Sacituzumab govitecan (SG) is a new treatment option for patients with metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancer. This antibody–drug conjugate is currently approved as monotherapy. Palliative radiotherapy is frequently used to treat symptomatic metastases locally. Concurrent use of SG and irradiation was excluded in clinical trials of SG, and there are currently limited published data. We report here a systematic review, as well as a retrospective multi-center study of 17 patients with triple-negative breast cancer who received concurrent SG and radiotherapy. In these patients, concurrent use was found to be efficient, safe and well tolerated. There were no apparent differences in moderate or severe acute toxicity according to the timing of SG administration. Full article

DNA damage is fundamental to tumorigenesis, and the inability to repair DNA damage is a hallmark of many human cancers. DNA is repaired via the DNA damage repair (DDR) apparatus, which includes five major pathways. DDR deficiencies in cancers give rise to potential therapeutic targets, as cancers harboring DDR deficiencies become increasingly dependent on alternative DDR pathways for survival. In this review, we summarize the DDR apparatus, and examine the current state of research efforts focused on identifying vulnerabilities in DDR pathways that can be therapeutically exploited in pediatric extracranial solid tumors. We assess the potential for synergistic combinations of different DDR inhibitors as well as combinations of DDR inhibitors with chemotherapy. Lastly, we discuss the immunomodulatory implications of targeting DDR pathways and the potential for using DDR inhibitors to enhance tumor immunogenicity, with the goal of improving the response to immune checkpoint blockade in pediatric solid tumors. We review the ongoing and future research into DDR in pediatric tumors and the subsequent pediatric clinical trials that will be critical to further elucidate the efficacy of the approaches targeting DDR. Full article

(1) Background: We assessed the test–re-test repeatability of radiomics in metastatic castration-resistant prostate cancer (mCPRC) bone disease on whole-body diffusion-weighted (DWI) and T1-weighted Dixon MRI. (2) Methods: In 10 mCRPC patients, 1.5 T MRI, including DWI and T1-weighted gradient-echo Dixon sequences, was performed twice on the same day. Apparent diffusion coefficient (ADC) and relative fat-fraction-percentage (rFF%) maps were calculated. Per study, up to 10 target bone metastases were manually delineated on DWI and Dixon images. All 106 radiomic features included in the Pyradiomics toolbox were derived for each target volume from the ADC and rFF% maps. To account for inter- and intra-patient measurement repeatability, the log-transformed individual target measurements were fitted to a hierarchical model, represented as a Bayesian network. Repeatability measurements, including the intraclass correlation coefficient (ICC), were derived. Feature ICCs were compared with mean ADC and rFF ICCs. (3) Results: A total of 65 DWI and 47 rFF% targets were analysed. There was no significant bias for any features. Pairwise correlation revealed fifteen ADC and fourteen rFF% feature sub-groups, without specific patterns between feature classes. The median intra-patient ICC was generally higher than the inter-patient ICC. Features that describe extremes in voxel values (minimum, maximum, range, skewness, and kurtosis) showed generally lower ICCs. Several mostly shape-based texture features were identified, which showed high inter- and intra-patient ICCs when compared with the mean ADC or mean rFF%, respectively. (4) Conclusions: Pyradiomics texture features of mCRPC bone metastases varied greatly in inter- and intra-patient repeatability. Several features demonstrated good repeatability, allowing for further exploration as diagnostic parameters in mCRPC bone disease. Full article

Melatonin, primarily synthesized in the pineal gland, plays a crucial role in regulating circadian rhythms and possesses significant antioxidative properties. By neutralizing free radicals and reducing oxidative stress, melatonin emerges as a promising agent for the prevention and therapy of many different disorders, including cancer. This paper reviews the relationship between the thyroid gland and melatonin, presenting experimental evidence on the protective effects of this indoleamine against oxidative damage to macromolecules in thyroid tissue caused by documented carcinogens (as classified by the International Agency for Research on Cancer, IARC) or caused by potential carcinogens. Furthermore, the possible influence on cancer therapy in humans and the overall well-being of cancer patients are discussed. The article highlights melatonin’s essential role in maintaining thyroid health and its contribution to management strategies in patients with thyroid cancer and other thyroid diseases. Full article

Colorectal liver metastasis (CRLM) is a disease entity that warrants special attention due to its high frequency and potential curability. Identification of “high-risk” patients is increasingly popular for risk stratification and personalization of the management pathway. Traditional regression-based methods have been used to derive prediction models for these patients, and lately, focus has shifted to artificial intelligence-based models, with employment of variable supervised and unsupervised techniques. Multiple endpoints, like overall survival (OS), disease-free survival (DFS) and development or recurrence of postoperative complications have all been used as outcomes in these studies. This review provides an extensive overview of available clinical prediction models focusing on the prognosis of CRLM and highlights the different predictor types incorporated in each model. An overview of the modelling strategies and the outcomes chosen is provided. Specific patient and treatment characteristics included in the models are discussed in detail. Model development and validation methods are presented and critically appraised, and model performance is assessed within a proposed framework. Full article

FGFR3::TACC3 fusion is a driver, potentially targetable, genetic alteration identified in approximately 4% of high-grade diffuse gliomas and rare cases with low-grade histology. Herein, we review the genetic and epigenetic features of these tumors and highlight the challenges in their classification and grading. Diffuse gliomas with FGFR3::TACC3 fusion display unique histopathological and molecular features, including an oligodendroglioma-like appearance, calcifications, and CD34 extravascular immunoreactivity. High-grade tumors exhibit molecular alterations and a DNA methylation profile typical of glioblastoma, suggesting that they may represent a subtype clinically characterized by a slightly better prognosis. Tumors with low-grade morphology are genetically and epigenetically heterogeneous. Some, exclusive to adults, have molecular alterations typical of glioblastoma, although most do not match any methylation classes, using version 12.5 of the Heidelberg classifier. Another group, which mostly affects children or adolescents, lacks the molecular features of glioblastoma and has a DNA methylation profile similar to that of low-grade glioneuronal tumors. In conclusion, diffuse gliomas with FGFR3::TACC3 fusion do not constitute a distinct nosological entity, owing to their genetic and epigenetic diversity. Further studies are warranted to clarify the biological aggressiveness of tumors with low-grade histology to refine the grading and determine the optimal treatment strategy. Full article

In the last decades, the development of PET/CT radiopharmaceuticals, targeting the Prostate-Specific Membrane Antigen (PSMA), changed the management of prostate cancer (PCa) patients thanks to its higher diagnostic accuracy in comparison with conventional imaging both in staging and in recurrence. Alongside molecular imaging, PSMA was studied as a therapeutic agent targeted with various isotopes. In 2021, results from the VISION trial led to the Food and Drug Administration (FDA) approval of [¹⁷⁷Lu]Lu-PSMA-617 as a novel therapy for metastatic castration-resistant prostate cancer (mCRPC) and set the basis for a radical change in the future perspectives of PCa treatment and the history of Nuclear Medicine. Despite these promising results, primary resistance in patients treated with single-agent [¹⁷⁷Lu]Lu-PSMA-617 remains a real issue. Emerging trials are investigating the use of [¹⁷⁷Lu]Lu-PSMA-617 in combination with other PCa therapies in order to cover the multiple oncologic resistance pathways and to overcome tumor heterogeneity. In this review, our aim is to retrace the history of PSMA-targeted therapy from the first preclinical studies to its future applications in PCa. Full article

This study assessed the prevalence of myopia, cataracts, glaucoma, and macular degeneration among Koreans over 40, utilizing data from the 7th Korea National Health and Nutrition Examination Survey (KNHANES VII, 2018). We analyzed 204,973 adults (44% men, 56% women; mean age 58.70 ± 10.75 years), exploring the association between myopia and these eye diseases through multivariate logistic regression, adjusting for confounders and calculating adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results showed a myopia prevalence of 44.6%, cataracts at 19.4%, macular degeneration at 16.2%, and glaucoma at 2.3%, with significant differences across ages and genders. A potential link was found between myopia and an increased risk of cataracts and macular degeneration, but not with glaucoma. Additionally, a higher dietary intake of carbohydrates, polyunsaturated and n-6 fatty acids, vitamins, and minerals correlated with lower risks of these diseases, underscoring the importance of the diet in managing and preventing age-related eye conditions. These findings highlight the need for dietary considerations in public health strategies and confirm myopia as a significant risk factor for specific eye diseases in the aging Korean population. Full article

The aim of the present study was to evaluate depressive-like, anxiety-like, and perseverative-like behaviors in a binge eating model. Juvenile Wistar rats, using the binge eating model, were compared to caloric restriction, induced stress, and control groups. Rats of the induced stress group presented binge-like behaviors in standard food intake in the second cycle of the experiment when compared to the caloric restriction group and the binge eating model group. Depressive-like behavior was observed in the binge eating model group with longer immobility time (p < 0.001) and less swim time (p < 0.001) in comparison to the control group. Anxiety-like behavior was observed by shorter duration of burying latency in the binge eating model group when compared to the induced stress group (p = 0.04) and a longer duration of burying time when compared to the control group (p = 0.02). We observed perseverative-like behavior by the binge model group, who made more entries to the new arm (p = 0.0004) and spent a longer time in the new arm when compared to the control group (p = 0.0001). Our results show differences in behaviors between the groups of rats studied. These results suggest that calorie restriction–refeeding, along with stress, may lead to depressive-like, anxiety-like, and perseverative-like behavioral changes in male Wistar rats. Full article

Children with disabilities have higher prevalence estimates of obesity than typically developing children. The Healthy Caregivers–Healthy Children Phase 3 (HC3) project implemented an obesity prevention program adapted for children with special health care needs (CSHCN) that includes dietary intake and physical activity (PA) components. The primary outcome was a change in dietary intake, PA, and the body mass index (BMI) percentile. Ten childcare centers (CCCs) serving low-resource families with ≥30 2- to 5-year-olds attending were randomized to either the intervention (n = 5) or control (n = 5). The HC3 CCCs received (1) snack, beverage, PA, and screen time policies via weekly technical assistance; (2) adapted lesson plans for CSHCN; and (3) parent curricula. The control CCCs received a behavioral health attention curriculum. HC3 was delivered over three school years, with data collected at five different timepoints. It was delivered weekly for six months in year one. To ensure capacity building, the HC3 tasks were scaled back, with quarterly intervention delivery in year 2 and annually in year 3. Adaptations were made to the curriculum to ensure appropriate access for CSHCN. Given that the program was being delivered during the COVID-19 pandemic, special modifications were made to follow CDC safety standards. The primary outcome measures included the Environment and Policy Assessment and Observation (EPAO) tool, standardized dietary intake and PA assessments, and the child BMI percentile. CCCs are an ideal setting for targeting CSHCN for obesity prevention efforts as they provide an opportunity to address modifiable risk factors. Full article

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular diseases (CVDs) that has become a global public health problem. Puerarin (PUE), the principal active compound of Pueraria lobata, has the effects of regulating glucose and lipid metabolism and protecting against cardiovascular damage. This study aimed to investigate whether dietary supplementation with PUE could ameliorate MetS and its associated cardiovascular damage. Rats were randomly divided into three groups: the normal diet group (NC), the high-fat/high-sucrose diet group (HFHS), and the HFHS plus PUE diet group (HFHS-PUE). The results showed that PUE-supplemented rats exhibited enhanced glucose tolerance, improved lipid parameters, and reduced blood pressure compared to those on the HFHS diet alone. Additionally, PUE reversed the HFHS-induced elevations in the atherogenic index (AI) and the activities of serum lactate dehydrogenase (LDH) and creatine kinase (CK). Ultrasonic evaluations indicated that PUE significantly ameliorated cardiac dysfunction and arterial stiffness. Histopathological assessments further confirmed that PUE significantly mitigated cardiac remodeling, arterial remodeling, and neuronal damage in the brain. Moreover, PUE lowered systemic inflammatory indices including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII). In conclusion, dietary supplementation with PUE effectively moderated metabolic disorders, attenuated systemic inflammation, and minimized cardiovascular damage in rats with MetS induced by an HFHS diet. These results provide novel insights into the potential benefits of dietary PUE supplementation for the prevention and management of MetS and its related CVDs. Full article

The presence of vitamin D3 deficiency associated with the presence of metabolic syndrome (MS) has important public health effects. This study aims to investigate the relationship between vitamin D3 deficiency, MS and vitamin D3 receptor (VDR), GC Vitamin D binding protein (GC), and cytochrome P450 family 2 subfamily R member 1 (CYP2R1) gene polymorphisms, and genes whose encoded proteins are responsible for vitamin D3 metabolism and transport. A total of 58 participants were included in this study (age 39 ± 12 years) and were selected over a 12-month period. They were divided into four groups, depending on the presence of polymorphisms in VDR, GC, and CYP2R1 genes and their weight status. At baseline, in months 3, 6, and 12, biochemical parameters including 25(OH)D3, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and homeostatic model assessment (HOMA index), the insulin resistance indicator were measured. Our results show that all subjects in the polymorphism group supplemented with vitamin D3 reached an optimal level of vitamin D3 associated with high concentrations of 25(OH)D3. Weight loss was most significant in patients in the POW group (overweight patients). Full article

Vitamin D3 (VD3) is a steroid hormone that plays pivotal roles in pathophysiology, and 1,25(OH)2D3 is the most active form of VD3. In the current study, the crucial role of VD3 in maintaining energy homeostasis under short-term fasting conditions was investigated. Our results confirmed that glucose-depriving pathways were inhibited while glucose-producing pathways were strengthened in zebrafish after fasting for 24 or 48 h. Moreover, VD3 anabolism in zebrafish was significantly suppressed in a time-dependent manner under short-fasting conditions. After fasting for 24 or 48 h, zebrafish fed with VD3 displayed a higher gluconeogenesis level and lower glycolysis level in the liver, and the serum glucose was maintained at higher levels, compared to those fed without VD3. Additionally, VD3 augmented the expression of fatty acids (FAs) transporter cd36 and lipogenesis in the liver, while enhancing lipolysis in the dorsal muscle. Similar results were obtained in cyp2r1^−/− zebrafish, in which VD3 metabolism is obstructed. Importantly, it was observed that VD3 induced the production of gut GLP-1, which is considered to possess a potent gluconeogenic function in zebrafish. Meanwhile, the gene expression of proprotein convertase subtilisin/kexin type 1 (pcsk1), a GLP-1 processing enzyme, was also induced in the intestine of short-term fasted zebrafish. Notably, gut microbiota and its metabolite acetate were involved in VD3-regulated pcsk1 expression and GLP-1 production under short-term fasting conditions. In summary, our study demonstrated that VD3 regulated GLP-1 production in zebrafish by influencing gut microbiota and its metabolite, contributing to energy homeostasis and ameliorating hypoglycemia under short-term fasting conditions. Full article

Acne vulgaris (AV) significantly reduces the quality of life (QoL) of young people, so it is important to look for factors that can improve their QoL. The aim of this study was to assess the relationship between dietary antioxidants measured using the new DAQI index and QoL measured using standardized tests. The DAQI included the following elements: antioxidant vitamins, minerals, carotenoids, polyphenols, phytosterols, lignans, and the total antioxidant capacity of the diet. The study involved 165 young women with AV, mainly students. A self-report survey was used to collect basic data on their sociodemographic status, anthropometric information, and lifestyle. The energy value of the diet and the content of vitamins, minerals, and carotenoids with antioxidant activity in the diet were estimated using 3-day food diaries and the Diet 6.0 program. The antioxidant potential of the diet and the content of polyphenols, phytosterols, lignans, and selenium were calculated based on the consumption of individual food products and available databases. The results of this study showed that the QoL of the young women with AV was impaired. However, greater adherence to an antioxidant diet reduces the risk of AV impact on the QoL by approximately 30–32% and the risk of depression by 33%. The DAQI may be used as a new indicator of diet quality in acne vulgaris. Full article

Background and Methods: Pancreatico-duodenectomy (PD) carries significant morbidity and mortality, with very few modifiable risk factors. Radiological evidence of sarcopenia is associated with poor outcomes. This retrospective study aimed to analyse the relationship between easy-to-use bedside nutritional assessment techniques and radiological markers of muscle loss to identify those patients most likely to benefit from prehabilitation. Results: Data were available in 184 consecutive patients undergoing PD. Malnutrition was present in 33–71%, and 48% had a high visceral fat-to-skeletal muscle ratio, suggestive of sarcopenic obesity (SO). Surgical risk was higher in patients with obesity (OR 1.07, 95%CI 1.01–1.14, p = 0.031), and length of stay was 5 days longer in those with SO (p = 0.006). There was no correlation between skeletal muscle and malnutrition using percentage weight loss or the malnutrition universal screening tool (MUST), but a weak correlation between the highest hand grip strength (HGS; 0.468, p < 0.001) and the Global Leadership in Malnutrition (GLIM) criteria (−0.379, p < 0.001). Conclusions: Nutritional assessment tools give widely variable results. Further research is needed to identify patients at significant nutritional risk prior to PD. In the meantime, those with malnutrition (according to the GLIM criteria), obesity or low HGS should be referred to prehabilitation. Full article

To assess the correlation between vitamin D status and body composition variables in adult women of childbearing age, a cross-sectional study was conducted involving women aged 20–49 years. The participants were categorized based on their vitamin D status and further divided according to body mass index (BMI). Anthropometric and biochemical data were collected to compute body composition indices, specifically body fat and muscle mass. The sample included 124 women, with 63.70% exhibiting vitamin D inadequacy. Women with inadequate vitamin D status demonstrated a higher waist-to-height ratio (WHtR) and body adiposity index (BAI), along with a lower BMI-adjusted muscle mass index (SMI _BMI), compared to those with adequate levels of vitamin D (p = 0.021; p = 0.019; and p = 0.039, respectively). A positive correlation was observed between circulating concentrations of 25(OH)D and SMI _BMI, while a negative correlation existed between circulating concentrations of 25(OH)D and waist circumference (WC), WHtR, conicity index (CI), fat mass index (FMI), body fat percentage (% BF), and fat-to-muscle ratio (FMR). These findings suggest that inadequate vitamin D status may impact muscle tissue and contribute to higher body adiposity, including visceral adiposity. It is recommended that these variables be incorporated into clinical practice, with a particular emphasis on WHtR and SMI _BMI, to mitigate potential metabolic consequences associated with vitamin D inadequacy. Full article

Recording large amounts of users’ sessions performed through 3D applications may provide crucial insights into interaction patterns. Such data can be captured from interactive experiences in public exhibits, remote motion tracking equipment, immersive XR devices, lab installations or online web applications. Immersive analytics (IA) deals with the benefits and challenges of using immersive environments for data analysis and related design solutions to improve the quality and efficiency of the analysis process. Today, web technologies allow us to craft complex applications accessible through common browsers, and APIs like WebXR allow us to interact with and explore virtual 3D environments using immersive devices. These technologies can be used to access rich, immersive spaces but present new challenges related to performance, network bottlenecks and interface design. WebXR IA tools are still quite new in the literature: they present several challenges and leave quite unexplored the possibility of synchronous collaborative inspection. The opportunity to share the virtual space with remote analysts in fact improves sense-making tasks and offers new ways to discuss interaction patterns together, while inspecting captured records or data aggregates. Furthermore, with proper collaborative approaches, analysts are able to share machine learning (ML) pipelines and constructively discuss the outcomes and insights through tailored data visualization, directly inside immersive 3D spaces, using a web browser. Under the H2IOSC project, we present the first results of an open-source pipeline involving tools and services aimed at capturing, processing and inspecting interactive sessions collaboratively in WebXR with other analysts. The modular pipeline can be easily deployed in research infrastructures (RIs), remote dedicated hubs or local scenarios. The developed WebXR immersive analytics tool specifically offers advanced features for volumetric data inspection, query, annotation and discovery, alongside spatial interfaces. We assess the pipeline through users’ sessions captured during two remote public exhibits, by a WebXR application presenting generative AI content to visitors. We deployed the pipeline to assess the different services and to better understand how people interact with generative AI environments. The obtained results can be easily adopted for a multitude of case studies, interactive applications, remote equipment or online applications, to support or accelerate the detection of interaction patterns among remote analysts collaborating in the same 3D space. Full article

The stability and reliability of the global Internet infrastructure heavily rely on the Border Gateway Protocol (BGP), a crucial protocol that facilitates the exchange of routing information among various Autonomous Systems, ensuring seamless connectivity worldwide. However, BGP inherently possesses a susceptibility to abnormal routing behaviors, potentially leading to significant connectivity disruptions. Despite extensive efforts, accurately detecting and effectively mitigating such abnormalities persist as tough challenges. To tackle these, this article proposes a novel statistical approach employing the median absolute deviation under certain constraints to proactively detect anomalies in BGP. By applying advanced analysis techniques, this research offers a robust method for the early detection of anomalies, such as Internet worms, configuration errors, and link failures. This innovative approach has been empirically validated, achieving an accuracy rate of 90% and a precision of 95% in identifying these disruptions. This high level of precision and accuracy not only confirms the effectiveness of the statistical method employed but also marks a significant step forward for enhancing the stability and reliability of the global Internet infrastructure. Full article

Understanding species from an ecological and phylogenetic perspective facilitates an understanding of their conservation status in relation to the changing world. The frog genus Pelophylax is among the largest in terms of amphibian biomass in the Palearctic, but species have not been thoroughly studied at the Asian continental scale. The phylogeographic relationship, behavioural ecology, and ecological requirements within the genus need clarification, despite generally good local coverage. Here, for the first time, we conducted a literature review focused on phylogeography and behavioural ecology, supported by ecological niche modelling of twelve Asian Pelophylax lineages. Finally, we compiled the known threats for each of the lineages. We first determined the presence of twelve species and species-candidate lineages. In terms of behavioural ecology, the main difference among lineages is the time to metamorphosis and the time to reach sexual maturity. The ecological models highlighted a match between the known presence of each clade and their suitable habitat and highlighted the Syr Darya drainage on the eastern shore of the Caspian Sea for the non-described Pelophylax “Syr Darya lineage”. Finally, we highlighted the greatest variation among lineages in terms of threats, as some lineages are threatened by numerous factors, whereas others are expanding. Full article

Pixel-level classification of very-high-resolution images is a crucial yet challenging task in remote sensing. While transformers have demonstrated effectiveness in capturing dependencies, their tendency to partition images into patches may restrict their applicability to highly detailed remote sensing images. To extract latent contextual semantic information from high-resolution remote sensing images, we proposed a gaze–saccade transformer (GSV-Trans) with visual perceptual attention. GSV-Trans incorporates a visual perceptual attention (VPA) mechanism that dynamically allocates computational resources based on the semantic complexity of the image. The VPA mechanism includes both gaze attention and eye movement attention, enabling the model to focus on the most critical parts of the image and acquire competitive semantic information. Additionally, to capture contextual semantic information across different levels in the image, we designed an inter-layer short-term visual memory module with bidirectional affinity propagation to guide attention allocation. Furthermore, we introduced a dual-branch pseudo-label module (DBPL) that imposes pixel-level and category-level semantic constraints on both gaze and saccade branches. DBPL encourages the model to extract domain-invariant features and align semantic information across different domains in the feature space. Extensive experiments on multiple pixel-level classification benchmarks confirm the effectiveness and superiority of our method over the state of the art. Full article

Water bodies can offer local microclimates that have the potential to attenuate the effects of urban heat islands by reducing local temperature. This capability is shaded when the river is channelized. In such cases, the river temperature rises during hot periods, leading to negative impacts on the water quality. The main aim of this paper is to develop a local simple model to predict the temperature of the Dâmbovița River at its exit from Bucharest City, the capital of Romania. The location is chosen based on the historical critical impacts, in terms of extreme heatwaves that took place during hot summers, as well as future possible risks due to climate change. The water temperature prediction model is based on an artificial neural network that uses the Levenberg–Marquardt algorithm, due to its stability and rapid convergence capabilities. The model forecasts, with an accuracy of ±1 °C, the water temperature in an ungauged, downstream location, as a function of measured air and upstream water temperatures. The proposed model represents a first attempt to provide water managers in Bucharest City with a useful tool that will allow them to take timely measures to counteract the unwanted effects that can be generated by high water temperatures. Full article