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Neuroendocrine neoplasms (NENs) are a diverse group of malignancies with a shared phenotype but varying prognosis and response to current treatments. Based on their morphological features and rate of proliferation, NENs can be classified into two main groups with a distinct clinical behavior and response to treatment: (i) well-differentiated neuroendocrine tumors (NETs) or carcinoids (with a low proliferation rate), and (ii) poorly differentiated small- or large-cell neuroendocrine carcinomas (NECs) (with a high proliferation rate). For certain NENs (such as pancreatic tumors, higher-grade tumors, and those with DNA damage repair defects), chemotherapy is the main therapeutic approach. Among the different chemotherapic agents, cisplatin and carboplatin, in combination with etoposide, have shown the greatest efficacy in treating NECs compared to NETs. The cytotoxic effects of cisplatin and carboplatin are primarily due to their binding to DNA, which interferes with normal DNA transcription and/or replication. Consistent with this, NECs, which often have mutations in pathways involved in DNA repair (such as Rb, MDM2, BRCA, and PTEN), have a high response to platinum-based chemotherapy. Identifying mutations that affect molecular pathways involved in the initiation and progression of NENs can be crucial in predicting the response to platinum chemotherapy. This review aims to highlight targetable mutations that could serve as predictors of therapeutic response to platinum-based chemotherapy in NENs. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of impostor syndrome among PhD students has increased rapidly in recent years, having very negative effects on their mental and psychological health as well as on their doctoral journey. This exploratory study aims to examine whether there is a causal correlation between impostor syndrome among PhD students and empathy among supervisors. Methods: This study encompasses 562 doctoral students (300 females, 262 males) and 152 Tunisian supervisors (68 females, 84 males). Results: Employing ANOVA, significant influences on impostor syndrome emerge for gender, marital status, professional status, and the doctoral enrollment level (p < 0.001). Concurrently, supervisors' empathy is significantly affected by gender, marital status, and experience (p < 0.001). Linear regression establishes a noteworthy negative correlation (p = 0.045): a 1-unit increase in empathy correlates with a 0.122-unit decrease in impostor syndrome. Discussion: These findings underscore the intricate relationship between socioprofessional factors, empathy, and impostor syndrome within the academic milieu, offering crucial insights for interventions and psychological support. The study aligns with the broader context of understanding mental health challenges in academia, emphasizing the imperative for ongoing support initiatives. [ABSTRACT FROM AUTHOR]

Platinum‐based chemotherapeutic agents are widely used in the treatment of cancer. However, their effectiveness is limited by severe adverse reactions, drug resistance, and poor water solubility. This study focuses on the synthesis and characterization of new water‐soluble cationic monofunctional platinum(II) complexes starting from the [PtCl(η1‐C2H4OEt)(phen)] (1, phen=1,10‐phenanthroline) precursor, specifically [Pt(NH3)(η1‐C2H4OEt)(phen)]Cl (2), [Pt(1‐hexyl‐1H‐imidazole)(η1‐C2H4OEt)(phen)]Cl (3), and [Pt(1‐hexyl‐1H‐benzo[d]imidazole)(η1‐C2H4OEt)(phen)]Cl (4), which deviate from traditional requirements for antitumor activity. These complexes were evaluated for their cytotoxic effects in comparison to cisplatin, using immortalized cervical adenocarcinoma cells (HeLa), human renal carcinoma cells (Caki‐1), and normal human renal cells (HK‐2). While complex 2 showed minimal effects on the cell lines, complexes 3 and 4 demonstrated higher cytotoxicity than cisplatin. Notably, complex 4 displayed the highest cytotoxicity in both cancer and normal cell lines. However, complex 3 exhibited the highest selectivity for renal tumor cells (Caki‐1) among the tested complexes, compared to healthy cells (HK‐2). This resulted in a significantly higher selectivity than that of cisplatin and complex 4. Therefore, complex 3 shows potential as a leading candidate for the development of a new generation of platinum‐based anticancer drugs, utilizing biocompatible imidazole ligands while demonstrating promising anticancer properties. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most lethal malignancies with an increasing incidence and a high mortality rate, due to its rapid progression, invasiveness, and resistance to anticancer therapies. In this work, we evaluated the antiproliferative and antimigratory activities of the two organometallic compounds, [Pt(η1-C2H4-OMe)(DMSO)(phen)]Cl (1) and [Pt(η1-C2H4-OEt)(DMSO)(phen)]Cl (2), on three human pancreatic ductal adenocarcinoma cell lines with different sensitivity to cisplatin (Mia PaCa-2, PANC-1, and YAPC). The two cationic analogues showed superimposable antiproliferative effects on the tested cells, without significant differences depending on alkyl chain length (Me or Et). On the other hand, they demonstrated to be more effective than cisplatin, especially on YAPC cancer cells. For the interesting cytotoxic activity observed on YAPC, further biological assays were performed, on this cancer cell line, to evaluate the apoptotic and antimetastatic properties of the considered platinum compounds (1 and 2). The cytotoxicity of 1 and 2 compounds appeared to be related to their intracellular accumulation, which was much faster than that of cisplatin. Both 1 and 2 compounds significantly induced apoptosis and cell cycle arrest, with a high accumulation of sub-G1 phase cells, compared to cisplatin. Moreover, phenanthroline-containing complexes caused a rapid loss of mitochondria membrane potential, ΔΨM, if compared to cisplatin, probably due to their cationic and lipophilic properties. On 3D tumor spheroids, 1 and 2 significantly reduced migrated area more than cisplatin, confirming an antimetastatic ability. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has caused significant changes in global sustainability, but specifically, this study analyses the impact of lockdown on health and behavior in the game of football. The 2020/2021 Italian football competitive season (indicated as "post-COVID"), taking place following an obliged lockdown and longer than the normal summery season break, was characterized by very short recovery times and was compared to the 2018–2019 "pre-COVID" season, which had a regular course. The comparisons were about anthropometric and hormonal responses, muscle damage, and the physical performance of players in the major league (Serie A), and were made considering two extreme points of the competitive seasons: before the preparatory period (T0) and at the end of the season (T1). Turning to the results, it is significant to note the following: (1) body fat percentage was lower at the start (T0) of the post-COVID season than at the start of the pre-COVID season. During both seasons, serum CK and LDH increased in T1 and were significantly higher in both T0 and T1 of the post-COVID season. (2) Cortisol and testosterone concentrations increased in both seasons from T0 to T1; however, in the post-COVID season, concentrations of both were higher than in the previous season. The testosterone to cortisol ratio increased at the end of the pre-COVID season, whilst strongly decreasing at T1 of the post-COVID season. (3) Blood lactate concentrations significantly decreased during the pre-COVID season but remained unchanged during the post-COVID season. We may conclude that the enforced suspension period and the consequent rapid resumption of all activities influenced the physical and physiological state of professional footballers. [ABSTRACT FROM AUTHOR]

NMR-based metabolomics is a very effective tool to assess the tumor response to drugs by providing insights for their mode of action. Recently, a novel Pt(II) complex, [Pt(ƞ1-C2H4OMe)(DMSO)(phen)]+ (phen = 1,10-phenanthroline), Pt-EtOMeSOphen, was synthesized and studied for its antitumor activity against eight human cancer cell lines. Pt-EtOMeSOphen showed higher cytotoxic effects than cisplatin in most of the cancer cell lines and in particular against the neuroblastoma cell line (SH-SY5Y). In this study, the mechanism of action of Pt-EtOMeSOphen on SH-SY5Y cells was investigated using 1H NMR-based metabolomics and compared with cisplatin. The observed time response of SH-SY5Y cells under treatment revealed a faster action of Pt-EtOMeSOphen compared with cisplatin, with a response already observed after six hours of exposure, suggesting a cytosolic target. NMR-based metabolomics demonstrated a peculiar alteration of the glutathione metabolism pathway and the diacylglycerol expression. [ABSTRACT FROM AUTHOR]

Information regarding cationic amino acid transport systems in thyroid is limited to Northern blot detection of [y.sup.+] LAT1 mRNA in the mouse. This study investigated cationic amino acid transport in PC cell line clone 3 (PC C13 cells), a thyroid follicular cell line derived from a normal Fisher rat retaining many features of normal differentiated follicular thyroid cells. We provide evidence that in PC C13 cells plasmalemmal transport of cationic amino acids is [Na.sup.+] independent and occurs, besides diffusion, with the contribution of high-affinity, carrier-mediated processes. Carrier-mediated transport is via [y.sup.+], [y.sup.+] L, and [b.sup.0, +] systems, as assessed by L-arginine uptake and kinetics, inhibition of L-arginine transport by N-ethylmaleimide and neutral amino acids, and L-cystine transport studies. [y.sup.+] L and [y.sup.+] systems account for the highest transport rate (with [y.sup.+] L > [y.sup.+]) and [b.sup.0, +] for a residual fraction of the transport. Uptake data correlate to expression of the genes encoding for CAT-1, CAT-2B, 4F2hc, [y.sup.+] LAT1, [y.sup.+] LAT2, rBAT, and [b.sup.0,+] AT, an expression profile that is also shown by the rat thyroid gland. In PC C13 cells cationic amino acid uptake is under TSH and/or cAMP control (with transport increasing with increasing TSH concentration), and upregulation of CAT-I, CAT-2B, 4F2hc/[y.sup.+] LAT1, and rBAT/[b.sup.0, +] AT occurs at the mRNA level under TSH stimulation. Our results provide the first description of an expression pattern of cationic amino acid transport systems in thyroid cells. Furthermore, we provide evidence that extracellular L-arginine is a crucial requirement for normal PC C13 cell growth and that long-term L-arginine deprivation negatively influences CAT-2B expression, as it correlates to reduction of CAT-2B mRNA levels. cationic amino acid transporters: heteromeric amino acid transporters: system [y.sup.+]: system [y.sup.+]L: system [b.sup.0, +]; thyrotropin: L-arginine