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Malignant tumors are a leading cause of death worldwide, second only to cardiovascular disease. They occur in every population and have a high risk of mortality. The etiopathogenesis of malignant tumors is diverse and there are still many unknowns, leading to huge diagnostic and therapeutic challenges. Therefore, the search for ideal diagnostic and therapeutic agents is ongoing. One of the promising factors affecting cancer is the nucleus accumbens associated protein 1 (NACC1). It is a transcriptional coregulator. Moreover, it plays a multifaceted role in promoting tumorigenesis. NACC1 expression analyses were performed using The Cancer Genome Atlas (TCGA) data accessed from the University of Alabama at Birmingham Cancer (UALCAN) database, and the expression data were interconnected with clinicopathological parameters. All statistical analyses were conducted using GraphPad Prism and Statistica. The results revealed that NACC1 was expressed in almost all of the analyzed cancers, and its expression level correlates with different clinicopathological parameters. This study demonstrates that NACC1 is potentially involved in the pathogenesis, invasion, and immune response associated with many cancers. However, NACC1 is not a suitable candidate as a diagnostic biomarker as it is not specific for any type of malignancy and there are discrepancies in its expression in relation to many clinicopathological parameters. The implementation of NACC1 as a therapeutic target may improve the effectiveness of cancer treatments.

Research on different types of ionizing radiation's effects has been ongoing for years, revealing its efficacy in damaging cancer cells. Solid tumors comprise diverse cell types, each being able to respond differently to radiation. This study evaluated the radiobiological response of established (MDA-MB-231 (Triple negative breast cancer, TNBC), MCF-7 (Luminal A)) and patient-derived malignant cell lines, cancer-associated fibroblasts, and skin fibroblasts following proton IRR. All cell line types were irradiated with the proton dose of 2, 4, and 6 Gy. The radiobiological response was assessed using clonogenic assay, γH2AX, and p53 staining. It was noticeable that breast cancer lines of different molecular subtypes displayed no significant variations in their response to proton IRR. In terms of cancer-associated fibroblasts extracted from the tumor tissue, the line derived from a TNBC subtype tumor demonstrated higher resistance to ionizing radiation compared to lines isolated from luminal A tumors. Fibroblasts extracted from patients' skin responded identically to all doses of proton radiation. This study emphasizes that tumor response is not exclusively determined by the elimination of breast cancer cells, but also takes into account tumor microenvironmental variables and skin reactions.

Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Although the incidence is decreasing in developed countries, the treatment results are still unsatisfactory. The standard treatment for locally advanced gastric cancer (LAGC) is gastrectomy with perioperative chemotherapy. The association of selected microRNAs (miRNAs) with chemoresistance was assessed using archival material of patients with LAGC. Histological material was obtained from each patient via a biopsy performed during gastroscopy and then after surgery, which was preceded by four cycles of neoadjuvant chemotherapy (NAC) according to the FLOT or FLO regimen. The expression of selected miRNAs in the tissue material was assessed, including miRNA-21-3p , miRNA-21-5p , miRNA-106a-5p , miRNA-122-3p , miRNA-122-5p , miRNA-143-3p , miRNA-143-5p , miRNA-203a-3p , miRNA-203-5p , miRNA-551b-3p , miRNA-551b-5p , and miRNA-574-3p . miRNA expression was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The response to NAC was assessed using computed tomography of the abdomen and chest and histopathology after gastrectomy. The statistical analyses were performed using GraphPad Prism 9. The significance limit was set at p < 0.05. We showed that the expression of miR-143-3p , miR-143-5p , and miR-574-3p before surgery, and miR-143-5p and miR-574-3p after surgery, decreased in patients with GC. The expression of miR-143-3p , miR-143-5p , miR-203a-3p , and miR-551b-5p decreased in several patients who responded to NAC. The miRNA most commonly expressed in these cases was miRNA-551b-5p . Moreover, it showed expression in a patient whose response to chemotherapy was inconsistent between the histopathological results and computed tomography. The expression of miR-143-3p , miR-143-5p , miR-203a-3p , and miR-551b-5p in formalin-fixed paraffin-embedded tissue (FFPET) samples can help differentiate between the responders and non-responders to NAC in LAGC. miR-143-3p , miR-143-5p , and miR-574-3p expression may be used as a potential diagnostic tool in GC patients. The presence of miR-551b-5p may support the correct assessment of a response to NAC in GC via CT.

Hypo-fractionated stereotactic body radiation therapy (SBRT) is an effective treatment for prostate cancer (PCa). Although many studies have investigated the effects of SBRT on the prostate and adjacent organs, little is known about the effects further out-of-field. The aim of this study was to investigate, both in vitro and in a quasi-humanoid phantom, the biological effects (using a dose-scaling approach) of radiation in the out-of-field peripheral organs delivered by 6 MV volumetric modulated arc therapy (VMAT) SBRT in a prostate cancer model. Healthy prostate cells were irradiated in a phantom at locations corresponding to the prostate, intestine, lung, thyroid, and brain. Seven 10 Gy fractions of VMAT SBRT were delivered to the target in a single session without intermission (scaled-up method). Radiochromic films were used to measure the doses. The radiobiological response was assessed by measuring DNA breaks, the cell survival fraction, and differences in gene expression profile. Our results showed a strong, multiparametric radiobiological response of the cells in the prostate. Outside of the radiation field, the highest doses were observed in the intestine and lung. A small increase (not statistically significant) in DNA damage and cell death was observed in the intestines. Several gene groups (cell cycle, DNA replication) were depleted in the lung and thyroid (DNA replication, endocytosis), but further analysis revealed no changes in the relevant biological processes. This study provides extensive evidence of the types and extent of radiobiological responses during VMAT SBRT in a prostate cancer model. Additional research is needed to determine whether the radiobiological effects observed in the peripheral organs are validated in a clinical context.

Among the most investigated hypotheses for a radiobiological explanation of the mechanism behind the FLASH effect in ultra-high dose rate radiotherapy, intertrack recombination between particle tracks arriving at a close spatiotemporal distance has been suggested. In the present work, we examine these conditions for different beam qualities and energies, defining the limits of both space and time where a non-negligible chemical effect is expected. To this purpose the TRAX-CHEM chemical track structure Monte Carlo code has been extended to handle several particle tracks at the same time, separated by pre-defined spatial and temporal distances. We analyzed the yields of different radicals as compared to the non-interacting track conditions and we evaluated the difference. We find a negligible role of intertrack for spatial distances larger than 1 μ m, while for temporal distances up to μ s, a non-negligible interaction is observed especially at higher LET. In addition, we emphasize the non-monotonic behavior of some relative yield as a function of the time separation, in particular of H 2 O 2 , due to the onset of a different reaction involving solvated electrons besides well-known O H · recombination. [ABSTRACT FROM AUTHOR]

Radiation therapy or radiotherapy is a medical treatment that uses high doses of ionizing radiation to eliminate cancer cells and shrink tumors. It works by targeting the DNA within the tumor cells restricting their proliferation. Radiotherapy has been used for treating cancer for more than 100 years. Along with surgery and chemotherapy, it is one of the three main and most common approaches used in cancer therapy. Nowadays, radiotherapy has become a standard treatment option for a wide range of cancers around the world, including lung, breast, cervical, and colorectal cancers. Around 50% of all patients will require radiotherapy, 60% of whom are treated with curative intent. Moreover, it is commonly used for palliative treatment. Radiotherapy provides 5-year local control and overall survival benefit in 10.4% and 2.4% of all cancer patients, respectively. The highest local control benefit is reported for cervical (33%), head and neck (32%), and prostate (26%) cancers. But no benefit is observed in pancreas, ovary, liver, kidney, and colon cancers. Such relatively low efficiency is related to the development of radiation resistance, which results in cancer recurrence, metastatic dissemination, and poor prognosis. The identification of radioresistance biomarkers allows for improving the treatment outcome. These biomarkers mainly include proteins involved in metabolism and cell signaling pathways. [ABSTRACT FROM AUTHOR]

The vast majority of breast cancer patients require radiotherapy but some of them will develop local recurrences and potentially metastases in the future. Recent data show that exosomal cargo is essential in these processes. Thus, we investigated the influence of ionising radiation on exosome properties and their ability to modify the sensitivity and biology of non-irradiated cells. Exosomes were isolated from breast cancer cell lines (MDA-MB-231, MCF7, and SKBR3) irradiated with 2 Gy (Exo 2 Gy) or no irradiation (Exo 0 Gy). Despite some differences in their molecular profiles, they did not affect cell viability, proliferation, cell cycle phase distribution, and radioresistance; however, both populations showed the ability to modify cell migration and invasion potential, as confirmed by the downregulation of β-catenin, which is responsible for maintaining the epithelial phenotype. Interestingly, exosomes from irradiated BCa cells were more actively deposited in the endothelial cells (EA.hy926). Furthermore, exosomes tend to lower the expression of CD31, which is responsible for maintaining intact vascularity. This preliminary study demonstrates the vital role of exosomes and their altered profile due to irradiation in the pathobiology of breast cancer. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cervical cancer is a significant global health concern, with high incidence and mortality rates, especially in less-developed regions. [18F]FDG PET/CT is now indicated at various stages of management, but its analysis is essentially based on SUVmax, a measure of [18F]FDG uptake. Radiomics, by extracting a multitude of parameters, promises to improve the diagnostic and prognostic performance of the examination. However, studies remain heterogeneous, both in terms of patient numbers and methods, so a synthesis is needed. Methods: This systematic review was conducted following PRISMA-P guidelines and registered in PROSPERO (CRD42024584123). Eligible studies on PET/CT radiomics in cervical cancer were identified through PubMed and Scopus and assessed for quality using the Radiomics Quality Score (RQS v2.0), with data extraction focusing on study design, population characteristics, radiomic methods, and model performances. Results: The review identified 22 studies on radiomics in cervical cancer, 19 of which focused specifically on locally advanced cervical cancer (LACC) and assessed various clinical outcomes, such as survival, relapse, treatment response, and lymph node involvement prediction. They reported significant associations between prognostic indicators and radiomic features, indicating the potential of radiomics to improve the predictive accuracy for patient outcomes in LACC; however, the overall quality of the studies was relatively moderate, with a median RQS of 12/36. Conclusions: While radiomic analysis in cervical cancer presents promising opportunities for survival prediction and personalized care, further well-designed studies are essential to provide stronger evidence for its clinical utility. [ABSTRACT FROM AUTHOR]

The gold standard assay for radiation response is the clonogenic assay, a normalized colony formation assay (CFA) that can capture a broad range of radiation-induced cell death mechanisms. Traditionally, this assay relies on two-dimensional (2D) cell culture conditions with colonies counted by fixing and staining protocols. While some groups have converted these to three-dimensional (3D) conditions, these models still utilize 2D-like media compositions containing serum that are incompatible with stem-like cell models such as brain tumor initiating cells (BTICs) that form self-aggregating spheroids in neural stem cell media. BTICs are the preferred patient-derived model system for studying glioblastoma (GBM) as they tend to better retain molecular and phenotypic characteristics of the original tumor tissue. As such, it is important that preclinical radiation studies should be adapted to BTIC conditions. In this study, we describe a series of experimental approaches for performing CFA experiments with BTIC cultures. Our results indicate that serum-free clonogenic assays are feasible for combination drug and radiation testing and may better facilitate translatability of preclinical findings. [ABSTRACT FROM AUTHOR]

Tooth and periodontal organoids from stem and progenitor cells represent a significant advancement in regenerative dentistry, offering solutions for tooth loss and periodontal diseases. These organoids, which mimic the architecture and function of real organs, provide a cutting-edge platform for studying dental biology and developing therapies. Recent methodologies have been developed to optimize conditions for organoid production, advancing dental regenerative medicine, disease modeling, and developmental studies. The integration of bioengineering strategies with culture techniques enhances both our understanding and the therapeutic potential of these organoids. Additionally, factors such as the extracellular matrix, growth factors, and culture systems profoundly influence organoid formation and maturation. This review explores various bioengineering approaches for generating organoids, emphasizing the pivotal role of stem and progenitor cells. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton minibeam radiation therapy (pMBRT) is a technique using spatial fractionation of a proton field to treat cancer. Evidence suggests there is improved sparing of healthy tissue when spatially fractionating the beam without any loss of tumor control. Development of this technique could therefore improve the clinical outcome for patients. Primary standard dosimetry will be required for safe implementation in the clinic. The spatial fractionation of the field, however, makes the dosimetry challenging, as small positioning uncertainties for devices used for dosimetry can lead to large differences in the measured dose. This work examined the current feasibility of operating a primary standard-level dosimetry device in an experimental pMBRT field, and suggests dosimetric improvements necessary to assist the adoption of the technique in the clinic. Background/Objectives: Spatial fractionation of proton fields as sub-millimeter beamlets to treat cancer has shown better sparing of healthy tissue whilst maintaining the same tumor control. It is critical to ensure primary standard dosimetry is accurate and ready to support the modality's clinical implementation. Methods: This work provided a proof-of-concept, using the National Physical Laboratory's Primary Standard Proton Calorimeter (PSPC) to measure average absorbed dose-to-water in a pMBRT field. A 100 MeV mono-energetic field and a 2 cm wide SOBP were produced with a spot-scanned proton beam incident on a collimator comprising 15 slits of 400 µm width, each 5 cm long and separated by a center-to-center distance of 4 mm. Results: The results showed the uncertainty on the absorbed dose-to-water in the mono-energetic beam was dominated by contributions of 1.4% and 1.1% ( k = 1) for the NPL PSPC and PTW Roos chambers, respectively, originating from the achievable positioning accuracy of the devices. In comparison, the uncertainty due to positioning in the SOBP for both the NPL PSPC and PTW Roos chambers were 0.4%. Conclusions: These results highlight that it may be more accurate and reliable to perform reference dosimetry measuring the Dose-Area Product or in an SOBP for spatially fractionated fields. [ABSTRACT FROM AUTHOR]

In radiation tumor therapy, irradiation, on one hand, should cause cell death to the tumor. On the other hand, the surrounding non-tumor tissue should be maintained unaffected. Therefore, methods of local dose enhancements are highly interesting. Gold nanoparticles, which are preferentially uptaken by very-fast-proliferating tumor cells, may enhance damaging. However, the results in the literature obtained from cell culture and animal tissue experiments are very contradictory, i.e., only some experiments reveal increased cell killing but others do not. Thus, a better understanding of cellular mechanisms is required. Using the breast cancer cell model SkBr3, the effects of gold nanoparticles in combination with ionizing radiation on chromatin network organization were investigated by Single-Molecule Localization Microscopy (SMLM) and applications of mathematical topology calculations (e.g., Persistent Homology, Principal Component Analysis, etc.). The data reveal a dose and nanoparticle dependent re-organization of chromatin, although colony forming assays do not show a significant reduction of cell survival after the application of gold nanoparticles to the cells. In addition, the spatial organization of γH2AX clusters was elucidated, and characteristic changes were obtained depending on dose and gold nanoparticle application. The results indicate a complex response of ALU-related chromatin and heterochromatin organization correlating to ionizing radiation and gold nanoparticle incorporation. Such complex whole chromatin re-organization is usually associated with changes in genome function and supports the hypothesis that, with the application of gold nanoparticles, not only is DNA damage increasing but also the efficiency of DNA repair may be increased. The understanding of complex chromatin responses might help to improve the gold nanoparticle efficiency in radiation treatment. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) has been shown to be a cornerstone of both palliative and curative tumor care. RT has generally been reported to be sharply limited by ionizing radiation (IR)-induced toxicity, thereby constraining the control effect of RT on tumor growth. FLASH-RT is the delivery of ultra-high dose rate (UHDR) several orders of magnitude higher than what is presently used in conventional RT (CONV-RT). The FLASH-RT clinical trials have been designed to examine the UHDR deliverability, the effectiveness of tumor control, the dose tolerance of normal tissue, and the reproducibility of treatment effects across several institutions. Although it is still in its infancy, FLASH-RT has been shown to have potential to rival current RT in terms of safety. Several studies have suggested that the adoption of FLASH-RT is very limited, and the incorporation of this new technique into routine clinical RT will require the use of accurate dosimetry methods and reproducible equipment that enable the reliable and robust measurements of doses and dose rates. The purpose of this review is to highlight the advantages of this technology, the potential mechanisms underpinning the FLASH-RT effect, and the major challenges that need to be tackled in the clinical transfer of FLASH-RT. [ABSTRACT FROM AUTHOR]

Simple Summary: Locally advanced cervical cancer (LACC) poses a significant challenge in oncology due to its heterogeneous nature and inconsistent response to standard chemoradiation therapy. The ability to predict response to treatment early in LACC has profound implications for enhancing patient care through tailored and adaptive therapies. Sequential FDG-PET imaging is crucial in managing LACC, offering a non-invasive method to assess tumor progression and response to chemoradiation over the course of treatment. The current study had recourse to longitudinal FDG-PET radiomics for early prediction of treatment response to chemoradiation in LACC. The implications of this study aid in demonstrating the potentially pivotal role of longitudinal radiomics in personalized medicine and improving therapeutic outcomes for LACC. Objectives: This study aimed to assess the capacity of longitudinal FDG-PET radiomics for early distinguishing between locally advanced cervical cancer (LACC) patients who responded to treatment and those who did not. Methods: FDG-PET scans were obtained before and midway through concurrent chemoradiation for a study cohort of patients with LACC. Radiomics features related to image textures were extracted from the primary tumor volumes and stratified for relevance to treatment response status with the aid of random forest recursive feature elimination. Predictive models based on the k-nearest neighbors time series classifier were developed using the top-selected features to differentiate between responders and non-responders. The performance of the developed models was evaluated using receiver operating characteristic (ROC) curve analysis and n-fold cross-validation. Results: The top radiomics features extracted from scans taken midway through treatment showed significant differences between the two responder groups (p-values < 0.0005). In contrast, those from pretreatment scans did not exhibit significant differences. The AUC of the mean ROC curve for the predictive model based on the top features from pretreatment scans was 0.8529, while it reached 0.9420 for those derived midway through treatment scans. Conclusions: The study highlights the potential of longitudinal FDG-PET radiomics extracted midway through treatment for predicting response to chemoradiation in LACC patients and emphasizes that interim PET scans could be crucial in personalized medicine, ultimately enhancing therapeutic outcomes for LACC. [ABSTRACT FROM AUTHOR]

The retina is crucial for converting light into neuronal signals for visual perception. Understanding the retina's structure, function, and development is essential for vision research. It is known that the thyroid hormone (TH) receptor type beta 2 (TRβ2) is a key element in the regulation of cone differentiation in the retina, but other elements of TH signaling, such as transporters and enzyme deiodinases, have also been implicated in retinal cell development and survival. In the present study, we investigated the expression profile of genes involved in TH signaling and analyzed the impact of thyroidal status on retinal morphology, opsin expression, cell death/proliferation profile, as well as color preference behavior during the early retina development of zebrafish larvae. mRNA expression analysis on dissected whole eyes revealed that TH signaling elements gradually increase during eye development, with dio3b being the component that shows the most dramatic change. Mutations generated by CRISPR/CAS9 in the dio3b gene, but not in the thrb gene, modifies the structure of the retina. Disruption in TH level reduces the cell number of the ganglion cell layer, increases cell death, and modifies color preference, emphasizing the critical importance of precise TH regulation by its signaling elements for optimal retinal development and function. [ABSTRACT FROM AUTHOR]

Multiciliated cells (MCCs) serve many important functions, including fluid propulsion and chemo- and mechanosensing. Diseases ranging from rare conditions to the recent COVID-19 global health pandemic have been linked to MCC defects. In recent years, the zebrafish has emerged as a model to investigate the biology of MCCs. Here, we review the major events in MCC formation including centriole biogenesis and basal body docking. Then, we discuss studies on the role of MCCs in diseases of the brain, respiratory, kidney and reproductive systems, as well as recent findings about the link between MCCs and SARS-CoV-2. Next, we explore why the zebrafish is a useful model to study MCCs and provide a comprehensive overview of previous studies of genetic components essential for MCC development and motility across three major tissues in the zebrafish: the pronephros, brain ependymal cells and nasal placode. Taken together, here we provide a cohesive summary of MCC research using the zebrafish and its future potential for expanding our understanding of MCC-related disease states. [ABSTRACT FROM AUTHOR]

Psychedelics have recently (re)emerged as therapeutics of high potential for multiple mental health conditions, including substance use disorders (SUDs). Despite early mid-20th century anecdotal reports and pilot studies demonstrating the possibility of these substances in efficaciously treating conditions such as alcohol and opioid use disorders, legal restrictions and social stigma have historically hindered further research into this area. Nevertheless, concurrent with the rise in SUDs and other mental health conditions, researchers have again turned their attention to these compounds, searching for differing pharmacological targets as well as more holistic treatments that might increase patient adherence and efficacy. The aim of this review is to examine the emerging evidence-based data with regards to the therapeutic treatment of SUDs with the psychedelic compounds psilocybin, ketamine, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), ayahuasca, ibogaine and peyote. [ABSTRACT FROM AUTHOR]

The linker of nucleoskeleton and cytoskeleton (LINC) complex, which spans the nuclear envelope, physically connects nuclear components to the cytoskeleton and plays a pivotal role in various cellular processes, including nuclear positioning, cell migration, and chromosomal configuration. Studies have revealed that the LINC complex is essential for different aspects of the nervous system, particularly during development. The significance of the LINC complex in neural lineage cells is further corroborated by the fact that mutations in genes associated with the LINC complex have been implicated in several neurological diseases, including neurodegenerative and psychiatric disorders. In this review, we aimed to summarize the expanding knowledge of LINC complex-related neuronal functions and associated neurological diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: This study establishes in vitro criteria for the safe and effective use of allogeneic canine mesenchymal stromal cells for potential orthopedic and therapeutic use. Allogeneic canine adipose-derived MSCs demonstrated MSC-specific characteristics and met in vitro requirements, providing a solid foundation for future in vivo research and clinical applications. Importantly, their shipping and cryobanking conditions and related procedures were also tested and validated. This validation ensures the establishment of an allogeneic canine adipose-derived mesenchymal stromal cell bank that can be used as an off-the-shelf therapy. In allogeneic MSC implantation, the cells are isolated from a donor different from the recipient. When tested, allogeneic MSCs have several advantages over autologous ones: faster cell growth, sufficient cell concentration, and readily available cells for clinics. To ensure the safe and efficient use of allogeneic MSCs in clinics, the MSCs need to be first tested in vitro. With this study, we paved the way by addressing the in vitro aspects of canine adipose-derived MSCs, considering the limited studies on the clinical use of canine cells. We isolated cAD-MSCs from canine falciform ligament fat and evaluated their viability and proliferation using an MTS assay. Then, we characterized the MSC-specific antigens using immunophenotyping and immunofluorescence and demonstrated their potential for in vitro differentiation. Moreover, we established shipping and cryobanking procedures to lead the study to become an off-the-shelf therapy. During expansion, the cells demonstrated a linear increase in cell numbers, confirming their proliferation quantitatively. The cells showed viability before and after cryopreservation, demonstrating that cell viability can be preserved. From a clinical perspective, the established shipping conditions demonstrated that the cells retain their viability for up to 48 h. This study lays the groundwork for the potential use of allogeneic cAD-MSCs in clinical applications. [ABSTRACT FROM AUTHOR]

This document provides a summary of a special issue titled "Advances in Particle Acceleration: Novel Techniques, Instruments, and Applications." The special issue covers various topics related to particle acceleration. It discusses recent advancements in accelerator technologies, including new materials, fabrication techniques, and novel acceleration methods. The document specifically focuses on the advancements in radiotherapy methods for cancer treatment, as well as the development of radioisotope therapy. It also explores the pursuit of compact light sources and advancements in accelerator technologies for enhanced miniaturization, power capacity, reliability, sustainability, and cost-efficiency. The special issue includes several papers that cover topics such as beam dynamics software, RF cavity optimization, niobium cavity coating, efficient accelerator lattice design, plasma accelerator concept, and improvements to electrostatic dust accelerators. Overall, the special issue provides valuable insights into the latest advancements in particle acceleration. [Extracted from the article]

Currently, the dominant gated communities (GCs) in Chinese cities have fragmented the urban road network, causing traffic congestion, energy consumption, carbon emissions, and environmental pollution. The morphological elements of GCs are key factors affecting road network connectivity. This paper aimed to explore the influence of the morphological elements of GCs on road network connectivity, to provide a quantitative basis for the evaluation and renovation of the connectivity of GCs, and to provide insights for urban planning and policy. This paper quantitatively analyzed the connectivity of GCs using 120 samples from the central districts of Jinan, China. Morphological elements were the independent variables, while route directness (RD) and the network distance (D) to the nearest entrance were the dependent variables. RD measured the internal connectivity, and D measured the connectivity between the internal and external road networks of GCs. GIS was used to measure RD and D, and SPSS was used to conduct a correlation analysis to identify significant variables. Multiple linear regression and LASSO regression were used to test the influence of these factors on RD and D. LASSO regression was employed to construct prediction models for RD and D. We found that intersection density had the greatest impact on RD, while the number of entrances and exits, and the scale of GCs, had the greatest impact on D. Using thresholds of D = 250 and RD = 1.3, the four types of GCs were classified and corresponding renovation measures were proposed. [ABSTRACT FROM AUTHOR]

Ampicillin (AMP) and amoxicillin (AMX) are popular antibiotics, which are penicillin derivatives, and are used in both human and veterinary medicine. In the conducted study, AMP, AMX and their mixtures did not cause major changes in the total bacterial counts in soil samples, and even an increase in the bacterial counts from 3,700,000 to 6,260,000 colony-forming units (cfu) per gram of soil dry weight (g of soil DW) was observed for minimal amounts of these drugs in the soil. The total abundance of fungi, on the other hand, increased from values ranging from 17,000 to 148,000 cfu∙g−1 of soil DW to a level of 32,000 to 131,000 cfu∙g−1 of soil DW. The tested antibiotics and their mixtures had no significant effect on the mortality and growth of H. incongruens. AMX and the AMP + AMX mixture also showed no effect on the plant fresh weight yield, plant aboveground part length and dry weight content of wheat seedlings. In contrast, AMP caused an increase in the plant fresh weight yield and wheat seedling length compared to the control. The drug also caused a slight decrease in the seedling dry weight content. Both AMP and AMX showed inhibitory effects on the plant root length at the highest concentrations of the compounds. [ABSTRACT FROM AUTHOR]

Ciliated epithelia are widespread in animals and play crucial roles in many developmental and physiological processes. Epithelia composed of multi-ciliated cells allow for directional fluid flow in the trachea, oviduct and brain cavities. Monociliated epithelia play crucial roles in vertebrate embryos, from the establishment of left–right asymmetry to the control of axis curvature via cerebrospinal flow motility in zebrafish. Cilia also have a central role in the motility and feeding of free-swimming larvae in a variety of marine organisms. These diverse functions rely on the coordinated orientation (rotational polarity) and asymmetric localization (translational polarity) of cilia and of their centriole-derived basal bodies across the epithelium, both being forms of planar cell polarity (PCP). Here, we review our current knowledge on the mechanisms of the translational polarity of basal bodies in vertebrate monociliated epithelia from the molecule to the whole organism. We highlight the importance of live imaging for understanding the dynamics of centriole polarization. We review the roles of core PCP pathways and of apicobasal polarity proteins, such as Par3, whose central function in this process has been recently uncovered. Finally, we emphasize the importance of the coordination between polarity proteins, the cytoskeleton and the basal body itself in this highly dynamic process. [ABSTRACT FROM AUTHOR]

Photoreceptors in the mammalian retina convert light signals into electrical and molecular signals through phototransduction and transfer the visual inputs to second-order neurons via specialized ribbon synapses. Two kinds of photoreceptors, rods and cones, possess distinct morphology and function. Currently, we have limited knowledge about rod versus (vs.) cone synapse development and the associated genes. The transcription factor neural retina leucine zipper (NRL) determines the rod vs. cone photoreceptor cell fate and is critical for rod differentiation. Nrl knockout mice fail to form rods, generating all cone or S-cone-like (SCL) photoreceptors in the retina, whereas ectopic expression of Nrl using a cone-rod homeobox (Crx) promoter (CrxpNrl) forms all rods. Here, we examined rod and cone pre-synapse development, including axonal elongation, terminal shaping, and synaptic lamination in the outer plexiform layer (OPL) in the presence or absence of Nrl. We show that NRL loss and knockdown result in delayed OPL maturation and plasticity with aberrant dendrites of bipolar neurons. The integrated analyses of the transcriptome in developing rods and SCLs with NRL CUT&RUN and synaptic gene ontology analyses identified G protein subunit beta (Gnb) 1 and p21 (RAC1) activated kinase 5 (Pak5 or Pak7) transcripts were upregulated in developing rods and down-regulated in developing SCLs. Notably, Gnb1 and Gnb5 are rod dominant, and Gnb3 is enriched in cones. NRL binds to the genes of Gnb1, Gnb3, and Gnb5. NRL also regulates pre-synapse ribbon genes, and their expression is altered in rods and SCLs. Our study of histological and gene analyses provides new insights into the morphogenesis of photoreceptor pre-synapse development and regulation of associated genes in the developing retina. [ABSTRACT FROM AUTHOR]

The formation of embryonic axes is a critical step during animal development, which contributes to establishing the basic body plan in each particular organism. Wnt signaling pathways play pivotal roles in this fundamental process. Canonical Wnt signaling that is dependent on β-catenin regulates the patterning of dorsoventral, anteroposterior, and left–right axes. Non-canonical Wnt signaling that is independent of β-catenin modulates cytoskeletal organization to coordinate cell polarity changes and asymmetric cell movements. It is now well documented that components of these Wnt pathways biochemically and functionally interact to mediate cell–cell communications and instruct cellular polarization in breaking the embryonic symmetry. The dysfunction of Wnt signaling disrupts embryonic axis specification and proper tissue morphogenesis, and mutations of Wnt pathway genes are associated with birth defects in humans. This review discusses the regulatory roles of Wnt pathway components in embryonic axis formation by focusing on vertebrate models. It highlights current progress in decoding conserved mechanisms underlying the establishment of asymmetry along the three primary body axes. By providing an in-depth analysis of canonical and non-canonical pathways in regulating cell fates and cellular behaviors, this work offers insights into the intricate processes that contribute to setting up the basic body plan in vertebrate embryos. [ABSTRACT FROM AUTHOR]

Previous research has highlighted significant phenotypic discrepancies between knockout and knockdown approaches in zebrafish, raising concerns about the reliability of these methods. However, our study suggests that these differences are not as pronounced as was once believed. By carefully examining the roles of maternal and zygotic gene contributions, we demonstrate that these factors significantly influence phenotypic outcomes, often accounting for the observed discrepancies. Our findings emphasize that morpholinos, despite their potential off-target effects, can be effective tools when used with rigorous controls. We introduce the concept of graded maternal contribution, which explains how the uneven distribution of maternal mRNA and proteins during gametogenesis impacts phenotypic variability. Our research categorizes genes into three types—susceptible, immune, and "Schrödinger" (conditional)—based on their phenotypic expression and interaction with genetic compensation mechanisms. This distinction provides new insights into the paradoxical outcomes observed in genetic studies. Ultimately, our work underscores the importance of considering both maternal and zygotic contributions, alongside rigorous experimental controls, to accurately interpret gene function and the mechanisms underlying disease. This study advocates for the continued use of morpholinos in conjunction with advanced genetic tools like CRISPR/Cas9, stressing the need for a meticulous experimental design to optimize the utility of zebrafish in genetic research and therapeutic development. [ABSTRACT FROM AUTHOR]

The visual system is essential for humans to perceive the environment. In the retina, rod and cone photoreceptor neurons are the initial sites where vision forms. The apical region of both cone and rod photoreceptors contains a light-sensing organelle known as the outer segment (OS), which houses tens of thousands of light-sensitive opsins. The OSs of photoreceptors are not static; they require rhythmic renewal to maintain normal physiological functions. Disruptions in OS renewal can lead to various genetic disorders, such as retinitis pigmentosa (RP). Understanding the patterns and molecular mechanisms of photoreceptor OS renewal remains one of the most intriguing topics in visual biology. This review aims to elucidate the structure of photoreceptor OSs, the molecular mechanisms underlying photoreceptor OS renewal, and the retinal diseases resulting from defects in this renewal process. Additionally, we will explore retinal diseases related to photoreceptor OS renewal and potential therapeutic strategies, concluding with a discussion on future research directions for OS renewal. [ABSTRACT FROM AUTHOR]

Cancer is one of the most complex and challenging human diseases, with rising incidences and cancer-related deaths despite improved diagnosis and personalized treatment options. Targeted alpha therapy (TαT) offers an exciting strategy emerging for cancer treatment which has proven effective even in patients with advanced metastatic disease that has become resistant to other treatments. Yet, in many cases, more sophisticated strategies are needed to stall disease progression and overcome resistance to TαT. The combination of two or more therapies which have historically been used as stand-alone treatments is an approach that has been pursued in recent years. This review aims to provide an overview on TαT and the four main pillars of therapeutic strategies in cancer management, namely external beam radiation therapy (EBRT), immunotherapy with checkpoint inhibitors (ICI), cytostatic chemotherapy (CCT), and brachytherapy (BT), and to discuss their potential use in combination with TαT. A brief description of each therapy is followed by a review of known biological aspects and state-of-the-art treatment practices. The emphasis, however, is given to the motivation for combination with TαT as well as the pre-clinical and clinical studies conducted to date. [ABSTRACT FROM AUTHOR]

One expanding area of bioinformatics is medical diagnosis through the categorization of biomedical characteristics. Automatic medical strategies to boost the diagnostic through machine learning (ML) methods are challenging. They require a formal examination of their performance to identify the best conditions that enhance the ML method. This work proposes variants of the Voting and Stacking (VC and SC) ensemble strategies based on diverse auto-tuning supervised machine learning techniques to increase the efficacy of traditional baseline classifiers for the automatic diagnosis of vertebral column orthopedic illnesses. The ensemble strategies are created by first combining a complete set of auto-tuned baseline classifiers based on different processes, such as geometric, probabilistic, logic, and optimization. Next, the three most promising classifiers are selected among k-Nearest Neighbors (kNN), Naïve Bayes (NB), Logistic Regression (LR), Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), Support Vector Machine (SVM), Artificial Neural Networks (ANN), and Decision Tree (DT). The grid-search K-Fold cross-validation strategy is applied to auto-tune the baseline classifier hyperparameters. The performances of the proposed ensemble strategies are independently compared with the auto-tuned baseline classifiers. A concise analysis evaluates accuracy, precision, recall, F1-score, and ROC-ACU metrics. The analysis also examines the misclassified disease elements to find the most and least reliable classifiers for this specific medical problem. The results show that the VC ensemble strategy provides an improvement comparable to that of the best baseline classifier (the kNN). Meanwhile, when all baseline classifiers are included in the SC ensemble, this strategy surpasses 95% in all the evaluated metrics, standing out as the most suitable option for classifying vertebral column diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation therapy stands out as a primary approach for managing individuals with non-small cell lung cancer (NSCLC). Nevertheless, the predominant impediment to achieving successful therapeutic outcomes lies in the resistance exhibited by tumor cells to radiation exposure. Mitochondrial structure abnormality and defects were found to be in high correlation with malignancy and radioresistance. The cytotoxic impact of radiation on cancer cells is most probably dependent on mitochondria; therefore, the exchange of mitochondrial organelles, DNA, or proteins could potentially serve as an effective strategy for modulating their sensitivity to radiation therapy. In this review, we aimed to uncover novel mechanisms for studying NSCLC's response to radiation. During the cell life cycle, extracellular vesicles (EVs) transport different cargos, including organelles, proteins, RNAs, DNAs, metabolites, etc., that influence cell proliferation and apoptosis in recipient cells. EVs from metastatic cancer cells remodel the extracellular matrix and cells of the tumor microenvironment (TME), promoting tumor invasion and metastatic niche preparation. Although the process is not fully understood, evidence suggests that EVs facilitate genetic material transfer between cells. In the context of NSCLC, EVs can mediate intercellular mitochondrial (Mt) transfer, delivering mitochondria organelle (MtO), mitochondrial DNA (mtDNA), and/or mtRNA/proteinaceous cargo signatures (MtS) through different mechanisms. On the other hand, certain populations of cancer cells can hijack the MtO from TME cells mainly by using tunneling nanotubes (TNTs). This transfer aids in restoring mitochondrial function, benefiting benign cells with impaired metabolism and enabling restoration of their metabolic activity. However, the impact of transferring mitochondria versus transplanting intact mitochondrial organelles in cancer remains uncertain and the subject of debate. Some studies suggest that EV-mediated mitochondria delivery to cancer cells can impact how cancer responds to radiation. It might make the cancer more resistant or more sensitive to radiation. In our review, we aimed to point out the current controversy surrounding experimental data and to highlight new paradigm-shifting modalities in radiation therapy that could potentially overcome cancer resistance mechanisms in NSCLC. [ABSTRACT FROM AUTHOR]

The morphodynamics of the Leucate double-crescent bar system was studied over twenty years using bathymetric data supplemented by satellite images and video monitoring. Eleven different bar typologies were identified, mostly based on existing beach state classifications (Low-Tide Terrace, Transverse Bar and Rip, Rhythmic Bar and Beach), also including new heterogeneous typologies (TBR/LTT, RBB HP/RBB, TBR/RBB). The inner bar shows greater variability, with 10 different typologies observed, while the outer bar shows only three different typologies. Summer low-energy periods are dominated by TBR/LTT and TBR typologies, while RBB, although common throughout the year, dominates winter periods along with disrupted bar configurations. The return to less energetic periods in spring is associated with the establishment of heterogeneous typologies. The outer bar has a fairly stable position, although breaches at the embayments and slight movements of its horns can occur following particularly energetic episodes. The inner bar, on the other hand, is much more dynamic, with more common breaches at the embayments and significant cross-shore movement of the horns. Seasonal changes in bar typology do not lead to bar renewal through destruction/reconstruction. Overall, the morphological and typological characteristics of the bar system described here seem somewhat unique compared to the existing literature. [ABSTRACT FROM AUTHOR]

The planar cell polarity (PCP) system is essential for positioning cells in 3D networks to establish the proper morphogenesis, structure, and function of organs during embryonic development. The PCP system uses inter- and intracellular feedback interactions between components of the core PCP, characterized by coordinated planar polarization and asymmetric distribution of cell populations inside the cells. PCP signaling connects the anterior–posterior to left–right embryonic plane polarity through the polarization of cilia in the Kupffer's vesicle/node in vertebrates. Experimental investigations on various genetic ablation-based models demonstrated the functions of PCP in planar polarization and associated genetic disorders. This review paper aims to provide a comprehensive overview of PCP signaling history, core components of the PCP signaling pathway, molecular mechanisms underlying PCP signaling, interactions with other signaling pathways, and the role of PCP in organ and embryonic development. Moreover, we will delve into the negative feedback regulation of PCP to maintain polarity, human genetic disorders associated with PCP defects, as well as challenges associated with PCP. [ABSTRACT FROM AUTHOR]

This comprehensive review consolidates insights from two sources to emphasize the transformative impact of scaffold-based drug delivery systems in revolutionizing oral cancer therapy. By focusing on their core abilities to facilitate targeted and localized drug administration, these systems enhance therapeutic outcomes significantly. Scaffolds, notably those coated with anti-cancer agents such as cisplatin and paclitaxel, have proven effective in inhibiting oral cancer cell proliferation, establishing a promising avenue for site-specific drug delivery. The application of synthetic scaffolds, including Poly Ethylene Glycol (PEG) and poly(lactic-co-glycolic acid) (PLGA), and natural materials, like collagen or silk, in 3D systems has been pivotal for controlled release of therapeutic agents, executing diverse anti-cancer strategies. A key advancement in this field is the advent of smart scaffolds designed for sequential cancer therapy, which strive to refine drug delivery systems, minimizing surgical interventions, accentuating the significance of 3D scaffolds in oral cancer management. These systems, encompassing local drug-coated scaffolds and other scaffold-based platforms, hold the potential to transform oral cancer treatment through precise interventions, yielding improved patient outcomes. Local drug delivery via scaffolds can mitigate systemic side effects typically associated with chemotherapy, such as nausea, alopecia, infections, and gastrointestinal issues. Post-drug release, scaffolds foster a conducive environment for non-cancerous cell growth, adhering and proliferation, demonstrating restorative potential. Strategies for controlled and targeted drug delivery in oral cancer therapy span injectable self-assembling peptide hydrogels, nanocarriers, and dual drug-loaded nanofibrous scaffolds. These systems ensure prolonged release, synergistic effects, and tunable targeting, enhancing drug delivery efficiency while reducing systemic exposure. Smart scaffolds, capable of sequential drug release, transitioning to cell-friendly surfaces, and enabling combinatorial therapy, hold the promise to revolutionize treatment by delivering precise interventions and optimized outcomes. In essence, scaffold-based drug delivery systems, through their varied forms and functionalities, are reshaping oral cancer therapy. They target drug delivery efficiency, diminish side effects, and present avenues for personalization. Challenges like fabrication intricacy, biocompatibility, and scalability call for additional research. Nonetheless, the perspective on scaffold-based systems in oral cancer treatment is optimistic, as ongoing advancements aim to surmount current limitations and fully leverage their potential in cancer therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: There are currently limited means by which radiotherapy treatment can be tailored to individual patient needs based on their tumour biology. Published studies of biomarkers aiming to predict tumour sensitivity to radiotherapy treatment for the clinic were reviewed. No gene expression signature biomarkers of sensitivity to radiotherapy are in routine clinical use, have been tested in advanced trials or are recommended for use in clinical guidelines. A pathway for future biomarker development that would enable tools for personalised clinical decision-making is proposed. This focusses on the need to improve the biological understanding of variation in sensitivity to radiotherapy, develop cost-effective assays and conduct large radiotherapy randomised controlled trials. Modern advanced radiotherapy techniques have improved the precision and accuracy of radiotherapy delivery, with resulting plans being highly personalised based on individual anatomy. Adaptation for individual tumour biology remains elusive. There is an unmet need for biomarkers of intrinsic radiosensitivity that can predict tumour response to radiation to facilitate individualised decision-making, dosing and treatment planning. Over the last few decades, the use of high throughput molecular biology technologies has led to an explosion of newly discovered cancer biomarkers. Gene expression signatures are now used routinely in clinic to aid decision-making regarding adjuvant systemic therapy. They have great potential as radiotherapy biomarkers. A previous systematic review published in 2015 reported only five studies of signatures evaluated for their ability to predict radiotherapy benefits in clinical cohorts. This updated systematic review encompasses the expanded number of studies reported in the last decade. An additional 27 studies were identified. In total, 22 distinct signatures were recognised (5 pre-2015, 17 post-2015). Seventeen signatures were 'radiosensitivity' signatures and five were breast cancer prognostic signatures aiming to identify patients at an increased risk of local recurrence and therefore were more likely to benefit from adjuvant radiation. Most signatures (15/22) had not progressed beyond the discovery phase of development, with no suitable validated clinical-grade assay for application. Very few signatures (4/17 'radiosensitivity' signatures) had undergone any laboratory-based biological validation of their ability to predict tumour radiosensitivity. No signatures have been assessed prospectively in a phase III biomarker-led trial to date and none are recommended for routine use in clinical guidelines. A phase III prospective evaluation is ongoing for two breast cancer prognostic signatures. The most promising radiosensitivity signature remains the radiosensitivity index (RSI), which is used to calculate a genomic adjusted radiation dose (GARD). There is an ongoing phase II prospective biomarker-led study of RSI/GARD in triple negative breast cancer. The results of these trials are eagerly anticipated over the coming years. Future work in this area should focus on (1) robust biological validation; (2) building biobanks alongside large radiotherapy randomised controlled trials with dose variance (to demonstrate an interaction between radiosensitivity signature and dose); (3) a validation of clinical-grade cost-effective assays that are deliverable within current healthcare infrastructure; and (4) an integration with biomarkers of other determinants of radiation response. [ABSTRACT FROM AUTHOR]

Simple Summary: Among head–neck tumors, squamous cell carcinoma is the most frequent histotype and includes a range of malignancies with different sites of origin as well as different therapeutic strategies and clinical outcomes. In daily practice, patients with head–neck squamous cell carcinoma are seen in various clinical settings, requiring a multidisciplinary approach to therapeutic decisions and clinical care. 18F-FDG PET/CT plays a well-defined role in the management of these tumors for pre-treatment staging and radiotherapy planning as well as treatment-response assessment and post-therapy follow-up. This paper is an overview of the standard use of 18F-FDG PET/CT in the various clinical scenarios of head–neck squamous cell carcinoma. Also, emerging applications will be reviewed, including the use of radiopharmaceuticals other than 18F-FDG, PET/MRI implementation in clinical practice, and the use of radiomics and machine learning. This article provides an overview of the use of 18F-FDG PET/CT in various clinical scenarios of head–neck squamous cell carcinoma, ranging from initial staging to treatment-response assessment, and post-therapy follow-up, with a focus on the current evidence, debated issues, and innovative applications. Methodological aspects and the most frequent pitfalls in head–neck imaging interpretation are described. In the initial work-up, 18F-FDG PET/CT is recommended in patients with metastatic cervical lymphadenectomy and occult primary tumor; moreover, it is a well-established imaging tool for detecting cervical nodal involvement, distant metastases, and synchronous primary tumors. Various 18F-FDG pre-treatment parameters show prognostic value in terms of disease progression and overall survival. In this scenario, an emerging role is played by radiomics and machine learning. For radiation-treatment planning, 18F-FDG PET/CT provides an accurate delineation of target volumes and treatment adaptation. Due to its high negative predictive value, 18F-FDG PET/CT, performed at least 12 weeks after the completion of chemoradiotherapy, can prevent unnecessary neck dissections. In addition to radiomics and machine learning, emerging applications include PET/MRI, which combines the high soft-tissue contrast of MRI with the metabolic information of PET, and the use of PET radiopharmaceuticals other than 18F-FDG, which can answer specific clinical needs. [ABSTRACT FROM AUTHOR]

Simple Summary: Chemoradiation as a standard treatment for locally advanced cervical cancer is known to induce severe hematologic toxicity. This systematic review aims to evaluate the relationship between pelvic bone marrow irradiation and hematologic toxicity in patients undergoing platin-based chemoradiation for locally advanced cervical cancer. We seek to summarize possible dose constraints for optimal bone marrow sparing and optimize clinical strategies to mitigate treatment-related toxicities. The standard treatment for locally advanced cervical cancer typically includes concomitant chemoradiation, a regimen known to induce severe hematologic toxicity (HT). Particularly, pelvic bone marrow dose exposure has been identified as a contributing factor to this hematologic toxicity. Chemotherapy further increases bone marrow suppression, often necessitating treatment interruptions or dose reductions. A systematic search for original articles published between 1 January 2006 and 7 January 2024 that reported on chemoradiotherapy for locally advanced cervical cancer and hematologic toxicities was conducted. Twenty-four articles comprising 1539 patients were included in the final analysis. HT of grade 2 and higher was observed across all studies and frequently exceeded 50%. When correlating active pelvic bone marrow and HT, significant correlations were found for volumes between 10 and 45 Gy and HT of grade 3 and higher. Several dose recommendations for pelvic bone and pelvic bone marrow sparing to reduce HT were established, including V10 < 90–95%, V20 < 65–86.6% and V40 < 22.8–40%. Applying dose constraints to the pelvic bone/bone marrow is a promising approach for reducing HT, and thus reliable implementation of therapy. However, prospective randomized controlled trials are needed to define precise dose constraints and optimize clinical strategies. [ABSTRACT FROM AUTHOR]

Wave-induced currents play a critical role in coastal dynamics, influencing sediment transport and shaping bottom topography. Traditionally, long- and cross-shore currents in coastal zones were analyzed independently, often with two-dimensional models for longshore currents and undertow being used. The introduction of quasi-three-dimensional models marked a significant advancement toward a more holistic understanding. Despite recent proposals for fully three-dimensional models, none have achieved widespread acceptance, primarily due to challenges in accurately capturing depth-dependent radiation stress. This paper presents an innovative analytical model advocating for comprehensive three-dimensional approaches in coastal hydrodynamics. The model, based on novel simplification rules, refines relationships governing turbulent stress tensors and provides valuable insights into wave-induced stresses. It offers analytical solutions for both homogeneous and general coastal zones, laying the foundation for future advancements in numerical modeling techniques. [ABSTRACT FROM AUTHOR]

This article reviews the literature covering the period from 1965 to 2020 dedicated to the issue of artificial beach nourishment along the Polish coast, with a particular focus on the Hel Peninsula. The primary sources used in this work include 34 reports from unpublished case studies and projects implemented by the Department of Maritime Hydrotechnics, Maritime Institute in Gdańsk, between 1971 and 2020. This paper also presents detailed information about the total fill volume in cubic meters of dredged material deposited along the Polish coast and lagoon shores in 1980–2020. During these 40 years, approximately 40.5 million m3 of sediment was deposited along the Polish coast and lagoon shores. Particular consideration was given to beach fills along the Hel Peninsula, which was at actual risk of breaking in its basal and central sections after intense storms at the turn of 1988 and 1989. The survey materials collected enabled the assessment of the coastal morphodynamics of the peninsula under the Coastal Protection Program through the prism of changes in the fill volume along the coastal sections, which were replenished with material coming from submarine deposits. The peninsula's stability was also assessed, taking into account the ongoing climate change. Moreover, this article discusses the proposed rules and terms for protecting the Polish coast by way of artificial nourishment. [ABSTRACT FROM AUTHOR]

Glypicans (Glps) are a family of heparan sulphate proteoglycans that are attached to the outer plasma membrane leaflet of the producing cell by a glycosylphosphatidylinositol anchor. Glps are involved in the regulation of many signalling pathways, including those that regulate the activities of Wnts, Hedgehog (Hh), Fibroblast Growth Factors (FGFs), and Bone Morphogenetic Proteins (BMPs), among others. In the Hh-signalling pathway, Glps have been shown to be essential for ligand transport and the formation of Hh gradients over long distances, for the maintenance of Hh levels in the extracellular matrix, and for unimpaired ligand reception in distant recipient cells. Recently, two mechanistic models have been proposed to explain how Hh can form the signalling gradient and how Glps may contribute to it. In this review, we describe the structure, biochemistry, and metabolism of Glps and their interactions with different components of the Hh-signalling pathway that are important for the release, transport, and reception of Hh. [ABSTRACT FROM AUTHOR]

The zebrafish (Danio rerio) has emerged as an appreciated and versatile model organism for studying cardiovascular and metabolic diseases, offering unique advantages for both basic research and drug discovery. The genetic conservation between zebrafish and humans and their high fecundity and transparent embryos allow for efficient large-scale genetic and drug-oriented screening studies. Zebrafish possess a simplified cardiovascular system that shares similarities with mammals, making them particularly suitable for modeling various aspects of heart development, function, and disease. The transparency of zebrafish embryos enables the real-time visualization of cardiovascular dynamics, offering insights into early embryonic events and facilitating the study of heart-related anomalies. In metabolic research, zebrafish provide a cost-effective platform for modeling obesity, type 2 diabetes, hyperlipidemia, and other metabolic disorders. Their high reproductive rate allows for the generation of large cohorts for robust statistical analyses, while advanced genetic tools, such as CRISPR/Cas9, enable precise gene editing with which to model specific genetic mutations associated with human diseases. Zebrafish metabolic models have been instrumental in elucidating the molecular mechanisms underlying metabolic diseases, studying the effects of environmental factors, and identifying potential therapeutic targets. Additionally, the permeability of zebrafish embryos to small molecules facilitates drug discovery and screening, offering a rapid and economical approach to identifying compounds with therapeutic potential. In conclusion, zebrafish cardiovascular and metabolic disease models continue to contribute significantly to our perception of disease pathogenesis, providing a platform for translational research and developing novel therapeutic interventions. The versatility, scalability, and genetic manipulability of zebrafish position them as an invaluable asset in unraveling the complexities of cardiovascular and metabolic diseases. This review presents an overview of the zebrafish model's key features and contributions to investigating cardiovascular and metabolic disorders. We discuss the benefits and drawbacks of using zebrafish models to study human disease and the critical findings revealed by the progress in this endeavor to date. [ABSTRACT FROM AUTHOR]

As one of the major cytokines implicated in the orchestration of immune responses, interleukin 6 (IL-6) can either act as a pro- or an anti-inflammatory factor, depending on the micro-environment. In micro-immunotherapy (MI) medicines, IL-6 is employed at low doses (LD) and ultra-low doses (ULD), expressed in centesimal Hahnemannian (CH), and used alone or in combination with other immune regulators to modulate patients' immune responses. The present study focused on assessing the in vitro immune-modulatory effects of two IL-6-containing MI products: (i) the unitary IL-6 (4 CH) and (ii) the complex MI-medicine (MIM) 2LALERG®, which includes IL-6 (17 CH) in association with other actives in its formulation. Our results showed that IL-6 (4 CH) activated granulocytes under basal conditions, and natural killer cells in the presence of an anti-CD3 signal, as assessed by their CD69 expression. In addition, IL-6 (4 CH) balanced the macrophages' differentiation toward a M2a profile. On the other hand, the tested 2LALERG® capsule inhibited the histamine degranulation of rats' peritoneal mast cells and reduced the release of IL-6 itself in inflamed human macrophages. Altogether, these data provide novel pieces of evidence on the double-edged potential of the LD and ULD of IL-6 in immune responses modulation, when employed in MI. [ABSTRACT FROM AUTHOR]

Breast cancer is the most frequently diagnosed cancer and leading cause of cancer-related deaths worldwide. Timely decision-making that enables implementation of the most appropriate therapy or therapies is essential for achieving the best clinical outcomes in breast cancer. While clinicopathologic characteristics and immunohistochemistry have traditionally been used in decision-making, these clinical and laboratory parameters may be difficult to ascertain or be equivocal due to tumor heterogeneity. Tumor heterogeneity is described as a phenomenon characterized by spatial or temporal phenotypic variations in tumor characteristics. Spatial variations occur within tumor lesions or between lesions at a single time point while temporal variations are seen as tumor lesions evolve with time. Due to limitations associated with immunohistochemistry (which requires invasive biopsies), whole-body molecular imaging tools such as standard-of-care [18F]FDG and [18F]FES PET/CT are indispensable in addressing this conundrum. Despite their proven utility, these standard-of-care imaging methods are often unable to image a myriad of other molecular pathways associated with breast cancer. This has stimulated interest in the development of novel radiopharmaceuticals targeting other molecular pathways and processes. In this review, we discuss validated and potential roles of these standard-of-care and novel molecular approaches. These approaches' relationships with patient clinicopathologic and immunohistochemical characteristics as well as their influence on patient management will be discussed in greater detail. This paper will also introduce and discuss the potential utility of novel PARP inhibitor-based radiopharmaceuticals as non-invasive biomarkers of PARP expression/upregulation. [ABSTRACT FROM AUTHOR]

Simple Summary: This research contributes to the ongoing scientific investigation of the benefits of particle therapy for left-sided breast cancer and presents the potential of the novel application of helium ion therapy. The results obtained reveal a significant improvement in target coverage for both proton and helium ion therapy compared to Volumetric Modulated Arc Therapy (VMAT). Furthermore, particle therapy leads to an increase sparing of surrounding healthy tissues, including the heart, the left anterior descending artery and the ipsilateral lung. Additionally, with the reduction of the low-dose exposure to the right side of the chest, the risk for secondary malignancies with particle therapy is potentially minimized compared to VMAT. Compared to proton therapy, helium could additionally reduce the risk of pneumonitis. Proton therapy presents a promising modality for treating left-sided breast cancer due to its unique dose distribution. Helium ions provide increased conformality thanks to a reduced lateral scattering. Consequently, the potential clinical benefit of both techniques was explored. An explorative treatment planning study involving ten patients, previously treated with VMAT (Volumetric Modulated Arc Therapy) for 50 Gy in 25 fractions for locally advanced, node-positive breast cancer, was carried out using proton pencil beam therapy with a fixed relative biological effectiveness (RBE) of 1.1 and helium therapy with a variable RBE described by the mMKM (modified microdosimetric kinetic model). Results indicated that target coverage was improved with particle therapy for both the clinical target volume and especially the internal mammary lymph nodes compared to VMAT. Median dose value analysis revealed that proton and helium plans provided lower dose on the left anterior descending artery (LAD), heart, lungs and right breast than VMAT. Notably, helium therapy exhibited improved ipsilateral lung sparing over protons. Employing NTCP models as available in the literature, helium therapy showed a lower probability of grade ≤ 2 radiation pneumonitis (22% for photons, 5% for protons and 2% for helium ions), while both proton and helium ions reduce the probability of major coronary events with respect to VMAT. [ABSTRACT FROM AUTHOR]

Simple Summary: As proton therapy evolves and becomes more accessible, it is important to explore its potential value for all patient cases to enable more informed treatment individualization. Currently, external beam radiotherapy for prostate cancer patients with hip prosthesis is limited to photons because traditional proton therapy beams interfere with the implanted hardware. The goal of this study was to investigate the dosimetric feasibility and robustness of novel proton therapy techniques, i.e., proton arc therapy and anterior beam directions for prostate cancer patients with unilateral hip prosthesis. It was demonstrated that proton therapy for prostate cancer in the setting of hip prosthesis is feasible and could potentially reduce the dose to some critical organs and hence reduce toxicities. Purpose: Given that the current standard of proton therapy (PT) for prostate cancer is through bilateral beams, this modality is typically avoided when it comes to treatment of patients with hip prosthesis. The purpose of this study was to evaluate whether novel PT methods, i.e., anterior proton beams and proton arc therapy (PArc), could be feasible options to treat this patient subpopulation. We evaluate PT methods in the context of dosimetry and robustness and compare with standard of practice volumetric modulated arc therapy (VMAT) to explore any potential benefits. Methods: Two PT and one VMAT treatment plans were retrospectively created for 10 patients who participated in a clinical trial with a weekly repeat CT (rCT) imaging component. All plans were robustly optimized and featured: (1) combination anterior oblique and lateral proton beams (AoL), (2) PArc, and (3) VMAT. All patients had hydrogel spacers in place, which enabled safe application of anterior proton beams. The planned dose was 70 Gy (RBE) to the entire prostate gland and 50 Gy (RBE) to the proximal seminal vesicles in 28 fractions. Along with plan dose–volume metrics, robustness to setup and interfractional variations were evaluated using the weekly rCT images. The linear energy transfer (LET)-weighted dose was evaluated for PArc plans to ensure urethra sparing given the typical high-LET region at the end of range. Results: Both PT methods were dosimetrically feasible and provided reduction of some key OAR metrics compared to VMAT except for penile bulb, while providing equally good target coverage. Significant differences in median rectum V35 (22–25%), penile bulb Dmean (5 Gy), rectum V61 (2%), right femoral head Dmean (5 Gy), and bladder V39 (4%) were found between PT and VMAT. All plans were equally robust to variations. LET-weighted dose in urethra was equivalent to the physical dose for PArc plans and hence no added urethral toxicity was expected. Conclusions: PT for treatment of prostate cancer patients with hip prosthesis is feasible and equivalent or potentially superior to VMAT in quality in some cases. The choice of radiotherapy regimen can be personalized based on patient characteristics to achieve the best treatment outcome. [ABSTRACT FROM AUTHOR]

The Japanese flounder (Paralichthys olivaceus) is a marine fish that undergoes a dramatic postembryonic metamorphosis, with the right eye shifting to the left and its lifestyle transitioning from planktonic to benthic. As the light environment of the habitat changes from bright to dim, its photoreceptor system also undergoes adaptive change. Growth differentiation factor 6a (Gdf6a) is a member of the BMP family, which plays a key role in regulating the dorsal–ventral pattern of the retina and photoreceptor fate, and the differentiation of different photoreceptors is also modulated by a thyroid hormone (TH) binding its receptor (TR). However, the relationship between gdf6a and TH and its role in the regulation of photoreceptors during flounder metamorphosis is still poorly understood. In this study, bioinformatics analysis showed that Gdf6a had a conserved TGFB structural domain and clusters with fishes. The expression analysis showed that the expression of gdf6a was highest in the eye tissue of adult flounder and tended to increase and then decrease during metamorphosis, reaching its highest levels at the peak of metamorphosis. Moreover, the expression of gdf6a increased in the early stages of metamorphosis after exogenous TH treatment, while it was inhibited after exogenous thiourea (a TH inhibitor, TU) treatment. To further investigate the targeting role of TH and gdf6a in the metamorphosis of flounder, the results of the Dual-Luciferase revealed that triiodothyronine (T3) may regulate the expression of gdf6a through TRβ. In conclusion, we speculate that TH influences the development of cone photoreceptors during the metamorphosis of the flounder by regulating the expression of gdf6a. [ABSTRACT FROM AUTHOR]

Polylactic Acid (PLA) and Acrylonitrile–Butadiene–Styrene (ABS) are commonly used polymers in 3D printing for biomedical applications. Dental Pulp Stem Cells (DPSCs) are an accessible and proliferative source of stem cells with significant differentiation potential. Limited knowledge exists regarding the biocompatibility and genetic safety of ABS and PLA when in contact with DPSCs. This study aimed to investigate the impact of PLA and ABS on the adhesion, proliferation, osteogenic differentiation, genetic stability, proteomics, and immunophenotypic profile of DPSCs. A total of three groups, 1- DPSC-control, 2- DPSC+ABS, and 3- DPSC+PLA, were used in in vitro experiments to evaluate cell morphology, proliferation, differentiation capabilities, genetic stability, proteomics (secretome), and immunophenotypic profiles regarding the interaction between DPSCs and polymers. Both ABS and PLA supported the adhesion and proliferation of DPSCs without exhibiting significant cytotoxic effects and maintaining the capacity for osteogenic differentiation. Genetic stability, proteomics, and immunophenotypic profiles were unaltered in DPSCs post-contact with these polymers, highlighting their biosafety. Our findings suggest that ABS and PLA are biocompatible with DPSCs and demonstrate potential in dental or orthopedic applications; the choice of the polymer will depend on the properties required in treatment. These promising results stimulate further studies to explore the potential therapeutic applications in vivo using prototyped polymers in personalized medicine. [ABSTRACT FROM AUTHOR]

Studies comparing the ocular toxicity potential between legacy and alternative PFAS are lacking. To address this research gap, zebrafish larvae were exposed to both legacy PFAS (i.e., perfluorooctanesulfonic acid [PFOS] and perfluorooctanoic acid [PFOA]) and their corresponding alternatives (i.e., perfluorobutanesulfonic acid [PFBS] and perfluorobutanoic acid [PFBA]). Alterations in their visual behaviors, such as phototactic and optomotor responses (OMR), were assessed at sublethal concentrations. Gene expression variations in visual function-associated pathways were also measured. Visual behavioral assessment revealed that PFOS exposure resulted in concentration-dependent reductions in phototactic responses at 10–1000 μg/L, with PFOA exerting reduction effects only at 100 mg/L. However, their two alternatives had no effect at all tested concentrations. Following an improved contrast-OMR (C-OMR) assessment, PFOS decreased the OMR to a water flow stimulus at 10, 100, and 1000 μg/L. The gene expression analysis revealed that PFOS exposure markedly downregulated most genes involved in the opsins in the photoreceptor and phototransduction cascade, which explains the observed visual behavior changes well. Our findings indicate that PFOS is the most likely PFAS to cause visual toxicity, with PFOA present but less likely, and their substitutes, PFBS and PFBA, cannot be classified as visually toxic to zebrafish. [ABSTRACT FROM AUTHOR]

Detecting skeletal or bone-related deformities in model and aquaculture fish is vital for numerous biomedical studies. In biomedical research, model fish with bone-related disorders are potential indicators of various chemically induced toxins in their environment or poor dietary conditions. In aquaculture, skeletal deformities are affecting fish health, and economic losses are incurred by fish farmers. This survey paper focuses on showcasing the cutting-edge image analysis tools and techniques based on artificial intelligence that are currently applied in the analysis of bone-related deformities in aquaculture and model fish. These methods and tools play a significant role in improving research by automating various aspects of the analysis. This paper also sheds light on some of the hurdles faced when dealing with high-content bioimages and explores potential solutions to overcome these challenges. [ABSTRACT FROM AUTHOR]

Rip currents are fast offshore currents generated during the breaking process of waves propagating nearshore, posing a potential life safety threat to coastal bathers. This study utilizes a Boussinesq phase-resolving model to investigate the formation mechanism of rip currents at Dadonghai Beach, based on its actual topography, and explores the characteristics of rip current formation under various wave conditions, with an emphasis on analyzing vortices, the mean water level and the spatial distribution of average velocity. The results indicate that rip current formation is significantly influenced by wave height and period. The increase in wave height and period results in more intense rip currents and higher water level fluctuations on arc-shaped beaches and on both sides of the bay, leading to complex vortex distributions. An increase in the angle of wave incidence hinders rip current formation in arc-shaped beach areas but is favorable to the generation of deflection rips on both sides of the bay. Furthermore, an increase in bottom friction inhibits rip current formation. When the water depth decreases in the channels, rip currents transition into longshore currents. The findings of this research offer valuable scientific insights into the formation mechanisms of rip currents and contribute to their prediction and prevention. [ABSTRACT FROM AUTHOR]

The eye is a complex sensory organ that enables visual perception of the world. The dysfunction of any of these tissues can impair vision. Conduction studies on laboratory animals are essential to ensure the safety of therapeutic products directly applied or injected into the eye to treat ocular diseases before eventually proceeding to clinical trials. Among these tissues, the cornea has unique homeostatic and regenerative mechanisms for maintaining transparency and refraction of external light, which are essential for vision. However, being the outermost tissue of the eye and directly exposed to the external environment, the cornea is particularly susceptible to injury and diseases. This review highlights the evidence for selecting appropriate animals to better understand and treat corneal diseases, which rank as the fifth leading cause of blindness worldwide. The development of reliable and human-relevant animal models is, therefore, a valuable research tool for understanding and translating fundamental mechanistic findings, as well as for assessing therapeutic potential in humans. First, this review emphasizes the unique characteristics of animal models used in ocular research. Subsequently, it discusses current animal models associated with human corneal pathologies, their utility in understanding ocular disease mechanisms, and their role as translational models for patients. [ABSTRACT FROM AUTHOR]