cancer cells and tumor microenvironment variations.

In the paper it is demonstrated that a valid path to a contradiction in complex number theory exists. In the path use is made of Euler’s identity and simple trigonometry. Each step can be easily verified.

Thanks to advanced semiconductor microfabrication technology, chip-scale integration and miniaturization of lab-on-a-chip components, silicon-based optical biosensors have made significant progress for the purpose of point-of-care diagnosis. In this review, we provide an overview of the state-of-the-art in evanescent field biosensing technologies including interferometer, microcavity, photonic crystal, and Bragg grating waveguide-based sensors. Their sensing mechanisms and sensor performances, as well as real biomarkers for label-free detection, are exhibited and compared. We also review the development of chip-level integration for lab-on-a-chip photonic sensing platforms, which consist of the optical sensing device, flow delivery system, optical input and readout equipment. At last, some advanced system-level CMOS-chip packaging examples are presented, indicating the commercialization potential for the low cost, high yield, portable biosensing platform leveraging CMOS processes.

We focus on macromolecules which are modelled as sequentially growing dual scale-free networks. The dual networks are built by replacing star-like units of the primal treelike scale-free networks through rings, which are then transformed in a small-world manner up to the complete graphs. In this respect, the parameter γ describing the degree distribution in the primal treelike scale-free networks regulates the size of the dual units. The transition towards the networks of complete graphs is controlled by the probability p of adding link between non-neighbouring nodes of the same initial ring. The relaxation dynamics of the polymer networks is studied in the framework of generalized Gaussian structures by using the full eigenvalue spectrum of the Laplacian matrix. The dynamical quantities on which we focus here are the averaged monomer displacement and the mechanical relaxation moduli. For several intermediate values of the parameter’s set (γ, p) we encounter for these dynamical properties regions of constant in-between slope.

We introduce optically clear and resilient free-form micro-optical of pure (non-photosensitized) organic-inorganic SZ2080 material made by femtosecond 3D laser lithography (3DLL). This is advantageous for rapid printing of 3D micro-/nanooptics, including their integration directly onto optical fibers. A systematic study on the fabrication peculiarities and quality of resultant structures is performed. Comparison of microlenses’ resiliency to CW and femtosecond pulsed exposure is determined. Experimental results prove that pure SZ2080 is ∼3 fold more resistant to high irradiance as compared with a standard photo-sensitized material and can sustain up to 1.91 GW/cm² intensity. 3DLL is a promising manufacturing approach for high-intensity micro-optics for emerging fields in astro-photonics and atto-second pulse generation. Additionally, pyrolysis is employed to shrink structures up to 40% by removing organic SZ2080 constituents. This opens a promising route towards downscaling photonic lattices and creation of mechanically robust glass-ceramic structures.

A three-dimensional vector field model is proposed, whose dimensions are the Hansen Solubility Parameters: dispersion parameter (δD), polarity parameter (δP), and hydrogen bonding parameter (δH). The vector space that defines the field has the peculiarity of having the dispersion vector with a magnitude of 2, as its base vector, while polarity and hydrogen bonding vectors have a magnitude of 1. A substance is characterised as a position vector, and the interaction between two substances is determined by calculating the vector difference of both, known as the interaction vector. Interaction among substances may involve solubility, swelling, cracking, surface tension, interface tension, and any physical phenomena where intermolecular energies of dispersion, polarity or hydrogen bonding come into play. This paper studies free surface energy (surface and interfacial tension). It has been found that free surface energy is directly proportional to the square of the magnitude of the interaction vector. The proportionality constant, τ, is expressed in length units, has a value of 0.025 nm, and does not depend on the chemical nature of the substance or state of matter (solid, liquid or gas). Constant value τ appears universal and aligns with the thickness of interfaces, thereby supporting Guggenheim's hypothesis. This hypothesis asserts that interfaces possess actual thickness and are not merely mathematical surfaces, as originally postulated by Gibbs. Moreover, it also has been found that interface thickness, τ, is approximately equal to half of the Bohr radius, a0, which is defined by universal constants. Because the solubility parameters of thousands of substances are known and can be easily determined from molecular structure, a good approximation of the surface and interfacial tension of any given substance can now be calculated. It has also been found that contact angles of sessile droplets in three-phased systems can be calculated from the interaction vectors of the implicated substances.

Thermodynamics of protein-ligand interactions seems to be associated to a narrow range of Gibbs Free Energy. As a consequence, a linear enthalpy-entropy relationship showing an apparent Enthalpy-Entropy compensation (EEC) is frequently observed associated to the study of protein-ligand interactions. This EEC affects negatively the design and discovery of new and more efficient drugs capable of binding protein-targets with a higher affinity. Originally attributed to experimental errors, compensation between H and TS values is a real observable fact, although its molecular origin has remained obscure and controversial. Herein we show the results of a data search of G values of 2558 protein-ligand interactions and 3025 “in vivo” ligand concentrations from the Protein Data Bank bind Database and the Metabolome Data Base (2020). These results, together with the mechano-statistical interpretation of the thermodynamic properties leads to the conclusion that the EEC has no basis in statistical thermodynamics. It can be plausibly explained as a consequence of the narrow range of G associated to protein-ligand interactions. The Gaussian distribution of the G values matches very well with that of ligands. These results suggest the hypothesis that the set of G values for the protein-ligand interactions is the result of the evolution of proteins. The conformation versatility of present proteins and the exchange of thousands (even millions) of minute amounts of energy with the environment may have functioned as a homeostatic mechanism to make G of proteins adaptive to changes in availability of ligands, and therefore achieve the maximum regulatory capacity of the protein function. Finally, a plausible strategy to avoid the EEC is suggested.

3D metal nanostructures are often the basis of several applications such as in catalysis, plasmonics, medical diagnosis, therapy, drug screening, ophthalmologic, and biomedical applications. Porous gold nanoparticles (PGNs) are intensively investigated due to their outstanding morphological as well as advantageous optical properties. Unfortunately, the thermal stability of these open-porous structures is poor, i.e. even as a result of low-temperature annealing (150$^\circ$C in air), their porosity disappears and they lose their favorable optical properties. In order to preserve their beneficial properties, a thin metal oxide coating can be applied. Changing the coating's thickness and/or composition, the optical response of the PGNs can also be tuned in a wide wavelength region. Moreover, these nanoparticles can be synthesized also in support-free form, which makes them more attractive from an application point of view. This review article summarizes some of the preparation modes of these complex nanostructures (fixed and support-free), as well as their thermal stability and optical responses.