Pyridoxal and pyridoxal 5′-phosphate are aldehyde forms of B₆ vitamin that can easily be transformed into each other in the living organism. The presence of a phosphate group, however, provides the related compounds (e.g., hydrazones) with better solubility in water. In addition, the phosphate group may sometimes act as a binding center for metal ions. In particular, a phosphate group can be a strong ligand for a gold(III) ion, which is of interest for researchers for the anti-tumor and antimicrobial potential of gold(III). This paper aims to answer whether the phosphate group is involved in the complex formation between gold(III) and hydrazones derived from pyridoxal 5′-phosphate. The answer is negative, since the comparison of the stability constants determined for the gold(III) complexes with pyridoxal- and pyridoxal 5′-phosphate-derived hydrazones showed a negligible difference. In addition, quantum chemical calculations confirmed that the preferential coordination of two series of phosphorylated and non-phosphorylated hydrazones to gold(III) ion is similar. The preferential protonation modes for the gold(III) complexes were also determined using experimental and calculated data. Full article

Remote passive sonar detection with underwater acoustic vector sensor (UAVS) has attracted increasing attention due to its merit in measuring the full sound field information. However, the accurate estimation of the direction-of-arrival (DOA) remains a challenging problem, especially under low signal-to-noise ratio (SNR) conditions. In this paper, a novel convolution (COV)-based single-vector acoustic preprocessing method is proposed on the basis of the single-vector acoustic preprocessing model. In view of the theoretical analysis of the classical single-vector acoustic DOA estimation method, the principle of preprocessing can be described as “to achieve an improved denoising performance in the constraint of equivalent amplitude gain and phase response.” This can be naturally guaranteed by our proposed COV method. In addition, the upper bound with matched filtering (MF) preprocessing is provided in the consideration of the optimal linear signal processing for weak signal detection under Gaussian noise. Numerical analyses demonstrate the effectiveness of our proposed preprocessing method with both vector array signal processing-based and intensity-based methods. Experimental verification conducted in South China Sea further verifies the effectiveness of our approach for practical applications. This work can lay a solid foundation in improving underwater remote vector acoustic DOA estimation under low SNR, and can provide important guidance for future research work. Full article

Cervical esophageal reconstruction is vital to improve the quality of life in cancer surgery patients. Microsurgery is crucial in providing vascularized tissue for defect repair, particularly in secondary cases with a higher risk of failure due to larger defects and damage from previous surgery and radiotherapy. The purpose of this study was to describe the clinical characteristics of a series of patients who underwent secondary repair of esophageal defects and provide practical information for the management and treatment of such cases based on the authors’ experience and the literature review. Methods: We retrospectively reviewed the electronic medical records of the Plastic Surgery Clinic at the University of Trieste to identify cases of patients who underwent secondary esophageal microsurgical reconstructions following oncological surgery. Patient demographics, the etiology of esophageal defects, previous surgical history, and preoperative assessments were collected from medical records. Surgical techniques utilized for reconstruction, such as pedicled flaps or free tissue transfers, were documented along with intraoperative information. Postoperative outcomes, including complications, graft viability, and functional outcomes, were evaluated during follow-up. Results: We treated 13 cases of secondary esophageal reconstructions between 2011 and 2022. Most commonly, Antero-Lateral Thigh (ALT) flaps were used in 10 cases, while 2 cases employed a radial forearm flap (RFF), and 1 case employed a chimeric parascapular flap. No flap failures occurred during a median 50-month follow-up. One ALT flap patient experienced postop stricture but maintained swallowing ability. A single tracheoesophageal fistula occurred in an RFF patient with a history of radiotherapy and complete lymph node dissection. Conclusions: Cervical esophageal reconstruction significantly impacts patients’ quality of life by restoring oral feeding and phonation. When local flaps fall short, microsurgical reconstruction with intestinal flaps is valuable but is burdened by limitations. For challenging secondary cases, ALT or RFF flaps emerge as safer options due to their robust pedicles, yielding low complication rates and positive functional outcomes. Full article

The concept of active aging has become central to the public debate in many Western countries, given the increasing aging of the population and the future challenges associated with it. This phenomenon is tightly intertwined with choices regarding the retirement period, which can be postponed for different reasons by individuals in a society. The purpose of this paper is to understand the personal and family characteristics that influence future choices about retirement date in Italy. Utilizing data provided by the Bank of Italy in the Survey on Household Income and Wealth (SHIW), a logistic regression is performed to observe the impact of different covariates on the hypothesized retirement date of individuals close to retirement, i.e., over the age of 50 who are still in working status. The results show that the decision to delay retirement has increased in recent years, and is influenced by personal (e.g., matrimonial status), work, and economic factors. In addition, these factors have different impacts between males and females. Full article

The present study investigated the potential use of blackmouth catshark (Galeus melastomus) skins for gelatin production by employing a combined alkaline and acidic process. The yield of dry gelatin was relatively high (13.95%), showing a high protein content (87.80%), but low moisture (10.64%), ash (1.34%) and lipid (0.03%) contents, on a wet weight basis. Fish skin gelatin showed better color properties (>L*, <+b* values) than porcine skin gelatin and exhibited similar gel strength (315.4 g) and higher viscosity (5.90 cP) than the latter (p < 0.05). Although the electrophoretic study revealed that fish skin gelatin was degraded to a lesser extent than its mammalian counterpart, the resulting fish skin gelatin gels melted at a significantly lower temperature (T_m = 21.5 °C), whereas the reverse process (i.e., gelling) also occurred at a lower temperature (T_s = 10.6 °C) and required more time (t_s = 29.5 min) compared to porcine skin gelatin gels (T_m = 30.4 °C, T_s = 19.4 °C and t_s = 20.7 min). These differences were attributed to the different imino acid content, which was greater in mammalian gelatin (p < 0.05). The results suggested that the skins from blackmouth catshark can be potentially used as an alternative raw material for gelatin production, which will fill the needs of more diverse cultures that do not consume pork- or cow-related products. Full article

Under many interactive environments in the real world, there is often a need to evaluate the minimization effects and subsequent allocation outcomes derived from these interactions under multiple considerations. For instance, in the context of product sales, it is necessary to evaluate how to minimize the manufacturing costs of various producing factors, and sometimes, from a holistic perspective, it may even be necessary to evaluate situations with minimal sales benefits. On the other hand, in order to evaluate related effects derived from interactions and subsequent allocation outcomes, many game-theoretical studies are based on interactive models to formulate evaluating mechanisms, and then they apply axiomatic processes to analyze the rationality of these mechanisms. Therefore, this study first proposes a mechanism for evaluating the minimization effects and subsequent allocation outcomes under multiple considerations. Additionally, considering that different environmental impacts result from varying participation factors, this study also presents several weighted derivatives based on participation factors and their behaviors. Concurrently, we utilize axiomatic results to demonstrate the mathematical correctness and practicality for these evaluating mechanisms. Full article

Adolescents are particularly vulnerable to inadequate provision of mental health and addictions care, as services have been traditionally conceptualized to serve the needs of children or adults. Additionally, rural communities have been largely excluded from research investigating mental healthcare access and exhibit unique barriers that warrant targeted interventions. Finally, perspectives from the target population will be most important when understanding how to optimize adolescent mental health and addictions care. Therefore, the purpose of this study was to identify what adolescents in a rural town perceive as barriers to accessing mental health services. We conducted a cross-sectional survey study with high school students to generate ranked lists of the top perceived individual-level, community-level, and overall barriers. A total of 243 high school students responded to the survey. Perceived barriers were predominantly at the community level. Overall, the top barriers reported were a lack of awareness and education regarding mental health, resources, and the nature of treatment. Students who had previously accessed mental health services identified primary barriers related to mental health professionals, whereas students who had not accessed care reported fear and uncertainty as primary barriers. Modifiable community-level factors related to (1) mental health literacy and (2) mental healthcare professionals were identified by adolescents as the main perceived barriers to accessing mental health and addiction services in a rural town. The findings of this preliminary study should inform intervention strategies and further rigorous research for this traditionally underserved target population. Full article

The heat of hydration, mechanical properties, pozzolanic activity, and microscopic characteristics of cement pastes incorporating co-combusted fly ash (CCFA) were investigated, and the disparities between the CCFA/cement system and the coal fly ash (CFA) binding system were also compared. The results indicate a decrease in the heat of hydration for both CFA and CCFA samples, with a more pronounced trend observed as the fly ash content increased from 10% to 30%. The distinction in the early hydration between CFA and CCFA samples primarily manifested in the rate of heat release, potentially correlated with variations in the active Al₂O₃ content in the fly ash. Neither CFA nor CCFA samples exhibited significant cementitious activity at 3 days, functioning solely as inert fillers in the cement paste. By 3 and 28 days, the mechanical properties of both CFA and CCFA samples were inferior to those of pure cement paste. However, by 180 days of hydration, the compressive strength of CCFA-blended mortar notably increased, with the highest strength observed in the 10% CCFA-blended sample. Both CFA and CCFA samples produced the secondary hydration product C-A-S-H and demonstrated comparable consumption of calcium hydroxide (CH). These findings underscore the potential of CCFA as a supplementary cementitious material (SCM) and lay a foundation for its widespread adoption. Full article

This experimental study investigates the damage effects of nanosecond pulse laser irradiation on silicon solar cells. It encompasses the analysis of transient pulse signal waveform characteristics at the cells’ output and changes in electrical parameters, such as I–V curves before and after laser irradiation under varying laser fluence and background light intensities, and explores the underlying action mechanisms of laser irradiation. The study reveals that as the laser fluence increases up to 4.0 J/cm², the peak value of the transient pulse signal increases by 47.5%, while the pulse width augments by 88.2% compared to the initial transient pulse signal. Furthermore, certain parameters, such as open-circuit voltage, short-circuit current, and peak power obtained, from the measured I–V curve indicate a threshold laser fluence for functional degradation of the solar cell at approximately 1.18 ± 0.42 J/cm². Results obtained from laser irradiation under different background light intensities underscore the significant influence of background light on laser irradiation of silicon cells, with the most severe damage occurring in the absence of light. Moreover, findings from laser irradiation at multiple locations on the silicon cell demonstrate a linear decrease in the output voltage of the silicon cell with an increase in the number of irradiation points. Full article

The aim of this study was to analyze the physical and chemical characteristics of chicken droppings (n = 73), which were collected during different age periods and classified by visual inspection into normal (N) and abnormal (A). Significant differences were found in the texture, pH, dry matter (DM), fatty acids (FAs), short-chain fatty acids (SCFAs), and volatile compounds (VCs) between the tested dropping groups (p ≤ 0.05). The age period of the chicken had a significant influence on the color coordinates, texture, pH, DM, and SCFA contents in N and A as well as on all FAs content in N (p ≤ 0.05). Droppings from the N group had a harder texture, lower values of a* and b* color coordinates, higher DM content, higher level of linoleic FA, and lower level of α-linolenic FA than the droppings from the A group in each age period (p ≤ 0.05). The predominant SCFA was acetic acid, the content of which was significantly lower in the N group compared to that of the A group. The alcohol and organic acid contents were the highest in most of the A group at different age periods, while ketones dominated in the N and A groups. In conclusion, the majority of the tested dropping characteristics were influenced by the age period. While certain characteristics demonstrate differences between N and A, a likely broader range of droppings is required to provide more distinct trends regarding the distribution of characteristics across different droppings. Full article

Adjacent cyclic explosions significantly impact the stability of underground anchored caverns. Based on the similar model test of the vault explosion of the anchored cavern, the dynamic analysis finite element software ANSYS/LSDYNA(18.0) was used to establish a model of the straight wall side explosion of the underground anchored cavern and conduct a numerical simulation. When the total amount of explosion load is the same, we compared the stress time history curve, displacement time history curve, tunnel wall displacement, and circumferential strain curve of the surrounding rock in the underground anchored cavern (under both a high-level single-side blast and a low-level cyclic side blast). We obtained the dynamic response rules of the surrounding rock. By comparing the damage evolution process of the surrounding rock in the two situations, the damage accumulation law of the surrounding rock was analyzed. At the same time, the axial stress distribution characteristics of underground anchor cavern anchors under the action of cyclic explosion were studied. The findings demonstrate that when the total level of blast load adjacent to the cavern is the same, the displacement and circumferential peak strain of surrounding rock and the axial stress of rock bolt in the high-level single explosion are greater than those in the low-level cyclic explosion. However, compared to a single explosion, the rock mass suffers more damage in the cyclic explosion. This study will provide engineers with information that will assist them with a better understanding of the cumulative damage mechanisms of surrounding rock, as well as the stress characteristics of rock bolts under dynamic loads near the explosion site, which will be used to design underground caves with anti-blast features. Full article

This study aimed to evaluate the earliest changes in the structure and function of the peripheral microcirculation using capillaroscopy and transcutaneous oxygen pressure measurement in children and adolescents with type 1 diabetes mellitus at baseline and during post-occlusive reactive hyperemia (PORH) in the function of diabetes duration. Sixty-seven patients with type 1 diabetes mellitus (T1D), aged 8 to 18 years, and twenty-eight age- and sex-matched healthy subjects were included in the analysis. Diabetic patients were divided into subgroups based on median disease duration. The subgroups differed in chronological age, lipid levels, and thyroid hormones. Capillaroscopy was performed twice: at baseline and then again after the PORH test. Transcutaneous oxygen pressure also was recorded under baseline conditions during and after the PORH test. Comparison of capillaroscopy and transcutaneous oxygen pressure parameters at rest and after the PORH showed no statistically significant difference between the subgroups. This remained true after adjusting for variables that differentiated the two subgroups. However, in the group of patients with long-standing diabetes, significant negative correlations were observed between the Coverage value after the PORH test and capillary reactivity with TcPO₂_zero (biological zero). Significant positive correlations were also found between distance after the PORH test and TcPO₂_zero. The results of our study indicate that in patients with a shorter duration of diabetes, the use of multiple tests provides a better characterization of the structure and function of microcirculation because the onset of dysfunction does not occur at the same time in all the tests. Full article

For complex equipment, it is easy to over-evaluate the impact of failure on production by estimating the reliability level only through failure probability. To remedy this problem, this paper proposes a statistical evaluation method based on fuzzy failure data considering the multi-state characteristics of equipment failures. In this method, the new reliability-evaluation scheme is firstly presented based on the traditional statistical analysis method using the Weibull distribution function. For this scheme, the failure-grade index is defined, and a fuzzy-evaluation method is also proposed by comprehensively considering failure severity, failure maintenance, time, and cost; this is then combined with the time between failures to characterize the failure state. Based on the fuzzy failure data, an improved adaptive-failure small-sample-expansion method is proposed based on the classical bootstrap method and the deviation judgment between distributions of the original and newborn samples. Finally, a novel reliability-evaluation model, related to the failure grade and its membership degree, is established to quantify the reliability level of equipment more realistically. Example cases for three methods of the scheme (the failure-grade fuzzy-evaluation method, the sample-expansion method, and the reliability-evaluation modeling method) are presented, respectively, to validate the effectiveness and significance of the proposed reliability-evaluation technology. Full article

Friction is an inevitable phenomenon in mechanical systems that affects the dynamic characteristics of systems. To reduce the modeling complexity of complex multi-rigid-body mechanisms, a novel explicit canonical dynamic modeling method considering joint friction is proposed. Based on the explicit dynamic modeling theory that we have proposed, the solution of the constraint force required by the joint friction modeling of multi-rigid-body mechanisms is derived and improved, which greatly simplifies the solution of the constraint force. According to the obtained explicit expression of the constraint force equations, two joint friction models of the Coulomb–viscous effect and Stribeck effect are derived in analytical form. Moreover, the Stribeck effect of the joint is experimentally analyzed. A five-axis tree-chain mechanism and a three-loop closed-chain mechanism are chosen to demonstrate the method and compared with ADAMS software. Moreover, the proposed model is analyzed and compared with other methods. Full article

Nitrogen oxides (NO_x), primarily generated from combustion processes, pose significant health and environmental risks. To improve the coordination of measures against excessive NO_x emissions, it is necessary to effectively monitor ambient NO_x concentrations, which requires the development of precise and cost-efficient detection methods. This study focuses on developing a microwave- or radio frequency (RF)-based gas dosimeter for NO_x detection and addresses the optimization of the dosimeter design by examining the dielectric properties of LTCC-based (Low-Temperature Co-fired Ceramics) sensor substrates and barium-based NO_x storage materials. The measurements taken utilizing the Microwave Cavity Perturbation (MCP) method revealed that these materials exhibit more pronounced changes in dielectric losses when storing NO_x at elevated temperatures. Consequently, operating such a dosimeter at high temperatures (above 300 °C) is recommended to maximize the sensor signal. To evaluate their high-temperature applicability, LTCC substrates were analyzed by measuring their dielectric losses at temperatures up to 600 °C. In terms of NO_x storage materials, coating barium on high-surface-area alumina resolved issues related to limited NO_x adsorption in pure barium carbonate powders. Additionally, the adsorption of both NO and NO₂ was enabled by the application of a platinum catalyst. The change in dielectric losses, which provides the main signal for an RF-based gas dosimeter, only depends on the stored amount of NO_x and not on the specific type of nitrogen oxide. Although the change in dielectric losses increases with the temperature, the maximum storage capacity of the material decreases significantly. In addition, at temperatures above 350 °C, NO_x is mostly weakly bound, so it will desorb in the absence of NO_x. Therefore, in the future development of a reliable RF-based NO_x dosimeter, the trade-off between the sensor signal strength and adsorption behavior must be addressed. Full article

Terraces, farmlands built along hillside contours, are common anthropogenically designed landscapes. Terraces control soil and water loss and improve land productivity; therefore, obtaining their spatial distribution is necessary for soil and water conservation and agricultural production. Spatial information of large-scale terraces can be obtained using satellite images and through deep learning. However, when extracting terraces, accurately segmenting the boundaries of terraces and identifying small terraces in diverse scenarios continues to be challenging. To solve this problem, we combined two deep learning modules, ANB-LN and DFB, to produce a new deep learning framework (NLDF-Net) for terrace extraction using remote sensing images. The model first extracted the features of the terraces through the coding area to obtain abstract semantic features, and then gradually recovered the original size through the decoding area using feature fusion. In addition, we constructed a terrace dataset (the HRT-set) for Guangdong Province and conducted a series of comparative experiments on this dataset using the new framework. The experimental results show that our framework had the best extraction effect compared to those of other deep learning methods. This framework provides a method and reference for extracting ground objects using remote sensing images. Full article

Motion capture technology plays a crucial role in optimizing athletes’ skills, techniques, and strategies by providing detailed feedback on motion data. This article presents a comprehensive survey aimed at guiding researchers in selecting the most suitable motion capture technology for sports science investigations. By comparing and analyzing the characters and applications of different motion capture technologies in sports scenarios, it is observed that cinematography motion capture technology remains the gold standard in biomechanical analysis and continues to dominate sports research applications. Wearable sensor-based motion capture technology has gained significant traction in specialized areas such as winter sports, owing to its reliable system performance. Computer vision-based motion capture technology has made significant advancements in recognition accuracy and system reliability, enabling its application in various sports scenarios, from single-person technique analysis to multi-person tactical analysis. Moreover, the emerging field of multimodal motion capture technology, which harmonizes data from various sources with the integration of artificial intelligence, has proven to be a robust research method for complex scenarios. A comprehensive review of the literature from the past 10 years underscores the increasing significance of motion capture technology in sports, with a notable shift from laboratory research to practical training applications on sports fields. Future developments in this field should prioritize research and technological advancements that cater to practical sports scenarios, addressing challenges such as occlusion, outdoor capture, and real-time feedback. Full article

Cayley and nilpotent graphs arise from the interaction between graph theory and algebra and are used to visualize the structures of some algebraic objects as groups and commutative rings. On the other hand, Green and Schroll introduced Brauer graph algebras and Brauer configuration algebras to investigate the algebras of tame and wild representation types. An appropriated system of multisets (called a Brauer configuration) induces these algebras via a suitable bounded quiver (or bounded directed graph), and the combinatorial properties of such multisets describe corresponding indecomposable projective modules, the dimensions of the algebras and their centers. Undirected graphs are examples of Brauer configuration messages, and the description of the related data for their induced Brauer configuration algebras is said to be the Brauer analysis of the graph. This paper gives closed formulas for the dimensions of Brauer configuration algebras (and their centers) induced by Cayley and nilpotent graphs defined by some finite groups and finite commutative rings. These procedures allow us to give examples of Hamiltonian digraph constructions based on Cayley graphs. As an application, some quantum entangled states (e.g., Greenberger–Horne–Zeilinger and Dicke states) are described and analyzed as suitable Brauer messages. Full article

This research confronts the persistent challenge of data scarcity in medical machine learning by introducing a pioneering methodology that harnesses the capabilities of Generative Pre-trained Transformers (GPT). In response to the limitations posed by a dearth of labeled medical data, our approach involves the synthetic generation of comprehensive patient discharge messages, setting a new standard in the field with GPT autonomously generating 20 fields. Through a meticulous review of the existing literature, we systematically explore GPT’s aptitude for synthetic data generation and feature extraction, providing a robust foundation for subsequent phases of the research. The empirical demonstration showcases the transformative potential of our proposed solution, presenting over 70 patient discharge messages with synthetically generated fields, including severity and chances of hospital re-admission with justification. Moreover, the data had been deployed in a mobile solution where regression algorithms autonomously identified the correlated factors for ascertaining the severity of patients’ conditions. This study not only establishes a novel and comprehensive methodology but also contributes significantly to medical machine learning, presenting the most extensive patient discharge summaries reported in the literature. The results underscore the efficacy of GPT in overcoming data scarcity challenges and pave the way for future research to refine and expand the application of GPT in diverse medical contexts. Full article

(1) Background: There is a huge unmet clinical need for novel treatment strategies in advanced and recurrent cervical cancer. Several cell membrane-bound molecules are up-regulated in cancer cells as compared to normal tissue and have revived interest with the introduction of antibody–drug conjugates (ADCs). (2) Methods: In this study, we characterize the expression of 10 potential ADC targets, TROP2, mesotheline, CEACAM5, DLL3, folate receptor alpha, guanylatcyclase, glycoprotein NMB, CD56, CD70 and CD138, on the gene expression level. Of these, the three ADC targets TROP2, CEACAM5 and CD138 were further analyzed on the protein level. (3) Results: TROP2 shows expression in 98.5% (66/67) of cervical cancer samples. CEACAM5 shows a stable gene expression profile and overall, 68.7% (46/67) of cervical cancer samples are CEACAM-positive with 34.3% (23/67) of cervical cancer samples showing at least moderate or high expression. Overall, 73.1% (49/67) of cervical cancer samples are CD138-positive with 38.8% (26/67) of cervical cancer samples showing at least moderate or high expression. (4) Conclusions: TROP2, CEACAM5 or CD138 do seem suitable for further clinical research and the data presented here might be used to guide further clinical trials with ADCs in advanced and recurrent cervical cancer patients. Full article

PTEN Hamartoma Tumour Syndrome (PHTS) encompasses diverse clinical phenotypes, including Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-like syndrome. This autosomal dominant genetic predisposition with high penetrance arises from heterozygous germline variants in the PTEN tumour suppressor gene, leading to dysregulation of the PI3K/AKT/mTOR signalling pathway, which promotes the overgrowth of multiple and heterogenous tissue types. Clinical presentations of CS range from benign and malignant disorders, affecting nearly every system within the human body. CS is the most diagnosed syndrome among the PHTS group, notwithstanding its weak incidence (1:200,000), for which it is considered rare, and its precise incidence remains unknown among other important factors. The literature is notably inconsistent in reporting the frequencies and occurrences of these disorders, adding an element of bias and uncertainty when looking back at the available research. In this review, we aimed to highlight the significant disparities found in various studies concerning CS and to review the clinical manifestations encountered in CS patients. Furthermore, we intended to emphasize the great significance of early diagnosis as patients will benefit from a longer lifespan while being unceasingly advised and supported by a multidisciplinary team. Full article

Epigenetic alterations my play a role in the aggressive behavior of Non-Small Cell Lung Cancer (NSCLC). Treatment with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat) has been reported to interfere with the proliferative and invasive potential of NSCLC cells. In addition, the DNA methyltransferase inhibitor azacytidine (AZA, vidaza) can modulate the levels of the metastasis suppressor KiSS-1. Thus, since cisplatin is still clinically available for NSCLC therapy, the aim of this study was to evaluate drug combinations between cisplatin and SAHA as well as AZA using cisplatin-sensitive H460 and -resistant H460/Pt NSCLC cells in relation to KiSS-1 modulation. An analysis of drug interaction according to the Combination-Index values indicated a more marked synergistic effect when the exposure to SAHA or AZA preceded cisplatin treatment with respect to a simultaneous schedule. A modulation of proteins involved in apoptosis (p53, Bax) was found in both sensitive and resistant cells, and compared to the treatment with epigenetic agents alone, the combination of cisplatin and SAHA or AZA increased apoptosis induction. The epigenetic treatments, both as single agents and in combination, increased the release of KiSS-1. Finally, the exposure of cisplatin-sensitive and -resistant cells to the kisspeptin KP10 enhanced cisplatin induced cell death. The efficacy of the combination of SAHA and cisplatin was tested in vivo after subcutaneous inoculum of parental and resistant cells in immunodeficient mice. A significant tumor volume inhibition was found when mice bearing advanced tumors were treated with the combination of SAHA and cisplatin according to the best schedule identified in cellular studies. These results, together with the available literature, support that epigenetic drugs are amenable for the combination treatment of NSCLC, including patients bearing cisplatin-resistant tumors. Full article