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Zebrafish are increasingly becoming an important model organism for studying the pathophysiological mechanisms of human diseases and investigating how these mechanisms can be effectively targeted using compounds that may open avenues to novel treatments for patients. The zebrafish skeleton has been particularly instrumental in modeling bone diseases as—contrary to other model organisms—the lower load on the skeleton of an aquatic animal enables mutants to survive to early adulthood. In this respect, the axial skeletons of zebrafish have been a good read-out for congenital spinal deformities such as scoliosis and degenerative disorders such as osteoporosis and osteoarthritis, in which aberrant mineralization in humans is reflected in the respective zebrafish models. Interestingly, there have been several reports of hereditary multisystemic diseases that do not affect the vertebral column in human patients, while the corresponding zebrafish models systematically show anomalies in mineralization and morphology of the spine as their leading or, in some cases, only phenotype. In this review, we describe such examples, highlighting the underlying mechanisms, the already-used or potential power of these models to help us understand and amend the mineralization process, and the outstanding questions on how and why this specific axial type of aberrant mineralization occurs in these disease models. [ABSTRACT FROM AUTHOR]

Djibouti, a developing economy, grapples with significant socioeconomic obstacles and the prevalence of infectious pathologies, including certain forms of neoplasms. These challenges are exacerbated by limited access to affordable medical technologies for diagnosis, coupled with a lack of preventive interventions, particularly in disadvantaged areas. The attention devoted to local phytotherapeutic treatments underscores the uniqueness of Djibouti's flora, resulting from its distinctive geographical position. International focus specifically centers on harnessing this potential as a valuable resource, emphasizing the phytoconstituents used to counter pathologies, notably carcinomas. This comprehensive overview covers a broad spectrum, commencing with an examination of the current state of knowledge, namely an in-depth investigation of oncological risk factors. Essential elements of control are subsequently studied, highlighting the fundamental prerequisites for effective management. The significance of dietary habits in cancer prevention and support is explored in depth, while traditional methods are examined, highlighting the cultural significance of indigenous essential oil therapies and encouraging further research based on the promising results. [ABSTRACT FROM AUTHOR]

Liver diseases represent a significant global health challenge, thereby necessitating extensive research to understand their intricate complexities and to develop effective treatments. In this context, zebrafish (Danio rerio) have emerged as a valuable model organism for studying various aspects of liver disease. The zebrafish liver has striking similarities to the human liver in terms of structure, function, and regenerative capacity. Researchers have successfully induced liver damage in zebrafish using chemical toxins, genetic manipulation, and other methods, thereby allowing the study of disease mechanisms and the progression of liver disease. Zebrafish embryos or larvae, with their transparency and rapid development, provide a unique opportunity for high-throughput drug screening and the identification of potential therapeutics. This review highlights how research on zebrafish has provided valuable insights into the pathological mechanisms of human liver disease. [ABSTRACT FROM AUTHOR]

In recent years, there has been a surge of interest in tumor microenvironment-associated cancer vaccine therapies. These innovative treatments aim to activate and enhance the body's natural immune response against cancer cells by utilizing specific antigens present in the tumor microenvironment. The goal is to achieve a complete clinical response, where all measurable cancer cells are either eliminated or greatly reduced in size. With their potential to revolutionize cancer treatment, these therapies represent a promising avenue for researchers and clinicians alike. Despite over 100 years of research, the success of therapeutic cancer vaccines has been variable, particularly in advanced cancer patients, with various limitations, including the heterogeneity of the tumor microenvironment, the presence of immunosuppressive cells, and the potential for tumor escape mechanisms. Additionally, the effectiveness of these therapies may be limited by the variability of the patient's immune system response and the difficulty in identifying appropriate antigens for each patient. Despite these challenges, tumor microenvironment-targeted vaccine cancer therapies have shown promising results in preclinical and clinical studies and have the potential to become a valuable addition to current cancer treatment and "curative" options. While chemotherapeutic and monoclonal antibody treatments remain popular, ongoing research is needed to optimize the design and delivery of these therapies and to identify biomarkers that can predict response and guide patient selection. This comprehensive review explores the mechanisms of cancer vaccines, various delivery methods, and the role of adjuvants in improving treatment outcomes. It also discusses the historical background of cancer vaccine research and examines the current state of major cancer vaccination immunotherapies. Furthermore, the limitations and effectiveness of each vaccine type are analyzed, providing insights into the future of cancer vaccine development. [ABSTRACT FROM AUTHOR]

Zebrafish (Danio rerio) eyes are widely used in modeling studies of human ophthalmic diseases, including glaucoma and myopia. These pathologies cause morphological variations in the anterior chamber elements, which can be quantitatively measured using morphometric parameters, such as the corneal curvature, central corneal thickness, and anterior chamber angle. In the present work, an automated method is presented for iris and corneal segmentation, as well as the determination of the above-mentioned morphometry from optical coherence tomography (OCT) scans of zebrafish. The proposed method consists of four stages; namely, preprocessing, segmentation, postprocessing, and extraction of morphometric parameters. The first stage is composed of a combination of wavelet and Fourier transforms as well as gamma correction for artifact removal/reduction. The segmentation step is achieved using the U-net convolutional neural network. The postprocessing stage is composed of multilevel thresholding and morphological operations. Finally, three algorithms are proposed for automated morphological extraction in the last step. The morphology obtained using our automated framework is compared against manual measurements to assess the effectiveness of the method. The obtained results show that our scheme allows reliable determination of the morphometric parameters, thereby allowing efficient assessment for massive studies on zebrafish anterior chamber morphology using OCT scans. [ABSTRACT FROM AUTHOR]

Definition: Flash radiotherapy (Flash-RT) is an innovative technique used in radiotherapy for cancer treatment because it delivers an extremely high dose of radiation (>40 Gy/s) to the tumour in a very short period of time, typically within a fraction of a second. This ultra-fast delivery of radiation distinguishes Flash-RT from conventional radiotherapy, which typically involves the delivery of radiation over a longer time period, often several minutes. Studies conducted in cell and preclinical models suggested that Flash-RT may spare normal tissues from radiation-related side effects, such as skin toxicity, gastrointestinal complications, and damage to organs-at-risk. This is believed to be due to the unique normal tissue response to the ultra-high dose rate. Nevertheless, while Flash-RT shows promising results in preclinical and early clinical studies, one should note that the technique is still in the early stages of development. This entry provides a comprehensive exploration of the immense potentials of Flash-RT, covering its background, mechanisms, radiation sources, recent experimental findings based on cell and preclinical models, and future prospects. It aims to provide valuable insights into this innovative radiotherapy technology for anyone interested in the subject. [ABSTRACT FROM AUTHOR]

Simple Summary: Total body irradiation (TBI) as a component of conditioning regimens prior to hematopoietic stem cell transplantation is performed differently by various radiotherapy centers. In general, conventional methods are predominantly applied. With the introduction of advanced irradiation techniques such as Helical TomoTherapy (HT) and Volumetric Modulated Arc Therapy (VMAT), dose-optimized total body irradiation could be realized with good target volume coverage and adequate dose reduction in organs at risk (OAR). This requires a well-coordinated team and suitable equipment capabilities. Centers similar to ours can offer HT treatment as a gold standard for highly conformal TBI. Based on the limited replacement equipment availability in case of HT device failure, we developed a method carrying out highly conformal VMAT irradiation with a linear accelerator originally suitable for radiosurgery or stereotactic radiotherapy. Using a dosimetric comparison between both modalities, we examined whether VMAT—even with linear accelerator radiosurgery technology—is capable of performing optimized conformal TBI. Modern irradiation techniques for optimized conformal TBI can be realized by Helical Tomotherapy (HT) or Volumetric Modulated Arc Therapy (VMAT), depending on the availability of suitable specialized equipment. In this dosimetric planning study, we compared both modalities and addressed the question of whether VMAT with small field sizes is also suitable as a backup in case of HT equipment malfunctions. For this purpose, we retrospectively used planning computed tomography (CT) data from 10 patients treated with HT with a total dose of 8 Gy (n = 5) or 12 Gy (n = 5) for treatment planning for VMAT with a small field size (36 × 22 cm). The target volume coverage, dose homogeneity at target volume, and dose reduction in organs at risk (OAR) (lungs, kidneys, lenses) were analyzed and compared. One patient was irradiated with both modalities due to a device failure of the HT equipment during the study, which facilitated a comparison in a real clinical setting. The findings indicate that in addition to a higher mean dose to the lenses in the 12 Gy group for VMAT and a better dose homogeneity in the target volume for HT, comparably good and adequate target dose coverage and dose reduction in the other OAR could be achieved for both modalities, with significantly longer treatment times for VMAT. In conclusion, after appropriate optimization of the treatment times, VMAT using linear accelerator radiosurgery technology can be used both as a backup in addition to HT and in clinical routines to perform optimized conformal TBI. [ABSTRACT FROM AUTHOR]

Simple Summary: Cervical and endometrial cancers are the fourth and sixth most common cancers in women, respectively. Radiation therapy, including brachytherapy, is an important component of their treatment. Commercially available brachytherapy applicators only come in limited sizes and designs and either do not fit in some patients or do not allow adequate dose delivery to the target volume. In recent years, customised 3D-printed applicators have been increasingly used in such cases. This review summarises the role of 3D printing in brachytherapy of gynaecological tumours. Radiation therapy, including image-guided adaptive brachytherapy based on magnetic resonance imaging, is the standard of care in locally advanced cervical and vaginal cancer and part of the treatment in other primary and recurrent gynaecological tumours. Tumour control probability increases with dose and brachytherapy is the optimal technique to increase the dose to the target volume while maintaining dose constraints to organs at risk. The use of interstitial needles is now one of the quality indicators for cervical cancer brachytherapy and needles should optimally be used in ≥60% of patients. Commercially available applicators sometimes cannot be used because of anatomical barriers or do not allow adequate target volume coverage due to tumour size or topography. Over the last five to ten years, 3D printing has been increasingly used for manufacturing of customised applicators in brachytherapy, with gynaecological tumours being the most common indication. We present the rationale, techniques and current clinical evidence for the use of 3D-printed applicators in gynaecological brachytherapy. [ABSTRACT FROM AUTHOR]

Deep inspiration breath-hold (DIBH) is an excellent technique to reduce the incidental radiation received by the heart during radiotherapy in patients with breast cancer. However, DIBH is costly and time-consuming for patients and radiotherapy staff. In Asian countries, the use of DIBH is restricted due to the limited number of patients with a high mean heart dose (MHD) and the shortage of radiotherapy personnel and equipment compared to that in the USA. This study aimed to develop, evaluate, and compare the performance of ten machine learning algorithms for predicting MHD using a patient's body mass index and single-slice CT parameters to identify patients who may not require DIBH. Machine learning models were built and tested using a dataset containing 207 patients with left-sided breast cancer who were treated with field-in-field radiotherapy with free breathing. The average MHD was 251 cGy. Stratified repeated four-fold cross-validation was used to build models using 165 training data. The models were compared internally using their average performance metrics: F2 score, AUC, recall, accuracy, Cohen's kappa, and Matthews correlation coefficient. The final performance evaluation for each model was further externally analyzed using 42 unseen test data. The performance of each model was evaluated as a binary classifier by setting the cut-off value of MHD ≥ 300 cGy. The deep neural network (DNN) achieved the highest F2 score (78.9%). Most models successfully classified all patients with high MHD as true positive. This study indicates that the ten models, especially the DNN, might have the potential to identify patients who may not require DIBH. [ABSTRACT FROM AUTHOR]

Simple Summary: FLASH radiotherapy (RT) delivering ultra-high dose rate radiation can reduce normal tissue toxicity while effectively treating tumors. However, implementing FLASH RT in clinical settings faces challenges like limited depth penetration and complex treatment planning. Monte Carlo simulation is a valuable tool to optimize FLASH RT. Radiation detectors, including diamond detectors like microDiamond and ionization chambers, play a crucial role in accurately measuring dose delivery. Moreover, optically stimulated luminescence dosimeters and radiochromic films are used for validation. Advancements are being made to improve detector accuracy in FLASH RT. Further research is needed to refine treatment planning and detector performance for widespread FLASH RT implementation, which can potentially revolutionize cancer treatment. Radiotherapy (RT) using ultra-high dose rate (UHDR) radiation, known as FLASH RT, has shown promising results in reducing normal tissue toxicity while maintaining tumor control. However, implementing FLASH RT in clinical settings presents technical challenges, including limited depth penetration and complex treatment planning. Monte Carlo (MC) simulation is a valuable tool for dose calculation in RT and has been investigated for optimizing FLASH RT. Various MC codes, such as EGSnrc, DOSXYZnrc, and Geant4, have been used to simulate dose distributions and optimize treatment plans. Accurate dosimetry is essential for FLASH RT, and radiation detectors play a crucial role in measuring dose delivery. Solid-state detectors, including diamond detectors such as microDiamond, have demonstrated linear responses and good agreement with reference detectors in UHDR and ultra-high dose per pulse (UHDPP) ranges. Ionization chambers are commonly used for dose measurement, and advancements have been made to address their response nonlinearities at UHDPP. Studies have proposed new calculation methods and empirical models for ion recombination in ionization chambers to improve their accuracy in FLASH RT. Additionally, strip-segmented ionization chamber arrays have shown potential for the experimental measurement of dose rate distribution in proton pencil beam scanning. Radiochromic films, such as GafchromicTM EBT3, have been used for absolute dose measurement and to validate MC simulation results in high-energy X-rays, triggering the FLASH effect. These films have been utilized to characterize ionization chambers and measure off-axis and depth dose distributions in FLASH RT. In conclusion, MC simulation provides accurate dose calculation and optimization for FLASH RT, while radiation detectors, including diamond detectors, ionization chambers, and radiochromic films, offer valuable tools for dosimetry in UHDR environments. Further research is needed to refine treatment planning techniques and improve detector performance to facilitate the widespread implementation of FLASH RT, potentially revolutionizing cancer treatment. [ABSTRACT FROM AUTHOR]

Fibroblast activation protein has a unique expression profile that manifests mainly in wounds and tumors, which anticipates it as an encouraging and selective target for anticancer therapy. However, research of the therapeutic potential of FAP is limited both by legal restraints when working in vivo and by the difficulty of obtaining standardized primary cultures of FAP-positive cancer-associated fibroblasts due to their high heterogeneity. We found that 3D spheroids of FAP-positive cell lines could serve as robust and convenient models of FAP expression, in contrast to monolayers. By exposing such spheroids to various factors and compounds, it is possible to study changes in FAP expression, which are easily detected by confocal microscopy. FAP expression increases under the influence of the TGFβ, does not depend on pH, and decreases during hypoxia and starvation. We believe that the proposed model could be used to organize large-scale high-throughput screening of drugs that target FAP expression. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the most common malignancy in females, accounting for the majority of cancer-related deaths worldwide. There is well-established understanding about the effective role of radiotherapy (RT) in BC therapeutic strategies, offering a better local–regional control, prolonged survival, and improved quality of life for patients. However, it has been proven that conventional RT modalities, especially in left-sided BC cases, are unable to avoid the administration of high RT doses to the heart, thus resulting in cardiotoxicity and promoting long-term cardiovascular diseases (CVD). Recent radiotherapeutic techniques, characterized by dosimetric dose restrictions, target volume revision/modifications, an increased awareness of risk factors, and consistent follow-ups, have created an advantageous context for a significant decrease inpost-RT CVD incidence. Aim: This review presents the fundamental role of current cardioprotective strategies in the prevention of cardiotoxic effects in left-BCRT. Material and Methods: A literature search was conducted up to January 2023 using the Cochrane Central Register of Controlled Trials and PubMed Central databases. Our review refers to new radiotherapeutic techniques carried out on patients after BC surgery. Specifically, a dose evaluation of the heart and left anterior descending coronary artery (LADCA) was pointed out for all the included studies, depending on the implemented RT modality, bed positioning, and internal mammary lymph nodes radiation. Results: Several studies reporting improved heart sparing with new RT techniques in BC patients were searched. In addition to the RT modality, which definitely determines the feasibility of achieving lower doses for the organs at risk (OARs), better target coverage, dose conformity and homogeneity, and the patient's position, characteristics, and anatomy may also affect the evaluated RT dose to the whole heart and its substructures. Conclusions: Modern BC RT techniques seem to enable the administration of lower doses to the OARs without compromising on the target coverage. The analysis of several anatomical parameters and the assessment of cardiac biomarkers potentiate the protective effect of these new irradiation modalities, providing a holistic approach to the radiation-associated risks of cardiac disease for BC patients. Despite technological advances, an inevitable cardiac radiation risk still exists, while adverse cardiac events may be observed even many years after RT. Studies with longer follow-ups are required in order to determine the effectiveness of modern breast RT techniques. [ABSTRACT FROM AUTHOR]

Worldwide, around 40,000 people progressively lose their eyesight as a consequence of retinitis pigmentosa (RP) caused by pathogenic variants in the ADGRV1 gene, for which currently no treatment options exist. A model organism that mimics the human phenotype is essential to unravel the exact pathophysiological mechanism underlying ADGRV1-associated RP, and to evaluate future therapeutic strategies. The introduction of CRISPR/Cas-based genome editing technologies significantly improved the possibilities of generating mutant models in a time- and cost-effective manner. Zebrafish have been recognized as a suitable model to study Usher syndrome-associated retinal dysfunction. Using CRISPR/Cas9 technology we introduced a 4bp deletion in adgrv1 exon 9 (adgrv1rmc22). Immunohistochemical analysis showed that Adgrv1 was absent from the region of the photoreceptor connecting cilium in the adgrv1rmc22 zebrafish retina. Here, the absence of Adgrv1 also resulted in reduced levels of the USH2 complex members usherin and Whrnb, suggesting that Adgrv1 interacts with usherin and Whrnb in zebrafish photoreceptors. When comparing adgrv1rmc22 zebrafish with wild-type controls, we furthermore observed increased levels of aberrantly localized rhodopsin in the photoreceptor cell body, and decreased electroretinogram (ERG) B-wave amplitudes which indicate that the absence of Adgrv1 results in impaired retinal function. Based on these findings we present the adgrv1rmc22 zebrafish as the first ADGRV1 mutant model that displays an early retinal dysfunction. Moreover, the observed phenotypic changes can be used as quantifiable outcome measures when evaluating the efficacy of future novel therapeutic strategies for ADGRV1-associated RP. [ABSTRACT FROM AUTHOR]

Retinoic acid (RA) is a metabolite of vitamin A (retinol) that plays various roles in development to influence differentiation, patterning, and organogenesis. RA also serves as a crucial homeostatic regulator in adult tissues. The role of RA and its associated pathways are well conserved from zebrafish to humans in both development and disease. This makes the zebrafish a natural model for further interrogation into the functions of RA and RA-associated maladies for the sake of basic research, as well as human health. In this review, we explore both foundational and recent studies using zebrafish as a translational model for investigating RA from the molecular to the organismal scale. [ABSTRACT FROM AUTHOR]

Simple Summary: This manuscript aims to address the diagnostic challenges of mediastinal bulky lymphomas with the baseline value of 18F-FDG PET/CT metabolic, volumetric and texture parameters, also relying on machine learning techniques, in patients with grey zone lymphoma, primary diffuse large B-cell lymphoma of the mediastinum and classical Hodgkin lymphoma. Different types of histology demonstrated several baseline 18F-FDG PET/CT radiomics parameters that were significantly different from one another, suggesting the possibility of identifying potential histological heterogeneity and aggressive transformation. Moreover, using radiomics-based imaging biomarkers, machine learning techniques offer a solution for separating not completely disjoint histological types. To date, the gold standard for diagnosis is biopsy, but machine learning methods could be combined with radiomics to build a histological representation of mediastinal bulky masses that is able to successfully identify different types of lymphomas. Finally, this preliminary study supports the potential of metabolic texture analyses as future imaging biomarkers, with a growing role in clinical diagnosis. Background: This study tested the diagnostic value of 18F-FDG PET/CT (FDG-PET) volumetric and texture parameters in the histological differentiation of mediastinal bulky disease due to classical Hodgkin lymphoma (cHL), primary mediastinal B-cell lymphoma (PMBCL) and grey zone lymphoma (GZL), using machine learning techniques. Methods: We reviewed 80 cHL, 29 PMBCL and 8 GZL adult patients with mediastinal bulky disease and histopathological diagnoses who underwent FDG-PET pre-treatment. Volumetric and radiomic parameters were measured using FDG-PET both for bulky lesions (BL) and for all lesions (AL) using LIFEx software (threshold SUV ≥ 2.5). Binary and multiclass classifications were performed with various machine learning techniques fed by a relevant subset of radiomic features. Results: The analysis showed significant differences between the lymphoma groups in terms of SUVmax, SUVmean, MTV, TLG and several textural features of both first- and second-order grey level. Among machine learning classifiers, the tree-based ensembles achieved the best performance both for binary and multiclass classifications in histological differentiation. Conclusions: Our results support the value of metabolic heterogeneity as an imaging biomarker, and the use of radiomic features for early characterization of mediastinal bulky lymphoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Brachytherapy for prostate cancer is a method where radiotherapy is directly delivered to the prostate via surgical insertion of the radioactive source. Brachytherapy can increase the amount of radiation delivered to the prostate cancer but sometimes at the cost of increased side effects. Here, we review promising early results from alternative non-invasive techniques that now exist and can deliver similar radiotherapy doses without the need for the surgical procedure required for brachytherapy. Prostate cancer (PC) is the most common malignancy in men. Internal radiotherapy (brachytherapy) has been used to treat PC successfully for over a century. In particular, there is level-one evidence of the benefits of using brachytherapy to escalate the dose of radiotherapy compared with standard external beam radiotherapy approaches. However, the use of PC brachytherapy is declining, despite strong evidence for its improved cancer outcomes. A method using external beam radiotherapy known as virtual high-dose-rate brachytherapy boost (vHDRB) aims to noninvasively mimic a brachytherapy boost radiation dose plan. In this review, we consider the evidence supporting brachytherapy boosts for PC and the continuing evolution of vHDRB approaches, culminating in the current generation of clinical trials, which will help define the role of this emerging modality. [ABSTRACT FROM AUTHOR]

Despite the obvious morphological differences in the visual system, zebrafish share a similar architecture and components of the same embryonic origin as humans. The zebrafish retina has the same layered structure and cell types with similar metabolic and phototransduction support as humans, and is functional 72 h after fertilization, allowing tests of visual function to be performed. The zebrafish genomic database supports genetic mapping studies as well as gene editing, both of which are useful in the ophthalmological field. It is possible to model ocular disorders in zebrafish, as well as inherited retinal diseases or congenital or acquired malformations. Several approaches allow the evaluation of local pathological processes derived from systemic disorders, such as chemical exposure to produce retinal hypoxia or glucose exposure to produce hyperglycemia, mimicking retinopathy of prematurity or diabetic retinopathy, respectively. The pathogenesis of ocular infections, autoimmune diseases, or aging can also be assessed in zebrafish larvae, and the preserved cellular and molecular immune mechanisms can be assessed. Finally, the zebrafish model for the study of the pathologies of the visual system complements certain deficiencies in experimental models of mammals since the regeneration of the zebrafish retina is a valuable tool for the study of degenerative processes and the discovery of new drugs and therapies. [ABSTRACT FROM AUTHOR]

Cilia are microtubule-based organelles that project from the cell surface. In humans and other vertebrates, possession of a single cilium structure enables an assortment of cellular processes ranging from mechanosensation to fluid propulsion and locomotion. Interestingly, cells can possess a single cilium or many more, where so-called multiciliated cells (MCCs) possess apical membrane complexes with several dozen or even hundreds of motile cilia that beat in a coordinated fashion. Development of MCCs is, therefore, integral to control fluid flow and/or cellular movement in various physiological processes. As such, MCC dysfunction is associated with numerous pathological states. Understanding MCC ontogeny can be used to address congenital birth defects as well as acquired disease conditions. Today, researchers used both in vitro and in vivo experimental models to address our knowledge gaps about MCC specification and differentiation. In this review, we summarize recent discoveries from our lab and others that have illuminated new insights regarding the genetic pathways that direct MCC ontogeny in the embryonic kidney using the power of the zebrafish animal model. [ABSTRACT FROM AUTHOR]

Podocytes are exquisitely fashioned kidney cells that serve an essential role in the process of blood filtration. Congenital malformation or damage to podocytes has dire consequences and initiates a cascade of pathological changes leading to renal disease states known as podocytopathies. In addition, animal models have been integral to discovering the molecular pathways that direct the development of podocytes. In this review, we explore how researchers have used the zebrafish to illuminate new insights about the processes of podocyte ontogeny, model podocytopathies, and create opportunities to discover future therapies. [ABSTRACT FROM AUTHOR]

For widespread cutaneous lymphoma, such as mycosis fungoides or leukemia cutis, in patients with acute myeloid leukemia (AML) and for chronic myeloproliferative diseases, total skin irradiation is an efficient treatment modality for disease control. Total skin irradiation aims to homogeneously irradiate the skin of the entire body. However, the natural geometric shape and skin folding of the human body pose challenges to treatment. This article introduces treatment techniques and the evolution of total skin irradiation. Articles on total skin irradiation by helical tomotherapy and the advantages of total skin irradiation by helical tomotherapy are reviewed. Differences among each treatment technique and treatment advantages are compared. Adverse treatment effects and clinical care during irradiation and possible dose regimens are mentioned for future prospects of total skin irradiation. [ABSTRACT FROM AUTHOR]

Spinal cord tumors constitute a diverse group of rare neoplasms associated with significant mortality and morbidity that pose unique clinical and surgical challenges. Diagnostic accuracy and outcome prediction are critical for informed decision making and can promote personalized medicine and facilitate optimal patient management. Machine learning has the ability to analyze and combine vast amounts of data, allowing the identification of patterns and the establishment of clinical associations, which can ultimately enhance patient care. Although artificial intelligence techniques have been explored in other areas of spine surgery, such as spinal deformity surgery, precise machine learning models for spinal tumors are lagging behind. Current applications of machine learning in spinal cord tumors include algorithms that improve diagnostic precision by predicting genetic, molecular, and histopathological profiles. Furthermore, artificial intelligence-based systems can assist surgeons with preoperative planning and surgical resection, potentially reducing the risk of recurrence and consequently improving clinical outcomes. Machine learning algorithms promote personalized medicine by enabling prognostication and risk stratification based on accurate predictions of treatment response, survival, and postoperative complications. Despite their promising potential, machine learning models require extensive validation processes and quality assessments to ensure safe and effective translation to clinical practice. [ABSTRACT FROM AUTHOR]

Variants in WDR19 (IFT144) have been implicated as another possible cause of Stargardt disease. The purpose of this study was to compare longitudinal multimodal imaging of a WDR19-Stargardt patient, harboring p.(Ser485Ile) and a novel c.(3183+1_3184-1)_(3261+1_3262-1)del variant, with 43 ABCA4-Stargardt patients. Age at onset, visual acuity, Ishihara color vision, color fundus, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (OCT) images, microperimetry and electroretinography (ERG) were evaluated. First symptom of WDR19 patient was nyctalopia at the age of 5 years. After the age of 18 years, OCT showed hyper-reflectivity at the level of the external limiting membrane/outer nuclear layer. There was abnormal cone and rod photoreceptor function on ERG. Widespread fundus flecks appeared, followed by perifoveal photoreceptor atrophy. Fovea and peripapillary retina remained preserved until the latest exam at 25 years of age. ABCA4 patients had median age of onset at 16 (range 5–60) years and mostly displayed typical Stargardt triad. A total of 19% had foveal sparing. In comparison to ABCA4 patients, the WDR19 patient had a relatively large foveal preservation and severe rod photoreceptor impairment; however, it was still within the ABCA4 disease spectrum. Addition of WDR19 in the group of genes producing phenocopies of Stargardt disease underlines the importance of genetic testing and may help to understand its pathogenesis. [ABSTRACT FROM AUTHOR]

Three-dimensional printing is widely used in many fields, including engineering, architecture and even medical purposes. The focus of the study is to obtain the ideal weight-to-performance ratio for making a 3D-printed part. The end products of the 3D-printed part are hugely affected by not only the material but also the printing parameters. The printing parameters to be highlighted for this study are the infill density, wall perimeter and layer height, which are the commonly adjusted parameters in 3D printing. The study will be divided into two parts, the simulation analysis and the experimental analysis, to confirm both results toward the trend of Young's modulus for the material. It will then be analyzed and discussed toward any differences between the two results. The results showed that increasing the value of all three parameters will increase the tensile elasticity of the part. [ABSTRACT FROM AUTHOR]

(1) Background: It was suspected that the COVID-19 pandemic would negatively affect health care, including cancer treatment. The aim of the study was to assess the impact of the COVID-19 pandemic on the number of radiotherapy procedures and patients treated with radical and palliative radiotherapy in Poland. (2) Methods: The study was carried out in Warmia and Masuria voivodeship. The number of procedures and treated patients one year before and in the first year of the COVID-19 pandemic were compared. (3) Results: In the first year of the COVID-19 pandemic, the number of radiotherapy procedures and cancer patients treated with radiotherapy in Warmia and Masuria voivodeship in Poland was stable compared to the period before the pandemic. The COVID-19 pandemic has not affected the ratio of palliative to radical procedures. The percentage of ambulatory and hostel procedures significantly increased with the reduction of inpatient care in the first year of the COVID-19 pandemic. (4) Conclusion: No significant decrease in patients treated with radiotherapy during the first year of the pandemic in Warmia and Masuria voivodeship in Poland could indicate the rapid adaptation of radiotherapy centers to the pandemic situation. Future studies should be carried out to monitor the situation because the adverse effects of the pandemic may be delayed. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) plays a crucial role in all stages of lung cancer. Data on recent real-world RT patterns and main drivers of RT decisions in lung cancer in Romania is scarce; we aimed to address these knowledge gaps through this physician-led medical chart review in 16 RT centers across the country. Consecutive patients with lung cancer receiving RT as part of their disease management between May–October 2019 (pre-COVID-19 pandemic) were included. Descriptive statistics were generated for all variables. This cohort included 422 patients: median age 63 years, males 76%, stages I–II 6%, III 43%, IV 50%, mostly adeno- and squamous cell carcinoma (76%), ECOG 0-1 50% at the time of RT. Curative intent RT was used in 36% of cases, palliative RT in 64%. Delays were reported in 13% of patients, mostly due to machine breakdown (67%). Most acute reported RT toxicity was esophagitis (19%). Multiple disease-, patient-, physician- and context-related drivers counted in the decision-making process. This is the first detailed analysis of RT use in lung cancer in Romania. Palliative RT still dominates the landscape. Earlier diagnosis, coordinated multidisciplinary strategies, and the true impact of the multimodal treatments on survival are strongly needed to improve lung cancer outcomes. [ABSTRACT FROM AUTHOR]

The glycine cleavage system (GCS) is a complex located on the mitochondrial membrane that is responsible for regulating glycine levels and contributing one-carbon units to folate metabolism. Congenital mutations in GCS components, such as glycine decarboxylase (gldc), cause an elevation in glycine levels and the rare disease, nonketotic hyperglycinemia (NKH). NKH patients suffer from pleiotropic symptoms including seizures, lethargy, mental retardation, and early death. Therefore, it is imperative to fully elucidate the pathological effects of gldc dysfunction and glycine accumulation during development. Here, we describe a zebrafish model of gldc deficiency that recapitulates phenotypes seen in humans and mice. gldc deficient embryos displayed impaired fluid homeostasis suggesting renal abnormalities, as well as aberrant craniofacial morphology and neural development defects. Whole mount in situ hybridization (WISH) revealed that gldc transcripts were highly expressed in the embryonic kidney, as seen in mouse and human repository data, and that formation of several nephron segments was disrupted in gldc deficient embryos, including proximal and distal tubule populations. These kidney defects were caused by alterations in renal progenitor populations, revealing that the proper function of Gldc is essential for the patterning of this organ. Additionally, further analysis of the urogenital tract revealed altered collecting duct and cloaca morphology in gldc deficient embryos. Finally, to gain insight into the molecular mechanisms underlying these disruptions, we examined the effects of exogenous glycine treatment and observed analogous renal and cloacal defects. Taken together, these studies indicate for the first time that gldc function serves an essential role in regulating renal progenitor development by modulating glycine levels. [ABSTRACT FROM AUTHOR]

The development of multicellular organisms requires a tightly coordinated network of cellular processes and intercellular signalling. For more than 20 years, it has been known that primary cilia are deeply involved in the mediation of intercellular signalling and that ciliary dysfunction results in severe developmental defects. Cilia-mediated signalling regulates cellular processes such as proliferation, differentiation, migration, etc. Another cellular process ensuring proper embryonic development is cell death. While the effect of cilia-mediated signalling on many cellular processes has been extensively studied, the relationship between primary cilia and cell death remains largely unknown. This article provides a short review on the current knowledge about this relationship. [ABSTRACT FROM AUTHOR]

Although cancer can be cured if detected early and treated effectively, it is still a leading cause of death worldwide. Tumor development can be limited by an appropiate immune response, but it can be promoted by chronic extensive inflammation through metabolic dysregulation and angiogenesis. In the past decade, numerous efforts have been made in order to identify novel candidates with predictive values in cancer diagnostics. In line with this, researchers have investigated the involvement of pentraxin-3 (PTX-3) in cellular proliferation and immune escape in various types of cancers, although it has not been clearly elucidated. PTX-3 is a member of the long pentraxin subfamily which plays an important role in regulating inflammation, innate immunity response, angiogenesis, and tissue remodeling. Increased synthesis of inflammatory biomarkers and activation of different cellular mechanisms can induce PTX-3 expression in various types of cells (neutrophils, monocytes, lymphocytes, myeloid dendritic cells, fibroblasts, and epithelial cells). PTX-3 has both pro- and anti-tumor functions, thus dual functions in oncogenesis. This review elucidates the potential usefulness of PTX-3 as a serum biomarker in cancer. While future investigations are needed, PTX-3 is emerging as a promising tool for cancer's diagnosis and prognosis, and also treatment monitoring. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is a mainstay of treatment for brain tumors. To minimize the risk of side effects while maximizing the therapeutic effects, personalized treatment plans, consisting mainly of genomics, radiomics, and mathematical modeling, are increasingly being used. We hypothesize that personality characteristics could influence treatment outcomes and thus could be used to help personalize RT. Therefore, the aim of this study was to identify the psychological characteristics associated with post-treatment physical status and quality of life (QoL) in patients with brain tumors undergoing RT. Two psychological tests—the Eysenck Personality Questionnaire and the State-Trait Anxiety Inventory—were administered prior to RT. Physical parameters before and after RT were also assessed through the following tests: hand grip strength, Timed Up and Go test, 6 Min Walk Test, and Functional Independence Measure. The Functional Assessment of Cancer Therapy–General (FACT-G) was used to assess QoL. The Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) was administered to assess fatigue. Neuroticism was significantly associated with low FACT-G Physical Well-Being scores. Psychoticism was associated with an improvement in physical fitness scores after RT. These findings suggest that personality traits should be considered when designing a personalized radiotherapy plan. [ABSTRACT FROM AUTHOR]

Simple Summary: The automatic diagnosis of fish diseases is an important task in smart aquaculture, and plays a key role in detecting fish conditions, understanding disease signs, and improving fish welfare and health. This paper reviews the latest advances in intelligent fish disease diagnosis techniques for aquatic applications. To acquire high-quality images to improve the accuracy of fish disease diagnosis, the paper reviews, in the second paragraph, how image-processing techniques can be used to acquire high-quality images. The third paragraph of this paper reviews the methods of intelligent fish disease diagnosis, including expert system detection, camera image detection, microscope image detection, spectral image detection, fluorescence image detection, ultrasonic image detection, and sensor detection methods. Additionally, the advantages and disadvantages of each detection method are summarized, including whether they cause damage to the fish body. Finally, we put forward the prospect of the intelligent detection of fish diseases and summarize the methods that may be used in the intelligent diagnosis of fish disease. Aquatic products, as essential sources of protein, have attracted considerable concern by producers and consumers. Precise fish disease prevention and treatment may provide not only healthy fish protein but also ecological and economic benefits. However, unlike intelligent two-dimensional diagnoses of plants and crops, one of the most serious challenges confronted in intelligent aquaculture diagnosis is its three-dimensional space. Expert systems have been applied to diagnose fish diseases in recent decades, allowing for restricted diagnosis of certain aquaculture. However, this method needs aquaculture professionals and specialists. In addition, diagnosis speed and efficiency are limited. Therefore, developing a new quick, automatic, and real-time diagnosis approach is very critical. The integration of image-processing and computer vision technology intelligently allows the diagnosis of fish diseases. This study comprehensively reviews image-processing technology and image-based fish disease detection methods, and analyzes the benefits and drawbacks of each diagnostic approach in different environments. Although it is widely acknowledged that there are many approaches for disease diagnosis and pathogen identification, some improvements in detection accuracy and speed are still needed. Constructing AR 3D images of fish diseases, standard and shared datasets, deep learning, and data fusion techniques will be helpful in improving the accuracy and speed of fish disease diagnosis. [ABSTRACT FROM AUTHOR]

This study aimed to develop a corneal epithelial injury model in zebrafish (Danio rerio) and investigate the effectiveness of polydeoxyribonucleotide (PDRN) treatment on in vivo corneal epithelial regeneration and wound healing. Chemical injury to zebrafish cornea was produced by placing a small cotton swab containing 3% acetic acid solution. PDRN treatment was performed by immersing corneal-injured zebrafish in water containing PDRN (2 mg/mL) for 10 min at 0, 24, 48, and 72 h post-injury (hpi). The level of corneal healing was evaluated by fluorescein staining, histological examination, transcriptional profiling, and immunoblotting techniques. Fluorescein staining results demonstrate that PDRN treatment significantly (p < 0.05) reduced the wounded area of the zebrafish eye at 48 and 72 hpi, suggesting that PDRN may accelerate the corneal re-epithelialization. Histopathological evaluation revealed that injured corneal epithelial cells were re-organized at 72 hpi upon PDRN treatment with increased goblet cell density and size. Moreover, transcriptional analysis results demonstrate that PDRN treatment induced the mRNA expression of adora2ab (6.3-fold), pax6a (7.8-fold), pax6b (29.3-fold), klf4 (7.3-fold), and muc2.1 (5.0-fold) after the first treatment. Besides, tnf-α (2.0-fold) and heat-shock proteins (hsp70; 2.8-fold and hsp90ab1; 1.6-fold) have modulated the gene expression following the PDRN treatment. Immunoblotting results convincingly confirmed the modulation of Mmp-9, Hsp70, and Tnf-α expression levels upon PDRN treatment. Overall, our corneal injury model in zebrafish allows for understanding the morphological and molecular events of corneal epithelial healing, and ophthalmic responses for PDRN treatment following acid injury in zebrafish. [ABSTRACT FROM AUTHOR]

Initially discovered as the smallest component of the intraflagellar transport (IFT) system, the IFT20 protein has been found to be implicated in several unconventional mechanisms beyond its essential role in the assembly and maintenance of the primary cilium. IFT20 is now considered a key player not only in ciliogenesis but also in vesicular trafficking of membrane receptors and signaling proteins. Moreover, its ability to associate with a wide array of interacting partners in a cell-type specific manner has expanded the function of IFT20 to the regulation of intracellular degradative and secretory pathways. In this review, we will present an overview of the multifaceted role of IFT20 in both ciliated and non-ciliated cells. [ABSTRACT FROM AUTHOR]

Background: Surface brachytherapy, usually characterized by a high dose gradient, allows the dose to be precisely deposited in the irradiated area while protecting critical organs. When the lesion is located in the nasal or ocular region, the organ of vision must be protected. The aim of this study was to verify the dose distributions near critical organs in the head and neck region during a brachytherapy procedure using lead shielding of the eye. Methods: Anthropomorphic phantom using 3D-printing technology was prepared. The doses deposited at a point in the lens of the eye and on the surface of the eyelid, directly under the lead shield were calculated and measured using EBT3 radiochromic films. Comparison of doses planned in the treatment planning system using the TG-43 formalism, TG-186 formalism, and measured were also performed. Results: Comparing the planned and calculated doses with TG186 formalism it can be assumed that the use of lead shields is a method for protecting the organ of vision from the adverse effects of ionizing radiation. Conclusions: The decision to use a lead shield during facial surface brachytherapy procedures should be made on a patient-by-patient basis and based on model-based calculation methods recommended by TG186. [ABSTRACT FROM AUTHOR]

(1) In breast-conserving therapy (BCT), adjuvant radiation, including tumor bed boost, is mandatory. Safely delivered thermal boost (TB) based on radio-sensitizing interstitial microwave hyperthermia (MWHT) preceding standard high-dose-rate (HDR) brachytherapy (BT) boost has the potential for local control (LC) improvement. The study is to report the long-term results regarding LC, disease-free survival (DFS), overall survival (OS), toxicity, and cosmetic outcome (CO) of HDR-BT boost ± MWHT for early breast cancer (BC) patients treated with BCT. (2) In the years 2006 and 2007, 57 diverse stages and risk (IA-IIIA) BC patients were treated with BCT ± adjuvant chemotherapy followed by 42.5–50.0 Gy whole breast irradiation (WBI) and 10 Gy HDR-BT boost. Overall, 25 patients (group A; 43.9%) had a BT boost, and 32 (group B; 56.1%) had an additional pre-BT single session of interstitial MWHT on a tumor bed. Long-term LC, DFS, OS, CO, and late toxicity were evaluated. (3) Median follow-up was 94.8 months (range 1.1–185.5). LC was 55/57, or 96.5% (1 LR in each group). DFS was 48/57, or 84.2% (4 failures in group A, 5 in B). OS was 46/57, or 80.7% (6 deaths in group A, 5 in B). CO was excellent in 60%, good in 36%, and satisfactory in 4% (A), and in 53.1%, 34.4%, and 9.4% (B), respectively. One poor outcome was noted (B). Late toxicity as tumor bed hardening occurred in 19/57, or 33.3% of patients (9 in A, 10 in B). In one patient, grade 2 telangiectasia occurred (group A). All differences were statistically insignificant. (4) HDR-BT boost ± TB was feasible, well-tolerated, and highly locally effective. LC, DFS, and OS were equally distributed between the groups. Pre-BT MWHT did not increase rare late toxicity. [ABSTRACT FROM AUTHOR]

Acetaminophen is a common analgesic, but its potential effects on early embryonic development are not well understood. Previous studies using zebrafish (Danio rerio) have described the effects of acetaminophen on liver development and physiology, and a few have described gross physiological and morphological defects. Using a high but non-embryonic lethal dose of acetaminophen, we probed for defects in zebrafish craniofacial cartilage development. Strikingly, acetaminophen treatment caused severe craniofacial cartilage defects, primarily affecting both the presence and morphology of pharyngeal arch-derived cartilages of the viscerocranium. Delaying acetaminophen treatment restored developing cartilages in an order correlated with their corresponding pharyngeal arches, suggesting that acetaminophen may target pharyngeal arch development. Craniofacial cartilages are derived from cranial neural crest cells; however, many neural crest cells were still seen along their expected migration paths, and most remaining cartilage precursors expressed the neural crest markers sox9a and sox10, then eventually col2a1 (type II collagen). Therefore, the defects are not primarily due to an early breakdown of neural crest or cartilage differentiation. Instead, apoptosis is increased around the developing pharyngeal arches prior to chondrogenesis, further suggesting that acetaminophen may target pharyngeal arch development. Many craniofacial muscles, which develop in close proximity to the affected cartilages, were also absent in treated larvae. Taken together, these results suggest that high amounts of acetaminophen can disrupt multiple aspects of craniofacial development in zebrafish. [ABSTRACT FROM AUTHOR]

Embryonic hyperglycemia negatively impacts retinal development, leading to abnormal visual behavior, altered timing of retinal progenitor differentiation, decreased numbers of retinal ganglion cells and Müller glia, and vascular leakage. Because synaptic disorganization is a prominent feature of many neurological diseases, the goal of the current work was to study the potential impact of hyperglycemia on retinal ribbon synapses during embryonic development. Our approach utilized reverse transcription quantitative PCR (RT-qPCR) and immunofluorescence labeling to compare the transcription of synaptic proteins and their localization in hyperglycemic zebrafish embryos, respectively. Our data revealed that the maturity of synaptic ribbons was compromised in hyperglycemic zebrafish larvae, where altered ribeye expression coincided with the delay in establishing retinal ribbon synapses and an increase in the immature synaptic ribbons. Our results suggested that embryonic hyperglycemia disrupts retinal synapses by altering the development of the synaptic ribbon, which can lead to visual defects. Future studies using zebrafish models of hyperglycemia will allow us to study the underlying mechanisms of retinal synapse development. [ABSTRACT FROM AUTHOR]

3D printing is a revolutionary additive manufacturing method that enables rapid prototyping and design flexibility. A variety of thermoplastic polymers can be used in printing. As it is necessary to reduce the consumption of petrochemical resources, alternative solutions are being researched, and the interest in using bioplastics and biocomposites is constantly growing. Often, however, the properties of biopolymers are insufficient and need to be improved to compete with petroleum-based plastics. The paper aims to analyze the available information on elements produced from more than one material, with additive manufacturing resulting from 3D printing using biopolymer Polylactic Acid (PLA). The study notes the possibility of modifying and improving the properties of PLA using layered printing or by modifying PLA filaments. Several modifications improving and changing the properties of PLA were also noted, including printing parameters when combined with other materials: process temperatures, filling, and surface development for various sample geometries. [ABSTRACT FROM AUTHOR]

The TGF-β superfamily is ubiquitously distributed from invertebrates to vertebrates with diverse cellular functioning such as cell adhesion, motility, proliferation, apoptosis, and differentiation. The present study aimed to characterize the TGF-β gene superfamily in buffalo through evolutionary, structural, and single nucleotide polymorphism (SNPs) analyses to find the functional effect of SNPs in selected genes. We detected 32 TGF-β genes in buffalo genome and all TGF-β proteins exhibited basic nature except INHA, INHBC, MSTN, BMP10, and GDF2, which showed acidic properties. According to aliphatic index, TGF-β proteins were thermostable but unstable in nature. Except for GDF1 and AMH, TGF-β proteins depicted hydrophilic nature. Moreover, all the detected buffalo TGF-β genes showed evolutionary conserved nature. We also identified eight segmental and one tandem duplication event TGF-β gene family in buffalo, and the ratio of Ka/Ks demonstrated that all the duplicated gene pairs were under selective pressure. Comparative amino acid analysis demonstrated higher variation in buffalo TGF-β gene family, as a total of 160 amino acid variations in all the buffalo TGF-β proteins were detected. Mutation analysis revealed that 13 mutations had an overall damaging effect that might have functional consequences on buffalo growth, folliculogenesis, or embryogenesis. [ABSTRACT FROM AUTHOR]

Centrosome-containing cells assemble their spindles exploiting three main classes of microtubules (MTs): MTs nucleated by the centrosomes, MTs generated near the chromosomes/kinetochores, and MTs nucleated within the spindle by the augmin-dependent pathway. Mammalian and Drosophila cells lacking the centrosomes generate MTs at kinetochores and eventually form functional bipolar spindles. However, the mechanisms underlying kinetochore-driven MT formation are poorly understood. One of the ways to elucidate these mechanisms is the analysis of spindle reassembly following MT depolymerization. Here, we used an RNA interference (RNAi)-based reverse genetics approach to dissect the process of kinetochore-driven MT regrowth (KDMTR) after colcemid-induced MT depolymerization. This MT depolymerization procedure allows a clear assessment of KDMTR, as colcemid disrupts centrosome-driven MT regrowth but not KDMTR. We examined KDMTR in normal Drosophila S2 cells and in S2 cells subjected to RNAi against conserved genes involved in mitotic spindle assembly: mast/orbit/chb (CLASP1), mei-38 (TPX2), mars (HURP), dgt6 (HAUS6), Eb1 (MAPRE1/EB1), Patronin (CAMSAP2), asp (ASPM), and Klp10A (KIF2A). RNAi-mediated depletion of Mast/Orbit, Mei-38, Mars, Dgt6, and Eb1 caused a significant delay in KDMTR, while loss of Patronin had a milder negative effect on this process. In contrast, Asp or Klp10A deficiency increased the rate of KDMTR. These results coupled with the analysis of GFP-tagged proteins (Mast/Orbit, Mei-38, Mars, Eb1, Patronin, and Asp) localization during KDMTR suggested a model for kinetochore-dependent spindle reassembly. We propose that kinetochores capture the plus ends of MTs nucleated in their vicinity and that these MTs elongate at kinetochores through the action of Mast/Orbit. The Asp protein binds the MT minus ends since the beginning of KDMTR, preventing excessive and disorganized MT regrowth. Mei-38, Mars, Dgt6, Eb1, and Patronin positively regulate polymerization, bundling, and stabilization of regrowing MTs until a bipolar spindle is reformed. [ABSTRACT FROM AUTHOR]

Calcium imaging has rapidly become a methodology of choice for real-time in vivo neuron analysis. Its application to large sets of data requires automated tools to annotate and segment cells, allowing scalable image segmentation under reproducible criteria. In this paper, we review and summarize the most recent methods for computational segmentation of calcium imaging. The contributions of the paper are three-fold: we provide an overview of the main algorithms taxonomized in three categories (signal processing, matrix factorization and machine learning-based approaches), we highlight the main advantages and disadvantages of each category and we provide a summary of the performance of the methods that have been tested on public benchmarks (with links to the public code when available). [ABSTRACT FROM AUTHOR]

Simple Summary: Diabetes is a chronic metabolic disease characterized by high blood glucose levels (hyperglycemia). Type 2 diabetes mellitus (T2DM) and its complications are a worldwide public health problem, affecting people from all developed and developing countries. Hyperglycemia can cause damage to the vascular system and dysfunction of organs, such as the kidneys, heart, retina of the eyes, and nerves. Diabetic nephropathy (DN) is one of the most severe micro-vascular complications, which can lead to ESRD (end-stage renal disease). Zebrafish are ideal for wide-scale analysis or screening, due to their small size, quick growth, transparent embryos, vast number of offspring, and gene similarity with humans, which combine to make zebrafish an ideal model for diabetes. The readily available tools for gene editing using morpholinos or CRISPR/Cas9, as well as chemical/drug therapy by microinjection or skin absorption, enable zebrafish diabetes mellitus models to be established in a number of ways. In this review, we emphasize the physiological and pathological processes relating to micro-vascular problems in zebrafish, as well as the many experimental zebrafish models used to research DN, and the DN-related outcomes and mechanisms observed in zebrafish. This study specifies the benefits and drawbacks and future perspective of using zebrafish as a disease model. Diabetes mellitus (DM) is a complicated metabolic illness that has had a worldwide impact and placed an unsustainable load on both developed and developing countries' health care systems. According to the International Diabetes Federation, roughly 537 million individuals had diabetes in 2021, with type 2 diabetes mellitus accounting for the majority of cases (T2DM). T2DM is a chronic illness defined by insufficient insulin production from pancreatic islet cells. T2DM generates various micro and macrovascular problems, with diabetic nephropathy (DN) being one of the most serious microvascular consequences, and which can lead to end-stage renal disease. The zebrafish (Danio rerio) has set the way for its future as a disease model organism. As numerous essential developmental processes, such as glucose metabolism and reactive metabolite production pathways, have been identified in zebrafish that are comparable to those seen in humans, it is a good model for studying diabetes and its consequences. It also has many benefits over other vertebrate models, including the permeability of its embryos to small compounds, disease-driven therapeutic target selection, in vivo validation, and deconstruction of biological networks. The organism can also be utilized to investigate and understand the genetic abnormalities linked to the onset of diabetes problems. Zebrafish may be used to examine and visualize the growth, morphology, and function of organs under normal physiological and diabetic settings. The zebrafish has become one of the most useful models for studying DN, especially when combined with genetic alterations and/or mutant or transgenic fish lines. The significant advancements of CRISPR and next-generation sequencing technology for disease modelling in zebrafish, as well as developments in molecular and nano technologies, have advanced the understanding of the molecular mechanisms of several human diseases, including DN. In this review, we emphasize the physiological and pathological processes relating to microvascular problems in zebrafish, as well as the many experimental zebrafish models used to research DN, and the DN-related outcomes and mechanisms observed in zebrafish. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize the ophthalmic and genetic features of Bardet Biedl (BBS) syndrome in a cohort of patients from a German specialized ophthalmic care center. Sixty-one patients, aged 5–56 years, underwent a detailed ophthalmic examination including visual acuity and color vision testing, electroretinography (ERG), visually evoked potential recording (VEP), fundus examination, and spectral domain optical coherence tomography (SD-OCT). Adaptive optics flood illumination ophthalmoscopy was performed in five patients. All patients had received diagnostic genetic testing and were selected upon the presence of apparent biallelic variants in known BBS-associated genes. All patients had retinal dystrophy with morphologic changes of the retina. Visual acuity decreased from ~0.2 (decimal) at age 5 to blindness 0 at 50 years. Visual field examination could be performed in only half of the patients and showed a concentric constriction with remaining islands of function in the periphery. ERG recordings were mostly extinguished whereas VEP recordings were reduced in about half of the patients. The cohort of patients showed 51 different likely biallelic mutations—of which 11 are novel—in 12 different BBS-associated genes. The most common associated genes were BBS10 (32.8%) and BBS1 (24.6%), and by far the most commonly observed variants were BBS10 c.271dup;p.C91Lfs*5 (21 alleles) and BBS1 c.1169T>G;p.M390R (18 alleles). The phenotype associated with the different BBS-associated genes and genotypes in our cohort is heterogeneous, with diverse features without genotype–phenotype correlation. The results confirm and expand our knowledge of this rare disease. [ABSTRACT FROM AUTHOR]

The Unc119 protein mediates transport of myristoylated proteins to the photoreceptor outer segment, a specialized primary cilium. This transport activity is regulated by the GTPase Arl3 as well as by Arl13b and Rp2 that control Arl3 activation/inactivation. Interestingly, Unc119 is also enriched in photoreceptor synapses and can bind to RIBEYE, the main component of synaptic ribbons. In the present study, we analyzed whether the known regulatory proteins, that control the Unc119-dependent myristoylated protein transport at the primary cilium, are also present at the photoreceptor synaptic ribbon complex by using high-resolution immunofluorescence and immunogold electron microscopy. We found Arl3 and Arl13b to be enriched at the synaptic ribbon whereas Rp2 was predominantly found on vesicles distributed within the entire terminal. These findings indicate that the synaptic ribbon could be involved in the discharge of Unc119-bound lipid-modified proteins. In agreement with this hypothesis, we found Nphp3 (Nephrocystin-3), a myristoylated, Unc119-dependent cargo protein enriched at the basal portion of the ribbon in close vicinity to the active zone. Mutations in Nphp3 are known to be associated with Senior–Løken Syndrome 3 (SLS3). Visual impairment and blindness in SLS3 might thus not only result from ciliary dysfunctions but also from malfunctions of the photoreceptor synapse. [ABSTRACT FROM AUTHOR]

Retinal organoids generated from human embryonic stem cells or iPSCs recreate the key structural and functional features of mammalian retinal tissue in vitro. However, the differences in the development of retinal organoids and normal retina in vivo are not well defined. Thus, in the present study, we analyzed the development of retinal organoids and zebrafish retina after inhibition of CXCR4, a key role in neurogenesis and optic nerve development, with the antagonist AMD3100. Our data indicated that CXCR4 was mainly expressed in ganglion cells in retinal organoids and was rarely expressed in amacrine or photoreceptor cells. AMD3100 treatment reduced the retinal organoid generation ratio, impaired differentiation, and induced morphological changes. Ganglion cells, amacrine cells, and photoreceptors were decreased and abnormal locations were observed in organoids treated with AMD3100. Neuronal axon outgrowth was also damaged in retinal organoids. Similarly, a decrease of ganglion cells, amacrine cells, and photoreceptors and the distribution of neural outgrowth was induced by AMD3100 treatment in zebrafish retina. However, abnormal photoreceptor ensembles induced by AMD3100 treatment in the organoids were not detected in zebrafish retina. Therefore, our study suggests that although retinal organoids might provide a reliable model for reproducing a retinal developmental model, there is a difference between the organoids and the retina in vivo. [ABSTRACT FROM AUTHOR]

In clinical radiotherapy, the most important aspects are the dose distribution in the target volume and healthy organs, including out-of-field doses in the body. Compared to photon beam radiation, dose distribution in electron beam radiotherapy has received much less attention, mainly due to the limited range of electrons in tissues. However, given the growing use of electron intraoperative radiotherapy and FLASH, further study is needed. Therefore, in this study, we determined out-of-field doses from an electron beam in a phantom model using two dosimetric detectors (diode E and cylindrical Farmer-type ionizing chamber) for electron energies of 6 MeV, 9 MeV and 12 MeV. We found a clear decrease in out-of-field doses as the distance from the field edge and depth increased. The out-of-field doses measured with the diode E were lower than those measured with the Farmer-type ionization chamber at each depth and for each electron energy level. The out-of-field doses increased when higher energy megavoltage electron beams were used (except for 9 MeV). The out-of-field doses at shallow depths (1 or 2 cm) declined rapidly up to a distance of 3 cm from the field edge. This study provides valuable data on the deposition of radiation energy from electron beams outside the irradiation field. [ABSTRACT FROM AUTHOR]

No clear criteria have yet been established to guide decision-making for patient selection and the optimal timing of adaptive radiotherapy (ART) based on image-guided radiotherapy (IGRT). We have developed a novel protocol—the Best for Adaptive Radiotherapy (B-ART) protocol—to guide patient selection for ART. The aim of the present study is to describe this protocol, to evaluate its validity in patients with head and neck (HN) cancer, and to identify the anatomical and clinical predictors of the need for replanning. We retrospectively evaluated 82 patients with HN cancer who underwent helical tomotherapy (HT) and subsequently required replanning due to soft tissue changes upon daily MVCT. Under the proposed criteria, patients with anatomical changes >3 mm on three to four consecutive scans are candidates for ART. We compared the volumes on the initial CT scan (iCT) and the replanning CT (rCT) scan for the clinical target volumes (CTV1, referring to primary tumor or tumor bed and CTV2, metastatic lymph nodes) and for the parotid glands (PG) and body contour (B-body). The patients were stratified by primary tumor localization, clinical stage, and treatment scheme. The main reasons for replanning were: (1) a planning target volume (PTV) outside the body contour (n = 70; 85.4%), (2) PG shrinkage (n = 69; 84.1%), (3) B-body deviations (n = 69; 84.1%), and (4) setup deviations (n = 40; 48.8%). The replanning decision was made, on average, during the fourth week of treatment (n = 47; 57.3%). The mean reductions in the size of the right and left PG volumes were 6.31 cc (20.9%) and 5.98 cc (20.5%), respectively (p < 0.001). The reduction in PG volume was ≥30% in 30 patients (36.6%). The volume reduction in all of the anatomical structures was statistically significant. Four variables—advanced stage disease (T3–T4), chemoradiation, increased weight loss, and oropharyngeal localization—were significantly associated with the need for ART. The B-ART protocol provides clear criteria to eliminate random errors, and to allow for an early response to relevant changes in target volumes. [ABSTRACT FROM AUTHOR]

The aim of the study was to determine the influence of a key treatment plan and beam parameters on overall dose distribution and on doses in organs laying in further distance from the target during prostate SBRT. Multiple representative treatment plans (n = 12) for TrueBeam and CyberKnife were prepared and evaluated. Nontarget doses were measured with anionization chamber, in a quasi-humanoid phantom at four sites corresponding to the intestines, right lung, thyroid, and head. The following parameters were modified: radiotherapy technique, presence or not of a flattening filter, degree of modulation, and use or not of jaw tracking function for TrueBeam and beam orientation set-up, optimization techniques, and number of MUs for CyberKnife. After usual optimization doses in intestines (near the target) were 0.73% and 0.76%, in head (farthest from target) 0.05% and 0.19% for TrueBeam and CyberKnife, respectively. For TrueBeam the highest peripheral (head, thyroid, lung) doses occurred for the VMAT with the flattening filter while the lowest for 3DCRT. For CyberKnife the highest doses were for gantry with caudal direction beams blocked (gantry close to OARs) while the lowest was the low modulated VOLO optimization technique. The easiest method to reduce peripheral doses was to combine FFF with jaw tracking and reducing monitor units at TrueBeam and to avoid gantry position close to OARs together with reduction of monitor units at CyberKnife, respectively. The presented strategies allowed to significantly reduce out-of-field and nontarget doses during prostate radiotherapy delivered with TrueBeam and CyberKnife. A different approach was required to reduce peripheral doses because of the difference in dose delivery techniques: non-coplanar using CyberKnife and coplanar using TrueBeam, respectively. [ABSTRACT FROM AUTHOR]

Aging is a continuous process over time that is mainly related to natural alterations in mechanical–biological processes. This phenomenon is due to several factors, including the time and energy of biological processes. Aging can be attributed to biological factors such as oxidative stress, cell longevity, and stem cell senescence. Currently, aging is associated with several diseases, such as neurodegenerative diseases, cancer, and other diseases related to oxidative stress. In addition, certain natural molecules, including those derived from vegetables, have shown the ability to delay the aging process. Their effects are linked to different mechanisms of action, such as tissue regeneration and the activation of longevity and anti-senescence genes. The present work discusses the impact of vegetables, and bioactive compounds isolated from vegetables, against the physiological and pathological aging process and accompanying human diseases. [ABSTRACT FROM AUTHOR]